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Search Results (1,344)

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Keywords = overall survival (OS) by stage

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12 pages, 693 KiB  
Article
Efficacy and Safety of the Combination of Durvalumab Plus Gemcitabine and Cisplatin in Patients with Advanced Biliary Tract Cancer: A Real-World Retrospective Cohort Study
by Eishin Kurihara, Satoru Kakizaki, Masashi Ijima, Takeshi Hatanaka, Norio Kubo, Yuhei Suzuki, Hidetoshi Yasuoka, Takashi Hoshino, Atsushi Naganuma, Noriyuki Tani, Yuichi Yamazaki and Toshio Uraoka
Biomedicines 2025, 13(8), 1915; https://doi.org/10.3390/biomedicines13081915 - 6 Aug 2025
Abstract
Background/Objectives: The TOPAZ-1 phase III trial reported a survival benefit of using durvalumab, an anti-programmed death ligand 1 (anti-PD-L1) antibody, in combination with gemcitabine and cisplatin (GCD) treatment in patients with advanced biliary tract cancer. This retrospective study investigated the efficacy and [...] Read more.
Background/Objectives: The TOPAZ-1 phase III trial reported a survival benefit of using durvalumab, an anti-programmed death ligand 1 (anti-PD-L1) antibody, in combination with gemcitabine and cisplatin (GCD) treatment in patients with advanced biliary tract cancer. This retrospective study investigated the efficacy and safety of GCD treatment for advanced biliary tract cancer in real-world conditions. Methods: The study subjects were 52 patients with biliary tract cancer who received GCD therapy between January 2023 and May 2024. The observation parameters included the modified Glasgow Prognostic Score (mGPS), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), tumor markers (CEA, CA19-9), overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. Results: The cohort included 36 men and 16 women, with a median age of 73.0 years. There were 36 cases of cholangiocarcinoma (distal: 10, perihilar: 19, intrahepatic: 7), 13 cases of gallbladder cancer, and 3 cases of ampullary carcinoma. The stages were locally advanced in 30 cases and metastatic in 22 cases. Biliary drainage was performed in 30 cases. There were 38 cases receiving first-line therapy and 14 cases receiving second-line or later treatments. The median values at the start of GCD therapy were ALB 3.7 g/dL, CRP 0.39 mg/dL, NLR 2.4, PLR 162.5, CEA 4.8 ng/mL, and CA19-9 255.9 U/mL. The mGPS distribution was 0:23 cases, 1:18 cases, and 2:11 cases. The treatment outcomes were ORR 25.0% (CR 2 cases, PR 11 cases), DCR 78.8% (SD 28 cases, PD 10 cases, NE 1 case), median PFS 8.6 months, and median OS 13.9 months. The PLR was suggested to be useful for predicting PFS. A decrease in CEA at six weeks after the start of treatment was a significant predictor of PFS and OS. Gallbladder cancer had a significantly poorer prognosis compared to other cancers. The immune-related adverse events included hypothyroidism in two cases, cholangitis in one case, and colitis in one case. Conclusions: The ORR, DCR, and PFS were comparable to those in the TOPAZ-1 trial. Although limited by its retrospective design and small sample size, this study suggests that GCD therapy is an effective treatment regimen for unresectable biliary tract cancer in real-world clinical practice. Full article
(This article belongs to the Special Issue Advanced Research in Anticancer Inhibitors and Targeted Therapy)
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12 pages, 616 KiB  
Article
Surgical Margin Analysis in Osteosarcoma: Impact on Survival and Local Control
by Sebastian Breden, Simone Beischl, Florian Hinterwimmer, Sarah Consalvo, Carolin Knebel, Rüdiger von Eisenhart-Rothe, Rainer Burgkart and Ulrich Lenze
Cancers 2025, 17(15), 2581; https://doi.org/10.3390/cancers17152581 - 6 Aug 2025
Abstract
Background/Objectives: The quality of surgical margins has been shown to be a prognostic factor in many sarcoma entities, yet its role in osteosarcoma remains controversial. While previous studies have shown that the outcome was not related to the margin width in bone, the [...] Read more.
