Medical Sciences

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24 pages, 13380 KB

Open AccessArticle

Beyond Lymphovascular Invasion: Site-Dependent Patterns of Lymphatic, Venous and Perineural Involvement in Laryngo-Hypopharyngeal Carcinoma

by Roxana-Andreea Popa, Cosmin-Gabriel Popa, Delia Hînganu, Marius Valeriu Hînganu, Cristinel Ionel Stan, Rares-Vasile Tracicaru and Otilia Boișteanu

Med. Sci. 2026, 14(5), 527; https://doi.org/10.3390/medsci14050527 - 28 Aug 2026

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Abstract

Background: Building on our recent characterization of a layer-specific neurovascular microenvironment in the normal human vocal fold, we examined how that unit behaves in laryngo-hypopharyngeal carcinoma, where lymphatic and venous involvement are conventionally reported together. Methods: We retrospectively analyzed 48 laryngo-hypopharyngeal squamous cell [...] Read more.

Background: Building on our recent characterization of a layer-specific neurovascular microenvironment in the normal human vocal fold, we examined how that unit behaves in laryngo-hypopharyngeal carcinoma, where lymphatic and venous involvement are conventionally reported together. Methods: We retrospectively analyzed 48 laryngo-hypopharyngeal squamous cell carcinomas (2017–2025) with complete TNM vascular reporting, confirmed by CD31 and neuron-specific enolase (NSE) immunohistochemistry. Lymphatic (L) versus venous (V) assignment rested on morphological criteria, since CD31 cannot discriminate lymphatic from blood vessels and D2-40 was unavailable. L, V and perineural (Pn) status were related to pT stage and topography and combined into a composite score (NV = L + V + Pn), reassessed after adjustment for pT. Results: Concordant patterns predominated (L0V0 60.4%, L1V1 27.1%); 12.5% were dissociated. Vascular invasion correlated with pT (ρ = 0.393, p = 0.006) and, unadjusted, with Pn, but not after adjustment for pT. NV tracked pT more strongly than any single axis (KR-20 = 0.725; ρ = 0.534, p < 0.001). Glottic-only carcinoma showed the lowest involvement on all axes. Conclusions: Reporting L, V and Pn separately—parameters already in routine TNM notation—may capture tumor aggressiveness more completely than LVI as a single entity. This series cannot establish stage-independent co-variation in these axes, validate the L/V distinction molecularly, or, lacking follow-up, demonstrate prognostic value. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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15 pages, 2276 KB

Open AccessArticle

Risk of Second Primary Cancers in Melanoma Survivors: A Retrospective Hospital-Based Cohort Study from Two Romanian Referral Centres

by Salomea-Ruth Halmágyi, Loredana Ungureanu, Alina Florentina Vasilovici, Mihail-Alexandru Badea, Ioana-Irina Trufin, Adina Patricia Apostu, Adrian Ilie Pascu and Simona Corina Şenila

Med. Sci. 2026, 14(4), 494; https://doi.org/10.3390/medsci14040494 - 19 Aug 2026

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Abstract

Background and objectives: Melanoma survivors may develop additional primary malignancies, but data from Eastern European hospital cohorts are scarce. We aimed to estimate the observed incidence of second primary cancers (SPCs) within a Romanian referral-centre cohort, identify associated factors, and explore the association [...] Read more.

Background and objectives: Melanoma survivors may develop additional primary malignancies, but data from Eastern European hospital cohorts are scarce. We aimed to estimate the observed incidence of second primary cancers (SPCs) within a Romanian referral-centre cohort, identify associated factors, and explore the association of SPC occurrence with overall survival. Methods: We conducted a retrospective, hospital-based cohort study of 394 patients with histopathologically confirmed cutaneous melanoma followed at two referral centres in Cluj-Napoca. Additional malignancies were counted as new primaries only when clinical and/or histopathological documentation distinguished them from recurrence or metastasis. Incidence density was expressed per 1000 person-years. Multivariable logistic regression assessed age, sex, residence, and Breslow thickness. Fixed-covariate Cox and Kaplan–Meier analyses were considered exploratory because of immortal-time and competing-risk limitations. Results: Over 1848 person-years, 79 patients (20.1%) developed at least one SPC (131 events; observed incidence 70.9/1000 person-years), most frequently cutaneous (53.6/1000 person-years). SPC occurrence increased with age (Cochran–Armitage Z = 5.63, p < 0.001); the Kaplan–Meier complement estimate reached 20.7% at five years. Age independently predicted SPC (OR 1.86 per decade, p < 0.001), whereas greater Breslow thickness was inversely associated (OR 0.86, p = 0.008). Actinic keratosis showed a strong unadjusted association (OR 6.64, p < 0.001) but was not included in the adjusted model. The fixed-status Cox model showed lower mortality among patients with an SPC (HR 0.36, p < 0.001), a finding vulnerable to detection and immortal-time bias. Conclusions: SPCs were frequent in this hospital cohort and predominantly cutaneous. Older age was an independent predictor, while actinic keratosis was a strong unadjusted marker. Prospective, population-based validation is needed before surveillance intensity is individualised. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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12 pages, 16048 KB

Open AccessArticle

Immunohistochemical Characterization of the Androgen Receptor in Breast Cancer and Its Relationship with Breast Cancer Subtypes

by María Luisa Sánchez-Ferrer, Alexandra Esteban Pedreño, Julián J. Gonzalo-Arense, Inmaculada Ruiz Boluda, Micaela Llamas Sarriá, Jose Luis Alonso Romero, Domingo Sánchez Martínez, Carlos Manuel Martínez-Cáceres, Jaime Mendiola and Alberto M. Torres Cantero

Med. Sci. 2026, 14(4), 479; https://doi.org/10.3390/medsci14040479 - 13 Aug 2026

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Abstract

Background/Objectives: Breast cancer is the most frequent malignant neoplasm in women and presents marked biological heterogeneity. The androgen receptor (AR) has emerged as a biomarker with important prognostic and therapeutic implications, its effect varying according to the molecular subtype. The objective of this [...] Read more.

Background/Objectives: Breast cancer is the most frequent malignant neoplasm in women and presents marked biological heterogeneity. The androgen receptor (AR) has emerged as a biomarker with important prognostic and therapeutic implications, its effect varying according to the molecular subtype. The objective of this study was to analyze AR expression in breast carcinoma samples and its relationship with the different molecular subtypes and clinicopathological variables. Methods: An observational, descriptive, cross-sectional, and prospective study was conducted based on the immunohistochemical analysis of 215 formalin-fixed, paraffin-embedded breast carcinoma samples. AR expression was digitally evaluated as the percentage of positive tumor cells after incubation with an anti-AR monoclonal antibody. Results: A high frequency of AR expression was demonstrated in the cohort, with a median of 53.3%. There were statistically significant differences between molecular subtypes (p < 0.001), detecting greater expression in luminal tumors and markedly low levels in triple-negative breast cancer (TNBC) (median 0.41%). A significant negative correlation was evidenced between AR expression and the Ki-67 proliferation index (ρ = −0.272; p < 0.001), both in the overall sample and in the TNBC subgroup. Conclusions: The androgen receptor is associated with specific molecular subtypes and lower tumor proliferation, suggesting a less aggressive phenotype and supporting its role as a biological biomarker and potential therapeutic target in the management of breast cancer. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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14 pages, 482 KB

Open AccessCommunication

Chemotherapy Before Radiotherapy in Adjuvant Breast Cancer: The Origins of a Convention and the Case for Revisiting Sequence in the Era of Hypofractionation

by Mihai-Teodor Georgescu

Med. Sci. 2026, 14(4), 477; https://doi.org/10.3390/medsci14040477 - 13 Aug 2026

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Abstract

Guidelines in early breast cancer place adjuvant chemotherapy before radiotherapy, permit radiotherapy concurrently with endocrine and anti-HER2 agents, but discourage it before or during cytotoxic chemotherapy. This narrative review asks whether that convention remains defensible. Its historical basis, a single randomised trial whose [...] Read more.

Guidelines in early breast cancer place adjuvant chemotherapy before radiotherapy, permit radiotherapy concurrently with endocrine and anti-HER2 agents, but discourage it before or during cytotoxic chemotherapy. This narrative review asks whether that convention remains defensible. Its historical basis, a single randomised trial whose distant-metastasis signal did not survive long-term follow-up, is weaker than is commonly assumed. Its contemporary basis is stronger and is stated here explicitly: an asymmetry of absolute benefit, in which a two-point gain in locoregional control yields roughly half a percentage point of mortality benefit once the EBCTCG four-to-one relationship is applied, whereas degradation of systemic therapy reaches mortality undiscounted. We specify three conditions under which a sequencing change could be justified and note that the absolute loss from a short chemotherapy delay cannot presently be quantified from randomised data. Meanwhile, chemotherapy has lengthened while radiotherapy has contracted to a one- to three-week whole-breast schedule, potentially extended when a sequential tumour-bed boost is required. The retrospective evidence is limited: one cohort offers a hypothesis-generating locoregional signal qualified by an unexpectedly high control-arm event rate and an unplanned subgroup analysis, while another supports only short-term feasibility and tolerability; neither demonstrates benefit in distant control or survival. We further argue that the population in which the question remains clinically live is narrow and probably contracting, since genomic de-escalation withdraws from chemotherapy the phenotypes with the most favourable arithmetic. Adjuvant sequencing is best regarded as an open, testable question within a defined population rather than a general case for change. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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22 pages, 1339 KB

Open AccessArticle

The Cervical Cancer Paradox in Eastern Europe: How Knowledge and Institutional Trust Shape HPV Vaccination Attitudes in Romania

by Ionel-Daniel Nati, Carmen Mihaela Mihu, Dan Mihu, Razvan Ciortea, Doru Diculescu, Mihaela Oancea, Carmen Bucuri, Maria Patricia Roman, Cristina Mihaela Ormindean, Viorela Suciu, Dumitru Rares Ciocoi-Pop and Andrei Mihai Malutan

Med. Sci. 2026, 14(4), 431; https://doi.org/10.3390/medsci14040431 - 25 Jul 2026

Cited by 1 | Viewed by 626

Abstract

Background: Although cervical cancer is a highly preventable malignancy, Romania continues to report critical mortality rates. This paradox is largely attributable to the suboptimal implementation of clinical guidelines and a passive, “opt-in” administrative framework. This cross-sectional study investigates the cognitive and behavioural determinants—specifically, [...] Read more.

Background: Although cervical cancer is a highly preventable malignancy, Romania continues to report critical mortality rates. This paradox is largely attributable to the suboptimal implementation of clinical guidelines and a passive, “opt-in” administrative framework. This cross-sectional study investigates the cognitive and behavioural determinants—specifically, human papillomavirus (HPV) knowledge, institutional trust in healthcare systems, and digital misinformation exposure—that modulate female attitudes toward HPV immunisation. Methods: An observational cross-sectional study was conducted between December 2025 and March 2026 across four obstetrics and gynaecology clinics. Data were collected via digital questionnaires administered to adult female patients aged 18 to 65 years. The assessment tool evaluated four primary domains: HPV knowledge, perceived vaccine safety, immunisation intention, and the degree of exposure to social media misinformation. Results: The cohort demonstrated a substantially low vaccination rate (28.6%). Statistical analysis elucidated significant positive correlations between HPV knowledge, trust in health authorities, and vaccination intention. Furthermore, reliance on official information sources strongly correlated with perceived vaccine safety. Conversely, exposure to negative online content exhibited a weak negative association with knowledge levels, yet it did not directly influence vaccination intention. Conclusions: Health literacy and institutional trust emerge as fundamental pillars for HPV vaccine acceptance. To overcome patient vaccine hesitancy, the national healthcare system must initiate a strategic paradigm shift, prioritising the neutralization of digital misinformation and transitioning from a passive model to a proactive, “opt-out” infrastructure. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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19 pages, 295 KB

Open AccessArticle

Agreement and Diagnostic Performance of Urinary HPV Testing Versus Clinician-Collected Cervico-Vaginal Sampling: A Prospective Cross-Sectional Study in a Romanian Cohort

by Ionel-Daniel Nati, Mihaela Oancea, Carmen Mihaela Mihu, Dan Mihu, Razvan Ciortea, Cristian Iuhas, Carmen Bucuri, Maria Patricia Roman, Cristina Mihaela Ormindean, Viorela Suciu, Razvan Chereches and Andrei Mihai Malutan

Med. Sci. 2026, 14(4), 423; https://doi.org/10.3390/medsci14040423 - 24 Jul 2026

Viewed by 478

Abstract

Background: Cervical cancer screening uptake in Romania remains below 20%, with invasive sampling cited as a major participation barrier. Urinary HPV testing is a non-invasive alternative, but data from Eastern European populations are scarce and reporting stratified by histological grade is inconsistent. Objectives: [...] Read more.

Background: Cervical cancer screening uptake in Romania remains below 20%, with invasive sampling cited as a major participation barrier. Urinary HPV testing is a non-invasive alternative, but data from Eastern European populations are scarce and reporting stratified by histological grade is inconsistent. Objectives: To evaluate the agreement between paired urinary and clinician-collected cervico-vaginal HPV testing, and to assess the diagnostic performance of urinary HPV testing for biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Methods: Prospective cross-sectional study in three outpatient obstetrics and gynecology clinics (May 2025–May 2026). A total of 230 women aged 25–70 years provided paired cervico-vaginal (PreservCyt^®) and first-void urine (Colli-Pee^®) specimens. To capture the full spectrum of disease probability, participants were recruited across three clinical scenarios: primary screening, cytology triage and HPV-positive triage. A multiplex RT-PCR assay targeted a total of 14 high-risk HPV genotypes, providing separate identification for HPV16 and HPV18, alongside a pooled detection for the remaining 12 high-risk strains. Colposcopy-guided cervical biopsy served as the reference standard. Results: Paired hrHPV testing achieved substantial agreement (κ = 0.696, 95% CI 0.604–0.788), with higher genotype-specific concordance for HPV16 (κ = 0.755) and HPV18 (κ = 0.789). Discordance was directionally asymmetric (30 cervical-positive/urine-negative versus 4 urine-positive/cervical-negative; McNemar p < 0.001). For biopsy-confirmed CIN2+ (59 of 230; 25.7%), urinary hrHPV showed a sensitivity of 86.4% (95% CI 75.5–93.0), specificity 56.7%, positive predictive value 40.8% and negative predictive value 92.4%, compared with 91.5%, 43.3%, 35.8% and 93.7% for cervico-vaginal testing. Urinary HPV positivity increased monotonically with histological severity (25.0% no-lesion, 69.0% CIN1, 86.4% CIN2+; linear-by-linear p < 0.001). Conclusions: Urinary HPV testing demonstrates substantial agreement with clinician-collected sampling, near-equivalent negative predictive value, and a robust dose–response with histological severity. It is a clinically credible non-invasive entry point for a triage cascade in settings such as Romania, where low participation rather than analytical performance is the principal screening barrier. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

15 pages, 1250 KB

Open AccessArticle

Improved Prognostic Staging in Endometrial Cancer: Clinical Impact of Aggressive Subtypes in a Multicenter Cohort

by Tatiana Cuesta-Guardiola, Alicia Quirós, Pluvio Jesús Coronado Martín and Augusto Pereira Sánchez

Med. Sci. 2026, 14(3), 414; https://doi.org/10.3390/medsci14030414 - 22 Jul 2026

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Abstract

Objectives: Assessment of the impact on survival of endometrial carcinoma according to the 2009 FIGO (International Federation of Gynecology and Obstetrics) classification and the new FIGO 2023 classification highlighting the worse prognosis of the aggressive subtypes. Methods: This multicenter retrospective study [...] Read more.

Objectives: Assessment of the impact on survival of endometrial carcinoma according to the 2009 FIGO (International Federation of Gynecology and Obstetrics) classification and the new FIGO 2023 classification highlighting the worse prognosis of the aggressive subtypes. Methods: This multicenter retrospective study included 1181 patients with endometrial cancer. Comprehensive clinical, pathological and treatment-related variables were collected. Primary outcomes included overall survival assessed through five-year follow-ups. Statistical analysis included comparative tests, Kaplan–Meier survival estimation, Cox proportional hazards models and ROC curves analysis to review prognostic accuracy. Results: Aggressive endometrial carcinoma (n = 353) showed significant worse overall survival compared with non-aggressive cases (35.7 versus 60 months). A novel classification based on FIGO 2023 was developed, integrating histological aggressiveness into a different stage and combining early non-aggressive stages in only one stage. While FIGO 2009 and 2023 classifications showed prognostic value, the new model improved risk stratification, clearly distinguishing high-risk groups. Multivariate analysis identified aggressive subtype, stage, age, diabetes, myometrial invasion and lymphovascular invasion as independent predictors. Conclusions: Aggressive histological subtype in endometrial cancer should carry greater prognostic weight in terms of survival and clinical management. Our findings support a potential shift in the current paradigm for these relatively rare but high-risk cases. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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26 pages, 3426 KB

Open AccessArticle

An Exploratory Study on the Interrelation of Breast Cancer Molecular Phenotypes with Breast Cancer-Associated Adipose Tissues (BCAATs), Neoadjuvant, and Adjuvant Therapies: A Focus on Prognosis and Survival

by Mihaela Maria Pasca Fenesan, Razvan George Bogdan, Andrei Alexandru Cosma, Vlad Vornicu, Eugen Melnic, Diana Veronica Radu, Patricia Baran, Zorin Crainiceanu, Rodica Elena Heredea, Olga Cernetchi and Anca Maria Cimpean

Med. Sci. 2026, 14(3), 403; https://doi.org/10.3390/medsci14030403 - 18 Jul 2026

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Abstract

Background/Aim. We previously described four distinct breast cancer (BC)-associated adipose tissue (BCAAT) subtypes that have a significant impact on survival. In this exploratory study, we aimed to determine whether these BCAAT subtypes exhibit significant correlations with neoadjuvant and adjuvant therapies and BC molecular [...] Read more.

