Int. J. Cancer [JOURNAL]
Sun
200 papers
Geographical Pattern of Testicular Cancer Points to Maternal Exposures Behind Increasing Incidence.
Kaipia A, Seppä K, Hirvonen E … +6 more , Mäkinen E, Malila N, Pitkäniemi J, Toppari J, Boström P, Seikkula H
Int J Cancer · 2026 Jul · PMID 42400384 · Publisher ↗
Evidence suggests that testicular cancer (TC) originates from germ cell neoplasia in situ arising during fetal development, implying that prenatal environmental exposures may influence disease risk. We investigated wheth...
Evidence suggests that testicular cancer (TC) originates from germ cell neoplasia in situ arising during fetal development, implying that prenatal environmental exposures may influence disease risk. We investigated whether maternal place of residence during pregnancy is associated with regional variation in TC incidence. We conducted a nationwide cohort study including 1,342,996 men born in Finland between 1960 and 1999. Participants were followed from birth until diagnosis of TC, death, emigration, or the end of follow-up (2021). A total of 2976 TC cases were identified. Information on municipality of birth was used as a proxy for maternal residence during pregnancy. Incidence rates and cumulative incidence were estimated by birth cohort and age at diagnosis. To examine regional variation, cumulative TC incidence by birth cohort and municipality was modeled using Bayesian hierarchical binomial regression allowing incidence to vary across municipalities. TC incidence increased across birth cohorts, peaking among men born in 1975-1979 (16.8 per 100,000). Cumulative incidence rose in all municipalities, ranging from 67.9 to 132.5 per 100,000 among men born in 1960-1969 and from 283.2 to 327.6 among those born in 1980-1989. Marked geographic clustering was observed. Incidence was consistently elevated among men born in southwestern Finland and remained high throughout the study period. Over successive birth cohorts, an eastward shift in higher incidence was observed. Although direct cohort evidence linking specific environmental exposures to TC remains limited, these findings support the hypothesis that prenatal environmental factors contribute to the pathogenesis of TC and may partly explain regional differences in incidence.
High Endothelial Venules in Small Cell Lung Cancer: Prognostic Subtypes and Therapeutic Implications for Immunoradiotherapy.
Fang J, Wang Z, Wang H … +2 more , Xue J, Kang K
Int J Cancer · 2026 Jul · PMID 42400206 · Publisher ↗
Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine malignancy with an immunosuppressive tumor microenvironment, and current immunotherapy provides limited benefit. This highlights the need to identify mi...
Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine malignancy with an immunosuppressive tumor microenvironment, and current immunotherapy provides limited benefit. This highlights the need to identify microenvironmental features enabling effective immune responses. High endothelial venules (HEVs) are critical for lymphocyte recruitment and antitumor immunity, yet their roles in SCLC remain poorly understood. To investigate HEV-related features among SCLC patients, five bulk RNA-seq datasets comprising 583 tumor samples were integrated. HEV-related signatures stratified SCLC patients into two subtypes, C1 and C2, associated with HEV-high and HEV-low states, respectively. C1 showed a more immune-active microenvironment and superior prognosis. Consistently, using single-cell RNA-seq data and validating the findings by immunofluorescence staining in an independent cohort of 80 patients with SCLC, we confirmed that the presence of HEV structures was associated with a favorable prognosis. We further established a prognostic model and identified five genes, PDCD1, CXCL9, ITK, ITGAL, and SH2D1A, as key favorable prognostic factors. A nomogram incorporating age, tumor stage, and the prognostic model was also developed and exhibited satisfactory performance. Additionally, we explored the translational potential of promoting HEV formation as a therapeutic strategy in SCLC. In murine SCLC models, radiotherapy combined with immunotherapy promoted HEV formation and enhanced antitumor efficacy. HEVs appeared to serve as a critical link underlying the therapeutic synergy between radiotherapy and immunotherapy. Collectively, these findings highlight the biological and clinical relevance of HEVs in SCLC and suggest that combination strategies aimed at promoting HEV formation may help overcome the limited efficacy of immunotherapy.
