Cancers

15 pages, 3038 KB

Open AccessArticle

A Logistic Regression Model Integrating Flow Cytometry−Derived Immune Cell Profiles and Hematological Parameters for Preoperative Prediction of Peritoneal Metastasis in Gastric Cancer

by Ruihu Zhao, Yuming Ju, Zhichao Yu, Yingwei Xue and Hongjiang Song

Cancers 2026, 18(17), 2813; https://doi.org/10.3390/cancers18172813 - 30 Aug 2026

Abstract

Background: Peritoneal metastasis (PM) is a lethal and often occult event in advanced gastric cancer (GC), and its preoperative detection remains difficult. The role of peripheral NK and NKT−like cells in predicting PM has not been well defined. Methods: We retrospectively analyzed 433 [...] Read more.

Background: Peritoneal metastasis (PM) is a lethal and often occult event in advanced gastric cancer (GC), and its preoperative detection remains difficult. The role of peripheral NK and NKT−like cells in predicting PM has not been well defined. Methods: We retrospectively analyzed 433 patients who underwent surgery for GC from 2016 to 2020. Patients were stratified by PM status and randomly assigned to training and held−out internal validation cohorts. Flow cytometry−derived lymphocyte subset percentages were treated as compositional data, and NK and NKT−like cell variables were entered into the model after log−ratio transformation. Candidate variables were selected using LASSO logistic regression in the training cohort and further assessed by multivariable logistic regression. Model performance was evaluated using AUROC, AUPRC, and confusion matrices in the validation cohort. Nomogram and SHAP analyses were used for model interpretation. Results: Seven predictors were retained in the final model: log−ratio−transformed NKT−like cells, direct bilirubin, prealbumin, lymphocyte count, lactate dehydrogenase, CA125, and log−ratio−transformed NK cells. The model achieved an AUROC of 0.879 (95% CI: 0.805–0.936) and an AUPRC of 0.698 (95% CI: 0.524–0.848) in the validation cohort. At the conventional threshold of 0.50, the model achieved an accuracy of 0.915, sensitivity of 0.821, specificity of 0.941, PPV of 0.793, and NPV of 0.950. At the Youden−optimal threshold of 0.101, sensitivity, specificity, accuracy, PPV, and NPV were 1.000, 0.892, 0.915, 0.718, and 1.000, respectively. Conclusions: A preoperative model integrating log−ratio−transformed NK/NKT−like cell variables and routine hematological parameters showed good ability to identify PM in GC and may help select patients for diagnostic laparoscopy or closer preoperative evaluation. Full article

(This article belongs to the Topic Biomarker Development and Application, 2nd Edition)

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14 pages, 819 KB

Open AccessArticle

Renal Cell Carcinoma After the COVID-19 Pandemic: Evidence of More Advanced Pathological Presentation from a Romanian Tertiary Center

by Adelina Vidac, Adrian Văduva, Robert Barna, Bianca Natarâș, Aura Jurescu, Ioana Hurmuz, Diana Nicolcea, Vlad Dema, Silviu Lațcu, Alin Cumpănaș and Alis Dema

Cancers 2026, 18(17), 2812; https://doi.org/10.3390/cancers18172812 - 30 Aug 2026

Abstract

Background/Objectives: The COVID-19 pandemic disrupted healthcare systems worldwide, raising concerns about delayed cancer diagnosis and treatment. This study evaluated whether renal cell carcinoma (RCC) diagnosed after the pandemic showed more advanced pathological features at presentation. Methods: This retrospective study included all partial and [...] Read more.

Background/Objectives: The COVID-19 pandemic disrupted healthcare systems worldwide, raising concerns about delayed cancer diagnosis and treatment. This study evaluated whether renal cell carcinoma (RCC) diagnosed after the pandemic showed more advanced pathological features at presentation. Methods: This retrospective study included all partial and radical nephrectomy specimens with a histopathological diagnosis of RCC examined between March 2018 and February 2023, stratified into pre-COVID (2018–2020), COVID (2020–2021), and post-COVID (2021–2023) periods. Pathological variables were compared using Pearson’s χ² and Kruskal–Wallis tests; odds ratios with 95% confidence intervals were calculated with Holm-Bonferroni correction, and multivariable logistic regression, adjusting for age, sex, tumor size, residence, and histological subtype, was performed for high pathological stage and vascular invasion. Results: A total of 297 RCC cases were included (121 pre-COVID, 46 COVID, 130 post-COVID). Post-COVID tumors more frequently showed advanced pathological stage (61.5% vs. 41.3% and 34.8%; p < 0.001) and vascular invasion (56.9% vs. 29.8% and 34.8%; p < 0.001) than pre-COVID and COVID tumors. These associations survived Holm-Bonferroni correction, except for the post-COVID vs. COVID vascular invasion comparison. Both associations remained significant, and numerically stronger, after multivariable adjustment (adjusted OR 2.91, 95% CI 1.61–5.25 for stage; adjusted OR 3.80, 95% CI 2.11–6.83 for vascular invasion). WHO/ISUP grade, tumor necrosis, and sarcomatoid/rhabdoid differentiation did not differ significantly among periods. Conclusions: This study demonstrates a temporal association between the post-pandemic period and more advanced RCC at surgery, independent of age, sex, tumor size, residence, and histological subtype. These findings are consistent with, though do not establish, pandemic-related delays in diagnosis and treatment as a contributing factor, underscoring the need for studies incorporating institutional healthcare-utilization and outcome data. Full article

(This article belongs to the Section Cancer Epidemiology and Prevention)

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16 pages, 1966 KB

Open AccessArticle

Adequacy of Visual Inspection with Acetic Acid (VIA) in Comparison to Pap Smear for Cervical Cancer Screening in Urban and Rural Settings of Tanzania

by Crispin Kahesa, Daniela Gonzalez, Kandali Samwel, Duan Loy, Cameron Klein, Abigail Shotwell, Martha Ricaurte, Julius Mwaiselage, Brenda B. Kweyamba, Asafu Munema, Monica K. Angeletti, Kessy Godwin, Elayna Brown, Gleb Haynatzki, Veenu Minhas, John T. West, Charles Wood and Peter C. Angeletti

Cancers 2026, 18(17), 2811; https://doi.org/10.3390/cancers18172811 - 29 Aug 2026

Abstract

Background/Objectives: Tanzania is a low-to-middle-income-country (LMIC) which endures significant adverse impact from HIV-1- and HPV-associated malignancies. We investigated the performance of visual inspection with acetic acid (VIA) compared to the Pap smear. Methods: Screening performance was assessed in a cross-sectional study design [...] Read more.