Background/Aim. We previously described four distinct breast cancer (BC)-associated adipose tissue (BCAAT) subtypes that have a significant impact on survival. In this exploratory study, we aimed to determine whether these BCAAT subtypes exhibit significant correlations with neoadjuvant and adjuvant therapies and BC molecular subtypes. Methods. Four BCAAT subtypes previously identified as fibroblast-rich (F^Rich_BCAAT), myofibroblast-rich (MyoF^Rich_BCAAT), vascular-rich (V^Rich_BCAAT), and mixed vascular- and inflammation-rich (VI^Rich_BCAAT) were analyzed according to their distribution in BC molecular subtypes, as well as in relation to neoadjuvant therapy and survival. Results. Triple-negative BC and Luminal B (LB) BC are related to V^Rich and VI^Rich BCAAT subtypes and were affected by Epirubicin/Cyclophosphamide (EC)+ paclitaxel (PTX) therapy, which significantly enhanced overall survival (OS) and disease-free survival (DFS). For the Luminal A (LA) BC subtype, EC + docetaxel (DTX) had significant impact on survival independent of BCAAT subtype. Conclusions. BCAAT subtypes strongly influenced neoadjuvant therapy response and survival depending on BC molecular subtype. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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17 pages, 885 KB

Open AccessArticle

Total Neoadjuvant Therapy Versus Long-Course Chemoradiotherapy in Locally Advanced Rectal Cancer: Real-World Tumor Response and Clinical Outcomes

by Sorinel Lunca, Wee Liam Ong, Stefan Morarasu, Ana Maria Musina, Cristian Ene Roata, Raluca Zaharia and Gabriel Mihail Dimofte

Med. Sci. 2026, 14(3), 393; https://doi.org/10.3390/medsci14030393 - 14 Jul 2026

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Abstract

Background: Total neoadjuvant therapy is becoming a preferred option for locally advanced rectal cancer, particularly in patients with high-risk baseline features. However, real-world evidence comparing tumor response, MRI-defined high-risk feature clearance, surgical outcomes, and survival after total neoadjuvant therapy versus conventional long-course chemoradiotherapy [...] Read more.

Background: Total neoadjuvant therapy is becoming a preferred option for locally advanced rectal cancer, particularly in patients with high-risk baseline features. However, real-world evidence comparing tumor response, MRI-defined high-risk feature clearance, surgical outcomes, and survival after total neoadjuvant therapy versus conventional long-course chemoradiotherapy remains limited. This study aimed to compare outcomes between total neoadjuvant therapy and long-course chemoradiotherapy in patients with locally advanced rectal cancer treated in routine clinical practice. Methods: This is a retrospective, single-centre cohort study focused on patients with stage II–III locally advanced rectal adenocarcinoma treated with curative-intent neoadjuvant therapy using either total neoadjuvant therapy or long-course chemoradiotherapy. Tumor response was assessed using restaging MRI, clinical complete response, and pathological complete response. Surgical outcomes and overall survival were evaluated. Results: A total of 110 patients were included. Patients treated with total neoadjuvant therapy had a higher baseline disease burden reflected by a greater proportion of cT4 tumors (40.6% vs. 19.2%; p = 0.014). Radiologic tumor-length response and clearance of MRI-defined high-risk features were comparable between treatment strategies. Clinical and pathological complete response rates were numerically higher in the total neoadjuvant therapy group, but the differences were not significant (cCR: 15.6% vs. 6.4%, p = 0.151; pCR: 18.5% vs. 9.7%, p = 0.301). Conclusions: In this real-world cohort, TNT was preferentially used in patients with more advanced baseline disease and showed numerically higher complete response rates, although differences were not statistically significant. Radiologic response, surgical outcomes, and short-term survival were comparable between treatment strategies. These findings support the feasibility of TNT in routine clinical practice but should be interpreted as exploratory and hypothesis-generating rather than evidence of treatment superiority. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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14 pages, 989 KB

Open AccessArticle

Lower Preoperative Skeletal Muscle Index in Patients with Pathological T4 Colorectal Cancer: An Exploratory Retrospective Cohort Study

by Botond-István Kiss, Árpád Török, Daniela Tatiana Sala, Renáta Moriczi, Szabolcs-Attila Gábor, Gabriel-Mircea Muresan, Tivadar Bara, Jr., Márton-István Dénes, Szilárd-Leó Kiss, Sr., Szilárd-Leó Kiss, Jr., Orsolya Kiss-Toth and Radu-Mircea Neagoe

Med. Sci. 2026, 14(3), 356; https://doi.org/10.3390/medsci14030356 - 29 Jun 2026

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Abstract

Background/Objectives: Low skeletal muscle index (SMI) has been linked to adverse outcomes in colorectal cancer, but its association with local pathological tumor extent is less clear. This study examined whether preoperative CT-derived SMI was associated with pathological T4 disease in patients undergoing colorectal [...] Read more.

Background/Objectives: Low skeletal muscle index (SMI) has been linked to adverse outcomes in colorectal cancer, but its association with local pathological tumor extent is less clear. This study examined whether preoperative CT-derived SMI was associated with pathological T4 disease in patients undergoing colorectal cancer resection. Methods: This retrospective single-center observational study included 147 consecutive adults who underwent colorectal resection for histologically confirmed adenocarcinoma between January 2022 and November 2025 and had suitable preoperative abdominal or abdomino-pelvic CT imaging within 90 days before surgery. Skeletal muscle area was measured on a single axial CT image at the L3 level, and SMI was calculated as muscle area/height². Patients were classified as having pathological T1–3 or T4 disease. Logistic regression assessed the association between SMI, expressed per 5 cm²/m² increase, and pathological T4 stage. Results: Patients with pathological T4 tumors had lower SMI than those with T1–3 disease (37.22 vs. 42.85 cm²/m², p = 0.016). Higher SMI was associated with lower odds of T4 disease in univariable analysis (OR 0.79, 95% CI 0.66–0.94; p = 0.008) and after adjustment for age and sex (OR 0.77, 95% CI 0.63–0.94; p = 0.009). Conclusions: Lower preoperative SMI was associated with pathological T4 colorectal cancer in this cohort. Because of the retrospective observational design, causality cannot be inferred. The association should be interpreted as hypothesis-generating and may reflect reverse causality, shared inflammatory–nutritional pathways, or residual confounding. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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15 pages, 634 KB

Open AccessArticle

Comparative Prognostic Performance of CARWL and Naples Prognostic Score in Stage IIIC Non-Small Cell Lung Cancer Treated with Definitive Chemoradiotherapy

by Erkan Topkan, Duriye Ozturk and Ugur Selek

Med. Sci. 2026, 14(2), 310; https://doi.org/10.3390/medsci14020310 - 12 Jun 2026

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Abstract

Background: Prognostic stratification remains challenging in patients with stage IIIC non-small cell lung cancer (NSCLC) treated with definitive chemoradiotherapy (CCRT), and the relative performance of host-related prognostic indices in this setting is unclear. The CARWL (C-reactive Protein, Albumin, and Recent Weight Loss) score [...] Read more.

Background: Prognostic stratification remains challenging in patients with stage IIIC non-small cell lung cancer (NSCLC) treated with definitive chemoradiotherapy (CCRT), and the relative performance of host-related prognostic indices in this setting is unclear. The CARWL (C-reactive Protein, Albumin, and Recent Weight Loss) score and the Naples prognostic score (NPS) have each been proposed as prognostic tools, but direct comparisons are lacking. This study compared their prognostic performance. Methods: We retrospectively analyzed 795 patients with stage IIIC NSCLC treated with CCRT between 2010 and 2020. Patients were stratified into three prognostic groups according to CARWL and NPS. Overall survival (OS) was the primary endpoint; progression-free survival (PFS) and locoregional PFS (LRPFS) were secondary endpoints. Survival was assessed using Kaplan–Meier analysis and Cox regression. Results: Both CARWL and NPS significantly stratified OS, PFS, and LRPFS (all p < 0.001). CARWL demonstrated modestly higher discriminatory performance across endpoints. The OS difference between unfavorable and favorable groups was larger with CARWL than with NPS (19.3 vs. 12.3 months). CARWL also provided greater separation for PFS (5.3 vs. 3.2 months) and LRPFS (4.9 vs. 3.4 months). In multivariable analyses, both indices retained independent prognostic significance; however, CARWL consistently exhibited stronger hazard gradients and maintained prognostic value when modeled alongside NPS. Conclusions: Both CARWL and NPS offered meaningful prognostic stratification in stage IIIC NSCLC treated with CCRT, but CARWL demonstrated a modest but more consistent prognostic discrimination than NPS. Pending external validation, CARWL represents a practical and biologically grounded tool for risk stratification in this population. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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15 pages, 3037 KB

Open AccessArticle

Effects of Benzo[a]pyrene on Targeted Therapy Response and Platelet-Activating Factor-Receptor-Mediated Microvesicle Particle Release in Non-Small Cell Lung Cancer

by Riya Rawal, Anita Thyagarajan and Ravi P. Sahu

Med. Sci. 2026, 14(2), 301; https://doi.org/10.3390/medsci14020301 - 11 Jun 2026

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Abstract

Background/Objectives: Non–small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality, driven by invasive behavior and frequent resistance to systemic therapies. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) benefit patients with EGFR-mutant NSCLC, but their efficacy is often limited by [...] Read more.

Background/Objectives: Non–small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality, driven by invasive behavior and frequent resistance to systemic therapies. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) benefit patients with EGFR-mutant NSCLC, but their efficacy is often limited by tumor-intrinsic and environmental resistance mechanisms. Benzo[a]pyrene (BaP), a ubiquitous polycyclic aromatic hydrocarbon from tobacco smoke, combustion, and dietary sources, is a known carcinogen; however, its role in modulating therapeutic responses is poorly understood. Studies, including ours, implicate the platelet-activating factor-receptor (PAFR) pathway in mediating environmental pollutant and therapy-induced effects on tumor growth and microvesicle particle (MVP) release. We hypothesized that PAFR activation mediates BaP-induced NSCLC progression and influences EGFR-TKI responses. Methods: We assessed the effects of BaP, PAFR agonist CPAF, EGFR-TKIs, and their combinations on cell viability, proliferation, migration, anchorage-independent growth, and MVP secretion. Results: BaP did not alter cell survival but significantly increased migration, growth, colony formation, and MVP release, similar to CPAF, and these effects were blocked by a PAFR antagonist or acid sphingomyelinase inhibitor. Notably, BaP did not significantly reduce EGFR-TKI efficacy at tested concentrations. Conclusions: These results show that environmental carcinogens modulate NSCLC behavior through PAFR signaling without compromising EGFR-TKI responsiveness, highlighting PAFR as a potential therapeutic target. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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16 pages, 4660 KB

Open AccessArticle

Image-Guided Thermal Ablation of Stage 1 Single and Multiple Primary Lung Carcinoma: Five-Year Outcomes

by Jamie E. Clarke, Noor Jahanshahi, Bianca Villegas, Grace Hyun J. Kim, Soheil Kooraki, Matthew Quirk, Scott Genshaft, Robert D. Suh and Fereidoun Abtin

Med. Sci. 2026, 14(2), 272; https://doi.org/10.3390/medsci14020272 - 27 May 2026

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Abstract

Background: Image-guided thermal ablation has been used for the treatment of primary lung carcinoma but its use in the treatment of multiple lung carcinoma and effects on survival have not been well established. Objective: This study compares the long-term survival metrics for stage [...] Read more.

Background: Image-guided thermal ablation has been used for the treatment of primary lung carcinoma but its use in the treatment of multiple lung carcinoma and effects on survival have not been well established. Objective: This study compares the long-term survival metrics for stage 1 single primary lung cancer and multiple primary lung cancer (MPLC) in patients treated with image-guided thermal ablation (IGTA). Methods: A retrospective institutional review included 37 NSCLC patients (mean age 71.6 ± 8.8 years) with ≥5 years follow-up. In total, 119 IGTA procedures were performed. Among patients with a single tumor (n = 14, 37.8%), each underwent a single ablation session. In contrast, patients with MPLC (n = 23, 62.2%) underwent 88 ablation sessions to treat 105 tumors. Data included demographics, tumor features, procedural details, safety, adverse events, and outcomes. Primary endpoints were 5-year overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CSS). Results: All ablations were completed successfully. Severe AEs occurred in 5.8% (7/119) of the ablations and were limited to pneumothorax requiring chest tube placement with hospitalization. At the time of ablation, individual nodules were staged at T1A = 46 (38.7%), T1B = 54 (45.4%), T1C = 16 (13.5%) and T2A = 3 (2.5%). Local recurrence was observed in 4/119 (3.3%) ablated tumors, all at stage T1B, and all were retreated with ablation. The 5-year OS was better for patients with MPLC at 85.6% compared to patients with a single tumor at 35.7% (HR = 0.14, p = 0.003, 95% CI: 0.037, 0.51). The 5-year OS for tumors based on T classification for T1A, T1B, TIC and T2A was 71.4%, 66.8%,66.7% and 0%. The 5-year PFS was 77.4% for patients with MPLC compared to 35.7% for patients with single primary lung cancer (HR = 0.25, p = 0.014, 95% CI: 0.084, 0.76). The 5-year CSS was 95.2% for patients with MPLC compared to 83.1% for patients with single primary lung cancer (HR = 0.21, p = 0.16, 95% CI: 0.018, 2.33). Conclusions: IGTA is an effective and safe treatment for patients with stage 1 single primary lung cancer and MPLC with limited local recurrence. Tumor size up to 3 cm did not have significant impact on survival. Overall survival was improved in patients with MPLC compared to those with single NSCLC. Clinical Impact: IGTA can be safely performed in patients with single primary lung cancer and MPLC, with limited local recurrence rate. Highlights: Key Findings: IGTA effectively treats patients with stage 1 single primary lung cancer and MPLC, with 3.3% recurrence, which can be retreated with ablation. The five-year OS was higher in patients with MPLC (85.6%) versus those with single lung cancer (35.7%, p = 0.003). OS by T classification: 71.4% for T1A, 66.8% for T1B, 66.7% for TIC, and 0% for T2A. Importance: IGTA effectively treats patients with single primary lung cancer and MPLC with low recurrence. Tumor size < 3 cm showed no impact on overall survival. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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18 pages, 3429 KB

Open AccessArticle

Loss of PTEN as an Independent Poor Prognosis Indicator in Lung Adenocarcinoma, but Not in Squamous Cell Carcinoma, Is Associated with an Immunosuppressive Tumor Microenvironment and Distinct Co-Mutational Profiles

by Maeva Houry, Shannon J. Silva, Maider Artola, Carmen Behrens, Katerina Politi, Ignacio Wistuba, Luis Montuenga, Francisco Exposito and Alfonso Calvo

Med. Sci. 2026, 14(2), 254; https://doi.org/10.3390/medsci14020254 - 14 May 2026

Viewed by 1231

Abstract

Background/Objectives: Non-small cell lung cancer (NSCLC) comprises biologically heterogeneous tumors, primarily lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), which differ in genomic landscape and clinical behavior. The tumor suppressor PTEN is a key negative regulator of the PI3K/AKT/mTOR pathway and is [...] Read more.

Background/Objectives: Non-small cell lung cancer (NSCLC) comprises biologically heterogeneous tumors, primarily lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), which differ in genomic landscape and clinical behavior. The tumor suppressor PTEN is a key negative regulator of the PI3K/AKT/mTOR pathway and is frequently inactivated in NSCLC through genetic and non-genetic mechanisms. Although reduced PTEN expression has been associated with poor outcomes in lung cancer, its prognostic relevance across these histological subtypes remains unclear. Methods: Here, we investigated the prognostic significance of PTEN in NSCLC subtypes using a multi-level approach combining protein, transcriptomic, and genomic analyses. PTEN protein expression was evaluated by immunohistochemistry in a tissue microarray from resected NSCLC patients, and findings were validated using publicly available datasets including TCGA-RPPA, GEO/EGA-based transcriptomic cohorts, and large genomic resources. In parallel, mutational landscapes and co-mutation patterns were analyzed in several independent datasets, and tumor immune microenvironment composition was inferred using CIBERSORT deconvolution analysis. Results: Low PTEN protein and mRNA levels, as well as PTEN mutations, were consistently associated with significantly worse overall survival (OS) in LUAD but not in LUSC. Multivariable Cox regression analysis confirmed PTEN as an independent prognostic factor in LUAD. Although PTEN mutations were more frequent in LUSC, they showed no prognostic value in this subtype. Co-mutation analyses revealed recurrent PTEN partnerships with TP53, EGFR, and APC in LUAD, with PTEN-TP53 co-alterations enriched in metastatic disease. Immune deconvolution demonstrated that PTEN-low LUAD tumors were characterized by an immunosuppressive microenvironment, including increased T regulatory cells and reduced inflammatory immune populations. Notably, increased M2-like macrophages were associated with shorter OS in PTEN-low LUADs, whereas a high number of total macrophages (CD68+ cells) emerged as an independent predictor of more favorable OS. Conclusions: Collectively, these results identify PTEN loss as a subtype-specific prognostic biomarker in LUAD and link its deficiency to immunosuppressive tumor microenvironment remodeling. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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23 pages, 4424 KB

Open AccessArticle

Patient-Reported Quality of Life Predicts First-Cycle Pharmacotherapy Survival in Breast Cancer: A Prospective Cohort Study

by Henry Sutanto, Merlyna Savitri, Een Hendarsih and Ami Ashariati

Med. Sci. 2026, 14(2), 247; https://doi.org/10.3390/medsci14020247 - 10 May 2026

Viewed by 804

Abstract

Objective: Patient-reported outcomes (PROs) provide direct insight into symptom burden and functional status, yet their utility in early pharmacotherapy outcomes in breast cancer remains underexplored. This study investigated whether baseline PROs from the EORTC QLQ-C30 and BR23 questionnaires are associated with and demonstrate [...] Read more.