Epigenetic Dysregulation of Somatostatin Receptors (SSTR) 1-5 and Therapeutic Implications in Neuroendocrine and Non-Neuroendocrine Malignancies.
Kumari N, Hoffmann P, Reichl L … +8 more , Schmutz M, Fischer N, Dang TTV, Ferrazzi F, Johann P, Kuhlen M, Lapa C, Claus R
Int J Cancer · 2026 Jul · PMID 42400125 · Publisher ↗
Somatostatin receptors (SSTR) mediate the antiproliferative, antisecretory, and proapoptotic effects of somatostatin and its synthetic analogs. Their surface expression on neuroendocrine tumor (NET) cells is required for...
Somatostatin receptors (SSTR) mediate the antiproliferative, antisecretory, and proapoptotic effects of somatostatin and its synthetic analogs. Their surface expression on neuroendocrine tumor (NET) cells is required for somatostatin analog therapy and radiopharmaceutical therapy (RPT). However, 20%-30% of gastroenteropancreatic NETs and most poorly differentiated neuroendocrine carcinomas show insufficient SSTR expression, limiting therapeutic eligibility. Accumulating evidence indicates that reversible epigenetic mechanisms contribute substantially to SSTR loss, alongside tumor dedifferentiation, lineage-state changes, and clonal evolution with DNA hypermethylation of the SSTR2 promoter representing a central event, complemented by chromatin remodeling and non-coding RNA-mediated regulation. Preclinical studies demonstrate that epigenetic therapies, including DNA methyltransferase and histone deacetylase inhibitors, can restore functional SSTR expression. Notably, the first-in-human LANTana trial provides clinical proof-of-concept that epigenetic priming with oral decitabine/cedazuridine can induce SSTR2 re-expression and enable subsequent RPT in receptor-negative tumors. This review synthesizes current knowledge of epigenetic regulation across all five SSTR subtypes (SSTR1-SSTR5), examines receptor silencing in neuroendocrine and non-neuroendocrine malignancies, and critically evaluates the preclinical and clinical evidence supporting therapeutic strategies that target these mechanisms.
Sex Hormone Receptors, HBV Integrations and Their Prognostic Predictive Value Among Hepatocellular Carcinoma Patients.
He D, Zeng X, Yin L … +4 more , Liu Y, Zhou W, Liu X, Zhao L
Int J Cancer · 2026 Jul · PMID 42400106 · Publisher ↗
Hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) infection predominantly affects males, yet few studies have investigated the association between sex hormones and HBV integrations, and their involvement...
Hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) infection predominantly affects males, yet few studies have investigated the association between sex hormones and HBV integrations, and their involvement in HCC prognosis. We assessed estrogen receptor alpha (ERα) and androgen receptor (AR) expression via immunohistochemistry on tissue microarrays constructed from 426 HBV-related HCC samples. HBV integration features were determined using HBV-captured sequencing data. Logistic regression models were utilized to evaluate the association between sex hormone receptor expression level and HBV integration features. Cox regression models, combined with machine learning (ML) methods, were implemented to investigate the prognostic value of sex hormone receptors and HBV integrations concerning overall survival. We found high AR expression level was significantly associated with higher HBV integration levels (adjusted odds ratio [aOR] = 1.84, 95% confidence interval [CI]: 1.09-3.11, P for trend = 0.012), TERT integration (aOR = 2.34, 95% CI: 1.16-4.74, P for trend = 0.047), intergenic integration (aOR = 2.25, 95% CI: 1.20-4.24, P for trend = 0.021), and promoter integration (aOR = 1.81, 95% CI: 1.00-3.31, P for trend = 0.034). The inclusion of sex hormone receptors and HBV integrations in the predictive models led to improvements across all performance metrics in the Cox regression analyses (AUC improvement: 0.014 [Training], 0.026 [Validation]) and the ML (AUC improvement: 0.022 [Training]), although a slight deterioration in performance was noted in the ML validation set. The results suggested a relationship between AR expression level and HBV integration events, as well as the potential utility of HBV integration biomarkers and sex hormone receptor profiles in assessing post-surgical prognosis among HCC patients.