Background/Objectives: Tanzania is a low-to-middle-income-country (LMIC) which endures significant adverse impact from HIV-1- and HPV-associated malignancies. We investigated the performance of visual inspection with acetic acid (VIA) compared to the Pap smear. Methods: Screening performance was assessed in a cross-sectional study design across rural catchment clinics in Bagamoyo and Chalinze, and an urban site, Ocean Road Cancer Institute (ORCI), in Dar es Salaam. Pap smears were performed and were read in triplicate by readers blinded to HIV status and patient demographic data. Blood samples were collected for HIV status confirmation. All cytopathology, VIA, and HIV status data were compared with patient demographic factors. Results: Here we present results from 672 patients. Analysis of participants across the cohort revealed a high rate of HIV (25%) and exchange of “sex for money” in the rural site of Chalinze. Bagamoyo and ORCI had slightly lower HIV rates of about 16% and 12%, respectively. Despite the high HIV rates in Chalinze (25%), there was a contrastingly low-level of detectable lesions by VIA (9%) in this region. Conclusions: Overall, VIA-positive cases were 26% HSIL-positive, whereas VIA-negative cases were 14% HSIL-positive, suggesting that performance of VIA is limited. Full article

(This article belongs to the Special Issue The Role of Human Papillomavirus (HPV) in Cancers: Epidemiology, Molecular Biology, and Advancements in Detection Methods)

17 pages, 18720 KB

Open AccessArticle

Comprehensive Genomic Profiling Reveals the Mutational Spectrum and Clinical Significance of BRCA1/2 and Other Cancer-Susceptibility Genes in Breast Cancer Patients from Southern Tunisia

by Nihel Ammous-Boukhris, Rania Abdelmaksoud-Dammak, Wala Ben Kridis, Dorra Ben-Ayed-Guerfali, Souhir Guidara, Ameni Feki, Hassen Kamoun, Afef Khanfir, Jamel Daoud, Gérard-Hubert Lizard, Ali Gargouri and Raja Mokdad-Gargouri

Cancers 2026, 18(17), 2810; https://doi.org/10.3390/cancers18172810 - 29 Aug 2026

Abstract

Background/Objectives: This study aims to investigate the mutational spectrum of BRCA1 and BRCA2 genes in a cohort of breast cancer (BC) patients from southern Tunisia, and to evaluate their clinical and prognostic significance. Additionally, this study explores the contribution of other cancer predisposition [...] Read more.

Background/Objectives: This study aims to investigate the mutational spectrum of BRCA1 and BRCA2 genes in a cohort of breast cancer (BC) patients from southern Tunisia, and to evaluate their clinical and prognostic significance. Additionally, this study explores the contribution of other cancer predisposition genes and the prevalence of variants of uncertain significance (VUS). Results: Among the 165 patients included, pathogenic or likely pathogenic variants (P/LPVs) in BRCA1/BRCA2 were identified in 19 cases (11.51%), including 8 in BRCA1 and 11 in BRCA2. The presence of BRCA P/LPVs associated with young patients (p = 0.006) and those with TNBC (p = 0.036). Beyond BRCA1/2, PV/LPVs were detected in other cancer-related genes, including TP53 (n = 3), CHEK2, RAD50 (n = 2 cases each), and MUTYH, BARD1, and BRIP1 (one case each). Furthermore, 56 VUS were identified; among them, 7 were prioritized based on in silico predictive analyses, suggesting a potential deleterious effect. However, these VUS should not be used for clinical decision-making without additional evidence from functional and familial segregation studies. Conclusions: Our findings provide novel insights into the genetic landscape of breast cancer in southern Tunisia, highlighting the clinical relevance of BRCA1/2 mutations and the contribution of other susceptibility genes. These results support the personalized management of breast cancer patients and the implementation of expanded multigene panel testing in routine clinical practice to improve genetic counseling. Full article

(This article belongs to the Section Cancer Causes, Screening and Diagnosis)

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17 pages, 2899 KB

Open AccessArticle

Immunohistochemical and Transcriptomic Assessment of Cytochrome 2J2 in Prostate and Renal Cancer

by Yousef M. Al-saraireh, Fatemah OFO Alshammari, Awad Dmour, Ahmed. A. Al-abadleh, Mohannad Ja’Awin, Marwan Herzallah, Fadi Sawaqed, Anas O. Satari, Sameeh A. Al-sarayreh, Sa’ed M. Al-dalain, Aiman Al-Qtaitat, Jehad M. Al Shuneigat, Abulmaaty M. Elsayed and Mohammad Salem Hareedy

Cancers 2026, 18(17), 2809; https://doi.org/10.3390/cancers18172809 - 29 Aug 2026

Abstract

Background: Cytochrome P450 2J2 (CYP2J2) has been implicated in tumor biology, but its expression pattern and clinical significance in prostate and renal cancers remain poorly characterized. Methods: Commercially available tissue microarrays containing 208 renal and 121 prostate tissue specimens were used for immunohistochemical [...] Read more.

Background: Cytochrome P450 2J2 (CYP2J2) has been implicated in tumor biology, but its expression pattern and clinical significance in prostate and renal cancers remain poorly characterized. Methods: Commercially available tissue microarrays containing 208 renal and 121 prostate tissue specimens were used for immunohistochemical (IHC) characterization of CYP2J2 protein expression. We performed transcriptomic analysis and examined correlations with clinicopathological features and survival using the OncoDB 2.0 platform. Results: CYP2J2 immunoreactivity was mainly cytoplasmic, with minimal protein expression in both cancers. We identified positive staining in 7/100 (7.0%) prostate adenocarcinomas and 2/192 (1.0%) clear cell renal cell carcinoma (ccRCC) specimens, with negative expression in corresponding normal tissues. We detected no significant associations between protein expression and clinicopathological features in either cohort (all p > 0.05). In contrast, transcriptomic analysis revealed elevated CYP2J2 mRNA expression in both malignancies, with a slight increase in prostate adenocarcinoma (log₂ fold change = 1.10) and marked overexpression in ccRCC (log₂ fold change = 5.24) compared with normal tissues. We observed significant associations between CYP2J2 mRNA expression and pathological T stage in prostate adenocarcinoma (p = 0.0019) and pathological M stage in ccRCC (p = 0.0079). Moreover, higher CYP2J2 mRNA expression was associated with longer overall survival in ccRCC (HR = 0.64, 95% CI: 0.47–0.86; log-rank p = 0.0029) but not in prostate adenocarcinoma; however, these findings remain exploratory and do not establish independent prognostic value. Conclusions: Despite elevated transcript expression, CYP2J2 protein expression was infrequent in prostate adenocarcinoma and ccRCC, suggesting limited clinicopathological relevance and warranting further investigation using functional techniques. Full article