Background/Objectives: The quality of surgical margins has been shown to be a prognostic factor in many sarcoma entities, yet its role in osteosarcoma remains controversial. While previous studies have shown that the outcome was not related to the margin width in bone, the impact of the extraosseous margin width (margin at the soft tissue invasion)—which needs to be close sometimes due to neurovascular structures—needs to be assessed. This study aims to evaluate the influence of soft tissue surgical margins on local recurrence and overall survival in patients with high-grade osteosarcoma. Methods: We conducted a retrospective, single-center study including 75 patients treated for high-grade osteosarcoma. All patients underwent standardized neoadjuvant chemotherapy followed by complete surgical resection. Patients were stratified into three groups based on the histological margin width of the extraosseous parts: group 1 (<1 mm), group 2 (1–5 mm), and group 3 (≥5 mm). Primary endpoints were local recurrence and overall survival (OS), analyzed using Kaplan–Meier estimates, log-rank tests, and Cox regression. Results: Local recurrence occurred in seven patients (9%). Although the overall comparison between the three groups was not statistically significant (p = 0.074), a subgroup analysis revealed a significantly higher recurrence rate in patients with margins < 1 mm compared to those with wider margins (p = 0.024). No significant differences in overall survival (OS) were observed between the groups (p = 0.896). Tumor location, metastatic status, and UICC stage were significant predictors for both endpoints in univariate analysis. However, none of these association were confirmed in multivariate analyses. Conclusions: Very close surgical margins (<1 mm) may increase the risk of local recurrence in high-grade osteosarcoma; however, they do not appear to affect overall survival. Full article
(This article belongs to the Special Issue Clinical Treatment of Osteosarcoma)
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13 pages, 1028 KiB  
Article
Survival and Prognostic Factors in Unresectable Head and Neck Cancer Patients
by Natsuki Oishi, Sara Orozco-Núñez, José Ramón Alba-García, Mar Gimeno-Coret and Enrique Zapater
J. Clin. Med. 2025, 14(15), 5517; https://doi.org/10.3390/jcm14155517 - 5 Aug 2025
Abstract
Background/Objectives: This single-cohort follow-up study describes the median overall survival (OS) in patients with unresectable head and neck squamous cell carcinoma (HNSCC) due to invasion of vital structures, which is under-represented in the current literature. Secondarily, subgroups were evaluated according to the type [...] Read more.
Background/Objectives: This single-cohort follow-up study describes the median overall survival (OS) in patients with unresectable head and neck squamous cell carcinoma (HNSCC) due to invasion of vital structures, which is under-represented in the current literature. Secondarily, subgroups were evaluated according to the type of presentation, in order to identify clinical characteristics and contribute to developing an appropriate treatment plan and managing patient’s expectations. Methods: This single-cohort observational study analysed the OS of 39 patients from the Otolaryngology Department with advanced-stage head and neck cancer with invasion of vital anatomical structures considered ineligible for surgical treatment. Secondarily, subgroups were evaluated according to type of presentation and various clinical characteristics. Results: A total of 39 patients radiologically classified as having unresectable HNSCC (i.e., unsuitable for surgical resection), with a mean age of 66.87 years, were included during a 24-month follow-up. By the end of the study, 56.4% of the patients had died. The median OS was 16.09 months. Statistically significant differences were observed when comparing human papilloma virus (HPV)-positive and -negative status and when comparing initial and recurrent tumours. Conclusions: The invasion of anatomical structures such as the skull base, internal carotid artery, and prevertebral space was associated with a marked decrease in survival, with an OS time of 16 months. This study provides valuable evidence in patients with unresectable HNSCC, highlighting tumour recurrence and HPV-negative status as important indicators of poor prognosis. Full article
(This article belongs to the Section Otolaryngology)
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14 pages, 1732 KiB  
Article
A Promising Prognostic Indicator for Pleural Mesothelioma: Pan-Immuno-Inflammation Value
by Serkan Yaşar, Feride Yılmaz, Ömer Denizhan Tatar, Hasan Çağrı Yıldırım, Zafer Arık, Şuayib Yalçın and Mustafa Erman
J. Clin. Med. 2025, 14(15), 5467; https://doi.org/10.3390/jcm14155467 - 4 Aug 2025
Viewed by 68
Abstract
Background: Pleural mesothelioma (PM) is a type of cancer that is difficult to diagnose and treat. Patients may have vastly varying prognoses, and prognostic factors may help guide the clinical approach. As a recently identified biomarker, the pan-Immune-Inflammation-Value (PIV) is a simple, comprehensive, [...] Read more.