MET Expression in Upper Gastrointestinal Adenocarcinoma: Prevalence, Prognostic Impact, and Implications for Anti-MET Antibody-Drug Conjugate Therapy.
Bedau T, Zander T, Anton Schlößer H … +5 more , Alakus H, Mustafov O, Büttner R, Bruns C, Quaas A
Int J Cancer · 2026 Jul · PMID 42394136 · Publisher ↗
MET is an actionable receptor tyrosine kinase, and MET-directed antibody-drug conjugates (ADCs) have recently entered clinical practice with FDA approval in non-small cell lung cancer and are now being evaluated across g...
MET is an actionable receptor tyrosine kinase, and MET-directed antibody-drug conjugates (ADCs) have recently entered clinical practice with FDA approval in non-small cell lung cancer and are now being evaluated across gastrointestinal malignancies, with patient selection based on MET immunohistochemistry (IHC) 3+ membranous staining at varying percentage thresholds. However, robust real-world data on MET protein expression and clinically relevant ADC-aligned thresholds in upper GI adenocarcinomas remain limited. We profiled 1532 upper GI adenocarcinomas using the clinically validated VENTANA MET (SP44) IHC assay. MET was stratified by (i) 3+ membranous staining fractions (any, ≥ 10%, ≥ 50%) reflecting contemporary ADC eligibility concepts and (ii) H-score (0-300; high ≥ 150). Overall survival analyses and multivariable Cox regression analyses were performed. High MET expression was uncommon (H-score ≥ 150: 2.3%; any 3+: 1.6%; ≥ 10% 3+: 1.3%; ≥ 50% 3+: 1.0%) and enriched in advanced T stage. MET IHC strongly predicted MET amplification (H-score ≥ 150: 63.6% amplified vs. 2.4% in negatives; any 3+: 75.0% vs. 2.6%; all p < 0.001). Any MET 3+ staining was independently associated with inferior overall survival (adjusted HR 2.22, 95% CI 1.29-3.83). Most MET 3+ tumors lacked concurrent HER2 positivity, Claudin-18.2 expression, or dMMR/MSI. In the largest real-world cohort to date, MET overexpression identifies a rare, biologically aggressive subset with poor outcomes. By applying the latest MET-ADC-relevant IHC criteria (including the ≥ 10% 3+ threshold), this study provides clinically translatable prevalence estimates and supports standardized MET testing to inform prospective MET-directed ADC trials in upper GI adenocarcinoma.
Leveraging Minimal Variables for Maximal Screening Yield: A Global Equity Perspective on Colorectal Cancer Risk Stratification.
Nie S, Wang C, Cao X … +2 more , Song S, Wang Y
Int J Cancer · 2026 Jul · PMID 42387824 · Publisher ↗
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Bispecific Antibody-Based Combination Therapies for B-Cell Lymphomas: Current Evidence and Future Perspectives.
Cheng M, Li W, Liu M … +1 more , Zou L
Int J Cancer · 2026 Jul · PMID 42385177 · Publisher ↗
The introduction of rituximab revolutionized the treatment landscape of B-cell lymphomas, establishing immunotherapy as a cornerstone of therapeutic strategies. Bispecific antibodies (BsAbs) have demonstrated remarkable...
The introduction of rituximab revolutionized the treatment landscape of B-cell lymphomas, establishing immunotherapy as a cornerstone of therapeutic strategies. Bispecific antibodies (BsAbs) have demonstrated remarkable efficacy in hematologic malignancies, including B-cell lymphomas, and select solid tumors. However, their single-agent activity remains limited by primary or acquired resistance. To overcome these challenges, current research has shifted toward exploring combination strategies integrating BsAbs with chemotherapy, targeted therapies, and other immunotherapies. This review comprehensively summarizes recent advances in BsAb-based combination therapies for B-cell lymphomas, with a focus on ongoing clinical trials and their preliminary outcomes. Furthermore, we discuss the mechanistic rationale, potential synergies, and challenges of these approaches, aiming to provide insights for optimizing future treatment paradigms.