(This article belongs to the Section Cancer Immunology and Immunotherapy)

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16 pages, 1183 KB

Open AccessArticle

Integrating Systemic Inflammation and Longitudinal Weight Trajectories Improves Prognostic Stratification in Gastrointestinal Cancers: A Real-World Retrospective Study

by Saunjoo L. Yoon, Jung A Kim, Oliver Grundmann, Debra Lynch-Kelly and Thomas J. George

Cancers 2026, 18(17), 2808; https://doi.org/10.3390/cancers18172808 - 29 Aug 2026

Abstract

Background/Objectives: This study examined whether the high-sensitivity modified Glasgow Prognostic Score (hs-mGPS) and daily weight change by percentile (DWtCP) are associated with overall survival in patients with gastrointestinal (GI) cancers, overall and across BMI categories. Methods: We analyzed de-identified electronic health record [...] Read more.

Background/Objectives: This study examined whether the high-sensitivity modified Glasgow Prognostic Score (hs-mGPS) and daily weight change by percentile (DWtCP) are associated with overall survival in patients with gastrointestinal (GI) cancers, overall and across BMI categories. Methods: We analyzed de-identified electronic health record data from 176 patients with GI cancers who had albumin, high-sensitivity C-reactive protein (hs-CRP), and longitudinal weight measurements. hs-mGPS was calculated from baseline albumin and hs-CRP. DWtCP, derived from serial weight measurements, was categorized as weight gain, moderate weight loss, or severe weight loss. Survival was evaluated using Kaplan–Meier and Cox proportional hazards models. Results: Nearly 70% of patients had hs-mGPS = 2, which was associated with poorer survival in the earlier part of follow-up (Breslow p = 0.011; log-rank p = 0.062), a pattern also observed in the high-BMI group (Breslow p = 0.045; log-rank p = 0.059). DWtCP was strongly associated with survival (log-rank p < 0.001; Breslow p < 0.001). Patients with moderate weight loss had the most favorable 1200-day Kaplan–Meier survival estimate (54.6%), compared with 5.1% for severe weight loss and 10.9% for weight gain. In multivariable analysis, moderate weight loss was associated with substantially lower mortality risk than weight gain (HR = 0.194, p < 0.001). In BMI-stratified models, DWtCP and primary cancer site remained independent predictors, whereas albumin and hs-CRP did not reach statistical individual significance, supporting the value of the composite hs-mGPS score. Conclusions: In this real-world retrospective cohort, hs-mGPS and DWtCP provided complementary prognostic information. Routine monitoring of systemic inflammation and longitudinal weight trajectories may enable pragmatic risk stratification and early identification of high-risk patients, particularly those with elevated BMI. Full article

(This article belongs to the Section Clinical Research in Cancer)

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19 pages, 17270 KB

Open AccessReview

Skin AllergoOncology: A Framework for Decoding the Context-Dependent Functions of the IgE–FcεRI Axis in Cutaneous Malignancies

by Zhengkui Zhang, Bing Wen and Kun Xie

Cancers 2026, 18(17), 2807; https://doi.org/10.3390/cancers18172807 - 29 Aug 2026

Abstract

The immunoglobulin E (IgE)–FcεRI axis, a central mediator of allergic inflammation, plays a dual role in cutaneous tumor immunity. Epidemiological evidence presents a paradox: atopic dermatitis (AD) promotes keratinocyte carcinogenesis, yet systemic allergic responses are associated with reduced melanoma risk. This review proposes [...] Read more.

The immunoglobulin E (IgE)–FcεRI axis, a central mediator of allergic inflammation, plays a dual role in cutaneous tumor immunity. Epidemiological evidence presents a paradox: atopic dermatitis (AD) promotes keratinocyte carcinogenesis, yet systemic allergic responses are associated with reduced melanoma risk. This review proposes the “Skin AllergoOncology” framework to resolve this paradox. The framework defines the skin as the only human organ in which two antagonistic IgE–FcεRI programs, protective immune surveillance and chronic pro-tumor inflammation, can be spatially juxtaposed. It is organized around three analytical dimensions: IgE repertoire quality, inflammatory kinetics, and effector-cell polarization state. We critically examine the epidemiological AD–keratinocyte carcinoma association, highlighting the confounding role of immunosuppressive therapies, and review the molecular infrastructure enabling dual functional outputs, including antigen focusing by trimeric FcεRI on Langerhans cells and microenvironment-dependent mast cell polarization. We contend that the absence of direct functional evidence for protective IgE in humans represents the central question for the next decade, and we propose a five-year dual-engine roadmap to identify the human protective IgE signature. This framework informs risk-stratified surveillance, engineered IgE antibody therapy, and the long-term oncological safety assessment of anti-allergic biologics. Full article

(This article belongs to the Special Issue Advances in Dermato-Oncology)

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15 pages, 1008 KB

Open AccessArticle

Association of Prior Local Therapy with Outcomes Within Systemic Therapy Regimen Cohorts in Advanced Soft Tissue Sarcoma: A Retrospective Cohort Study

by Ryotaro Ohkuma, Tomoyuki Ishiguro, Hirotsugu Ariizumi, Masahiro Shimokawa, Go Ikeda, Takahiro Yoshizawa, Yuya Hirasawa, Risako Suzuki, Toshiaki Tsurui, Emiko Mura, Rika Sasaki, Shuichi Komori, Kosuke Toyofuku, Masako Kato, Kanae Shimada, Shingo Miyamoto, Kouzou Murakami, Yoshihiro Nakagami, Kazuhiko Oshinomi, Yutaro Kubota, Hiroo Ishida, Takeshi Aoki, Masahiko Murakami, Kiyoshi Yoshimura, Satoshi Wada, Katsuhito Takahashi, Takuya Tsunoda and Atsushi Horiike Show full author list Hide full author list

Cancers 2026, 18(17), 2806; https://doi.org/10.3390/cancers18172806 - 29 Aug 2026

Abstract

Background/Objectives: Evidence regarding associations between local therapy before an indexed systemic regimen and subsequent outcomes in advanced soft tissue sarcoma (STS) remains limited. We evaluated outcomes within four regimen-defined cohorts and explored associations with prior local-therapy history. Methods: This retrospective cohort included 75 [...] Read more.