Background: Pleural mesothelioma (PM) is a type of cancer that is difficult to diagnose and treat. Patients may have vastly varying prognoses, and prognostic factors may help guide the clinical approach. As a recently identified biomarker, the pan-Immune-Inflammation-Value (PIV) is a simple, comprehensive, and peripheral blood cell-based biomarker. Methods: The present study represents a retrospective observational analysis carried out within a single-center setting. Ninety-five patients with PM stages I–IV were enrolled in the study. We analyzed the correlation between patients’ demographic characteristics, clinicopathological factors such as histological subtypes, surgery status, tumor thickness, blood-based parameters, and treatment options with their prognoses. PIV was calculated by the following formula: (neutrophil count × monocyte count × platelet count)/lymphocyte count. Additionally, blood-based parameters were used to calculate the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII). Results: We categorized the patients into two groups, low PIV group (PIV ≤ 732.3) and high PIV group (PIV > 732.3) according to the determined cut-off value, which was defined as the median. It was revealed that high PIV was associated with poor survival outcomes. The median follow-up period was 15.8 months (interquartile range, IQR, 7.1 to 29.8 months). The median overall survival (OS) was significantly longer in patients in the low PIV group (median 29.8 months, 95% confidence interval (CI), 15.6 to 44) than the high PIV group (median 14.7 months, 95% CI, 10.8 to 18.6 p < 0.001). Furthermore, the study revealed that patients with low PIV, NLR, and SII values were more likely to be eligible for surgery and were diagnosed at earlier stages. Additionally, these markers were identified as potential predictors of disease-free survival (DFS) in the surgical cohort and of treatment response across the entire patient population. Conclusions: In addition to well-established clinical factors such as stage, histologic subtype, resectability, and Eastern Cooperative Oncology Group (ECOG) performance status (PS), PIV emerged as an independent and significant prognostic factor of overall survival (OS) in patients with PM. Moreover, PIV also demonstrated a remarkable independent prognostic value for disease-free survival (DFS) in this patient population. Additionally, some clues are provided for conditions such as treatment responses, staging, and suitability for surgery. As such, in this cohort, it has outperformed the other blood-based markers based on our findings. Given its ease of calculation and cost-effectiveness, PIV represents a promising and practical prognostic tool in the clinical management of pleural mesothelioma. It can be easily calculated using routinely available laboratory parameters for every cancer patient, requiring no additional cost or complex procedures, thus facilitating its integration into everyday clinical practice. Full article
(This article belongs to the Section Oncology)
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21 pages, 1031 KiB  
Article
Waiting Times for Surgery and Radiotherapy Among Breast Cancer Patients in Switzerland: A Cancer Registry-Based Cross-Sectional and Longitudinal Analysis
by Christoph Oehler, Michel Eric Nicolas Zimmermann, Mohsen Mousavi, Kattic Ram Joorawon, Marcel Blum, Christian Herrmann and Daniel Rudolf Zwahlen
Radiation 2025, 5(3), 23; https://doi.org/10.3390/radiation5030023 - 3 Aug 2025
Viewed by 245
Abstract
Background: Delays in breast cancer treatment negatively affect prognosis and have increased over time. Data on waiting times in Switzerland are limited. Patients and Methods: This study analyzed cancer registry data from 2003 to 2005 (2628 patients) and 2015 to 2017 (421 patients) [...] Read more.
Background: Delays in breast cancer treatment negatively affect prognosis and have increased over time. Data on waiting times in Switzerland are limited. Patients and Methods: This study analyzed cancer registry data from 2003 to 2005 (2628 patients) and 2015 to 2017 (421 patients) to evaluate waiting times for diagnosis, surgery, and radiotherapy; temporal trends; and survival in women with stage I–III invasive breast cancer treated with surgery without chemotherapy. Associations with demographic/clinical factors and overall survival (OS) were assessed using ANOVA, uni-/multivariable regression, Kaplan–Meier, and Cox regression. Results: From 2003 to 2005, mean intervals were biopsy-to-diagnosis 4.3 days, diagnosis-to-surgery 18.8 days, biopsy-to-surgery 26.8 days, and surgery-to-radiotherapy 56.7 days. Longer diagnosis-to-surgery times were associated with metropolitan areas, public hospitals, basic insurance, mastectomy, and older age (all p < 0.001). Radiotherapy delays were also longer in metropolitan areas and after mastectomy (p < 0.001). Between 2003–2005 and 2015–2017, diagnosis-to-surgery times rose in Eastern Switzerland (from 21.3 to 31.2 days), while radiotherapy timing remained stable. Five-year overall survival improved (from 76.7% to 88.4%), but was not significantly impacted by diagnosis-to-surgery intervals. Conclusions: Despite timely surgery in Switzerland (2003–2005), disparities existed, and time to surgery increased by 2015–2017. Reducing waiting times remains important despite no significant short-term OS impact. Full article
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18 pages, 836 KiB  
Article
CAPOX vs. FOLFOX for Colorectal Cancer—Real World Outcomes in Ontario, Canada
by Deepro Chowdhury, Gregory R. Pond and John R. Goffin
Curr. Oncol. 2025, 32(8), 435; https://doi.org/10.3390/curroncol32080435 - 31 Jul 2025
Viewed by 193
Abstract
CAPOX and FOLFOX are widely used chemotherapy regimens for colorectal cancer (CRC). The superiority of one regimen over the other in a real-world setting (RWE) could have significant clinical implications given their common use, but such RWE is limited. This study analyzed provincial [...] Read more.