Cancer Survival for Selected Cancers in Türkiye (2008-2017): A Population-Based Study.
Zahwe M, Eser S, Bardot A … +11 more , Karakilinc H, Akpinar GC, Akin U, Karasahin EF, Kurnali B, Yakut C, Altinisik M, Ucuncu N, Sunguc C, Znaor A, Soerjomataram I
Int J Cancer · 2026 Jul · PMID 42384957 · Publisher ↗
This study estimates population-based cancer survival for selected cancers in Türkiye over a 10-year period and investigates differences across provinces. We utilised data for patients diagnosed with five most common can...
This study estimates population-based cancer survival for selected cancers in Türkiye over a 10-year period and investigates differences across provinces. We utilised data for patients diagnosed with five most common cancers (lung, breast, colorectum, prostate and thyroid) from eight population-based cancer registries (PBCRs) in Türkiye (Antalya, Bursa, Edirne, Erzurum, Eskisehir, Izmir, Samsun and Trabzon) in 2008-2012 and 2013-2017. We estimated 5-year age-standardised relative survival (ASRS) by age, sex and extent of disease. Five-year ASRS for the leading cancers in Türkiye increased by 1.4 to 4.6 percentage points between subsequent 5-year periods, in particular for breast, prostate and colorectal cancers. Thyroid cancer consistently showed the highest 5-year ASRS, exceeding 89%, while lung cancer had the lowest 5-year ASRS, with Edirne reporting the lowest survival at approximately 10% in both periods. Improvement in 5-year ASRS was greatest in the older age group (≥ 65 years) except for lung cancer (0.6 percentage point increase in ≥ 65 years vs. 3.2 percentage points for < 65 years). Antalya and Trabzon showed the greatest 5-year ASRS and the largest survival gains over time across most cancers, while survival improvements in Erzurum were limited. In 2013-2017, 5-year ASRS for localised cancers were > 95% for breast cancer in 7 out of 8 PBCRs, and > 75% for colorectal cancer in all PBCRs. While survival for the most common cancers in Türkiye has improved, likely due to advances in the availability of and access to cancer treatment, further efforts are needed to address regional disparities and inform policy decisions across the provinces in Türkiye.
Cardiovascular-Kidney-Metabolic Syndrome, Healthy Lifestyles, and Risk of Cancer Incidence and Mortality: A Prospective Cohort Study.
Qie R, Liu H, Liu Y … +11 more , Guo X, Chen Q, Xu H, Wang X, Kang R, Cheng C, Zhao M, Wang H, Zheng L, Liu S, Zhang S
Int J Cancer · 2026 Jun · PMID 42381231 · Publisher ↗
Cardiovascular-kidney-metabolic (CKM) syndrome has been proposed, yet its utility for cancer risk stratification and behavior modification remains unclear. The study included 227,330 cancer-free participants from UK Biob...
Cardiovascular-kidney-metabolic (CKM) syndrome has been proposed, yet its utility for cancer risk stratification and behavior modification remains unclear. The study included 227,330 cancer-free participants from UK Biobank. CKM stages were defined using the American Heart Association (AHA) criteria, and lifestyle factors included smoking, alcohol consumption, physical activity, and diet. The hazard ratios (HRs) and lifetime risks of cancer were estimated using the Cox model and Fine and Gray's model, respectively. During a median follow-up of 11.46-13.65 years, 24,916 cancer cases and 7791 deaths were identified. Risks of cancer incidence and mortality increased progressively with advancing CKM stages (P < 0.001), with HRs (95% CIs) of 1.23 (1.15-1.30), and 1.58 (1.41-1.78) for stage 4. Compared with participants with unfavorable lifestyle, those with favorable lifestyle were associated with decreased risks across stages 0-4, with risk reductions of 14%-24% for cancer incidence, and 22%-40% for cancer mortality. Joint analyses showed that the increased cancer risks associated with CKM stages were eliminated or attenuated by adopting favorable lifestyle, particularly in stages 1-2. Participants in stage 4/unfavorable lifestyle had the highest risks of cancer incidence and mortality, with HRs (95% CI) of 1.54 (1.39-1.70) and 2.43 (1.97-2.99), and cumulative risks by age 80 of 34.77% and 11.65%, respectively. Furthermore, CKM stage 4/unfavorable lifestyle was associated with higher incidence of breast, colorectal, lung, kidney, pancreas, bladder, head and neck, esophagus, and liver cancers. These findings support the potential utility of CKM stages for cancer risk stratification and highlight the importance of lifestyle intervention.