Background/Objectives: Evidence regarding associations between local therapy before an indexed systemic regimen and subsequent outcomes in advanced soft tissue sarcoma (STS) remains limited. We evaluated outcomes within four regimen-defined cohorts and explored associations with prior local-therapy history. Methods: This retrospective cohort included 75 patients with recurrent or metastatic STS who contributed 155 treatment episodes: doxorubicin (n = 44), trabectedin (n = 31), pazopanib (n = 42), and eribulin (n = 38). Progression-free survival (PFS) and overall survival (OS) were measured from initiation of the indexed regimen. Surgery, local ablative therapy, and radiation therapy were assessed separately and in combined categories. Post hoc analyses were restricted to leiomyosarcoma. Results: Median PFS was 3.4, 3.1, 5.1, and 3.9 months, respectively. PFS was longer with any local therapy and surgery and/or ablation in the trabectedin cohort (p = 0.0342 and p = 0.0111) and with surgery and/or ablation in the eribulin cohort (p = 0.0352). Longer indexed-regimen OS was observed in surgery-containing categories in the doxorubicin and eribulin cohorts. In selected multivariable models, local therapy was associated with OS in doxorubicin- and eribulin-treated episodes and with PFS in eribulin-treated episodes. Leiomyosarcoma-restricted analyses did not consistently reproduce the full-cohort findings. Conclusions: Prior local-therapy history was associated with PFS or OS in selected within-cohort analyses. The associations may reflect local-treatment effects, differences among selected patients, or both; however, the study cannot distinguish these contributions. No between-regimen differences were formally tested. These findings support individualized multidisciplinary assessment and external validation. Full article

(This article belongs to the Special Issue Strategies and Techniques in Diagnosing, Treating and Surveying Sarcoma)

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13 pages, 945 KB

Open AccessArticle

Clinical Outcomes and Prognostic Factors Following Routine CT-Based Image-Guided Adaptive Brachytherapy for Cervical Cancer: A Retrospective Cohort Study

by Pooriwat Muangwong, Ekkasit Tharavichitkul, Somvilai Chakrabandhu, Pitchayaponne Klunklin, Wimrak Onchan, Bongkot Jia-Mahasap, Piyapasara Toapichattrakul, Wannapha Nobnop, Anirut Watcharawipha, Razvan M. Galalae and Imjai Chitapanarux

Cancers 2026, 18(17), 2805; https://doi.org/10.3390/cancers18172805 - 28 Aug 2026

Abstract

Background/Objectives: Magnetic resonance imaging (MRI)-based image-guided adaptive brachytherapy (IGABT) is the preferred standard for cervical cancer, but access remains limited in many settings. Computed tomography (CT)-based IGABT provides a practical alternative. We evaluated clinical outcomes and prognostic factors following its routine implementation. [...] Read more.

Background/Objectives: Magnetic resonance imaging (MRI)-based image-guided adaptive brachytherapy (IGABT) is the preferred standard for cervical cancer, but access remains limited in many settings. Computed tomography (CT)-based IGABT provides a practical alternative. We evaluated clinical outcomes and prognostic factors following its routine implementation. Methods: This retrospective cohort study included patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage I–IVA cervical carcinoma treated with definitive radiotherapy incorporating CT-based IGABT from January 2019 to December 2021. Patients received pelvic external beam radiotherapy (45–50.4 Gy in 23–28 fractions), with or without concurrent platinum-based chemotherapy, followed by four high-dose-rate brachytherapy fractions. Local control and overall survival were estimated using Kaplan–Meier analysis, and prognostic factors were evaluated using Cox regression. Results: Among 237 patients, 56.9% had FIGO stage III–IV disease, and hybrid intracavitary/interstitial brachytherapy was used in 30.2% of fractions. The mean high-risk clinical target volume D90 (HR-CTV D90) was 85.4 ± 2.7 Gy EQD₂. Median follow-up was 59.9 months for local control and 71.1 months for overall survival. The 5-year local control and overall survival rates were 84.4% (95% CI, 79.1–88.5%) and 62.9% (95% CI, 56.3–68.8%), respectively. Squamous histology was independently associated with improved local control and overall survival. HR-CTV D90 ≥ 85 Gy EQD₂ was associated with improved local control, whereas ≥4 chemotherapy cycles and overall treatment time ≤ 56 days were associated with improved overall survival. Conclusions: Routine CT-based IGABT achieved clinically meaningful outcomes despite the high proportion of advanced-stage disease. Achieving HR-CTV D90 ≥ 85 Gy EQD₂, delivering ≥4 chemotherapy cycles, and completing treatment within 56 days were associated with improved outcomes. Full article

(This article belongs to the Special Issue Brachytherapy in the Treatment of Gynaecological Malignancies)

27 pages, 3087 KB

Open AccessSystematic Review

Outcomes of Percutaneous Stabilization for Pelvic Metastatic Bone Disease: A Systematic Review and Meta-Analysis

by Alyssa A. Federico, Zachary A. Carter, Alexander W. Iwasyk, Golpira Elmi Assadzadeh, Michael J. Monument, Matthew G. Cable and Joseph K. Kendal

Cancers 2026, 18(17), 2804; https://doi.org/10.3390/cancers18172804 - 28 Aug 2026

Abstract

Background/Objectives: Metastatic bone disease (MBD) of the pelvis is commonly managed with open reconstruction despite substantial morbidity and high complication rates ranging from 16–32%. Percutaneous fixation techniques have emerged as a lower morbidity alternative; however, robust evaluations of outcomes remain limited. Therefore, the [...] Read more.