CAPOX and FOLFOX are widely used chemotherapy regimens for colorectal cancer (CRC). The superiority of one regimen over the other in a real-world setting (RWE) could have significant clinical implications given their common use, but such RWE is limited. This study analyzed provincial database records of 13,461 Canadian patients treated from 2005 to 2017. The primary outcomes were rates of Emergency Department visits and/or hospitalizations (ED/H) and overall survival (OS). CAPOX was used less frequently (8.4%) than FOLFOX (91.6%), often in older patients (p < 0.003 for Stage I–III; p < 0.001 for Stage IV). CAPOX recipients had shorter treatment durations (median 15 vs. 20 weeks, p = 0.002) and higher unadjusted ED/H rates (60.8% vs. 50.9%, p < 0.001), though this difference was nonsignificant on multivariate analysis (MVA) (HR 1.05 (0.92, 1.20), p = 0.466). Patients receiving CAPOX had worse OS than those on FOLFOX, (5-year OS 70.1% vs. 77.2% (p < 0.001) non-metastatic; 16.6% vs. 33.2% (p < 0.001) metastatic). MVA confirmed inferior OS with CAPOX (HR 1.42, p < 0.001). Other predictors of shorter OS included older age, male sex, comorbidities, rural residence, and lower income. This administrative data is at risk of bias but highlights the need for careful patient selection and informed treatment decision making. Full article
(This article belongs to the Section Gastrointestinal Oncology)
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15 pages, 1188 KiB  
Article
Delta Changes in [18F]FDG PET/CT Parameters Can Prognosticate Clinical Outcomes in Recurrent NSCLC Patients Who Have Undergone Reirradiation–Chemoimmunotherapy
by Brane Grambozov, Nazanin Zamani-Siahkali, Markus Stana, Mohsen Beheshti, Elvis Ruznic, Zarina Iskakova, Josef Karner, Barbara Zellinger, Sabine Gerum, Falk Roeder, Christian Pirich and Franz Zehentmayr
Biomedicines 2025, 13(8), 1866; https://doi.org/10.3390/biomedicines13081866 - 31 Jul 2025
Viewed by 161
Abstract
Background and Purpose: Stratification based on specific image biomarkers applicable in clinical settings could help optimize treatment outcomes for recurrent non-small cell lung cancer patients. For this purpose, we aimed to determine the clinical impact of positive delta changes (any difference above [...] Read more.
Background and Purpose: Stratification based on specific image biomarkers applicable in clinical settings could help optimize treatment outcomes for recurrent non-small cell lung cancer patients. For this purpose, we aimed to determine the clinical impact of positive delta changes (any difference above zero > 0) between baseline [18F]FDG PET/CT metrics before the first treatment course and reirradiation. Material/Methods: Forty-seven patients who underwent thoracic reirradiation with curative intent at our institute between 2013 and 2021 met the inclusion criteria. All patients had histologically verified NSCLC, ECOG (Eastern Cooperative Oncology Group) ≤ 2, and underwent [18F]FDG PET/CT for initial staging and re-staging before primary radiotherapy and reirradiation, respectively. The time interval between radiation treatments was at least nine months. Quantitative metabolic volume and intensity parameters were measured before first irradiation and before reirradiation, and the difference above zero (>0; delta change) between them was statistically correlated to locoregional control (LRC), progression-free survival (PFS), and overall survival (OS). Results: Patients were followed for a median time of 33 months after reirradiation. The median OS was 21.8 months (95%-CI: 16.3–27.3), the median PFS was 12 months (95%-CI: 6.7–17.3), and the median LRC was 13 months (95%-CI: 9.0–17.0). Multivariate analysis revealed that the delta changes in SULpeak, SUVmax, and SULmax of the lymph nodes significantly impacted OS (SULpeak p = 0.017; SUVmax p = 0.006; SULmax p = 0.006), PFS (SULpeak p = 0.010; SUVmax p = 0.009; SULmax p = 0.009), and LRC (SULpeak p < 0.001; SUVmax p = 0.003; SULmax p = 0.003). Conclusions: Delta changes in SULpeak, SUVmax, and SULmax of the metastatic lymph nodes significantly impacted all clinical endpoints (OS, PFS and LRC) in recurrent NSCLC patients treated with reirradiation. Hence, these imaging biomarkers could be helpful with regard to patient selection in this challenging clinical situation. Full article
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13 pages, 873 KiB  
Article
Recurrence Patterns, Treatment Outcomes, and Prognostic Factors of Thymic Carcinoma: A Multicenter Study
by Natsuo Tomita, Shunichi Ishihara, Yoshihito Nomoto, Akinori Takada, Katsumasa Nakamura, Kenta Konishi, Kohei Wakabayashi, Yukihiko Ohshima, Maho Yamada, Masayuki Matsuo, Masaya Ito, Katsuhiro Okuda, Taiki Takaoka, Dai Okazaki, Nozomi Kita, Seiya Takano and Akio Hiwatashi
Cancers 2025, 17(15), 2513; https://doi.org/10.3390/cancers17152513 - 30 Jul 2025
Viewed by 136
Abstract
Objectives: This multicenter study aimed to clarify the recurrence patterns; treatment outcomes; and prognostic factors of thymic carcinoma, a rare cancer. Methods: We analyzed 101 patients with thymic carcinoma who underwent multidisciplinary treatment, including radiotherapy. The median age was 62 years, with 27 [...] Read more.