Objective: Patient-reported outcomes (PROs) provide direct insight into symptom burden and functional status, yet their utility in early pharmacotherapy outcomes in breast cancer remains underexplored. This study investigated whether baseline PROs from the EORTC QLQ-C30 and BR23 questionnaires are associated with and demonstrate discriminative ability for short-term survival during the first pharmacotherapy cycle in breast cancer patients. Methods: We conducted a prospective cohort study at two secondary referral hospitals in Indonesia from January to October 2025. Women with breast cancer initiating systemic pharmacotherapy were enrolled and followed through completion of the first treatment cycle. The primary outcome was survival of the first cycle, defined as a combined endpoint of death or treatment discontinuation due to adverse effects. Baseline demographic, clinical, and tumor characteristics, along with PROs (EORTC QLQ-C30 and BR23), were compared between survivors (n = 99) and non-survivors (n = 7). Statistical comparisons used Mann–Whitney U tests for PROs. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the discriminative performance of PRO domains. Results: Non-survivors were more likely to present with metastatic disease (71.4% vs. 25.3%). Baseline PROs showed marked differences, with survivors reporting higher global health (83.3 vs. 41.7; p < 0.001) and better physical, role, emotional, and social functioning (all p < 0.05). Symptom burden—including pain, appetite loss, constipation, systemic side effects, arm symptoms, and financial difficulty—was higher among non-survivors (all p < 0.05). ROC analysis demonstrated strong discriminative performance for global health status (AUC 0.907; p < 0.001), emotional functioning (AUC 0.846; p = 0.002), and social functioning (AUC 0.843; p = 0.003), with moderate performance for physical functioning (AUC 0.737; p = 0.037). Symptom domains showed lower and inverse AUC values, reflecting scale directionality and limited discriminative capacity. Conclusions: Baseline PROs using EORTC QLQ-C30 and BR23 were strongly associated with early pharmacotherapy survival and demonstrated meaningful discriminative ability, particularly in global and functional domains. Integrating PRO assessments before treatment initiation may enhance early risk stratification, guide supportive care, and improve treatment continuity in breast cancer. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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25 pages, 830 KB

Open AccessArticle

Chronic Stress, Immune Suppression, and Cancer Occurrence: Unveiling the Connection Using Survey Data and Predictive Models

by Teddy Lazebnik and Vered Aharonson

Med. Sci. 2026, 14(2), 245; https://doi.org/10.3390/medsci14020245 - 8 May 2026

Viewed by 874

Abstract

Chronic stress has been implicated in cancer occurrence, but a direct causal connection has not been consistently established. Machine learning and causal modeling offer opportunities to explore complex causal interactions between psychological chronic stress and cancer occurrences. We developed predictive models employing variables [...] Read more.

Chronic stress has been implicated in cancer occurrence, but a direct causal connection has not been consistently established. Machine learning and causal modeling offer opportunities to explore complex causal interactions between psychological chronic stress and cancer occurrences. We developed predictive models employing variables from stress indicators, cancer history, and demographic data from self-reported surveys to examine the direct association between chronic stress and cancer occurrence, as well as a hypothesized immune-suppression-mediated pathway. The models were corroborated by traditional statistical methods. Our findings indicated significant associations between stress frequency, stress level, perceived health impact, and cancer occurrence. Although stress alone showed limited predictive power, integrating socio-demographic and familial cancer history data significantly enhanced model accuracy. These results highlight the multidimensional nature of cancer risk, with stress emerging as a notable factor alongside genetic predisposition. These findings strengthen the case for addressing chronic stress as a modifiable cancer risk factor, supporting its integration into personalized prevention strategies and public health interventions to reduce cancer incidence. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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13 pages, 565 KB

Open AccessArticle

Beyond PSA—Can Systemic Inflammatory Indices Improve Prostate Cancer Detection?

by Marius Ivănuță, Abdallah Shurrab, Dragoș Puia, Ana-Maria Ivănuță, Mihaela Corlade-Andrei, Nicolae Stoican and Cătălin Pricop

Med. Sci. 2026, 14(2), 243; https://doi.org/10.3390/medsci14020243 - 7 May 2026

Viewed by 1168

Abstract

Background: Prostate-specific antigen (PSA) remains the primary biomarker for prostate cancer detection; however, its limited specificity leads to unnecessary biopsies. Systemic inflammatory indices derived from routine blood tests have been proposed as potential adjunctive diagnostic tools. This study aimed to evaluate the diagnostic [...] Read more.

Background: Prostate-specific antigen (PSA) remains the primary biomarker for prostate cancer detection; however, its limited specificity leads to unnecessary biopsies. Systemic inflammatory indices derived from routine blood tests have been proposed as potential adjunctive diagnostic tools. This study aimed to evaluate the diagnostic performance of these indices in patients undergoing prostate biopsy for suspected prostate cancer. Methods: A retrospective observational study was conducted, including 307 patients who underwent transrectal ultrasound-guided prostate biopsy for elevated PSA between January 2021 and January 2023. Patients were classified as benign prostatic hyperplasia (BPH) or prostate cancer (PCa) based on histopathological findings. Inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), systemic immune–inflammation index (SII), Systemic Inflammation Response Index (SIRI), and aggregate index of systemic inflammation (AISI), were calculated. Logistic regression and receiver operating characteristic (ROC) analyses were performed to assess diagnostic performance. Results: PCa was diagnosed in 65.1% of patients. Several inflammatory indices were significantly higher in the PCa group. Among them, AISI showed diagnostic performance comparable to PSA. The integration of inflammatory indices into multivariable models improved predictive accuracy, with the combined model demonstrating the highest discriminative ability. In contrast, these markers showed limited capacity in distinguishing tumour aggressiveness. Conclusions: Systemic inflammatory indices are associated with prostate cancer presence and may enhance diagnostic performance when used alongside PSA. However, their role remains complementary, as they provide limited value in risk stratification and should not be considered standalone diagnostic tools. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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18 pages, 1571 KB

Open AccessArticle

Prognostic Significance of SULF2 Expression in Surgically Resected Non-Small Cell Lung Cancer

by Hakan Taban, Murat Ozdede, Orkun Akman, Sevgen Celik Onder and Saadettin Kılıckap

Med. Sci. 2026, 14(2), 215; https://doi.org/10.3390/medsci14020215 - 26 Apr 2026

Viewed by 859

Abstract

Background: Sulfatase 2 (SULF2) is an extracellular enzyme involved in the modulation of multiple oncogenic signaling pathways and has been implicated in tumor progression across several malignancies. However, its prognostic significance in surgically resected non-small cell lung cancer (NSCLC) remains incompletely defined. Methods: [...] Read more.

Background: Sulfatase 2 (SULF2) is an extracellular enzyme involved in the modulation of multiple oncogenic signaling pathways and has been implicated in tumor progression across several malignancies. However, its prognostic significance in surgically resected non-small cell lung cancer (NSCLC) remains incompletely defined. Methods: SULF2 expression was evaluated by immunohistochemistry in tumor specimens from patients with stage I–III NSCLC who underwent curative-intent surgical resection between 2009 and 2016. Expression levels were quantified using an H-score-based system and categorized as low or high. Associations between SULF2 expression, clinicopathological characteristics, and survival outcomes, including overall survival (OS) and disease-free survival (DFS), were analyzed using Kaplan–Meier estimates and Cox proportional hazards models. Eighty-three patients were included, of whom 65 (78.3%) were male; 42.2% had stage I disease, 32.5% stage II, and 25.3% stage III. Results: SULF2 expression was detected in 94.0% of tumors, with 43 patients (51.8%) classified as high and 40 (48.2%) as low expression based on H-score. Overall survival and DFS did not differ significantly between SULF2-low and SULF2-high groups (log-rank p = 0.213 and p = 0.660, respectively). Median OS was 113.2 months (95% CI: 84.0–142.4) in the SULF2-low group and 54.9 months (95% CI: 39.4–186.9) in the SULF2-high group, while median DFS was 88.3 months (95% CI: 46.5–130.2) and 53.3 months, respectively, with numerically shorter survival in the SULF2-high group. Subgroup analyses stratified by pathological stage and histological subtype revealed no significant associations between SULF2 expression and survival outcomes. In multivariate analysis, SULF2 expression was not independently associated with either OS or DFS. Conclusions: SULF2 expression was highly prevalent in surgically resected NSCLC; although higher expression showed numerically poorer survival, this difference did not reach statistical significance. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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14 pages, 514 KB

Open AccessArticle

Real-World Clinical Outcomes of Azacitidine Versus Best Supportive Care in Higher-Risk Myelodysplastic Neoplasms: A Single-Center Cohort Study

by Mihai-Emilian Lapadat, Oana Stanca, Irina Nicoleta Triantafyllidis, Anca Mariana Ciobanu, Nicoleta Mariana Berbec, Cristina Negotei, Cristian Tudor Barta, Ana Maria Bordea, Madalina Marilena Oprea and Andrei Colita

Med. Sci. 2026, 14(2), 212; https://doi.org/10.3390/medsci14020212 - 24 Apr 2026

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Abstract

Background: Higher-risk myelodysplastic neoplasms (HR-MDS) are associated with poor survival and a substantial risk of leukemic transformation. Although azacitidine is a standard treatment in this setting, comparative real-world data remain limited. We evaluated the association between azacitidine exposure and clinical outcomes in [...] Read more.

Background: Higher-risk myelodysplastic neoplasms (HR-MDS) are associated with poor survival and a substantial risk of leukemic transformation. Although azacitidine is a standard treatment in this setting, comparative real-world data remain limited. We evaluated the association between azacitidine exposure and clinical outcomes in patients with HR-MDS. Methods: We performed a retrospective single-center cohort study including 72 adults with HR-MDS, defined by the Revised International Prognostic Scoring System(IPSS-R) as High or Very High risk. Patients were categorized as azacitidine-treated (Aza, n = 44) or managed with best supportive care alone (No Aza, n = 28). Overall survival (OS) was defined from diagnosis to death from any cause. Progression-free survival (PFS) was defined as the time to acute myeloid leukemia transformation or death. Leukemic transformation (LT) was analyzed using Kaplan–Meier estimates and competing-risk cumulative incidence, with death without prior LT treated as a competing event. Univariable and multivariable Cox regression models were applied. Results: Azacitidine exposure was associated with longer OS compared with best supportive care, with a median OS of 13 vs.10 months and 24-month OS rates of 27% vs. 14% (p = 0.0239). PFS was also prolonged in the Aza group, with a median of 11 vs. 7 months (p = 0.0406). LT-related outcomes similarly favored azacitidine. In multivariable analyses, azacitidine remained independently associated with improved OS, PFS, and LT-related outcomes. IPSS-R Very High risk remained an adverse prognostic factor across endpoints, while a higher baseline bone marrow blast percentage independently predicted leukemic transformation. Conclusions: In this real-world HR-MDS cohort, azacitidine exposure was associated with improved survival outcomes and delayed leukemic transformation compared with best supportive care alone. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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17 pages, 1167 KB

Open AccessArticle

Supervised (Home-Based Exercise) Prehabilitation Program in Pancreatic Cancer Patients Undergoing to Neoadjuvant Chemotherapy: A Pilot Feasibility Study

by Gennaro Boccia, Luca Beratto, Cantor Tarperi, Alberto Rainoldi, Chiara Calliera, Daniele Ierace, Maria Antonietta Satolli, Simona Bo and Paola Costelli

Med. Sci. 2026, 14(2), 184; https://doi.org/10.3390/medsci14020184 - 7 Apr 2026

Viewed by 1559

Abstract

Background: Patients with pancreatic cancer (PC) commonly present with reduced aerobic fitness, sarcopenia, and malnutrition, which may increase perioperative risk and compromise access to chemotherapy treatments. Although exercise-based prehabilitation can improve physical fitness, its implementation is often limited by short diagnostic-to-surgery intervals and [...] Read more.

Background: Patients with pancreatic cancer (PC) commonly present with reduced aerobic fitness, sarcopenia, and malnutrition, which may increase perioperative risk and compromise access to chemotherapy treatments. Although exercise-based prehabilitation can improve physical fitness, its implementation is often limited by short diagnostic-to-surgery intervals and treatment-related toxicity. Methods: We conducted a pilot prospective pretest–posttest feasibility study in Torino, Italy. Patients with PC undergoing neoadjuvant chemotherapy prior to surgery were offered a 4-week, partially supervised, home-based bimodal exercise prehabilitation program (single-arm design) combining remotely monitored high-intensity interval training (HIIT) on a cycle ergometer with functional and resistance exercises. The primary outcome was adherence to prescribed exercise frequency, intensity, and duration, objectively assessed via remote monitoring. Secondary outcomes included cardiorespiratory fitness (CPET), muscle function, body composition, fatigue, quality of life, and circulating inflammatory markers. Results: From July 2022 to February 2024, 23 patients were screened; 15 were eligible and 10 enrolled. Four participants discontinued the intervention (two due to asthenia/fatigue, one due to chemotherapy-related adverse events, and one for organizational reasons), leaving six participants who completed the program. Among completers, fatigue and quality of life did not change meaningfully. Aerobic capacity and muscle function outcomes were generally stable, with few pre–post changes exceeding the minimum clinically important difference (MCID) thresholds used. Body composition markers and the assessed circulating cytokines/chemokines remained unchanged except for IL-6 levels, which decreased significantly (p < 0.05). Conclusions: A partially supervised, home-based HIIT-based prehabilitation program is feasible for a subset of PC patients undergoing neoadjuvant therapy, but a substantial attrition rate suggests the need for more flexible symptom-adapted prescriptions and enhanced supportive strategies. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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17 pages, 1414 KB

Open AccessArticle

Long-Term Clinical Consequences of Severe Oral Mucositis in Survivors of Lip, Oral Cavity, and Pharynx Cancer Versus Leukemia: A Propensity-Score-Matched Comparative Cohort Study Using Real-World Data

by Poolakkad S. Satheeshkumar, Venu Gopalakrishnan, Joel B. Epstein and Roberto Pili

Med. Sci. 2026, 14(1), 142; https://doi.org/10.3390/medsci14010142 - 18 Mar 2026

Cited by 1 | Viewed by 1449

Abstract

Background/Objectives: Severe oral mucositis is widely viewed as a transient toxicity of antineoplastic therapy. Whether its long-term consequences differ between cancers that directly damage the upper aerodigestive tract (cancers of the lip, oral cavity, pharynx [CLOP]) and systemic hematologic malignancies is unknown. The [...] Read more.