HPV Serology and Circulating Viral DNA for Detection, Genotyping, and Measurement of Disease Burden in Oropharyngeal Cancer.
Penny L, Stutheit-Zhao EY, Michels BE … +21 more , Rosing F, Zhao Z, Zheng Y, Zou J, Huang SH, Carlton J, McPartlin A, de Almeida JR, Goldstein D, Hope A, Hosni A, Kim J, Liu FF, Tsai CJ, Waldron JN, Spreafico A, Sanz-Garcia E, Siu LL, Waterboer T, Liu G, Bratman SV
Int J Cancer · 2026 Jun · PMID 42380047 · Publisher ↗
The incidence of human papillomavirus-positive (HPV+) oropharyngeal cancer (OPC) has increased rapidly, and HPV early antigen serology has been proposed as a scalable and cost-effective early detection test. HPV seroposi...
The incidence of human papillomavirus-positive (HPV+) oropharyngeal cancer (OPC) has increased rapidly, and HPV early antigen serology has been proposed as a scalable and cost-effective early detection test. HPV seropositivity can precede clinical presentation of OPC by several years, so additional surveillance procedures may be necessary to optimize early cancer detection. The potential for HPV circulating tumor DNA (ctDNA) to confirm a diagnosis of OPC in seropositive individuals is poorly understood. Here, we assess the relationship between HPV serology and HPV ctDNA with disease burden in a large cohort of HPV+ OPC. We analyzed baseline blood samples from 262 patients using a multiplex serology assay and an HPV-targeted deep sequencing assay (HPV-seq), and HPV-seq results were validated by an orthogonal droplet digital PCR assay. Both assays identified HPV16 as the most prevalent genotype (84%), with serology results indicating a total of 4 HPV genotypes and HPV ctDNA results indicating a total of 6 HPV genotypes. HPV ctDNA results demonstrated higher sensitivity and lower cross-reactivity between HPV types compared with HPV serology results. Furthermore, HPV ctDNA but not HPV16 E6 antibody levels were positively associated with disease burden as determined by N-category, overall stage, and by tumor volume (ctDNA vs. volume, r = 0.48 p = 6.4e-12; E6 vs. volume, r = -0.079 p = 0.26). Overall, this is the largest cohort to compare HPV serology and HPV ctDNA results in OPC, and these findings highlight the potential for ctDNA to augment future strategies for blood-based early detection of HPV+ OPC.
Asymptomatic Cardiotoxicity After High-Dose Anthracycline Treatment in Sarcoma Patients Assessed by Biomarkers and Echocardiography.
Polomski EAS, Speetjens FM, Jukema JW … +4 more , Heemelaar JC, van de Sande MAJ, Gelderblom H, Antoni ML
Int J Cancer · 2026 Jun · PMID 42380046 · Publisher ↗
Treatment of sarcoma includes high-dose anthracyclines, which can cause cardiotoxicity. This study assesses the correlation of cardiac biomarkers and echocardiographic parameters on asymptomatic cardiotoxicity in sarcoma...