Background/Objectives: Metastatic bone disease (MBD) of the pelvis is commonly managed with open reconstruction despite substantial morbidity and high complication rates ranging from 16–32%. Percutaneous fixation techniques have emerged as a lower morbidity alternative; however, robust evaluations of outcomes remain limited. Therefore, the primary aim of this systematic review was to evaluate changes in pain and function following percutaneous fixation for pelvic MBD, and to determine the complication and reoperation rates of these procedures. Methods: A systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. MEDLINE, Embase, Scopus, and Cochrane Library databases were searched from inception through 15 May 2025. Studies evaluating percutaneous fixation for pelvic MBD in adults were included. Pooled estimates of visual analog scale (VAS) pain scores, Eastern Cooperative Oncology Group (ECOG) performance status scores, complication rates, and reoperation rates were generated using meta-analysis techniques. Results: Twenty-five studies were included in the final analysis. VAS pain scores were reported in 15 studies, with an average decrease of 5.0 points (95% CI: 3.9–6.1) from pre- to postoperative. ECOG performance status scores were reported in 8 studies, with an average improvement of 1.1 points (95% CI: 0.7–1.5) from pre- to postoperative. Complications were reported in 24 studies, with a pooled complication rate of 8% (95% CI: 6–12%) and reoperation rate of 4% (95% CI: 2–7%). Conclusions: Percutaneous fixation for pelvic MBD provides meaningful improvements in pain and function with relatively low complication rates. However, substantial study heterogeneity exists in the patient population, surgical techniques, and implant selection, reflecting the novelty of this treatment strategy and the absence of standardized guidelines. Full article

(This article belongs to the Special Issue Advances in Musculoskeletal Oncology)

18 pages, 4331 KB

Open AccessArticle

C-Reactive Protein-Based Composite Indices for Predicting Tumor Overgrowth Restenosis After Partially Covered Duodenal Stenting in Gastric Cancer: A Cohort Study

by Hyuk Lee, Young Eun Oh, Tae-Se Kim, Yang Won Min, Byung-Hoon Min and Jun Haeng Lee

Cancers 2026, 18(17), 2803; https://doi.org/10.3390/cancers18172803 - 28 Aug 2026

Abstract

Background/Objectives: Partially covered duodenal stents rapidly relieve malignant gastric outlet obstruction, but tumor overgrowth restenosis limits durability. We compared six preprocedural inflammatory, nutritional, and immune indices for predicting this outcome in patients with gastric cancer. Methods: We retrospectively analyzed 68 consecutive patients from [...] Read more.

Background/Objectives: Partially covered duodenal stents rapidly relieve malignant gastric outlet obstruction, but tumor overgrowth restenosis limits durability. We compared six preprocedural inflammatory, nutritional, and immune indices for predicting this outcome in patients with gastric cancer. Methods: We retrospectively analyzed 68 consecutive patients from a prospectively maintained cohort. The primary endpoint was endoscopically or radiologically confirmed tumor overgrowth restenosis. Discrimination was assessed using receiver operating characteristic curves (pairwise DeLong tests with Bonferroni correction) and time-dependent areas under the curve (AUCs) accounting for death as a competing risk. Multivariable cause-specific Cox models were restricted to preprocedural covariates; post-stenting chemotherapy or radiotherapy was examined in time-dependent sensitivity analyses. Results: Technical and clinical success rates were 100% and 94.1%. Seventeen patients (25.0%) developed restenosis at a median of 66 days. The C-reactive protein–albumin–lymphocyte (CALLY) index showed the highest AUC (0.859), followed by the C-reactive protein-to-albumin ratio (CAR; 0.822) and neutrophil-to-lymphocyte ratio (0.774); these three indices did not differ significantly. At an exploratory, internally derived cutoff of ≤0.110, CALLY had 76.5% sensitivity and 84.3% specificity and remained associated with restenosis after adjustment for stenosis site and stent length (adjusted hazard ratio, 12.30; 95% confidence interval, 3.89–38.83; C-index, 0.836), with consistent results in continuous, time-dependent, and tumor-covariate-adjusted analyses. The 180-day cumulative incidence was 52.4% with low CALLY versus 4.3% with high CALLY. Conclusions: C-reactive protein-based indices showed the highest numerical discrimination, although pairwise differences among CALLY, CAR, and NLR were not statistically significant. CALLY is a promising exploratory biomarker for restenosis risk stratification, but its cutoff should not guide clinical decisions until externally validated. Full article

(This article belongs to the Special Issue Advances in Clinical Therapy and Prognosis of Gastrointestinal Cancer)

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30 pages, 2018 KB

Open AccessReview

From Pixels to Stroma: AI-Driven Spatial Profiling of Cancer-Associated Fibroblasts on H&E and Its Implications for Immunotherapy

by Dalani Tarun, Wong Kwun Hin Jerry, Jialin Wu, Xin Fang, Tiejun Feng, Fuda Xie, Muyang Huang, Yuanke Liang, Ka Fai To, Wei Kang, Haoyu Lin and Bonan Chen

Cancers 2026, 18(17), 2802; https://doi.org/10.3390/cancers18172802 - 28 Aug 2026

Abstract

Immune checkpoint blockade (ICB) has transformed cancer therapy, but clinical responses remain heterogeneous across tumor types and patient populations. Cancer-associated fibroblasts (CAFs) are key stromal components of the tumor microenvironment and can contribute to immunotherapy resistance through immune exclusion, extracellular matrix remodeling, chemokine [...] Read more.

Immune checkpoint blockade (ICB) has transformed cancer therapy, but clinical responses remain heterogeneous across tumor types and patient populations. Cancer-associated fibroblasts (CAFs) are key stromal components of the tumor microenvironment and can contribute to immunotherapy resistance through immune exclusion, extracellular matrix remodeling, chemokine signaling, and interactions with suppressive immune cells. Although CAF-directed strategies are under active investigation, their clinical translation is limited by marked CAF heterogeneity and the lack of scalable biomarkers for patient stratification. Computational pathology based on hematoxylin and eosin (H&E) whole-slide images (WSIs) provides a potential approach for extracting stromal and spatial features from routine histology, although digitized WSIs and the infrastructure required for large-scale AI analysis are not universally available. In this review, we synthesize current evidence on CAF classification, CAF-mediated immunotherapy resistance, H&E-based computational pathology, and emerging histology-based biomarker models. We further propose a conceptual roadmap for developing CAF-aware H&E spatial signatures with potential relevance to future immunotherapy stratification. Current evidence supports the biological rationale and computational feasibility of this approach, whereas its clinical utility remains to be established through rigorous external validation and prospective clinical evaluation. Full article

(This article belongs to the Special Issue Cancer-Associated Fibroblasts and Translational Biomarkers in Tumor Progression, Metastasis and Therapy Response)

17 pages, 928 KB

Open AccessReview

Prevention and Management of Carboplatin Nephrotoxicity

by Renato A. Caires, Elerson C. Costalonga and Verônica Torres Costa e Silva

Cancers 2026, 18(17), 2801; https://doi.org/10.3390/cancers18172801 - 28 Aug 2026

Abstract

Carboplatin, a second-generation platinum-based therapy, is widely indicated for first-line treatment of selected solid tumors. Furthermore, it represents a well-established alternative to cisplatin in populations characterized by chronic kidney disease (CKD) or clinical frailty. The renal profile of carboplatin toxicity is most commonly [...] Read more.