Background/Objectives: Severe oral mucositis is widely viewed as a transient toxicity of antineoplastic therapy. Whether its long-term consequences differ between cancers that directly damage the upper aerodigestive tract (cancers of the lip, oral cavity, pharynx [CLOP]) and systemic hematologic malignancies is unknown. The aim of this study was to compare lifetime risks of mortality, dysphagia, malnutrition, respiratory disease, and cardiovascular disease in propensity-score-matched survivors of CLOP cancer versus leukemia with and without a history of ulcerative oral mucositis. Methods: Population-based retrospective cohort study using the TriNetX US Collaborative Network (90 healthcare organizations, >110 million patients). We identified 80,526 adults with a personal history of CLOP cancer (ICD-10-CM Z85.81) and 43,684 with leukemia (Z85.6) from 2005 to 2024. Cohorts were stratified by presence/absence of severe oral mucositis (K12.31 or K12.33 at any time). Separate 1:1 propensity-score matching was performed within each cancer type on age, sex, race/ethnicity, hypertension, diabetes, BMI, ECOG status, and external causes of morbidity. Exposures included documented severe (ulcerative) oral mucositis. Main outcomes and measures were all-cause mortality and incident dysphagia, malnutrition, respiratory disease (J00–J99), influenza/pneumonia (J09–J18), and circulatory disease (I00–I99) after the index date. Results: After 1:1 matching, 4181 CLOP patients with mucositis were compared with 4181 without, and 2508 leukemia patients with mucositis were compared with 2508 without. In CLOP survivors, mucositis was associated with markedly higher lifetime mortality (adjusted HR 1.94, 95% CI 1.87–2.01), dysphagia (HR 3.42, 95% CI 3.28–3.57), malnutrition (HR 2.81, 95% CI 2.66–2.97), any respiratory disease (HR 1.68, 95% CI 1.63–1.73), and influenza/pneumonia (HR 1.79, 95% CI 1.72–1.86). In leukemia survivors, mucositis conferred only modest or null excess risk (mortality HR 1.12, 95% CI 1.05–1.19; dysphagia HR 1.18, 95% CI 1.07–1.30; malnutrition HR 1.24, 95% CI 1.12–1.37; any respiratory disease HR 1.09, 95% CI 1.03–1.15). Conclusions and Relevance: Severe oral mucositis is a powerful, durable prognostic determinant in cancers of the upper aerodigestive tract, where it identifies patients associated with elevated lifelong risk of swallowing dysfunction, aspiration-related lung disease, malnutrition, and premature death. The markedly attenuated effect in leukemia survivors suggests that direct high-dose radiation-induced structural damage to the pharynx and oral cavity—rather than systemic immunosuppression or chemotherapy intensity alone—is the dominant mechanism. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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28 pages, 12236 KB

Open AccessArticle

The Effect of Viniferin on Liver Cancer: Research Based on Network Pharmacology, Molecular Docking and Molecular Dynamics Simulation

by Saowanee Maungchanburi, Onwara Wongmek, Poolsak Baitahay, Asron Saweak, Maroof Wangkaranae, Wanmai Kongwattananon, Suphasarang Sirirattanakul, Moragot Chatatikun, Atthaphong Phongphithakchai, Jason C. Huang, Aman Tedasen and Chutima Jansakun

Med. Sci. 2026, 14(1), 130; https://doi.org/10.3390/medsci14010130 - 11 Mar 2026

Cited by 2 | Viewed by 1771

Abstract

Background/Objectives: Hepatocellular carcinoma (HCC) is a primary malignancy often driven by metabolic syndrome, fatty liver disease, and chronic hepatitis. These conditions foster a pro-inflammatory microenvironment that promotes tumor progression. Viniferin, a natural oligostilbene, has gained attention for its potential bioactivity. This study utilized [...] Read more.

Background/Objectives: Hepatocellular carcinoma (HCC) is a primary malignancy often driven by metabolic syndrome, fatty liver disease, and chronic hepatitis. These conditions foster a pro-inflammatory microenvironment that promotes tumor progression. Viniferin, a natural oligostilbene, has gained attention for its potential bioactivity. This study utilized an in silico network pharmacology approach to elucidate the pharmacokinetic properties and molecular mechanisms of ε- and δ-viniferin against HCC within the context of metabolic and inflammatory liver pathologies. Methods: ADMET profiles were characterized using SwissADME and pkCSM. Therapeutic targets were identified by intersecting viniferin-associated molecules with disease genes from GeneCards. A protein–protein interaction (PPI) network was constructed, supplemented by GO and KEGG enrichment analyses. Molecular docking and 200 ns of molecular dynamics (MD) simulations evaluated the binding affinity and structural stability between viniferin isomers and identified hub proteins. Results: Both ε- and δ-viniferin showed favorable drug-like properties, including high gastrointestinal absorption and low hepatotoxicity. We identified 247 overlapping targets, with network analysis highlighting ten essential hub genes, including AKT1, HSP90AA1, ESR1, HIF1A, NFKB1, GSK3B, PTGS2, APP, MTOR, and PIK3CA. Enrichment analysis confirmed their involvement in critical oncogenic pathways. Molecular docking showed strong interactions with APP, HSP90AA1, and AKT1, while MD simulations validated the long-term stability of ε-viniferin within the APP binding pocket. Conclusions: These findings provide mechanistic insights into viniferin as a multi-target agent for HCC, justifying further experimental validation in pre-clinical models. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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13 pages, 870 KB

Open AccessArticle

Natural Language Processing-Assisted Incidental Pulmonary Nodule Evaluation Program: Impact on Lung Cancer Outcomes

by Noa Tamam Shenholz, Keren Hod, Liat Toderis, Noam Fink, Arnon Makori, Michael Peer, Evgeni Gershman, Merav A. Ben-David and Elizabeth Dudnik

Med. Sci. 2026, 14(1), 104; https://doi.org/10.3390/medsci14010104 - 21 Feb 2026

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Abstract

Introduction: Early detection and timely treatment (Tx) initiation are critical to improving lung cancer (LC) outcomes. This study assessed the natural language processing (NLP)-assisted incidental pulmonary nodule (IPN) evaluation program, which employs chest computer tomography (CT) report analysis as an LC diagnostic [...] Read more.

Introduction: Early detection and timely treatment (Tx) initiation are critical to improving lung cancer (LC) outcomes. This study assessed the natural language processing (NLP)-assisted incidental pulmonary nodule (IPN) evaluation program, which employs chest computer tomography (CT) report analysis as an LC diagnostic screening (LCS) tool to identify suspicious lung findings (SLF) necessitating further investigation, and evaluated its impact on prognosis and diagnostic work-up and Tx timelines for patients with LC. Materials and Methods: Consecutive LC patients (n = 200) diagnosed at Assuta Medical Centers (AMC) between January 2019 and December 2022 were retrieved from the AMC electronic database using the MDClone big data platform, and divided into two groups: group A (NLP-assisted IPN evaluation, n = 100) and group B (traditional referral for evaluation of SLF by the community physician, n = 100). Stage at diagnosis, different diagnostic work-up and Tx timelines, and overall survival (OS) were assessed. Results: The NLP-assisted IPN evaluation program led to a significant stage shift (stage I disease: 48% vs. 27% in groups A and B, respectively, p = 0.013). Although the time from imaging to Tx initiation was similar (2.1 ± 5.3 months vs. 2.6 ± 5.9 months in groups A and B, respectively, p = 0.654), the time to systemic Tx (p = 0.035) and the time to radiotherapy (p = 0.044) were significantly shorter in group A. Conclusions: Implementing an NLP-assisted IPN evaluation program may enable earlier LC detection, driving a stage shift towards earlier diagnosis, improved diagnostic efficiency, and expedited time-critical interventions. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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12 pages, 224 KB

Open AccessArticle

Ciprofloxacin Versus Fosfomycin for Empirical Prophylaxis Before Transrectal Prostate Biopsy: Clinical, Microbiological, and Patient-Reported Outcomes from a Prospective Study

by Edgaras Burzinskis, Ieva Janulaityte, Guoda Burzinskiene, Darijus Skaudickas, Albinas Naudziunas and Astra Vitkauskiene

Med. Sci. 2026, 14(1), 91; https://doi.org/10.3390/medsci14010091 - 14 Feb 2026

Viewed by 1353

Abstract

Background: Transrectal ultrasound-guided prostate biopsy remains the gold standard in diagnosing prostate cancer, but is associated with infectious and non-infectious complications. Increasing fluoroquinolone resistance and regulatory restrictions have prompted evaluation of alternative prophylactic strategies, including fluoroquinolone-sparing agents and targeted prophylaxis. This study compared [...] Read more.

Background: Transrectal ultrasound-guided prostate biopsy remains the gold standard in diagnosing prostate cancer, but is associated with infectious and non-infectious complications. Increasing fluoroquinolone resistance and regulatory restrictions have prompted evaluation of alternative prophylactic strategies, including fluoroquinolone-sparing agents and targeted prophylaxis. This study compared ciprofloxacin and fosfomycin as empirical prophylactic agents, focusing on microbiological concordance, clinical outcomes, and patient-reported outcomes. Methods: In this prospective observational study, 265 men undergoing transrectal ultrasound-guided prostate biopsy received empirical antibiotic prophylaxis with either ciprofloxacin (n = 146) or fosfomycin trometamol (n = 119). Rectal swabs were obtained prior to biopsy, and antimicrobial susceptibility was analyzed post hoc. Infectious and non-infectious complications were recorded. Lower urinary tract symptoms (IPSS), erectile function (IIEF-5), and patient-reported quality of life were assessed before and after biopsy. Results: Microbiological concordance between administered prophylaxis and rectal flora susceptibility was higher in the ciprofloxacin group than in the fosfomycin group (80.1% vs. 65.0%, p = 0.007), while resistance rates were similar (10.9% vs. 10.2%). Post-biopsy fever occurred in 5.3% of patients, and hospitalization was required in 3.1%, with no significant differences between prophylaxis groups. IPSS increased significantly after biopsy (p < 0.001), while IIEF-5 scores remained unchanged. Patients with microbiological concordance reported significantly better post-biopsy quality of life (p = 0.006). Conclusions: Ciprofloxacin and fosfomycin showed similar safety profiles as empirical prophylaxis before transrectal prostate biopsy. Although ciprofloxacin achieved higher microbiological concordance, fosfomycin remains a viable alternative. The link between microbial concordance and improved patient-reported quality of life underscores the importance of targeted prophylaxis and supports antimicrobial stewardship in prostate cancer diagnostics. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

17 pages, 18068 KB

Open AccessArticle

Single-Cell RNA Sequencing Reveals the Cellular and Molecular Differences Between Myxofibrosarcoma and Undifferentiated Pleomorphic Sarcoma

by Timur I. Fetisov, Alexander V. Ikonnikov, Elena E. Kopantseva, Polina A. Shtompel, Sofya A. Khazanova, Ekaterina S. Trapeznikova, Victoria Y. Zinovieva, Svetlana N. Zuevskaya, Anastasia A. Tararykova, Beniamin Yu. Bokhyan, Gennady A. Belitsky, Ekaterina A. Lesovaya, Marianna G. Yakubovskaya, Evgeny V. Denisov and Kirill I. Kirsanov

Med. Sci. 2026, 14(1), 77; https://doi.org/10.3390/medsci14010077 - 10 Feb 2026

Cited by 1 | Viewed by 2010

Abstract

Objective: Myxofibrosarcoma (MXF) and undifferentiated pleomorphic sarcoma (UPS) are common and aggressive subtypes of cancer differing by clinical characteristics and prognosis; however, their differential diagnosis is difficult. Elucidation of cellular and transcriptomic discrepancies between these diseases that could improve their identification was the [...] Read more.

Objective: Myxofibrosarcoma (MXF) and undifferentiated pleomorphic sarcoma (UPS) are common and aggressive subtypes of cancer differing by clinical characteristics and prognosis; however, their differential diagnosis is difficult. Elucidation of cellular and transcriptomic discrepancies between these diseases that could improve their identification was the aim of our study. Methods: We applied single-cell RNA sequencing to compare MXF and UPS by tumor cell clusters and cell–cell ligand–receptor interactions, using five tumor samples of both subtypes. Results: We identify nine major cell types in all tumors analyzed. Any significant differences in their proportions between MXF and UPS were not found. Further reclusterization of lymphoid cells showed that cytotoxic CD8+ T cell proportion was higher in the MXF samples. In UPS cancer cells, the pathways maintaining extracellular matrix components (including collagens, proteoglycans, and other proteins) were highly active, while MXF cells were characterized by high activity of growth factors and angiogenesis pathways. The ligand–receptor interactions between cancer cells and the microenvironment differed significantly between MXF and UPS. In UPS, CD80 of dendritic cells and macrophages prominently interacted with T cell co-inhibitory CTLA-4 receptors, whereas the activating CD80-CD28 interaction was predominant in MXF. Moreover, in UPS, CD44 and integrins of cytotoxic CD8+ T cells prominently interacted with COL1A1/2, while in MXF CD44, interaction with FN1, COL6A1, and LAMC1 prevailed. Conclusions: Differences were identified between UPS and MFS in the composition of lymphoid cell populations and in the intercellular interactions. This proposes deeper understanding of the biological differences between these sarcoma subtypes and may be important for the development of new therapeutic approaches, although further validation of the findings is required. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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17 pages, 8188 KB

Open AccessArticle

Leptin Drives Breast Cancer Aggressiveness Acting Through the Activation of the NCOA1/STAT3 Pathway

by Khouloud Ayed, Amal Gorrab, Hichem Bouguerra, Rym Akrout, Sami Zekri, Wassim Y. Almawi, Rahma Boughriba, Khalil Choukri, Dhouha Bacha, Alessandra Pagano, Jean-François Louet, Hervé Kovacic, Mounia Tannour-Louet and Asma Gati

Med. Sci. 2026, 14(1), 32; https://doi.org/10.3390/medsci14010032 - 8 Jan 2026

Cited by 3 | Viewed by 1730

Abstract

Background/Objectives: Obesity-associated hyperleptinemia has been linked to breast cancer (BC) progression via mechanisms that remain incompletely understood. This study explores the role of leptin and its receptor (LEPR) in facilitating BC cell proliferation, migration, epithelial–mesenchymal transition (EMT), and STAT3 signaling pathway activation. [...] Read more.

Background/Objectives: Obesity-associated hyperleptinemia has been linked to breast cancer (BC) progression via mechanisms that remain incompletely understood. This study explores the role of leptin and its receptor (LEPR) in facilitating BC cell proliferation, migration, epithelial–mesenchymal transition (EMT), and STAT3 signaling pathway activation. Methods: We analyzed gene expression and survival data from TCGA BRCA dataset. MCF-7 and MDA-MB-231 BC cells were exposed to leptin at 10 ng/mL (lean-associated levels) and 100 ng/mL (elevated levels linked to obesity). MTT assays, colony formation tests, wound-healing and tumor spheroid dissemination experiments evaluated cell proliferation and migration. Immunofluorescence and Western blot analysis assessed changes in EMT markers and cytoskeletal alterations, while Western blotting and qPCR assessed STAT3 and NCOA1 expression and activation levels. Results: Elevated LEPR expression was linked with unfavorable prognosis in BC patients. Higher doses of leptin (100 ng/mL) significantly enhanced cellular proliferation rates and migratory capabilities, in both cell lines, and promoted EMT characteristics marked by downregulated E-cadherin and cytoskeleton structural changes. Whereas heightened JAK2/STAT3 signaling correlated with elevated leptin dosages, STAT3 inhibition using AG490 reversed leptin-induced migration while reinstating E-cadherin levels to baseline. Furthermore, leptin upregulated NCOA1, an essential STAT3 coactivator, facilitating increased expression of Cyclin D1 and VEGF target genes. Clinical positive relationships were seen between LEP/LEPR expressions and NCOA1 levels and between NCOA1 and various gene signatures related to STAT3/P-STAT3 within BC specimens. Conclusions: Obesity-associated hyperleptinemia enhances aggressiveness in BC through a mechanism involving LEPR-mediated activation pathways encompassing NCOA1/STAT3, which drive proliferation, migration, and EMT. This assigns a potential therapeutic utility for obesity-related advancements found within BC pathology. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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21 pages, 1249 KB

Open AccessArticle

Preoperative Prognostic Score for Patients with Intrahepatic Cholangiocarcinoma Undergoing Curative-Intent Resection

by Jarin Chindaprasirt, Thanachai Sanlung, Piyakarn Watcharenwong, Vasin Thanasukarn, Apiwat Jareanrat, Natcha Khuntikeo, Tharatip Srisuk, Prakasit Sa-Ngiamwibool, Chaiwat Aphivatanasiri, Watcharin Loilome, Piya Prajumwongs and Attapol Titapun

Med. Sci. 2026, 14(1), 23; https://doi.org/10.3390/medsci14010023 - 5 Jan 2026

Cited by 1 | Viewed by 1305

Abstract

Background: Preoperative inflammatory and nutrition-related markers—including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score—have shown prognostic relevance in various malignancies. However, their comparative utility in predicting recurrence and survival across clinically relevant subgroups in [...] Read more.

Background: Preoperative inflammatory and nutrition-related markers—including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score—have shown prognostic relevance in various malignancies. However, their comparative utility in predicting recurrence and survival across clinically relevant subgroups in patients with intrahepatic cholangiocarcinoma (iCCA) undergoing curative-intent resection remains unclear. Methods: This retrospective study included 213 patients with histologically confirmed iCCA who underwent curative-intent resection between 2015 and 2021. Preoperative NLR, LMR, PNI, and CONUT scores were calculated from laboratory data obtained within one week before resection. Clinicopathological variables, recurrence, and survival outcomes were analyzed using Cox regression and Kaplan–Meier methods. Results: A preoperative NLR ≥ 2.4 was independently associated with poorer DFS (HR = 1.66, p = 0.025) and OS (HR = 1.94, p = 0.006). This effect remained significant in patients with R0 resection (DFS: HR = 1.66, p = 0.004; OS: HR = 2.11, p = 0.014) and in those who subsequently developed recurrence (OS: HR = 1.83, p = 0.004). The CONUT score was correlated with OS in both R0 and recurrent subgroups. Tumor morphology, consistent with prior reports, was identified as a postoperative pathological factor associated with worse prognosis. Conclusions: Preoperative NLR was associated with poorer DFS and OS in iCCA patients undergoing curative-intent resection. This association was consistently observed in subgroups with R0 resection and in those who developed recurrence. Meanwhile, the CONUT score showed limited independent significance only among patients with R0 resection who experienced recurrence. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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20 pages, 5337 KB

Open AccessArticle

Obesogenic Dysregulation of Human Periprostatic Adipose Tissue Promotes the Viability of Prostate Cells and Reduces Their Sensitivity to Docetaxel and Cabazitaxel

by Mariana Feijó, Lara R. S. Fonseca, Gonçalo Catarro, Cátia V. Vaz, Carlos Rabaça, Bruno J. Pereira, Eugenia Gallardo, Endre Kiss-Toth, Sara Correia and Sílvia Socorro

Med. Sci. 2025, 13(4), 322; https://doi.org/10.3390/medsci13040322 - 16 Dec 2025

Viewed by 1595

Abstract

Background: Periprostatic adipose tissue (PPAT) has been shown to play a significant role in prostate cancer (PCa) development and progression. This relationship is further exacerbated by obesity, as PPAT-secreted factors increase PCa aggressiveness and have also been implicated in chemotherapy resistance. Therefore, identifying [...] Read more.