Objectives: This multicenter study aimed to clarify the recurrence patterns; treatment outcomes; and prognostic factors of thymic carcinoma, a rare cancer. Methods: We analyzed 101 patients with thymic carcinoma who underwent multidisciplinary treatment, including radiotherapy. The median age was 62 years, with 27 patients in stage I–II; 44 in stage III; and 30 in stage IV by the TNM classification. Seventy-two patients underwent surgery with radiotherapy; and 29 patients underwent definitive radiotherapy. Image-guided radiotherapy (IGRT) and elective nodal irradiation (ENI) were used for 35 and 23 patients, respectively. Local recurrence-free survival (LRFS); progression-free survival (PFS); and overall survival (OS) were calculated, and univariate and multivariate analyses were performed. Results: With a median follow-up of 68 months, we observed 17 local recurrences; 27 regional recurrences; and 35 distant metastases. The 5-year LRFS; PFS; and OS were 82%, 41%, and 76%, respectively. Multivariate analysis revealed that stage was the only factor associated with LRFS; PFS; and OS (p = 0.040; p < 0.0001; and p = 0.048, respectively), while treatment modality was associated with only LRFS (p = 0.015). IGRT and ENI were also associated with LRFS (p = 0.002 and 0.013, respectively). PFS and OS of stage IV patients were comparable between the surgery with radiotherapy and definitive radiotherapy groups (p = 0.99 and 0.98, respectively). Conclusions: Our results suggest the importance of stage-specific treatment strategies rather than resectability, especially for stage IV patients. These results should be validated in a prospective study. Our results also suggest that radiotherapy methods influence recurrence Full article
(This article belongs to the Section Clinical Research of Cancer)
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18 pages, 3824 KiB  
Article
Prognostic Risk Model of Megakaryocyte–Erythroid Progenitor (MEP) Signature Based on AHSP and MYB in Acute Myeloid Leukemia
by Ting Bin, Ying Wang, Jing Tang, Xiao-Jun Xu, Chao Lin and Bo Lu
Biomedicines 2025, 13(8), 1845; https://doi.org/10.3390/biomedicines13081845 - 29 Jul 2025
Viewed by 307
Abstract
Background: Acute myeloid leukemia (AML) is a common and aggressive adults hematological malignancies. This study explored megakaryocyte–erythroid progenitors (MEPs) signature genes and constructed a prognostic model. Methods: Uniform manifold approximation and projection (UMAP) identified distinct cell types, with differential analysis between [...] Read more.
Background: Acute myeloid leukemia (AML) is a common and aggressive adults hematological malignancies. This study explored megakaryocyte–erythroid progenitors (MEPs) signature genes and constructed a prognostic model. Methods: Uniform manifold approximation and projection (UMAP) identified distinct cell types, with differential analysis between AML-MEP and normal MEP groups. Univariate and the least absolute shrinkage and selection operator (LASSO) Cox regression selected biomarkers to build a risk model and nomogram for 1-, 3-, and 5-year survival prediction. Results: Ten differentially expressed genes (DEGs) related to overall survival (OS), six (AHSP, MYB, VCL, PIM1, CDK6, as well as SNHG3) were retained post-LASSO. The model exhibited excellent efficiency (the area under the curve values: 0.788, 0.77, and 0.847). Pseudotime analysis of UMAP-defined subpopulations revealed that MYB and CDK6 exert stage-specific regulatory effects during MEP differentiation, with MYB involved in early commitment and CDK6 in terminal maturation. Finally, although VCL, PIM1, CDK6, and SNHG3 showed significant associations with AML survival and prognosis, they failed to exhibit pathological differential expression in quantitative real-time polymerase chain reaction (qRT-PCR) experimental validations. In contrast, the downregulation of AHSP and upregulation of MYB in AML samples were consistently validated by both qRT-PCR and Western blotting, showing the consistency between the transcriptional level changes and protein expression of these two genes (p < 0.05). Conclusions: In summary, the integration of single-cell/transcriptome analysis with targeted expression validation using clinical samples reveals that the combined AHSP-MYB signature effectively identifies high-risk MEP-AML patients, who may benefit from early intensive therapy or targeted interventions. Full article
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19 pages, 1570 KiB  
Article
Real-World Outcomes of Chemoradiotherapy in Patients with Stage II/III Non-Small-Cell Lung Cancer in the Durvalumab Era: An Observational Study
by Jörg Andreas Müller, Jonas Buchberger, Elias Schmidt-Riese, Clara Pitzschel, Miriam Möller, Wolfgang Schütte, Daniel Medenwald and Dirk Vordermark
Cancers 2025, 17(15), 2498; https://doi.org/10.3390/cancers17152498 - 29 Jul 2025
Viewed by 395
Abstract
Background: Consolidation therapy with durvalumab after definitive chemoradiotherapy (CRT) has become the standard care for patients with stage III non-small-cell lung cancer (NSCLC) following the PACIFIC trial. However, real-world data evaluating outcomes under routine clinical conditions remain limited, particularly in European cohorts. Methods: [...] Read more.