Carboplatin, a second-generation platinum-based therapy, is widely indicated for first-line treatment of selected solid tumors. Furthermore, it represents a well-established alternative to cisplatin in populations characterized by chronic kidney disease (CKD) or clinical frailty. The renal profile of carboplatin toxicity is most commonly linked to hypomagnesemia, and less frequently to acute kidney injury (AKI) or a persistent decline in GFR. While hypomagnesemia is the most frequent renal adverse effect, severe episodes that impact anticancer treatment are uncommon. Reductions in GFR carry significant clinical implications because they directly affect carboplatin dosing and drive cumulative hematologic toxicity that leads to adverse clinical events, which may be more relevant in older and sarcopenic patients. Carboplatin toxicity is highly dependent on systemic exposure and is quantified by the area under the concentration–time curve (AUC). Inaccurate estimation of GFR, particularly when using the Cockcroft–Gault (CG) equation, frequently leads to GFR overestimation and carboplatin overdose. Thus, precise dose adjustment according to GFR is of the utmost importance. In this review, we examine the renal complications associated with carboplatin, including the reported incidence and clinical patterns of kidney injury, with particular emphasis on dose-adjustment strategies based on GFR, encompassing patients with CKD and those receiving dialysis, as well as practical considerations for the prevention and management of carboplatin nephrotoxicity. Full article

(This article belongs to the Special Issue Treatment of Acute Kidney Injury in Cancer Patients: From Theory to Practice)

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21 pages, 1259 KB

Open AccessArticle

Evaluating the Prognostic Relevance of Pre-Treatment Epstein–Barr Virus Levels in Non-Endemic Pediatric Nasopharyngeal Carcinoma

by Ahmed Farrag, Yanbo Yang, Jin Piao, Lindsay Younis, Hans-Joachim Wagner, Hans Christiansen, Tristan Römer, Allison Poore, Christopher Szot, Nadia Thibeau, Sue S. Yom, Benjamin A. Pinsky, Quynh-Thu Le, Junne Kamihara, David T. Ting, Theodore W. Laetsch, Kenneth S. Chen, Carlos Rodriguez-Galindo, Randall T. Hayden, Udo Kontny and Robyn D. Gartrell Show full author list Hide full author list

Cancers 2026, 18(17), 2800; https://doi.org/10.3390/cancers18172800 - 28 Aug 2026

Abstract

Background/Objectives: Pediatric nasopharyngeal carcinoma (NPC) is a very rare childhood cancer strongly associated with Epstein–Barr virus (EBV) infection. We investigated the prognostic value of EBV DNA on staging and outcome in pediatric NPC from two large study centers, the Children’s Oncology Group (COG) [...] Read more.

Background/Objectives: Pediatric nasopharyngeal carcinoma (NPC) is a very rare childhood cancer strongly associated with Epstein–Barr virus (EBV) infection. We investigated the prognostic value of EBV DNA on staging and outcome in pediatric NPC from two large study centers, the Children’s Oncology Group (COG) in North America and the German Society of Pediatric Oncology and Hematology (GPOH) in Europe. Methods: Samples collected from NPC patients treated on the COG study ARAR0331 between 2006 and 2012 and the GPOH NPC protocol between 2003 and 2021 were retrospectively analyzed for the level of available plasma (P-EBV) or whole-blood EBV DNA (WB-EBV), both pre-treatment and post-induction chemotherapy. Patients were dichotomized into high and low groups based on the median pre-treatment EBV value. Results: Pre-treatment EBV DNA levels from 102 patients (50 and 23 P-EBV DNA from the COG and GPOH, respectively, and 29 WB-EBV from GPOH) and post-induction EBV DNA levels from 61 patients (31 and 12 P-EBV DNA from the COG and GPOH, respectively, and 18 WB-EBV DNA from GPOH) were evaluated. Patient characteristics, including age and disease stage, were not associated with high and low P-EBV values in any cohort. Disease stage correlated with high EBV levels in the WB-EBV GPOH cohort (p = 0.014). Pre-treatment P-EBV and WB-EBV levels showed no significant association with 5-year event-free survival (EFS: COG p = 0.65, GPOH P-EBV: p = 0.08, GPOH WB-EBV: p = 0.75) or 5-year overall survival (OS: COG p = 0.90, GPOH P-EBV p = 0.17, GPOH WB-EBV p = 0.19). Conclusions: Our study could not establish a significant correlation between outcome and pre-treatment EBV DNA in pediatric NPC patients from non-endemic areas. Full article

(This article belongs to the Section Pediatric Oncology)

19 pages, 587 KB

Open AccessSystematic Review

Surgical Management of Parapharyngeal Metastases from Thyroid Carcinoma: A Systematic Review and Patient-Level Analysis of the Role of Lateral Neck Dissection

by Francesco Chiari, Marika Reppucci, Matteo Fermi, Giulia Di Dalmazi, Vincenzo Palatino, Daria Maria Filippini, Giovanni Motta, Giuseppe Mercante, Livio Presutti, Claudio Donadio Caporale and Pierre Guarino

Cancers 2026, 18(17), 2799; https://doi.org/10.3390/cancers18172799 - 28 Aug 2026

Abstract

Background/Objectives: Parapharyngeal space (PPS) metastases from thyroid carcinoma are rare, and evidence guiding their surgical management, particularly the role of concomitant lateral neck dissection (LND) in patients with a clinically node-negative (cN0) neck, remains limited. This systematic review and patient-level analysis evaluated [...] Read more.