Background: Periprostatic adipose tissue (PPAT) has been shown to play a significant role in prostate cancer (PCa) development and progression. This relationship is further exacerbated by obesity, as PPAT-secreted factors increase PCa aggressiveness and have also been implicated in chemotherapy resistance. Therefore, identifying the molecular mediators of PPAT–prostate interorgan communication and the factors that disrupt this crosstalk is pivotal for better disease management. Obesogens, i.e., endocrine-disrupting chemicals that dysregulate adipose tissue towards an “obese” phenotype, have recently been implicated in disrupting this crosstalk, with an impact on prostate cell fate. Objectives: This study aimed to investigate whether obesogenic dysregulation of human PPAT secretory activity affects PCa cell viability and their response to docetaxel and cabazitaxel. Methods/Results: Through ex vivo culture of human PPAT and conditioned medium assays, we demonstrated that exposure to the model obesogen tributyltin (TBT) induced an “obese” phenotype in human PPAT, characterised by adipocyte enlargement and increased secretion of leptin and C-C motif chemokine ligand 7. The TBT-treated PPAT secretome enhanced cell viability and decreased the sensitivity of PCa cells to taxanes. Conclusions: This study provides preliminary evidence that lays the groundwork for future investigations, dissecting the molecular pathways underpinning prostate carcinogenesis and resistance to chemotherapy induced by obesogen-dysregulated PPAT. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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13 pages, 594 KB

Open AccessArticle

Outcome and Toxicity of Moderately Hypofractionated Post-Prostatectomy Radiotherapy: A Retrospective Study

by Rocchina Vilella, Fiorella D’Auria, Luciana Valvano, Barbara D’Andrea, Antonietta Montagna, Giovanni Castaldo, Ilaria Benevento, Angela Pia Solazzo, Manuela Botte, Grazia Lazzari, Teodora Statuto and Luciana Rago

Med. Sci. 2025, 13(4), 315; https://doi.org/10.3390/medsci13040315 - 12 Dec 2025

Cited by 1 | Viewed by 1148

Abstract

Background: In this study, we retrospectively analyzed clinical and toxicity outcomes of 67 prostate cancer (PCa) patients undergoing moderately hypofractionated radiotherapy (RT) after prostatectomy, with adjuvant or salvage intent. Methods: Irradiation was delivered by volumetric modulated arc therapy. The median follow-up [...] Read more.

Background: In this study, we retrospectively analyzed clinical and toxicity outcomes of 67 prostate cancer (PCa) patients undergoing moderately hypofractionated radiotherapy (RT) after prostatectomy, with adjuvant or salvage intent. Methods: Irradiation was delivered by volumetric modulated arc therapy. The median follow-up was 48 months. The 3- and 5-year biochemical relapse-free survival rates were 80% and 69%. The RT schedule consisted of a median total dose of 67.5 Gy with a median number of 25 fractions and a median fraction dose of 2.7 Gy to the prostate bed (PB) and 60% of patients simultaneously received whole pelvis irradiation (WP; fraction dose: 1.8 Gy, median total dose of 46.8 Gy). Results: The rate of acute toxicity was 54% for gastrointestinal (GI) and 36% for genitourinary (GU). No grade 3 acute toxicity was observed. Late toxicity was as follows: G1, G2, and G3 GI events in 25.5%, 3.6%, and 1.8% of the cases, respectively; G1, G2, and G3 GU events in 37.1%, 11.1%, and 7.4%, respectively. The toxicity-free survival (TFS) curves showed a different trend for acute and late toxicity. TFS was significantly associated with RT volume, except for acute GI toxicity. Specifically, the concomitant irradiation of PB and WP appeared to be a significant risk factor for late GI and GU toxicity (p = 0.029 and p = 0.012, respectively). Conclusions: At the 48-month median timepoint considered by our study, postoperative hypofractionated RT achieved promising results in terms of clinical outcomes with acceptable toxicity. Only the irradiated volume seems to be an important predictor for toxicity. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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21 pages, 1744 KB

Open AccessArticle

Virtual Biomarkers and Simplified Metrics in the Modeling of Breast Cancer Neoadjuvant Therapy: A Proof-of-Concept Case Study Based on Diagnostic Imaging

by Graziella Marino, Maria Valeria De Bonis, Marisabel Mecca, Marzia Sichetti, Aldo Cammarota, Manuela Botte, Giuseppina Dinardo, Maria Imma Lancellotti, Antonio Villonio, Antonella Prudente, Alexios Thodas, Emanuela Zifarone, Francesca Sanseverino, Pasqualina Modano, Francesco Schettini, Andrea Rocca, Daniele Generali and Gianpaolo Ruocco

Med. Sci. 2025, 13(4), 242; https://doi.org/10.3390/medsci13040242 - 24 Oct 2025

Cited by 1 | Viewed by 1398

Abstract

Background: Neoadjuvant chemotherapy (NAC) is a standard preoperative intervention for early-stage breast cancer (BC). Dynamic contrast-enhanced magnetic resonance imaging (CE-MRI) has emerged as a critical tool for evaluating treatment response and pathological complete response (pCR) following NAC. Computational modeling offers a robust framework [...] Read more.

Background: Neoadjuvant chemotherapy (NAC) is a standard preoperative intervention for early-stage breast cancer (BC). Dynamic contrast-enhanced magnetic resonance imaging (CE-MRI) has emerged as a critical tool for evaluating treatment response and pathological complete response (pCR) following NAC. Computational modeling offers a robust framework to simulate tumor growth dynamics and therapy response, leveraging patient-specific data to enhance predictive accuracy. Despite this potential, integrating imaging data with computational models for personalized treatment prediction remains underexplored. This case study presents a proof-of-concept prognostic tool that bridges oncology, radiology, and computational modeling by simulating BC behavior and predicting individualized NAC outcomes. Methods: CE-MRI scans, clinical assessments, and blood samples from three retrospective NAC patients were analyzed. Tumor growth was modeled using a system of partial differential equations (PDEs) within a reaction–diffusion mass transfer framework, incorporating patient-specific CE-MRI data. Tumor volumes measured pre- and post-treatment were compared with model predictions. A 20% error margin was applied to assess computational accuracy. Results: All cases were classified as true positive (TP), demonstrating the model’s capacity to predict tumor volume changes within the defined threshold, achieving 100% precision and sensitivity. Absolute differences between predicted and observed tumor volumes ranged from 0.07 to 0.33 cm³. Virtual biomarkers were employed to quantify novel metrics: the biological conversion coefficient ranged from 4 × 10⁻⁷ to 6 × 10⁻⁶ s⁻¹, while the pharmacodynamic efficiency coefficient ranged from 1 × 10⁻⁷ to 4 × 10⁻⁴ s⁻¹, reflecting intrinsic tumor biology and treatment effects, respectively. Conclusions: This approach demonstrates the feasibility of integrating CE-MRI and computational modeling to generate patient-specific treatment predictions. Preliminary model training on retrospective cohorts with matched BC subtypes and therapy regimens enabled accurate prediction of NAC outcomes. Future work will focus on model refinement, cohort expansion, and enhanced statistical validation to support broader clinical translation. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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12 pages, 659 KB

Open AccessCommunication

Is Night Shift Work Associated with Ovarian Cancer? A Systematic Review and Meta-Analysis

by Ahmed Arafa, Mazin Alhussein, Amin Alayyan, Haytham A. Sheerah, Mona S. Ibrahim, Abeer S. Alasmari, Sarah A. Barzanji, Samah A. Bukhari, Alhanouf K. Althaydi, Ehab Elkady, Tarig A. Y. Ali and Abdulrahman Almazrooa

Med. Sci. 2025, 13(4), 228; https://doi.org/10.3390/medsci13040228 - 12 Oct 2025

Cited by 1 | Viewed by 2766

Abstract

Background: Night shift work has been classified as a probable carcinogen due to its disruption of circadian rhythms. However, whether night shift work can increase the risk of ovarian cancer remains unclear. Herein, we investigated this association using a systematic review and [...] Read more.

Background: Night shift work has been classified as a probable carcinogen due to its disruption of circadian rhythms. However, whether night shift work can increase the risk of ovarian cancer remains unclear. Herein, we investigated this association using a systematic review and meta-analysis. Methods: We systematically searched several databases until June 2025 for relevant studies. Effect estimates were extracted and pooled using a random-effects model to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity across studies was assessed using the I² statistic, and publication bias was assessed using Egger’s regression test and funnel plot asymmetry. Results: Seven studies (eight cohorts) involving >2.5 million women were included. Overall, night shift work was not significantly associated with ovarian cancer (OR = 1.13; 95% CI: 0.96, 1.32; I² = 49%). However, significant associations were observed in case–control studies (OR = 1.36; 95% CI: 1.12, 1.66; I² = 0.8%) and in high-quality studies (OR = 1.17; 95% CI: 1.00, 1.37; I² = 52%). Sensitivity analyses suggested that exposure misclassification in some cohort studies attenuated risk estimates. No publication bias was detected (z = −0.63, p = 0.53). Conclusions: While the overall findings did not demonstrate a statistically significant association, evidence from case–control studies that collected detailed information about night shift work suggests an increased ovarian cancer risk in night shift workers. Future large-scale prospective studies with detailed exposure assessments are warranted to confirm these findings. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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26 pages, 12279 KB

Open AccessArticle

Mast Cell Association with the Microenvironment of a Phosphaturic Mesenchymal Tumour Secreting Fibroblast Growth Factor 23

by Andrey Kostin, Alexei Lyundup, Alexander Alekhnovich, Aleksandra Prikhodko, Olga Patsap, Sofia Gronskaia, Zhanna Belaya, Olga Lesnyak, Galina Melnichenko, Natalia Mokrysheva, Igor Buchwalow, Markus Tiemann and Dmitrii Atiakshin

Med. Sci. 2025, 13(3), 195; https://doi.org/10.3390/medsci13030195 - 16 Sep 2025

Cited by 2 | Viewed by 1702

Abstract

Background: Phosphaturic mesenchymal tumours secreting fibroblast growth factor 23 (hereinafter referred to as FGF23+ PMT) are rare neoplasms that can cause hypophosphataemic osteomalacia, owing to excessive FGF23 production. Mast cells (MCs) play a key role in tumour biology by modulating proliferative activity of [...] Read more.

Background: Phosphaturic mesenchymal tumours secreting fibroblast growth factor 23 (hereinafter referred to as FGF23+ PMT) are rare neoplasms that can cause hypophosphataemic osteomalacia, owing to excessive FGF23 production. Mast cells (MCs) play a key role in tumour biology by modulating proliferative activity of atypical cells, resistance to innate and acquired immunity, angiogenesis, and metastatic behaviour. However, MCs associated with FGF23+ PMT have not previously been investigated. This study, to our knowledge, is the first to characterise features of the tumour microenvironment through spatial phenotyping of the immune and stromal landscape, together with histotopographic mapping of intercellular MC interactions with other subcellular populations in FGF23+ PMT. Methods: Histochemical staining (haematoxylin and eosin, toluidine blue, Giemsa solution, picro-Mallory protocol, silver impregnation), as well as monoplex and multiplex immunohistochemical staining with spatial phenotyping, were performed to detect atypical FGF23-secreting cells, immune cells (CD3, CD4, CD8, CD14, CD20, CD38, CD68, or CD163), stromal components (CD31, α-SMA, or vimentin), and specific MC proteases (tryptase, chymase, or carboxypeptidase A3). Bioinformatics analysis using artificial intelligence technologies was applied for spatial profiling of MC interactions with tumour, immunocompetent, and stromal cells in the tumour microenvironment. Results: Bioinformatic analysis of the entire tumour histological section, comprising over 70,000 cells stained using monoplex and multiplex immunohistochemical protocols, enabled identification of more than half of the cell population. The most abundant were CD14+ (30.7%), CD163+ (23.2%), and CD31+ (17.9%) cells. Tumour-associated MCs accounted for 0.7% of the total pool of immunopositive cells and included both mucosal and connective tissue subpopulations, predominantly of the tryptase + chymase-CPA3-specific protease phenotype. This pattern reflected combined multidirectional morphogenetic processes in the patient’s FGF23+ PMT. More than 50% of MCs were colocalized with neighbouring cells of the tumour microenvironment within 20 μm, most frequently with monocytes (CD14+CD68+), M2 macrophages (CD68+CD163+), and endothelial cells (CD31+). In contrast, colocalization with atypical FGF23-secreting cells was rare, indicating minimal direct effects on tumour cell activity. Interaction with T lymphocytes, including CD8+, was also infrequent, excluding their activation and the development of antitumour effects. Mapping of MC histotopography validated the hypothesis of their inductive role in monocyte differentiation into M2 macrophages and probable polarisation of macrophages from M1 into M2, thereby contributing to slow tumour growth. MCs were further involved in extracellular matrix remodelling and participated in the formation of pro-osteogenic niches within the FGF23+ PMT microenvironment, leading to pathological osteoid development. Conclusions: This study demonstrated active MC participation in the evolution of the FGF23+ PMT microenvironment. The findings may be applied in translational medicine to develop novel algorithms for personalised therapy in patients with FGF23-secreting tumours, offering an alternative when surgical removal of the tumour is not feasible. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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10 pages, 979 KB

Open AccessCommunication

Combining Immune Checkpoint Inhibitors and Anti-Angiogenesis Approaches: Treatment of Advanced Non-Small Cell Lung Cancer

by Tate Barney, Anita Thyagarajan and Ravi P. Sahu

Med. Sci. 2025, 13(3), 143; https://doi.org/10.3390/medsci13030143 - 19 Aug 2025

Cited by 7 | Viewed by 3167

Abstract

Combining immune checkpoint inhibitors (ICIs) and anti-angiogenic pharmacologic agents is an encouraging therapeutic approach in the treatment of non-small cell lung cancer (NSCLC). Currently, the only FDA-approved therapy combining an immune checkpoint inhibitor and a vascular endothelial growth factor (VEGF) inhibitor is atezolizumab, [...] Read more.

Combining immune checkpoint inhibitors (ICIs) and anti-angiogenic pharmacologic agents is an encouraging therapeutic approach in the treatment of non-small cell lung cancer (NSCLC). Currently, the only FDA-approved therapy combining an immune checkpoint inhibitor and a vascular endothelial growth factor (VEGF) inhibitor is atezolizumab, bevacizumab, and chemotherapy in first-line metastatic NSCLC patients. However, the combination of nivolumab, a programmed death-1 (PD-1) inhibitor, and bevacizumab has also shown encouraging results in patients with NSCLC with minimal adverse effects, respectively. This communication aims to highlight the efficacy of nivolumab and bevacizumab in NSCLC patients without sensitizing mutations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or ROS proto-oncogene 1 (ROS1). In addition, the combination of nivolumab/atezolizumab and bevacizumab with other therapeutic agents is also discussed. We also underscore the adverse effects and limitations of such combinations in NSCLC patients. Future studies should focus on large-scale trials and biomarker identification to establish the benefits of these combination therapies in NSCLC patients. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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22 pages, 1030 KB

Open AccessEditor’s ChoiceArticle

Current and Emerging Therapeutic Strategies for Limited- and Extensive-Stage Small-Cell Lung Cancer

by Walid Shalata, Rashad Naamneh, Wenad Najjar, Mohnnad Asla, Adam Abu Gameh, Mahmoud Abu Amna, Leonard Saiegh and Abed Agbarya

Med. Sci. 2025, 13(3), 142; https://doi.org/10.3390/medsci13030142 - 18 Aug 2025

Cited by 10 | Viewed by 6988

Abstract

Background: Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine malignancy characterized by rapid growth, early metastatic dissemination, and a dismal prognosis. For decades, treatment paradigms remained largely stagnant, particularly for extensive-stage disease (ES-SCLC). However, the last five years have witnessed a significant [...] Read more.