Treatment of sarcoma includes high-dose anthracyclines, which can cause cardiotoxicity. This study assesses the correlation of cardiac biomarkers and echocardiographic parameters on asymptomatic cardiotoxicity in sarcoma patients treated with anthracyclines. Consecutive patients diagnosed with sarcoma and treated with anthracyclines were included in this retrospective cohort study using registry data. Echocardiography was performed before start of anthracycline chemotherapy (baseline), after completing treatment (short-term follow-up), and 6-12 months after termination of treatment (long-term follow-up). The primary endpoint was the occurrence of asymptomatic cardiotoxicity at short-term follow-up. We included 44 patients (29.6% female) with a median age of 28.9 [22.2-38.7] years. Baseline left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) decreased significantly from 58.4% ± 5.0% to 54.2% ± 9.3% (p = 0.013) and -19.1% ± 2.2% to -17.2% ± 3.5% at short-term follow-up (p = 0.002), respectively. After Cycle 1, 86.5% of the patients showed NT-proBNP ≥ 125 ng/L compared to 3.9% at baseline (p < 0.001), and after completion of therapy, 65.5% had elevated cardiac Troponin T (cTnT) ≥ 14 ng/L compared to 11.5% at baseline (p = 0.003). Asymptomatic cardiotoxicity was observed in 30 patients (68.2%). Mean follow-up was 2.4 [1.5-2.9] years. cTnT ≥ 14 ng/L after Cycle 4 was associated with cardiotoxicity (HR: 3.75 [1.28-11.0], p = 0.016), and NT-proBNP per 100 units increase after Cycle 1 was associated with an increased risk of mortality (HR: 1.36 [1.004-1.85], p = 0.047). Sarcoma patients treated with high-dose anthracyclines are at increased risk of developing cardiac dysfunction as assessed by LVEF and GLS. cTnT and NT-proBNP levels increase significantly during treatment and can be valuable markers to improve the risk stratification of patients treated with high-dose anthracyclines.
Triage Performance of FAM19A4/miR124-2 Methylation: 18-Month Follow-Up Results From a Prospective Observational Study Within the Dutch Primary HPV-Based Cervical Screening Program.
Verhoef L, Griffioen MS, Bleeker MCG … +7 more , Hinrichs JWJ, Siebers AG, Hesselink AT, Meijer CJLM, Steenbergen RDM, Berkhof J, Heideman DAM
Int J Cancer · 2026 Jun · PMID 42373539 · Publisher ↗
DNA methylation analysis of the genes FAM19A4 and miR124-2 has emerged as a promising triage strategy for high-risk (hr) human papillomavirus (HPV)-positive women in cervical screening. This study reports a prospective e...
DNA methylation analysis of the genes FAM19A4 and miR124-2 has emerged as a promising triage strategy for high-risk (hr) human papillomavirus (HPV)-positive women in cervical screening. This study reports a prospective evaluation of the diagnostic accuracy of FAM19A4/miR124-2 methylation in a large population-based primary HPV-based screening cohort with 18 months of follow-up. In this prospective observational study, clinician-collected cervical samples from 3848 consecutive hrHPV-positive women who participated in the Dutch national primary HPV-based screening program were tested with the QIAsure Methylation Test, a quantitative methylation-specific PCR assessing FAM19A4 and miR124-2 methylation. Through linkage to the Dutch Nationwide Pathology Databank (Palga), 11 cases of cervical carcinoma, 293 cervical intraepithelial neoplasia grade 3 (CIN3), and 29 adenocarcinoma in situ (AIS) were identified during 18 months of follow-up. Clinical performance for CIN3, AIS, and cancer (CIN3+) detection was assessed based on (I) the threshold of the QIAsure Methylation Test, and (II) thresholds corresponding with clinical specificities of 70% and 80% in this hrHPV-positive study population. The sensitivity and specificity of FAM19A4/miR124-2 methylation for CIN3+ detection using the QIAsure Methylation Test threshold (I) were 57.4% (95% CI: 52.0-62.7) and 88.3% (95% CI: 87.2-89.5), respectively. At predefined specificities of 70% and 80%, FAM19A4/miR124-2 methylation (II) demonstrated a CIN3+ sensitivity of 75.4% (95% CI: 70.7-80.0) and 66.1% (95% CI: 61.0-71.2), respectively. In conclusion, FAM19A4/miR124-2 methylation analysis showed good triage performance in a primary HPV-based screening setting. These findings support the use of methylation-based testing as a triage strategy in primary HPV-based screening programs, with an appropriate follow-up policy for hrHPV-positive women who test methylation-negative.