Background: Consolidation therapy with durvalumab after definitive chemoradiotherapy (CRT) has become the standard care for patients with stage III non-small-cell lung cancer (NSCLC) following the PACIFIC trial. However, real-world data evaluating outcomes under routine clinical conditions remain limited, particularly in European cohorts. Methods: In this retrospective single-center study, we analyzed clinical data from 72 patients with stage III NSCLC treated with definitive CRT between 2017 and 2022. The patients were stratified by receipt of durvalumab consolidation. Univariable and multivariable Cox regression models were used to assess overall survival (OS) and progression-free survival (PFS). Stepwise variable selection based on the Akaike Information Criterion (AIC) was used to construct an optimized multivariable model. A sensitivity analysis with adjustment for treatment period (2017–2018 vs. 2019–2022) was conducted to account for the introduction of durvalumab into routine clinical practice. Results: Among 72 patients, 35 received durvalumab and 37 did not. The median OS was 2.08 years; the 3- and 5-year OS rates were 38.6% and 30.3%, respectively. Multivariable regression revealed significantly improved OS associated with Karnofsky performance status (KPS) > 80% (HR 0.29, p = 0.003), Charlson Comorbidity Index (CCI) ≤ 2 (HR 0.39, p = 0.009), and durvalumab treatment (HR 3.99, p = 0.008). PD-L1 expression ≥ 1% showed a trend toward improved OS (HR 3.72, p = 0.063). The median progression-free survival (PFS) for the total cohort was 1.17 years. The estimated 3- and 5-year PFS rates were 31.1% and 26.3%, respectively. Patients treated with durvalumab had a longer median PFS (20.5 months) compared to those without durvalumab (12.0 months). In the multivariable analysis, KPS > 80% (HR 0.29, p < 0.001), CCI ≤ 2 (HR 0.53, p = 0.048), and durvalumab treatment (HR 2.81, p = 0.023) were significantly associated with improved PFS. A sensitivity analysis adjusting for treatment period—reflecting the introduction of durvalumab into routine clinical practice from 2019—confirmed the robustness of these findings. Conclusions: Our findings support the clinical benefit of durvalumab consolidation following CRT in a real-world population, especially in patients with good performance status and low comorbidity burden. These results confirm and extend the PACIFIC trial findings into routine clinical practice, highlighting the prognostic value of functional status and comorbidity alongside PD-L1 expression. Full article
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15 pages, 970 KiB  
Article
Iron Dysregulation Signature in Pediatric Leukemia: In-Depth Biomarkers of Iron Metabolism Involving Matriptase-2 and Neogenin-1
by Monika Łęcka, Artur Słomka, Katarzyna Albrecht, Michał Romiszewski and Jan Styczyński
Cancers 2025, 17(15), 2495; https://doi.org/10.3390/cancers17152495 - 29 Jul 2025
Viewed by 296
Abstract
Background: Acute leukemia (AL) is the most prevalent pediatric malignancy and is frequently associated with systemic iron dysregulation, often leading to iron overload. This study aimed to characterize the regulatory mechanisms of iron metabolism in children with AL, considering treatment stages and associated [...] Read more.
Background: Acute leukemia (AL) is the most prevalent pediatric malignancy and is frequently associated with systemic iron dysregulation, often leading to iron overload. This study aimed to characterize the regulatory mechanisms of iron metabolism in children with AL, considering treatment stages and associated clinical parameters. Methods: A total of 149 children were stratified into four groups: newly diagnosed AL (n = 43), patients post-chemotherapy (n = 55), patients following hematopoietic cell transplantation (HCT; n = 32), and healthy controls (n = 19). Serum concentrations of matriptase-2 (TMPRSS6), neogenin-1 (NEO1), and soluble hemojuvelin (sHJV) were quantified using ELISA. Results: Compared to healthy children, significantly higher serum concentrations of TMPRSS6 and NEO1 were found in patients post-chemotherapy and post-HCT, while sHJV levels were markedly decreased. Higher TMPRSS6 and NEO1 levels and lower sHJV were associated with increased ferritin levels and greater numbers of transfused packed red blood cell (PRBC) units. sHJV negatively correlated with TMPRSS6, NEO1, ferritin, C-reactive protein (CRP), and PRBC transfusions. TMPRSS6 and NEO1 showed a positive correlation. Among the analyzed biomarkers, Kaplan–Meier analysis revealed no statistically significant associations with overall survival (OS) or event-free survival (EFS) within the chemotherapy and HCT subgroups. Conclusions: AL in pediatric patients is associated with profound disruptions of systemic iron homeostasis. Our investigation identified notable perturbations in TMPRSS6, NEO1, and sHJV, suggesting that these proteins could contribute mechanistically to the pathophysiological alterations underlying iron dysregulation observed in pediatric AL. Full article
(This article belongs to the Special Issue New Insights of Hematology in Cancer)
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12 pages, 1442 KiB  
Article
Does BRCA Mutation Status Influence Ovarian Cancer Onset Timing and Patients’ Treatment Outcomes?
by Kaja Michalczyk, Agata Mokrzycka, Marianna Rudzińska, Barbara Michalczyk, Janusz Menkiszak and Anita Chudecka-Głaz
Genes 2025, 16(8), 883; https://doi.org/10.3390/genes16080883 - 27 Jul 2025
Viewed by 432
Abstract
Background/Objectives: Mutations in the BRCA1 and BRCA2 genes are well-known risk factors for ovarian cancer. They are also associated with response to platinum-based chemotherapy; however, their definitive impact on patient prognosis remains not fully understood. This study aimed to investigate the influence of [...] Read more.