Background: Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine malignancy characterized by rapid growth, early metastatic dissemination, and a dismal prognosis. For decades, treatment paradigms remained largely stagnant, particularly for extensive-stage disease (ES-SCLC). However, the last five years have witnessed a significant evolution in the therapeutic landscape. Methods: The information for this article was gathered by synthesizing data from several key sources. This article synthesizes the evidence supporting current standards of care for both limited-stage (LS-SCLC) and ES-SCLC, incorporating data from pivotal clinical trials, a network meta-analysis of first-line chemoimmunotherapy regimens, and a critical appraisal of international treatment guidelines, and a critical analysis of international treatment guidelines from prominent organizations like the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO). This comprehensive approach allows for a robust and well-supported summary of the current therapeutic landscape. Results: For limited-stage SCLC (LS-SCLC), concurrent chemoradiotherapy (cCRT) remains the curative-intent standard, but its efficacy is now being augmented by consolidative immunotherapy, as demonstrated by the landmark ADRIATIC trial. The role of prophylactic cranial irradiation (PCI) in LS-SCLC is being re-evaluated in the era of high-sensitivity brain imaging and concerns over neurotoxicity. For ES-SCLC, the treatment paradigm has been fundamentally transformed by the integration of immune checkpoint inhibitors (ICIs) with platinum–etoposide chemotherapy, establishing a new standard of care that offers a modest but consistent survival benefit. Conclusions: The treatment of SCLC has been significantly advanced by the integration of immunotherapy, particularly for extensive-stage disease, which has established a new standard of care and improved patient outcomes. Looking to the future, the quest for predictive biomarkers and the development of novel therapeutic classes, such as Bi-specific T-cell Engagers (BiTEs) and antibody–drug conjugates, promise to build upon recent progress and offer new hope for improving the dismal prognosis associated with this disease. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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Review

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15 pages, 494 KB

Open AccessReview

PAP Versus DIEP Flap Breast Reconstruction: Current Evidence and the Unresolved Question of Timing and Oncologic Safety—A Narrative Review

by Maximilian Vlad Muntean, Radu Alexandru Ilieș, Vlad Alexandru Gâta, Ștefan Țîțu, Ioan Constantin Pop, Alex Victor Orădan, Gerald Gheorghe Filip, Roxana Pintican, Nicoleta Zenovia Antone and Patriciu Andrei Achimaș-Cadariu

Med. Sci. 2026, 14(2), 295; https://doi.org/10.3390/medsci14020295 - 6 Jun 2026

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Abstract

Background/Objectives: Deep inferior epigastric perforator (DIEP) flap reconstruction represents the gold standard for autologous breast reconstruction, while profunda artery perforator (PAP) flap reconstruction has developed as a reliable alternative, particularly in patients with low body mass index or inadequate abdominal tissue. Even [...] Read more.

Background/Objectives: Deep inferior epigastric perforator (DIEP) flap reconstruction represents the gold standard for autologous breast reconstruction, while profunda artery perforator (PAP) flap reconstruction has developed as a reliable alternative, particularly in patients with low body mass index or inadequate abdominal tissue. Even though several comparative studies have evaluated surgical and patient-reported outcomes between PAP and DIEP flaps, evidence regarding reconstructive timing, oncologic safety, and interactions with adjuvant therapies remains scarce, especially for PAP reconstruction. Methods: A narrative review of the literature was conducted using PubMed. Studies assessing PAP and DIEP flap breast reconstruction were included, with particular focus on surgical outcomes, patient-reported outcomes, reconstructive timing (immediate or delayed reconstruction), oncologic safety, recurrence, and the effects of radiotherapy and chemotherapy. Comparative studies, cohort studies, systematic reviews, and meta-analyses were synthesized through a narrative review. Results: Twenty studies were included. Comparative evidence showed similar flap survival rates and overall patient satisfaction between the two methods, with flap success rates approaching 98–100%. PAP reconstruction was associated with increased donor-site wound complications and, in some studies, increased fat necrosis rates, while long-term patient-reported and aesthetic outcomes remained equivalent between techniques. In contrast to the relatively limited PAP literature, DIEP reconstruction has been widely studied in terms of reconstructive timing and oncologic safety. Current evidence indicates that immediate DIEP reconstruction does not increase the risk of flap loss, major complications, or recurrence in comparison with delayed reconstruction and might optimize early postoperative recovery and patient-reported outcomes. Nevertheless, none of the identified studies directly compared PAP and DIEP reconstruction with respect to immediate versus delayed timing, exposure to radiotherapy or chemotherapy, or long-term oncologic outcomes. Conclusions: PAP flap appears to represent a reliable alternative to DIEP flap reconstruction. However, major gaps in the literature persist involving PAP reconstruction in oncologic and timing-related settings. Future prospective multicenter studies that directly compare PAP and DIEP flaps according to reconstructive timing, exposure to adjuvant therapy, recurrence, and patient-reported outcomes are warranted to establish evidence-based reconstructive strategies for oncologic breast reconstruction. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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14 pages, 4957 KB

Open AccessReview

Diagnostic Aspects and Management Strategies in Primary and Metastatic Intestinal Melanoma: A Literature Review

by Alexandra Caziuc, Radu Alexandru Ilieș, George Ionuț Golea, Andrada Larisa Deac and George Călin Dindelegan

Med. Sci. 2026, 14(2), 281; https://doi.org/10.3390/medsci14020281 - 31 May 2026

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Abstract

Background/Objectives: Intestinal malignant melanoma is a rare entity, most commonly presenting as metastatic disease from a cutaneous primary source. The distinction between primary and secondary intestinal melanoma remains challenging, yet it has important diagnostic, therapeutic, and prognostic implications. This study aims to [...] Read more.

Background/Objectives: Intestinal malignant melanoma is a rare entity, most commonly presenting as metastatic disease from a cutaneous primary source. The distinction between primary and secondary intestinal melanoma remains challenging, yet it has important diagnostic, therapeutic, and prognostic implications. This study aims to highlight the diagnostic difficulties and therapeutic considerations associated with intestinal melanoma. Methods: A narrative literature review was conducted using the PubMed database, only including articles published between January 2015 and December 2025. Case reports, case series, and reviews that described primary-like (i.e., presumed primary) or metastatic small bowel melanoma were considered eligible. Extracted data consisted of clinical presentation, diagnostic workup, histopathological and immunohistochemical features, treatment strategies, and outcomes. Results: Twenty articles met the inclusion criteria, comprising ten reporting primary intestinal melanoma and ten reporting metastatic intestinal melanoma. Primary-like intestinal melanoma was frequently solitary, amelanotic, and occurred in patients without a prior history of melanoma, whereas metastatic disease was usually multifocal and associated with a known cutaneous primary source. Clinical manifestations were nonspecific, most frequently including anemia, gastrointestinal bleeding, abdominal pain, or intestinal obstruction. Immunohistochemistry confirmed melanocytic origin in each case, but could not reliably differentiate primary from metastatic disease. Surgical resection remained the cornerstone of treatment, with systemic therapy reserved primarily for metastatic cases. Conclusions: Diagnosis of primary intestinal melanoma relies on excluding other primary sites through comprehensive clinical and imaging evaluations. Early detection using advanced endoscopic techniques and multidisciplinary management are vital for optimizing outcomes. While metastatic intestinal melanoma carries a poor prognosis, complete surgical resection of primary lesions has been associated with improved outcomes in selected patients. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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42 pages, 9695 KB

Open AccessReview

Beyond the Scan: Adapting Multimodal Lung Cancer Screening for Central and Eastern Europe—Overcoming Systemic Barriers and Epidemiological Confounders

by Rodica Anghel, Antonia-Ruxandra Folea, Vlad-Luca Moga, Cristian Pavel, Diana Troncotă, Matei Celea, Corneliu-Octavian Dumitru, Andreea-Iren Șerban and Liviu Bîlteanu

Med. Sci. 2026, 14(2), 259; https://doi.org/10.3390/medsci14020259 - 18 May 2026

Viewed by 1442

Abstract

Background/Objectives: Lung cancer remains the leading cause of cancer-related mortality in Central and Eastern Europe (CEE), where late-stage diagnosis, structural healthcare limitations, and regional epidemiological confounders complicate early detection. This review aimed to synthesize the evidence from Romania, Poland, Hungary, and Bulgaria and [...] Read more.

Background/Objectives: Lung cancer remains the leading cause of cancer-related mortality in Central and Eastern Europe (CEE), where late-stage diagnosis, structural healthcare limitations, and regional epidemiological confounders complicate early detection. This review aimed to synthesize the evidence from Romania, Poland, Hungary, and Bulgaria and to outline a context-adapted multimodal screening strategy for CEE settings. Methods: A structured review of PubMed-, Scopus-, and Web of Science-indexed literature published from 2010 through 27 December 2025 was performed, focusing on lung cancer epidemiology, screening, implementation barriers, risk stratification, and adjunctive diagnostic approaches in the four selected CEE countries. A total of 297 articles were included. Results: The evidence confirms a persistently high burden of late-stage lung cancer across CEE, driven by tobacco exposure, air pollution, radon, comorbidities, diagnostic delays, fragmented registries, workforce shortages, and marked socioeconomic and geographic inequalities. In addition, tuberculosis-related granulomatous lesions and chronic inflammatory lung disease complicate nodule interpretation and reduce screening specificity in parts of the region. Screening experience from Poland and Hungary supports the feasibility of low-dose computed tomography (LDCT) when paired with volumetric assessment and structured follow-up. Risk-prediction models may improve participant selection, while biological triage may help reduce unnecessary invasive procedures, although prospective validation remains limited. Conclusions: In CEE, lung cancer screening should be implemented as a multimodal, context-adapted program combining risk-based enrollment, volumetric LDCT, selective biological triage, smoking-cessation support, and centralized multidisciplinary delivery. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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60 pages, 15903 KB

Open AccessReview

Sputum Liquid Biopsy for Lung Cancer Screening, Diagnosis, Subtyping, Surveillance, Response Prediction, and Prognostication: A Scoping Review

by Abdul Rehman, Muhammad Awais, Hafiza Noor Ul Ain Baloch, Muhammad Omer Leghari, Arfa Ahmad and Hafiz Javed

Med. Sci. 2026, 14(2), 231; https://doi.org/10.3390/medsci14020231 - 30 Apr 2026

Viewed by 2119

Abstract

Background/Objectives: Liquid biopsy (LB) is transforming cancer care by enabling minimally invasive tumor profiling. While current research and clinical pathways mostly focus on blood LB, sputum represents a non-invasive, readily available respiratory specimen that may offer unique advantages for lung cancer (LC) [...] Read more.

Background/Objectives: Liquid biopsy (LB) is transforming cancer care by enabling minimally invasive tumor profiling. While current research and clinical pathways mostly focus on blood LB, sputum represents a non-invasive, readily available respiratory specimen that may offer unique advantages for lung cancer (LC) care. Despite its potential, the maturity, breadth, and clinical applicability of sputum-based LB remain elusive. Methods: We conducted a scoping review to systematically map the existing literature on sputum LB in LC. Electronic databases were searched for studies evaluating sputum-derived biomarkers—cytologic, genomic, epigenetic, transcriptomic, proteomic, metabolomic, metagenomic, and extracellular vesicle–derived products—across the LC care continuum. Study designs, technologies, clinical contexts, and reported outcomes were extracted and synthesized qualitatively. Results: The literature demonstrated substantial heterogeneity in sputum collection, processing, and analytical platforms. Early work focused on cytometry and genetic alterations, while recent studies increasingly explore DNA methylomics, microRNAs, extracellular vesicle-derived products, and multi-omics approaches. The evidence suggests potential utility of sputum biomarkers for early detection and risk stratification, particularly in high-risk populations, with emerging data supporting roles in molecular subtyping, response monitoring, prognostication, and surveillance. However, few studies report prospective validation, direct comparison with blood-based LB, or impact on actual patient outcomes. Conclusions: Sputum LB is a promising yet underdeveloped modality in LC care. This scoping review highlights technological innovations alongside significant methodological heterogeneity and translational gaps. Future research should focus on standardization, prospective validation, impact on patient outcomes, and integration with blood- and other body fluid–based LB, as well as imaging biomarkers. This will enable incorporation of sputum-based LB into actual clinical pathways of LC care. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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28 pages, 1333 KB

Open AccessReview

A One Health Perspective on Cancer: A Narrative Review

by Sílvia A. C. Duarte, Rosário Pinto-Leite and Felisbina L. Queiroga

Med. Sci. 2026, 14(2), 221; https://doi.org/10.3390/medsci14020221 - 29 Apr 2026

Cited by 1 | Viewed by 1691

Abstract

Cancer is a major public health challenge worldwide, with increasing incidence and a growing economic and societal burden. Despite therapeutic advances, prevention remains the most effective strategy to reduce its impact. The One Health approach, which recognizes the interconnection between human, animal, and [...] Read more.

Cancer is a major public health challenge worldwide, with increasing incidence and a growing economic and societal burden. Despite therapeutic advances, prevention remains the most effective strategy to reduce its impact. The One Health approach, which recognizes the interconnection between human, animal, and environmental health, provides a valuable framework to address cancer risk factors in a more integrated and sustainable way. This narrative review addresses cancer through a One Health lens. Human health aspects include the global burden, major lifestyle and infectious risk factors, and key prevention strategies. Environmental determinants of cancer are summarized with emphasis on climate change, air pollution, occupational exposures, microplastics, ultraviolet radiation, and nutrition/food safety. Animal health contributions include insights from comparative oncology, which offer translational opportunities for prevention, diagnosis, and treatment, and from microbiome research revealing promising biomarkers for early detection and treatment response. Integrating cancer prevention into the One Health framework is essential for addressing the complex interplay between environmental, animal, and human health. A multidisciplinary approach can enhance public health policies, promote sustainable prevention measures, and improve early detection and treatment strategies, ultimately reducing healthcare costs and advancing global health outcomes. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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26 pages, 2414 KB

Open AccessReview

Spirulina and Its Bioactive Compounds as Multi-Target Anticancer Agents: Mechanisms, Immune Modulation, and Translational Potential

by Rym Akrout, Khouloud Ayed, Hela Mrizak, Ludovic Leloup, Orace Mathieu Kenou, Fidèle Fassinou, Dhouha Bacha, Rahma Boughriba, Hanen Attia, Hervé Kovacic, Wassim Y. Almawi and Asma Gati

Med. Sci. 2026, 14(2), 189; https://doi.org/10.3390/medsci14020189 - 10 Apr 2026

Cited by 2 | Viewed by 1821

Abstract

Marine-derived natural products are increasingly recognized for their therapeutic potential in cancer and other chronic diseases. Despite significant advances, current cancer treatments remain challenged by toxicity, drug resistance, and limited survival benefits. Natural compounds offer promising alternatives due to their multi-target mechanisms and [...] Read more.

Marine-derived natural products are increasingly recognized for their therapeutic potential in cancer and other chronic diseases. Despite significant advances, current cancer treatments remain challenged by toxicity, drug resistance, and limited survival benefits. Natural compounds offer promising alternatives due to their multi-target mechanisms and favorable safety profiles. Among them, Spirulina, a filamentous cyanobacterium, stands out for its rich composition and diverse biological activities. Its anticancer effects involve apoptosis induction via intrinsic and extrinsic pathways, cell cycle arrest at G1/S or G2/M phases, inhibition of angiogenesis through the VEGF/VEGFR2 axis, and suppression of epithelial–mesenchymal transition. These activities are mainly attributed to C-phycocyanin, allophycocyanin, phenolic compounds, and immunomodulatory polysaccharides. Spirulina also exhibits potent immunomodulatory effects by enhancing natural killer cell activity, promoting M1 macrophage polarization, and regulating Th1 and Th17 cytokine responses, highlighting its potential as both an immunotherapeutic and chemoprotective agent. Moreover, preclinical findings suggest it may reduce chemotherapy-associated side effects. However, translation into clinical therapy remains limited by low bioavailability, lack of standardized extracts, and scarce clinical evidence. This review summarizes current mechanistic and immunological insights and highlights the need for optimized formulations, defined dosing strategies, and well-designed clinical trials to validate Spirulina’s potential in cancer treatment. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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23 pages, 3201 KB

Open AccessReview

Multimodal Radiogenomic Imaging in Oropharyngeal Squamous Cell Carcinoma: Implications for Dentomaxillofacial Radiology

by Elaine Dinardi Barioni, Kaan Orhan, Ana Cristina Borges-Oliveira, Sérgio Lúcio Pereira de Castro Lopes and Andre Luiz Ferreira Costa

Med. Sci. 2026, 14(2), 174; https://doi.org/10.3390/medsci14020174 - 31 Mar 2026

Cited by 1 | Viewed by 1349

Abstract

Radiogenomics examines associations between imaging phenotypes and underlying biological characteristics across cancer types. This structured narrative review focuses on oropharyngeal squamous cell carcinoma (OPSCC) and evaluates how genomic programs characteristic of HPV-positive and HPV-negative tumors have been investigated across computed tomography (CT), magnetic [...] Read more.

Radiogenomics examines associations between imaging phenotypes and underlying biological characteristics across cancer types. This structured narrative review focuses on oropharyngeal squamous cell carcinoma (OPSCC) and evaluates how genomic programs characteristic of HPV-positive and HPV-negative tumors have been investigated across computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) as variations in heterogeneity, diffusion patterns, perfusion and metabolic activity. A structured literature search was conducted in PubMed/MEDLINE, Scopus and Web of Science to identify studies on radiomics and radiogenomics in OPSCC and related head and neck cancers. After screening and eligibility assessment, 81 studies were included in the narrative synthesis. The reviewed literature indicates that imaging-derived features have been associated with HPV status, hypoxia-related signatures, extranodal extension and treatment outcomes. However, the current evidence base remains heterogeneous and is largely composed of retrospective, single-institution studies with relatively small cohorts. Methodological challenges, including variability in imaging acquisition, segmentation and feature harmonization, limit reproducibility and generalizability. Although cone-beam computed tomography (CBCT) is not used for primary OPSCC staging and no CBCT-based radiogenomic studies in OPSCC have been reported, existing radiomics research in dentomaxillofacial imaging suggests its potential as a hypothesis-generating modality for future investigation. Overall, current evidence supports the biological plausibility of radiogenomic imaging signatures in OPSCC, while emphasizing the need for larger multicenter datasets, standardized imaging protocols and prospective validation before clinical implementation. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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21 pages, 966 KB

Open AccessReview

Translating Fibrosis to Malignancy: Biomarkers and Therapeutic Opportunities in Liver Fibrosis and Hepatocellular Carcinoma

by Daniel Neureiter, Tobias Kiesslich and Matthias Ocker

Med. Sci. 2026, 14(1), 110; https://doi.org/10.3390/medsci14010110 - 25 Feb 2026

Cited by 2 | Viewed by 2084

Abstract

Background/Objectives: Hepatocellular carcinoma (HCC) commonly arises from chronic liver diseases that show progressing fibrosis and cirrhosis. The molecular mechanisms driving the transition from advanced fibrosis to overt malignancy remain poorly defined, representing a key knowledge gap in current hepatology research. This review delineates [...] Read more.