Adjuvant Chemotherapy Regimens in Resected Biliary Tract Cancers: National, Comparative, Observational Study (TOG/GI-SAFRADJU-2501).
Akkus E, Kayaalp M, Ergözoğlu MA … +58 more , Koç Kuş I, Bayram D, Kılıçtaş B, Ayvaz Güneyin E, Kalem A, Temizyürek H, Çatlı MM, Akarca MS, Mıldanoğlu MM, Turhan G, Kara M, Arak H, Arslan Tan F, Paçacı B, Yeşilyurt B, Akdoğan O, Çetin EB, Çelik S, Keskin Uzundere F, Şahin E, Sadak Öcal Z, Şeker Can L, Köylü B, Fidan MC, Kaplan Tüzün E, Şakalar T, Sertesen Çamöz E, Yüksel HÇ, Balçık OY, Peker P, Yılmaz M, Ala Enli Ş, Kölemen E, Oyucu Orhan S, Düzköprü Y, Ersoy M, Akın Telli T, Yılmaz M, İlhan Y, Yıldırım A, Coşar R, Ürün M, Önder AH, Araz M, Bayram E, Yeşil Çınkır H, Alkan A, Gürbüz M, Avcı N, Paksoy Türköz F, Kara İO, Köse F, Ünek İT, Bilici A, Bal Ö, Yalçın Ş, Rimassa L, Yaşar HA
Int J Cancer · 2026 Jun · PMID 42372083 · Publisher ↗
The recommended adjuvant chemotherapy (adj-ChT) regimen for resected biliary tract cancers (BTC) is capecitabine (Cape); yet, the recommendation is based on limited evidence. Although varied adj-ChTs have been employed i...
The recommended adjuvant chemotherapy (adj-ChT) regimen for resected biliary tract cancers (BTC) is capecitabine (Cape); yet, the recommendation is based on limited evidence. Although varied adj-ChTs have been employed in practice, robust real-world data is scarce. We conducted a national, multicenter, hospital-based registry study to evaluate adj-ChTs in resected BTCs. Patients who received adj-ChT (± radiotherapy) between 2010 and 2024 were included. Recurrence-free (RFS) and overall survival (OS) were analyzed by adjusted Cox-regression and propensity score-based inverse-probability-of-treatment-weighting (IPTW), addressing selection bias. Among 617 patients from 44 centers, 513 were eligible. The most frequent adj-ChTs were Cape (35.5% [n = 182]), gemcitabine-cisplatin (Gem-Cis; 22.4% [n = 115]), gemcitabine-capecitabine (Gem-Cape; 20.1% [n = 103]), and gemcitabine (Gem; 10.7% [n = 55]). Median RFS and OS with Cape were 19.7 (95% Confidence Interval [95% CI]: 14.2-41.1) and 41.9 months (95% CI: 25.9-69.2). In adjusted/controlled comparisons with Cape, no differences in RFS or OS were observed with Gem-Cis (RFS: Hazard Ratio [HR] 1.13 [95% CI: 0.77-1.66]; OS: HR: 1.03 [95% CI: 0.66-1.61]), Gem-Cape (RFS: HR 0.97 [95% CI: 0.68-1.38]; OS: HR: 0.81 [95% CI: 0.52-1.24]), or Gem (RFS: HR 1.00 [95% CI: 0.63-1.59]; OS: HR: 0.93 [95% CI: 0.55-1.57]). Similarly, IPTW analyses showed no difference in RFS and OS. Radiotherapy appeared to be associated with improved survival. Performance status, T-stage, lymph-node positivity, and R1-resection were independently associated with RFS and OS. In conclusion, this real-world study did not identify a regimen superior to Cape. Given the modest benefit of adj-ChTs, novel approaches, including neoadjuvant and targeted/immunotherapy strategies, are needed.
Milestones in Hereditary Colorectal Cancer Research.