Background/Objectives: Mutations in the BRCA1 and BRCA2 genes are well-known risk factors for ovarian cancer. They are also associated with response to platinum-based chemotherapy; however, their definitive impact on patient prognosis remains not fully understood. This study aimed to investigate the influence of BRCA mutation status on the age of ovarian cancer onset and on treatment outcomes in patients with high-grade serous ovarian cancer. Methods: This single-center retrospective analysis included newly diagnosed FIGO stage III and IV HGSOC patients treated between June 2018 and April 2023. Patients’ age, tumor histology, CA125 levels, BRCA mutation status, type of treatment (neoadjuvant or adjuvant chemotherapy), and surgical outcomes were collected and analyzed. Survival analyses were performed using the Kaplan–Meier method and log-rank test. Results: Pathogenic mutations were identified in 25 patients (15 in BRCA1, 10 in BRCA2). Patients with a BRCA mutation were diagnosed at a significantly younger age (median 58.78 years) compared to non-carriers (66.81 years; p < 0.001), with BRCA1 carriers being diagnosed the youngest (median 46.52 years). The study found no statistically significant difference in progression-free survival (PFS) between BRCA carriers and non-carriers. However, a significant improvement in overall survival (OS) was observed for patients with a BRCA1 mutation (p = 0.036). No significant OS difference was found for BRCA2 carriers. Conclusions: BRCA mutations, particularly in the BRCA1 gene, are associated with an earlier onset ovarian cancer. BRCA1 mutation appears to be a favorable prognostic factor for overall survival in patients with HGSOC. Our findings demonstrate the clinical implications of different BRCA mutations and support the need for further research in larger cohorts to confirm their influence on prognostic effects. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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20 pages, 2340 KiB  
Article
Characterization of the Population, Treatment Patterns, and Outcomes of Patients with Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC) with Epidermal Growth Factor Receptor Mutation (EGFRm): A Retrospective Cohort Study from IPO Porto
by Ana Rodrigues, Marta Pina, Rita Calisto, Pedro Leite-Silva, Pedro Medeiros, Catarina Silva, Ana Sofia Silva, Patrícia Redondo, João Ramalho-Carvalho, Susana Ferreira Santos and Maria José Bento
Curr. Oncol. 2025, 32(8), 414; https://doi.org/10.3390/curroncol32080414 - 24 Jul 2025
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Abstract
Most patients with non-small-cell lung cancer (NSCLC) present with advanced/metastatic disease at diagnosis, and molecular profiling is critical in guiding treatment decisions. This retrospective cohort study aimed to characterize EGFR mutations (EGFRm) in advanced/metastatic NSCLC patients, treatment patterns, and real-world outcomes. Adults diagnosed [...] Read more.
Most patients with non-small-cell lung cancer (NSCLC) present with advanced/metastatic disease at diagnosis, and molecular profiling is critical in guiding treatment decisions. This retrospective cohort study aimed to characterize EGFR mutations (EGFRm) in advanced/metastatic NSCLC patients, treatment patterns, and real-world outcomes. Adults diagnosed between 2018 and 2021 and treated at a Comprehensive Care Center were included. Time-to-event outcomes were analyzed using the Kaplan–Meier method. A total of 110 patients were included, with a median age of 69.0 years (range, 37–93), 76.4% female, and 83.2% non-smokers. About 97.3% had adenocarcinomas, with 93.6% at stage IV, 40.9% with ≥ three metastatic sites (brain metastases in 24.5%), 33.6% ECOG 2–4, and 58.2% with an EGFR exon-19 deletion. A minority started supportive care or curative-intent treatment, and 81.8% underwent first-line palliative systemic therapy (TKIs, 91.1%; chemotherapy, 8.9%). Median real-world overall survival (rwOS) was 18.9 months (95% CI, 13.8–28.1). Worse rwOS was observed in patients with ECOG 2–4 versus ECOG 0–1 (10.3 vs. 22.8 months; HR 1.82, 95% CI 1.17–2.85; p = 0.008) and in patients with exon-21 L858R versus exon 19 deletions (15.8 vs. 24.2 months; HR 1.59, 95% CI 1.00–2.54; p = 0.048). In patients treated with palliative systemic treatment, median progression-free survival was 10.9 months (95% CI, 8.8–13.6). This study provides important insights regarding real-world characteristics, treatment patterns, and outcomes from a cohort of EGFRm advanced/metastatic NSCLC patients. Full article
(This article belongs to the Special Issue The Role of Real-World Evidence (RWE) in Thoracic Malignancies)
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15 pages, 4111 KiB  
Article
Impact of Tumor Budding in Head and Neck Cancers on Neck Lymph Node Metastasis and Prognosis
by Oğuz Gül, Özlem Çelebi Erdivanlı, Mehmet Birinci, Suat Terzi, Metin Çeliker, Oğuzhan Okçu, Çiğdem Öztürk, Tuğba Yemiş, Fatma Beyazal Çeliker, Zerrin Özergin Coşkun and Engin Dursun
J. Clin. Med. 2025, 14(15), 5224; https://doi.org/10.3390/jcm14155224 - 23 Jul 2025
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Abstract
Background/Objectives: Tumor budding (TB)—clusters of one to five tumor cells at the invasive front—has emerged as a prognostic marker in various cancers. Its prognostic value in head and neck squamous cell carcinoma (HNSCC) is unclear. Methods: We retrospectively analyzed 98 HNSCC patients. The [...] Read more.