Background/Objectives: Hepatocellular carcinoma (HCC) commonly arises from chronic liver diseases that show progressing fibrosis and cirrhosis. The molecular mechanisms driving the transition from advanced fibrosis to overt malignancy remain poorly defined, representing a key knowledge gap in current hepatology research. This review delineates shared pathways like TGFβ/SMAD, WNT/β-catenin, Hedgehog, NOTCH, Hippo/YAP-TAZ and MAPK, linking fibrosis to HCC and opening avenues for dual antifibrotic/antitumor therapies. Results and Conclusions: So far, validated biomarker tools for fibrosis, like FIB-4, Enhanced Liver Fibrosis (ELF) and combined direct/indirect markers of liver damage and tissue remodeling, are used for fibrosis staging, while HCC detection leverages serum parameters like α-fetoprotein (AFP) or, more recently, multi-omics approaches (miRNA, cfDNA, metabolomics). Understanding the interconnection of these pathways can lead to novel targeted therapies (e.g., TGFβ inhibitors) that may show dual antifibrotic and antitumor activity in future studies. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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20 pages, 1599 KB

Open AccessReview

Breaking Barriers: Advancements in CNS Drug Delivery for Glioblastoma

by Nicole Al Fidawi, Cecile Z. Attieh, Lara Baghdadi, Chahine El Bekai, Safaa Sayadi, Ghassan Nabbout, François Sahyoun, Hilda E. Ghadieh, Sami Azar and Frederic Harb

Med. Sci. 2026, 14(1), 73; https://doi.org/10.3390/medsci14010073 - 5 Feb 2026

Cited by 3 | Viewed by 2304

Abstract

Glioblastoma is known as the most aggressive primary brain tumor in adults, and it is still largely not curable, with a median survival of approximately 15 months when standard multimodal therapy is applied. The standard treatment nowadays is maximal safe surgical resection, associated [...] Read more.

Glioblastoma is known as the most aggressive primary brain tumor in adults, and it is still largely not curable, with a median survival of approximately 15 months when standard multimodal therapy is applied. The standard treatment nowadays is maximal safe surgical resection, associated with radiotherapy and temozolomide. Treatment effectiveness is limited not only by an impassable blood–brain barrier (BBB) to drug delivery to the brain, but also by the heterogeneity of the tumors and intrinsic or acquired drug resistance, resulting in a certain and inescapable tumor relapse. Therefore, novel drug delivery systems are being designed to overcome the BBB and improve therapeutic efficacy. These approaches include nanoparticle-mediated delivery systems, convection-enhanced intra-tumoral infusion, implantable drug-releasing devices, and noninvasive focused ultrasound technology, which induced transient disruption of the BBB. These approaches are designed to enhance local drug exposure and reduce systemic toxicity with promising preclinical and early clinical results. However, many clinical and technical challenges remain, especially the need for safety, homogeneous drug delivery, and translation of these advances into effective clinical therapies. Current glioblastoma treatment landscape and opportunities include maturing delivery systems, novel therapeutic approaches, including targeted molecular therapies and immunotherapy, as well as personalized regimens. This multidisciplinary modality may have the capacity to help not only patients with GBM but others as well through a multimodal approach of targeted drug delivery and innovative therapy in the long run to improve clinical outcomes of GBM in patients. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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18 pages, 1196 KB

Open AccessReview

Repurposing Itraconazole in Combination with Chemotherapy and Immune Checkpoint Inhibitor for Cancer

by Camille E. Zonfa, Anita Thyagarajan and Ravi P. Sahu

Med. Sci. 2026, 14(1), 55; https://doi.org/10.3390/medsci14010055 - 22 Jan 2026

Cited by 3 | Viewed by 2981

Abstract

Cancer remains a significant global health burden despite advances in diagnosis and treatment. In recent years, drug repurposing has emerged as a promising strategy in oncology, offering reduced costs and shorter development timelines compared with de novo drug discovery. Among repurposed agents, the [...] Read more.

Cancer remains a significant global health burden despite advances in diagnosis and treatment. In recent years, drug repurposing has emerged as a promising strategy in oncology, offering reduced costs and shorter development timelines compared with de novo drug discovery. Among repurposed agents, the antifungal drug itraconazole has demonstrated anticancer activity across multiple tumor types, particularly when used in combination with other therapeutic modalities. In this review, we summarize current preclinical and clinical evidence supporting the use of itraconazole in cancer therapy, with a specific focus on its combination with chemotherapeutic agents and programmed cell death protein 1 (PD-1) immune checkpoint inhibitors. We highlight proposed mechanisms underlying this synergy, including modulation of tumor metabolism, angiogenesis, and immune signaling pathways. Additionally, we discuss key challenges and limitations, such as drug–drug interactions and toxicity considerations, that must be addressed to optimize clinical translation. Overall, the combination of itraconazole with chemotherapy or anti-PD-1 therapy represents a promising therapeutic strategy warranting further investigation in well-designed trials. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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26 pages, 2736 KB

Open AccessReview

COVID-19 and Lung Cancer Interactions: A Literature Review

by Szabolcs-Attila László, Edith-Simona Ianoși, Anca-Meda Văsieșiu, Mioara Szathmáry, Maria Beatrice Ianoși, Delia-Liana Rachiș, Gabriel Nistor and Gabriela Jimborean

Med. Sci. 2025, 13(4), 295; https://doi.org/10.3390/medsci13040295 - 30 Nov 2025

Cited by 2 | Viewed by 1683

Abstract

This review aims to discuss the apparent reduction in pulmonary cancer incidence in the general population during and shortly after the COVID-19 pandemic from a biological and pathophysiological mechanistic point of view. While the epidemiological evidence points to a disruption in the early- [...] Read more.

This review aims to discuss the apparent reduction in pulmonary cancer incidence in the general population during and shortly after the COVID-19 pandemic from a biological and pathophysiological mechanistic point of view. While the epidemiological evidence points to a disruption in the early- and mid-stage diagnostic process, which causes a shift to late-stage lung cancer discovery with no impact on its actual prevalence, an alternative hypothesis based on the intersection of viral and cancer biology could have a real effect on lung carcinogenesis as an independent phenomenon. By weaving together population-level trends, mechanistic insights, and translational oncology, we discuss whether the pandemic-associated decline in lung cancer diagnoses reflects primarily a temporary diagnostic artifact or whether it also reveals biologically relevant intersections between SARS-CoV-2 and pulmonary oncogenesis. The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has exerted profound and multifaceted effects on global healthcare systems, altering patterns of disease detection, management, and outcomes across nearly all medical disciplines. These disruptions generated what has been termed a “diagnostic deficit”, producing a backlog of undetected cancers that have only partially been recovered in subsequent years. This phenomenon, sometimes described as a “COVID-19 debt” in oncology, is thought to contribute to excess late-stage diagnoses and potentially worse medium-term survival outcomes. Beyond the disruption of medical systems, the pandemic also raised a more speculative but biologically intriguing question: could SARS-CoV-2 infection itself, through direct or indirect mechanisms, influence lung cancer biology? Our review aims to critically synthesize the evidence across seven domains to address this dual hypothesis. (1) We examine the observed effects of the pandemic on cancer incidence, highlighting global registry and health-system data; (2) we review SARS-CoV-2 infection biology, including viral entry, replication, protein functions, and treatment implications; (3) we summarize the pathogenesis of lung cancer; (4) we explore the role of immune checkpoints in tumor immune evasion, followed by (5) analyses of immune dysregulation in acute infection and (6) in long COVID; and (7) finally, we evaluate proposed oncogenic mechanisms of SARS-CoV-2, integrating molecular virology with cancer immunology. We conclude that the “diagnostic deficit” phenomenon was a reality during and immediately post-pandemic. However, a definitive answer to the questions related to the impact of the infection as an independent phenomenon would require advanced research information covering the biology of the viral infection and lung cancer oncogenesis: processes that are not currently implemented in routine clinical laboratory investigations. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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22 pages, 2210 KB

Open AccessReview

Mapping Cognitive Oncology: A Decade of Trends and Research Fronts

by Anna Tsiakiri, Akyllina Despoti, Panagiota Koutsimani, Kalliopi Megari, Spyridon Plakias and Angeliki Tsapanou

Med. Sci. 2025, 13(3), 191; https://doi.org/10.3390/medsci13030191 - 15 Sep 2025

Cited by 3 | Viewed by 2822

Abstract

Background: Cognitive and neuropsychological effects of cancer and its treatments have gained increasing attention over the past decade, with growing evidence of persistent deficits across multiple cancer types. While numerous studies have examined these effects, the literature remains fragmented, and no comprehensive bibliometric [...] Read more.

Background: Cognitive and neuropsychological effects of cancer and its treatments have gained increasing attention over the past decade, with growing evidence of persistent deficits across multiple cancer types. While numerous studies have examined these effects, the literature remains fragmented, and no comprehensive bibliometric synthesis has been conducted to map the field’s intellectual structure and emerging trends. Methods: A bibliometric and science mapping analysis was performed using the Scopus database to identify peer-reviewed articles published between 2015 and 2025 on neuropsychological or cognitive outcomes in adult cancer populations. Data from 179 eligible publications were analyzed with VOSviewer and Microsoft Power BI, applying performance metrics and network mapping techniques, including co-authorship, bibliographic coupling, co-citation, and keyword co-occurrence analyses. Results: Publication output increased steadily over the decade, with leading contributions from the Journal of Neuro-Oncology, Psycho-Oncology, and Brain Imaging and Behavior. Co-citation analysis identified three core intellectual pillars: (i) clinical characterization of cancer-related cognitive impairment, (ii) mechanistic and neuroimaging-based investigations, and (iii) neurosurgical and neuropathological research in brain tumors. Keyword mapping revealed emerging themes in sleep and circadian rhythm research, biological contributors to cognitive decline, and scalable rehabilitation strategies such as web-based cognitive training. Collaborative networks, while showing dense local clusters, remained moderately fragmented across disciplines. Conclusions: This review provides the first quantitative, decade-spanning map of cognitive oncology research, highlighting both consolidated knowledge areas and underexplored domains. Future efforts should prioritize methodological standardization, cross-disciplinary collaboration, and integration of cognitive endpoints into survivorship care, with the ultimate aim of improving functional outcomes and quality of life for cancer survivors. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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29 pages, 1889 KB

Open AccessReview

Advances in Adoptive Cell Therapies in Cancer: From Mechanistic Breakthroughs to Clinical Frontiers and Overcoming Barriers

by Syed Arman Rabbani, Mohamed El-Tanani, Yahia El-Tanani, Rakesh Kumar, Shrestha Sharma, Mohammad Ahmed Khan, Suhel Parvez, Alaa A. A. Aljabali, Mohammad I. Matalka and Manfredi Rizzo

Med. Sci. 2025, 13(3), 190; https://doi.org/10.3390/medsci13030190 - 15 Sep 2025

Cited by 7 | Viewed by 6179

Abstract

Adoptive cell therapies (ACTs) have revolutionized cancer treatment by harnessing the specificity and potency of T lymphocytes. Chimeric antigen receptor (CAR)-T cells have achieved landmark successes in B-cell malignancies and multiple myeloma. Tumor-infiltrating lymphocytes (TILs) and T-cell receptor (TCR)-engineered T cells offer complementary [...] Read more.

Adoptive cell therapies (ACTs) have revolutionized cancer treatment by harnessing the specificity and potency of T lymphocytes. Chimeric antigen receptor (CAR)-T cells have achieved landmark successes in B-cell malignancies and multiple myeloma. Tumor-infiltrating lymphocytes (TILs) and T-cell receptor (TCR)-engineered T cells offer complementary strategies to target solid tumors and intracellular antigens. Despite these advances, ACTs face challenges including cytokine release syndrome, neurotoxicity, on-target/off-tumor effects, manufacturing scalability, and immunosuppressive tumor microenvironments. Innovative strategies, such as dual-antigen targeting, localized delivery, checkpoint blockade combinations, gene-editing, and machine-learning-guided antigen discovery, are being used to mitigate toxicity, enhance efficacy, and streamline production. As CAR-T, TIL, and TCR modalities converge with advances in manufacturing and computational biology, the next generation of “living drugs” promises broader applicability across hematologic and solid tumors, improved safety profiles, and better treatment outcomes for patients. This review details the evolution of ACTs from first-generation CAR constructs to next-generation “armored” designs. It also focuses on the development and clinical deployment of TIL and TCR therapies. Furthermore, it synthesizes mechanisms, pivotal clinical trial outcomes, and ongoing challenges of ACTs. It also highlights strategies that will drive broader, safer, and more durable applications of these therapies across hematologic and solid tumors. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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23 pages, 4589 KB

Open AccessReview

The Novel Achievements in Oncological Metabolic Radio-Therapy: Isotope Technologies, Targeted Theranostics, Translational Oncology Research

by Elena V. Uspenskaya, Ainaz Safdari, Denis V. Antonov, Iuliia A. Valko, Ilaha V. Kazimova, Aleksey A. Timofeev and Roman A. Zubarev

Med. Sci. 2025, 13(3), 107; https://doi.org/10.3390/medsci13030107 - 1 Aug 2025

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Abstract

Background/Objectives. This manuscript presents an overview of advances in oncological radiotherapy as an effective treatment method for cancerous tumors, focusing on mechanisms of action within metabolite–antimetabolite systems. The urgency of this topic is underscored by the fact that cancer remains one of the [...] Read more.

Background/Objectives. This manuscript presents an overview of advances in oncological radiotherapy as an effective treatment method for cancerous tumors, focusing on mechanisms of action within metabolite–antimetabolite systems. The urgency of this topic is underscored by the fact that cancer remains one of the leading causes of death worldwide: as of 2022, approximately 20 million new cases were diagnosed globally, accounting for about 0.25% of the total population. Given prognostic models predicting a steady increase in cancer incidence to 35 million cases by 2050, there is an urgent need for the latest developments in physics, chemistry, molecular biology, pharmacy, and strict adherence to oncological vigilance. The purpose of this work is to demonstrate the relationship between the nature and mechanisms of past diagnostic and therapeutic oncology approaches, their current improvements, and future prospects. Particular emphasis is placed on isotope technologies in the production of therapeutic nuclides, focusing on the mechanisms of formation of simple and complex theranostic compounds and their classification according to target specificity. Methods. The methodology involved searching, selecting, and analyzing information from PubMed, Scopus, and Web of Science databases, as well as from available official online sources over the past 20 years. The search was structured around the structure–mechanism–effect relationship of active pharmaceutical ingredients (APIs). The manuscript, including graphic materials, was prepared using a narrative synthesis method. Results. The results present a sequential analysis of materials related to isotope technology, particularly nucleus stability and instability. An explanation of theranostic principles enabled a detailed description of the action mechanisms of radiopharmaceuticals on various receptors within the metabolite–antimetabolite system using specific drug models. Attention is also given to radioactive nanotheranostics, exemplified by the mechanisms of action of radioactive nanoparticles such as Tc-99m, AuNPs, wwAgNPs, FeNPs, and others. Conclusions. Radiotheranostics, which combines the diagnostic properties of unstable nuclei with therapeutic effects, serves as an effective adjunctive and/or independent method for treating cancer patients. Despite the emergence of resistance to both chemotherapy and radiotherapy, existing nuclide resources provide protection against subsequent tumor metastasis. However, given the unfavorable cancer incidence prognosis over the next 25 years, the development of “preventive” drugs is recommended. Progress in this area will be facilitated by modern medical knowledge and a deeper understanding of ligand–receptor interactions to trigger apoptosis in rapidly proliferating cells. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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9 pages, 402 KB

Open AccessBrief Report

Higher Levels of BRCA1 Gene Methylation in Sporadic Breast Cancer Patients with a Lower Incidence of Recurrence

by Grasiela Agnes, Andrea Pires Souto Damin, Guilherme Watte, Giuliano Rizzotto Guimarães, Adriana Vial Roehe and Jenifer Saffi

Med. Sci. 2026, 14(2), 251; https://doi.org/10.3390/medsci14020251 - 13 May 2026

Viewed by 867

Abstract

Background: Breast cancer is the most prevalent malignant disease among women. Here, we investigate whether there is an association between disease recurrence in breast cancer patients and the quantitative methylation pattern of seven genes of different DNA repair pathways. Methods: Clinical [...] Read more.