Background/Objectives: Parapharyngeal space (PPS) metastases from thyroid carcinoma are rare, and evidence guiding their surgical management, particularly the role of concomitant lateral neck dissection (LND) in patients with a clinically node-negative (cN0) neck, remains limited. This systematic review and patient-level analysis evaluated the clinicopathological characteristics, surgical management, and oncologic outcomes of PPS metastases, with particular emphasis on the management of the cN0 neck. Methods: A PRISMA 2020-compliant systematic review of PubMed, Scopus, and the Cochrane Library was performed. Patient-level data were analyzed according to clinical neck status and timing of PPS metastasis presentation. Results: Thirty-two studies including 162 patients were analyzed. Papillary thyroid carcinoma accounted for 94.4% of cases, while PPS metastases presented as primary disease in 48.8% and recurrent disease in 51.2% of patients. The transcervical approach (TCA) was the predominant surgical technique (79.1%), whereas LND was performed in 70.2% of patients with available data. Among the 19 patients with a cN0 neck, 10 had a previously undissected lateral neck; of these, 6 underwent elective LND and 4 underwent isolated PPS metastasectomy. No occult cervical lymph node metastases were identified following elective LND. Patients with recurrent PPS metastases had significantly higher overall recurrence (47.5% vs. 13.2%, p < 0.001) and disease-specific mortality (22.8% vs. 5.6%, p = 0.003) than those with primary PPS metastases. Conclusions: TCA remains the reference surgical strategy for PPS metastases from thyroid carcinoma. Although based on a very limited cN0 subgroup, current evidence suggests that routine elective LND may not be necessary in carefully selected patients presenting with isolated PPS metastases and a cN0 neck. Recurrent PPS metastases are associated with poorer oncologic outcomes. Full article

(This article belongs to the Special Issue Contemporary Head and Neck Oncology: Progress, Clinical Dilemmas, and Future Directions)

42 pages, 9376 KB

Open AccessReview

PIK3CA in Cancer: Structure, Biology, Alterations, and Actionability

by Alessandro Ottaiano, Carmine Picone, Mariachiara Santorsola, Massimiliano Berretta, Carmen Cutolo, Andrea Belli, Francesco Izzo, Nadia Di Carluccio, Aniello Acampora, Luca Tarotto, Salvatore Stilo, Marco Correra, Maurizio Capuozzo, Anna Chiara Carratù, Michele Caraglia, Guglielmo Nasti and Giovanni Savarese

Cancers 2026, 18(17), 2798; https://doi.org/10.3390/cancers18172798 - 28 Aug 2026

Abstract

PIK3CA, which encodes the p110α catalytic subunit of phosphoinositide 3-kinase (PI3K), is one of the most frequently altered oncogenes in human cancer and a major driver of tumor initiation, progression, metastasis, and therapeutic resistance. Over the past two decades, advances in structural [...] Read more.

PIK3CA, which encodes the p110α catalytic subunit of phosphoinositide 3-kinase (PI3K), is one of the most frequently altered oncogenes in human cancer and a major driver of tumor initiation, progression, metastasis, and therapeutic resistance. Over the past two decades, advances in structural biology, cancer genomics, and translational research have substantially expanded our understanding of PIK3CA function and established the PI3K pathway as a clinically actionable therapeutic target. This review provides an overview of the structural organization and physiological functions of the PI3Kα complex, the molecular mechanisms underlying oncogenic activation, and the diverse spectrum of PIK3CA alterations across human malignancies. We also summarize the current landscape of PI3K-targeted therapies, highlighting both approved agents and emerging therapeutic strategies. Clinical evidence supports the rational integration of PI3K inhibitors with endocrine therapy, CDK4/6 inhibitors, MAPK pathway inhibitors, dual PI3K/mTOR inhibition, and immune checkpoint blockade. In addition, accumulating evidence indicates that PIK3CA plays a pivotal role in shaping the tumor immune microenvironment, providing a biological rationale for combining PI3K inhibition with immunotherapy. Finally, we discuss future directions in precision oncology, emphasizing integrated molecular profiling, liquid biopsy, single-cell and spatial technologies, functional genomics, and evolutionary approaches as complementary strategies to refine patient selection, overcome therapeutic resistance, and optimize clinical outcomes. Full article

(This article belongs to the Special Issue Advances in Cancer Targeted Therapy)

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20 pages, 431 KB

Open AccessSystematic Review

CT-Based Radiomics in Renal Tumors: Current Evidence, Methodological Challenges, and Future Perspectives for Precision Oncology

by Anna Colarieti, Sergio Milazzo, Alessandro Pozzo Giuffrida and Alessandro Carriero

Cancers 2026, 18(17), 2797; https://doi.org/10.3390/cancers18172797 - 28 Aug 2026

Abstract

Background: CT-based radiomics may provide non-invasive imaging biomarkers for renal-tumor characterization and risk stratification. This systematic review evaluates the clinical evidence and translational readiness of radiomics in renal oncology and reports an exploratory methodological appraisal of a clearly delimited subgroup. Methods: PubMed/MEDLINE and [...] Read more.

Background: CT-based radiomics may provide non-invasive imaging biomarkers for renal-tumor characterization and risk stratification. This systematic review evaluates the clinical evidence and translational readiness of radiomics in renal oncology and reports an exploratory methodological appraisal of a clearly delimited subgroup. Methods: PubMed/MEDLINE and Embase were searched from database inception through 15 August 2026 using controlled vocabulary and free-text terms for renal tumors, computed tomography, and radiomics or quantitative image analysis. Eligibility was restricted to English-language original studies published from 1 January 2020 to 15 August 2026 that were available in full text. Engineered-feature radiomics constituted the primary evidence base; end-to-end deep-learning studies were considered separately. Owing to clinical and methodological heterogeneity, findings were synthesized narratively. Results: The searches retrieved 1521 records (PubMed/MEDLINE, n = 357; Embase, n = 1164). The PubMed/MEDLINE stream yielded 242 unique records after removal of 115 duplicates; 72 full-text reports were assessed and included. Cross-deduplication and screening of the Embase records identified no additional eligible study. Contemporary evidence supports potential applications in benign–malignant differentiation, histological subtype classification, WHO/ISUP grade and pathological-stage prediction, and postoperative outcome assessment. Reported discrimination was frequently high, but performance estimates were not directly comparable and often declined in independent testing. Within the illustrative, non-representative 28-report detailed appraisal subset, 25 engineered-radiomics studies had an available numerical RQS (median, 16; interquartile range, 15–20; range, 12–24; 44.4% of the maximum). Conclusions: CT radiomics is technically promising but not yet ready for routine clinical use. Quality-related findings apply only to the assessed subgroup and cannot characterize the entire evidence base. Standardized acquisition and feature definitions, transparent analysis, clinically relevant comparators, prospective multicenter validation, formal risk-of-bias assessment in future reviews, and impact studies are needed. Full article