Background/Objectives: Tumor budding (TB)—clusters of one to five tumor cells at the invasive front—has emerged as a prognostic marker in various cancers. Its prognostic value in head and neck squamous cell carcinoma (HNSCC) is unclear. Methods: We retrospectively analyzed 98 HNSCC patients. The tumor buds were counted on hematoxylin–eosin-stained sections as per the 2016 International Tumor Budding Consensus Conference (ITBCC) guidelines. An optimal cutoff was determined by ROC analysis using excisional lymph nodes and five-year overall survival (OS) as the endpoint, stratifying patients into low- (≤4 buds) and high-risk (>4 buds) groups. The associations with clinicopathological features, OS, and disease-free survival (DFS) were assessed using Kaplan–Meier curves and Cox regression. Results: Among the 98 patients (median follow-up 58 months, range 18–108), 32 (32.7%) died. The optimal TB cutoff was 4.5 (AUC 0.85, 95% CI 0.76–0.93). High TB was associated with poorer five-year OS (26.4% vs. 85.3%). Multivariate Cox regression identified TB and extranodal extension as independent predictors of OS (TB HR: 3.4, 95% CI 1.3–9.2, p = 0.013). In the laryngeal cancer subgroup, TB was associated with worse survival in the univariate analysis (HR 7.5, 95% CI 1.6–35.6, p = 0.011), though this was not significant in the multivariate modeling. High TB independently predicted neck lymph node metastasis (multivariate OR 4.9, 95% CI 1.2–20.5, p = 0.029), which was present in 65.8% of the high-TB vs. 31.7% of the low-TB patients. High TB correlated with advanced AJCC stage and lymphovascular invasion. No clinicopathological factors, including TB, independently predicted DFS, in either the full cohort or the laryngeal subgroup. Conclusions: High tumor budding denotes an aggressive HNSCC phenotype and may guide decisions on elective neck dissection. Its assessment is simple, cost-effective, and potentially valuable for routine pathology, pending external validation. Full article
(This article belongs to the Section Otolaryngology)
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15 pages, 867 KiB  
Article
Prognostic Factors and Survival Outcomes in Resected Biliary Tract Cancers: A Multicenter Retrospective Analysis
by Michele Ghidini, Fausto Petrelli, Matteo Paccagnella, Massimiliano Salati, Francesca Bergamo, Margherita Ratti, Caterina Soldà, Barbara Galassi, Ornella Garrone, Massimo Rovatti, Arianna Zefelippo, Lucio Caccamo, Enrico Gringeri, Alessandro Zerbi, Guido Torzilli, Silvia Bozzarelli, Lorenza Rimassa and Gianluca Tomasello
Cancers 2025, 17(15), 2445; https://doi.org/10.3390/cancers17152445 - 23 Jul 2025
Viewed by 224
Abstract
Background/Objectives: Biliary tract cancers (BTCs) are aggressive malignancies with a poor prognosis. Surgery remains the only curative option, yet recurrence rates are high, and the role of adjuvant chemotherapy remains debated. This study aims to evaluate the impact of adjuvant chemotherapy and [...] Read more.
Background/Objectives: Biliary tract cancers (BTCs) are aggressive malignancies with a poor prognosis. Surgery remains the only curative option, yet recurrence rates are high, and the role of adjuvant chemotherapy remains debated. This study aims to evaluate the impact of adjuvant chemotherapy and prognostic factors on survival outcomes in resected BTCs. Methods: We conducted a retrospective multicenter study analyzing patients diagnosed with intrahepatic (iCCA) and extrahepatic cholangiocarcinoma (eCCA) or gallbladder cancer (GBC) who underwent curative-intent surgical resection between 1999 and 2023. Demographic, clinicopathological, and treatment data were collected from institutional databases. Survival outcomes were assessed using Kaplan–Meier analysis, and prognostic factors were identified through Cox proportional hazards regression. Results: A total of 155 patients were included, with a median follow-up of 84.6 months. The cohort comprised 38.7% iCCA, 31.6% eCCA, and 29.7% GBC. R0 resection was achieved in 77.4% of cases, while lymph node involvement was present in 39.4%. Median overall survival (OS) significantly varied by stage (p < 0.001), ranging from >60 months for stage I to ~12 months for stage IVA. Eastern Cooperative Oncology Group (ECOG) performance status (PS) emerged as the strongest independent prognostic factor for OS (p < 0.001). Adjuvant chemotherapy, administered to 49.0% of patients, did not significantly improve OS in the overall cohort (p = 0.899). However, subgroup analyses suggested potential benefits in iCCA and eCCA but not in GBC. High CA19-9 levels and vascular invasion were associated with poorer survival outcomes. Conclusions: This study highlights the prognostic significance of ECOG PS, resection margin status, lymph node involvement, and CA19-9 levels in resected BTCs. The lack of a clear survival benefit from adjuvant chemotherapy underscores the need for improved therapeutic strategies. Future research should focus on refining risk stratification models and identifying more effective adjuvant treatments to enhance long-term survival outcomes in patients with BTC. Full article
(This article belongs to the Special Issue Clinical Surgery for Hepato-Pancreato-Biliary (HPB) Cancer)
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