Background: Breast cancer is the most prevalent malignant disease among women. Here, we investigate whether there is an association between disease recurrence in breast cancer patients and the quantitative methylation pattern of seven genes of different DNA repair pathways. Methods: Clinical and pathological data from 30 patients treated for sporadic breast cancer were selected according to the following inclusion criteria: follow-up of 5 years, adjuvant chemotherapy and recurrence. Histopathology was verified, and genomic DNA was accessed by tumor cryosectioning. We also determined the methylation levels of seven DNA repair genes (BRCA1, BRCA2, XRCC1, PARP1, ERCC4, MGMT, and XPC). Results: Patients without recurrence demonstrated a higher index of positive progesterone receptor status compared to patients with recurrence (p = 0.025). All other clinical characteristics of the patients did not differ between the groups. BRCA1 and BRCA2 genes showed methylation, and there was a higher level of BRCA1 gene methylation in patients without recurrence. BRCA1 methylation was not associated with the clinical characteristics of patients. All other genes analyzed showed no difference in methylation between patients with and without recurrence. Conclusions: We showed that sporadic breast cancer patients with a lower incidence of recurrence demonstrate a higher level of BRCA1 gene methylation after 5 years of follow-up, suggesting its role as a predictive biomarker. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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15 pages, 3207 KB

Open AccessSystematic Review

Disseminated Intracranial and Spinal Dysembryoplastic Neuroepithelial Tumor: A Case Report with a Systematic Review

by Maksymilian Niemczyk, Justyna Fercho, Oskar G. Chasles, Bogdan Jabłoński, Jakub Soboń, Przemysław Nagórka, Maciej Mielczarek, Jacek Szypenbejl, Mariusz Siemiński and Jacek Furtak

Med. Sci. 2026, 14(2), 250; https://doi.org/10.3390/medsci14020250 - 13 May 2026

Viewed by 1037

Abstract

Background: Disseminated intracranial and spinal dysembryoplastic neuroepithelial tumors (DNETs) are exceptionally rare, with only five prior cases reported. Methods: This study presents a case of a 47-year-old woman with DNETs in the right hippocampus and lumbar spine, treated surgically, and systematically reviews the [...] Read more.

Background: Disseminated intracranial and spinal dysembryoplastic neuroepithelial tumors (DNETs) are exceptionally rare, with only five prior cases reported. Methods: This study presents a case of a 47-year-old woman with DNETs in the right hippocampus and lumbar spine, treated surgically, and systematically reviews the existing literature (total n = 6). Results: While primary tumors occurred in both locations, secondary lesions were predominantly spinal (83%). The key features included frequent obstructive hydrocephalus (67%, often requiring shunting) but rare epilepsy (n = 1, 17%). Two fatal outcomes were possibly associated with West Nile virus infection (the S100B protein pathway). MRI was performed in all cases, and surgical intervention (craniotomy/laminectomy) constituted the primary treatment modality (67%). Conclusions: This multifocal presentation poses significant challenges, underscoring the potential need for spinal MRI in intracranial DNET cases and multidisciplinary management. Further molecular studies and case registries are crucial to understand pathogenesis and optimize care. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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21 pages, 4923 KB

Open AccessSystematic Review

Radiologic–Pathologic Discordance After Image-Guided Breast Biopsy: A Systematic Review of Prevalence and Outcomes

by Pirada Yincharoen, Crystal Pravina Sharma and Weeratian Tawanwongsri

Med. Sci. 2026, 14(2), 229; https://doi.org/10.3390/medsci14020229 - 30 Apr 2026

Viewed by 1376

Abstract

Background: Radiologic–pathologic discordance remains an important concern owing to the absence of standardized guidelines. This systematic review aimed to summarize the prevalence of discordant benign outcomes, defined as suspicious imaging findings with benign biopsy histology insufficient to explain the imaging abnormality, and to [...] Read more.

Background: Radiologic–pathologic discordance remains an important concern owing to the absence of standardized guidelines. This systematic review aimed to summarize the prevalence of discordant benign outcomes, defined as suspicious imaging findings with benign biopsy histology insufficient to explain the imaging abnormality, and to quantify malignancy upgrades subsequent to additional tissue assessment. Methods: This review was conducted in accordance with PRISMA 2020 guidelines and was prospectively registered. Eligible studies reported primary patient-level or aggregated data on radiologic–pathologic correlations post-image-guided breast biopsy and provided extractable data on discordant benign prevalence and/or subsequent malignancy upgrades. Results: Twenty-three studies were included. Lesion-/biopsy-based cohorts focused on biopsied abnormalities for analysis. Twelve studies directly estimated discordant-benign prevalence, whereas 11 studies did not, as study designs were discrepant-only, lesion-defined, or excision-restricted. Unselected cohorts with a cohort-wide correlation reported 1.2–5.3% discordant benign prevalence for all biopsies. When restricted to excised lesions, the discordant benign ascertainment rate was 7.4%, representing an excision-ascertained subset rather than the cohort-wide prevalence. Using benign-biopsy denominators, the discordance rate was 1.5–19.2%. Malignancy upgrades among discordant benign lesions ranged from 0 to 100% in selected subsets; however, several clinically relevant cohorts reported representative rates of approximately 20–40%, with some high-risk cohorts exceeding 50%. Conclusions: Discordant benign biopsy results are rare in unselected biopsy populations but carry a clinically meaningful upgrade risk, which warrants structured radiologic–pathologic correlation and prompt diagnostic resolution through repeat sampling or excision. Improvements in comparability and management algorithms require standardized definitions, uniform denominators aligned with all biopsied lesions, and prospective multicenter designs. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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20 pages, 8673 KB

Open AccessSystematic Review

by Maksymilian Niemczyk, Justyna Fercho, Szymon Goldszmyt, Bogdan Jabłoński, Oskar G. Chasles, Jakub Soboń, Marcin Birski, Jacek Szypenbejl, Maciej Mielczarek, Marek Harat, Mariusz Siemiński and Jacek Furtak

Med. Sci. 2026, 14(2), 211; https://doi.org/10.3390/medsci14020211 - 24 Apr 2026

Viewed by 1328

Abstract

Background: Intraventricular central nervous system (CNS) lymphoma is an atypical presentation of extranodal lymphoma, whether primary or secondary. The most commonly diagnosed subtype of lymphoma is diffuse large B-cell lymphoma (DLBCL). There is a documented relation of HIV, EBV and KSHV infections [...] Read more.

Background: Intraventricular central nervous system (CNS) lymphoma is an atypical presentation of extranodal lymphoma, whether primary or secondary. The most commonly diagnosed subtype of lymphoma is diffuse large B-cell lymphoma (DLBCL). There is a documented relation of HIV, EBV and KSHV infections with lymphomagenesis. AIDS-related lymphomas (ARLs) are described as a defining illness of the acquired immunodeficiency syndrome (AIDS). This study presents a novel case and systematic review of clinical, radiographic and histopathological features of intraventricular lymphomas. Methods: We report on a 27-year-old woman with a left lateral ventricle DLBCL with surrounding edema treated with steroids. A systematic review of 147 additional cases (1977–2025) was conducted, analyzing patient demographics, tumor characteristics, clinical features, imaging, treatment, and outcomes. The tumor locations were divided into three groups depending on the extent of ventricular involvement. Descriptive statistics summarized findings. Findings: 147 cases (mean age, 54.2 years; range, 3–87; 63.3% male) were analyzed. Immunodeficiency in patients was unusual (6.1%). Fully intraventricular lesions were the most common presentation (52.4%), with systemic involvement solely in 10 cases (6.8%). The lesions were predominantly located in the lateral ventricles or fourth ventricles (46 times each), and bilateral involvement was noted 37 additional times. DLBCL was diagnosed in 101 cases (78.9%). Interpretation: Intraventricular involvement in central nervous system lymphoma poses a diagnostic and therapeutic challenge due to non-specific symptoms and atypical locations. Adding to the diagnostic difficulty of intraventricular masses in young patients, we wish to highlight that immunocompromised patients are a notably insignificant subgroup of patients in our study. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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18 pages, 807 KB

Open AccessSystematic Review

Breast Cancer Risk in over 1.3 Million Women on Antipsychotic Therapy: Life-Saving Drugs or Hidden Trigger for Breast Cancer?

by Enrico Altiero Giusto, Vittorio Oteri, Giorgio Guido, Delia Anamaria Bogdan, Jacopo Giuliani, Carlotta Giorgi, Paolo Pinton and Francesco Fiorica

Med. Sci. 2026, 14(2), 205; https://doi.org/10.3390/medsci14020205 - 20 Apr 2026

Cited by 1 | Viewed by 1205

Abstract

Introduction: Antipsychotic (AP) medications are widely prescribed beyond psychotic disorders, yet their long-term safety profile regarding breast cancer (BC) risk remains uncertain. Methods: We conducted a systematic review and meta-analysis of observational studies evaluating the association between AP exposure and incident BC. Eligible [...] Read more.

Introduction: Antipsychotic (AP) medications are widely prescribed beyond psychotic disorders, yet their long-term safety profile regarding breast cancer (BC) risk remains uncertain. Methods: We conducted a systematic review and meta-analysis of observational studies evaluating the association between AP exposure and incident BC. Eligible studies reported adjusted odds ratios (ORs) with 95% confidence intervals for any AP, prolactin-increasing antipsychotics (PIAPs), or prolactin-sparing antipsychotics (PSAPs). Study quality was assessed using the modified Newcastle-Ottawa Scale (mNOS), and certainty of evidence was graded with the GRADE framework. Random-effect models were used to pool effect estimates by exposure category, duration, and cumulative Defined Daily Dose (DDD). Results: Nine high-quality observational studies encompassing 108 effect estimates were included. Most studies achieved mNOS scores of 9, yet GRADE certainty ranged from very low to moderate, with the overall body of evidence graded as low certainty due primarily to residual confounding. Any AP exposure was associated with a modestly increased BC risk, particularly with long-term use: use for >5 years yielded pooled ORs around 1.5–1.6, while short-to-medium duration (1–5 years) showed smaller increases (pooled ORs in the range 1.2–1.3). For PIAPs, both longer duration (>5 years) and higher cumulative exposure (>1000–2000 DDDs) were consistently associated with ORs/HRs in the 1.3–1.6 range, suggesting a possible dose–response pattern. Histological analyses indicated stronger associations for ductal than lobular BC, and elevated risks were observed across age strata, including women aged <55 and ≥70 years. Discussion: This meta-analysis suggests that chronic exposure to prolactin-increasing antipsychotics is associated with a potentially clinically relevant increase in BC risk, whereas prolactin-sparing agents do not show a clear signal of harm. However, the certainty of this association is limited by inconsistently measured confounders and by the observational nature of the data. These findings support a cautious, individualized approach in which clinicians preferentially consider PSAPs when appropriate, discuss BC risk as part of shared decision-making, and integrate tailored screening strategies for women requiring long-term PIAP therapy. Further high-quality pharmacoepidemiologic studies with better confounder control and mechanistic integration are needed to refine risk estimates and inform preventive neuropsychopharmacology. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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Graphical abstract

12 pages, 1197 KB

Open AccessBrief Report

Do Socio-Economic Determinants Influence DPYD Testing? A Real-World Study of 1478 Cancer Patients Receiving Fluoropyrimidine Chemotherapy

by Bahaaeldin Baraka, Navin Mathiyalagan, Maryam Al-Ani, Gaurav Mohindru, Torran Semple, Hrushikesh Divyateja, Grazziela Figueredo, Philip Quinlan, Guruprasad Padur Aithal and Srinivasan Madhusudan

Med. Sci. 2026, 14(1), 49; https://doi.org/10.3390/medsci14010049 - 17 Jan 2026

Viewed by 1116

Abstract

Background: The DPYD gene encodes dihydropyrimidine dehydrogenase (DPD), an enzyme essential for metabolising chemotherapeutic agents such as capecitabine, 5-fluorouracil (5-FU), and tegafur. Variants in this gene can increase the toxicity of these treatments. Methods: This study analysed data from 1478 cancer patients at [...] Read more.

Background: The DPYD gene encodes dihydropyrimidine dehydrogenase (DPD), an enzyme essential for metabolising chemotherapeutic agents such as capecitabine, 5-fluorouracil (5-FU), and tegafur. Variants in this gene can increase the toxicity of these treatments. Methods: This study analysed data from 1478 cancer patients at Nottingham University Hospitals who received chemotherapy between December 2021 and December 2023. The study assessed the prevalence of DPYD variants across different tumour types, ethnic groups, and socioeconomic factors. Results: Overall, DPYD variants were identified in 7% of patients, with higher rates in colorectal cancer (7.9%) and among Caucasian patients (7.4%). The most frequent variant was c.1129-5923C>G (HapB3), found in 75.7% of variant-positive cases. No significant differences in DPYD testing rates were observed across socioeconomic groups or between ethnic backgrounds within our cohort. Conclusions: DPYD variants were prevalent in 7% of the cohort, and testing access was not influenced by socioeconomic status. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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10 pages, 758 KB

Open AccessSystematic Review

A Systematic Review Exploring the Phytochemical Composition and Anticancer Activities of Acacia catechu

by Navya Rana, Madhu Bala, Vinod Kumar, Rohitash Yadav, Neeraj Jain, Don Mathew, Khushboo Bisht, Rakesh Kumar and Sunil Kumar

Med. Sci. 2025, 13(3), 161; https://doi.org/10.3390/medsci13030161 - 1 Sep 2025

Cited by 2 | Viewed by 3547

Abstract

Background: Acacia catechu is an important traditional medicinal plant that has been used to manage several ailments. Many in vitro and in vivo studies have demonstrated that it exhibits chemopreventive and antineoplastic effects by modulating diverse signaling pathways and molecular targets involved in [...] Read more.

Background: Acacia catechu is an important traditional medicinal plant that has been used to manage several ailments. Many in vitro and in vivo studies have demonstrated that it exhibits chemopreventive and antineoplastic effects by modulating diverse signaling pathways and molecular targets involved in cancer progression. This review attempts to systematically investigate the anticancer mechanisms of A. catechu, encompassing antiapoptotic, antioxidant, and antiproliferative activities. Material and Methods: This review was conducted using scientific databases such as Scopus, Web of Science, and Google Scholar, covering the studies from 2000 to 2024. The PRISMA methodology was applied, using the keywords A. catechu, phytoconstituents, and cancer. Results: A total of 39 studies were compiled from various databases that cited the biological use of A. catechu. The plant has an abundance of phenolic compounds, including catechin, epicatechin, epigallocatechin-3-O-gallate, and epicatechin-3-O-gallate, which show strong anticancer activities. The anticancer potential of A. catechu is explained as it regulates several modulators like reactive oxygen species and cytokines, and downregulates oncogenic molecules like c-myc and various signaling pathways, such as c-Jun and NF-κB. Conclusions: Our findings suggest that A. catechu and its bioactive constituents have the potential for cancer prevention and therapy. However, further mechanistic investigations using pure compounds, along with preclinical and clinical trials, are essential to translate this potential into clinical applications. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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15 pages, 452 KB

Open AccessEditor’s ChoiceSystematic Review

The Efficacy of Neoantigen-Loaded Dendritic Cell Vaccine Immunotherapy in Non-Metastatic Gastric Cancer

by Menelaos Papakonstantinou, Paraskevi Chatzikomnitsa, Areti Danai Gkaitatzi, Athanasia Myriskou, Alexandros Giakoustidis, Dimitrios Giakoustidis and Vasileios N. Papadopoulos

Med. Sci. 2025, 13(3), 90; https://doi.org/10.3390/medsci13030090 - 11 Jul 2025

Cited by 5 | Viewed by 3813

Abstract

Introduction: Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. Even though surgery and chemotherapy are the mainstay of treatment, immunotherapy, and more specifically anti-tumor vaccination, has gained popularity over the past years due to the lower related toxicity and [...] Read more.

Introduction: Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. Even though surgery and chemotherapy are the mainstay of treatment, immunotherapy, and more specifically anti-tumor vaccination, has gained popularity over the past years due to the lower related toxicity and fewer long-term side effects. Dendritic cell (DC) vaccines have been shown to induce tumor specific cytotoxic T-cell (CTL) responses both in vitro and in vivo; however, due to the nature of the disease, resistance to immunotherapy is often developed. Various modifications, such as the implementation of viral vectors, tumor RNA, or even tumor-specific peptides (neoantigens), have been studied as a means to avoid resistance and enhance the effectiveness of the vaccines. In this review, we aim to assess the effects of neoantigen-loaded DC vaccines (naDCVs) on the immune response against gastric cancer cells. Materials and methods: A thorough literature search was conducted on PubMed and clinicaltrials.gov for studies assessing the efficacy of naDCVs against gastric cancer both in vivo and in vitro. The studies were assessed for eligibility by two independent reviewers based on predetermined inclusion and exclusion criteria. The search was completed following the PRISMA guidelines. Results: Eleven studies were included in our systematic review. In five of the studies, the effects of the naDCVs were tested in vitro; in two and in four they were examined both in vitro and in vivo. The in vitro studies showed that the naDCVs resulted in a more robust immune response against the cancer cells in the study groups compared to the control groups. The in vivo studies conducted on mice showed that tumor volume was reduced in the groups treated with the naDCV compared to the untreated groups. What is more, the cytotoxic effect of CTLs against tumor cells was also increased in the vaccine groups. One of the studies was conducted on humans as a phase I study. The results show increased CTL proliferation and cytokine production in the vaccinated group compared to the control, but no difference regarding the tumor size was observed. Conclusions: Neoantigen-loaded DC vaccines can stimulate a strong immune response against specific gastric cancer cell peptides and enhance tumor cell lysis, therefore hindering or even reversing disease progression, offering great potential for the treatment of patients with gastric cancer. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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