(This article belongs to the Special Issue Artificial Intelligence in Urological Oncology: Applications in Imaging, Prognostics, and Precision Disease Management)

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16 pages, 27454 KB

Open AccessArticle

Characterizing the Immune Landscape of a Syngeneic Mouse Model with Regional Lymph Node Metastasis and Distant Lung Metastasis

by Deyi Xiao, Wenxuan Zhang, Austin McMasters, Chuanlin Ding, Hong Li, Yi Zou, Alisa Sweazy, Quinn Piamonte, Jun Yan, Kelly McMasters, Haixun Guo and Hongying Hao

Cancers 2026, 18(17), 2796; https://doi.org/10.3390/cancers18172796 - 28 Aug 2026

Abstract

Background/Objectives: Tumor-draining lymph nodes (TDLNs) play a critical role in shaping a pre-metastatic and immunosuppressive niche that facilitates tumor dissemination. However, a robust in vivo model that recapitulates regional lymph node and distant metastasis remains elusive. We sought to establish and characterize [...] Read more.

Background/Objectives: Tumor-draining lymph nodes (TDLNs) play a critical role in shaping a pre-metastatic and immunosuppressive niche that facilitates tumor dissemination. However, a robust in vivo model that recapitulates regional lymph node and distant metastasis remains elusive. We sought to establish and characterize an animal model that reliably mimics spontaneous human melanoma progression from primary tumor to regional lymph node and distant organ metastasis. Methods: B16F10-Luc2 melanoma cells were subcutaneously implanted from the hock area into the lower medial thigh of C57BL/6J mice to establish a metastatic melanoma mouse model with reliable regional lymph node metastasis and distant metastasis. Tumor growth was monitored over time. ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and bioluminescence imaging (BLI) were used to track lymph node and lung metastases in vivo. Immunocytochemistry (IHC) was performed to confirm the metastatic melanoma cells in tissues. The immune landscape of metastatic lymph nodes was characterized by Cytometry by Time-Of-Flight (CyTOF). Results: This implantation strategy resulted in consistent primary tumor growth accompanied by reproducible metastasis to ipsilateral inguinal lymph nodes (IILN) and subsequent lung metastasis. Multi-modal imaging (PET/CT and BLI) enabled non-invasive monitoring of metastatic progression in vivo. Histological analyses confirmed melanoma cell infiltration in lymph nodes and lung tissues. Notably, CyTOF profiling revealed a distinct immunological remodeling within the TDLN, characterized by immunosuppressive phenotypes in the tumor-draining ipsilateral inguinal lymph node (IILN) compared with naïve nodes, indicative of a potential immunotolerant environment in tumor-bearing mice associated with metastatic progression. Conclusions: We present a reproducible and clinically relevant syngeneic melanoma mouse model that recapitulates lymphatic dissemination to regional lymph nodes and distant lung metastasis, and mimics the immunosuppressive phenotypes in the tumor-draining lymph node microenvironment seen in human melanoma patients. This model provides a valuable platform for investigating the mechanisms of lymphatic metastasis and the immunological dynamics of TDLNs, with potential applications in evaluating therapeutic strategies targeting metastatic progression. Full article

(This article belongs to the Special Issue Advancements in Preclinical Models for Solid Cancers)

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24 pages, 1347 KB

Open AccessArticle

Silent Verb Generation During fMRI Reveals Post-Radiotherapy Alterations in Cerebellar–Cerebral Language Regions in Patients Treated for Medulloblastoma

by Josue Luiz Dalboni da Rocha, Ping Zou Stinnett, Stu McAfee, Carolina Torres-Rojas, Matthew A. Scoggins, Askery Canabarro, Pankaj Pandey, Thomas E. Merchant, Giles Robinson, Amar Gajjar, Heather M. Conklin and Ranganatha Sitaram

Cancers 2026, 18(17), 2795; https://doi.org/10.3390/cancers18172795 - 28 Aug 2026

Abstract

Background/Objectives: Medulloblastoma is the most common malignant pediatric brain tumor. Although radiotherapy improves survival, it is often associated with neurocognitive impairments affecting language and executive functions in developing brains. We investigated treatment-related changes in task-evoked activation using silent verb-generation functional magnetic resonance imaging [...] Read more.

Background/Objectives: Medulloblastoma is the most common malignant pediatric brain tumor. Although radiotherapy improves survival, it is often associated with neurocognitive impairments affecting language and executive functions in developing brains. We investigated treatment-related changes in task-evoked activation using silent verb-generation functional magnetic resonance imaging (fMRI). Methods: Thirty-one children and adolescents with medulloblastoma enrolled on SJMB12 (18 males; mean age 14.1 ± 4.7 years) completed visual and auditory noun-cued covert verb generation during fMRI before radiotherapy and again within 6 weeks after completing radiotherapy. A two-stage, nested feature-selection framework coupled with a linear Support Vector Machine differentiated pre- from post-irradiation scans using fully nested leave-one-subject-out cross-validation, in which the sign-consistency threshold was re-selected within each training fold, and was evaluated against the 50% chance level of the paired forced-choice design. Results: In fully nested leave-one-subject-out evaluation, the pipeline correctly ordered the paired pre- and post-radiotherapy scans for 22 of 31 participants (71.0%; 95% CI, 52.0–85.8%; one-sided permutation p = 0.015). Descriptive cohort-derived mapping at the modal inner-loop sign-consistency threshold implicated reduced activity in bilateral cerebellar hemispheres (Crus I/II, lobules VI–VIII), left inferior frontal gyrus, left insula, left putamen, supragenual anterior cingulate, and left middle temporal gyrus. Reduced task-negative responses were observed in a large cluster overlapping right precuneus, right superior parietal, right paracentral, and right postcentral cortices, alongside increased engagement of the left supramarginal gyrus and left inferior parietal lobule. Conclusions: In this single-center pilot cohort, silent verb-generation fMRI detected early post-radiotherapy activation changes within cerebellar–cerebral language and control networks. These findings require independent validation, test–retest controls, and longitudinal neurocognitive outcomes before being interpreted as clinical biomarkers. Full article

(This article belongs to the Section Pediatric Oncology)

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