Boland CR, Yurgelun MB
Int J Cancer · 2026 Jun · PMID 42370808 · Publisher ↗
This reviews the historical evolution of our understanding of the familial gastrointestinal cancer syndromes. It begins centuries ago with the appreciation of the gastrointestinal polyposis syndromes and the relationship...
This reviews the historical evolution of our understanding of the familial gastrointestinal cancer syndromes. It begins centuries ago with the appreciation of the gastrointestinal polyposis syndromes and the relationship between adenomatous polyps and cancer. However, it was not until 1991 that the APC gene was cloned and linked to familial adenomatous polyposis. Mutated oncogenes and inactivated tumor suppressor genes were discovered in the 1970s, and it was appreciated by the late 1980s that these genetic alterations occurred sequentially during the evolution of gastrointestinal tumors. During the exploration of this process, it was unexpectedly recognized in the early 1990s that hereditary non-polyposis colorectal cancers had a specific mutational signature that was the result of inactivation of the DNA mismatch repair system. This disease involved a unique group of mutational targets, distinctive pathways to tumor development, and the remarkable recognition in the 21st century of novel and highly effective therapeutic approaches to tumor control. Mixed in with these discoveries was the appreciation of multiple unique hamartomatous polyposis syndromes. The progress made over the past 50 years is remarkable and highlights the rapid evolution of new technologies and insightful research.
HPV Testing Versus Cytology for Cervical Cancer Screening Among Women 50 Years and Older: Evidence From the HPV FOCAL Randomized Controlled Trial.
Alam MS, Smith LW, Gondara L … +10 more , Cook D, Martin RE, Peacock S, Proctor L, Stuart G, Patrick D, Franco EL, Krajden M, Gottschlich A, Ogilvie GS
Int J Cancer · 2026 Jun · PMID 42363777 · Publisher ↗
Evidence on the comparative effectiveness of HPV testing versus cytology specifically in women aged ≥ 50 years who are approaching screening cessation remains limited. This analysis included 6471 women aged ≥ 50 at basel...
Evidence on the comparative effectiveness of HPV testing versus cytology specifically in women aged ≥ 50 years who are approaching screening cessation remains limited. This analysis included 6471 women aged ≥ 50 at baseline screening in the HPV FOCAL randomized clinical trial. Women were randomly allocated to receive cytology (Control Group, n = 3248, 50.19%) or HPV testing (Intervention Group, n = 3223, 49.81%) at baseline, with co-testing at 48-month exit. We calculated incidence rates and risk ratios for CIN2+ detection over follow-up and compared missed lesions at exit by screening method. At the 48-month exit, CIN2+ detection was lower among HPV baseline-negative women than among those in the cytology group (1.61/1000 [95% CI, 0.52-3.76] vs. 3.15/1000 [95% CI, 1.51-5.78]; risk ratio, 0.51 [95% CI, 0.11-0.91]), reflecting higher baseline detection with HPV testing and fewer prevalent lesions at exit. Even with cytology re-screening at 2 years, 50% of CIN2+ cases were missed compared to 30% with HPV testing. After adjusting for age, education, smoking status, and lifetime sexual partners, the hazard ratio for CIN2+ comparing HPV to cytology was 0.44 (95% CI, 0.22-0.88). Among women aged ≥ 50 years, HPV primary screening was more effective than cytology at detecting CIN2+ lesions and was associated with a continued lower subsequent risk following a negative HPV test, supporting its use in cervical cancer screening programs in this age cohort.
Reassessing the Incidence and Risk Factors of Radiation Pneumonitis in Treatment-Naive EGFR-Mutant NSCLC With Concurrent Third-Generation EGFR-TKI and Thoracic Radiotherapy.
Zheng S, Jia W, Jing X … +6 more , Tian Y, Chen F, Li L, Guo Z, Yu J, Zhu H
Int J Cancer · 2026 Jun · PMID 42363769 · Publisher ↗
This single-center retrospective study evaluated radiation pneumonitis (RP) in 209 treatment-naive EGFR-mutant non-small cell lung cancer (NSCLC) patients receiving first-line third-generation EGFR tyrosine kinase inhibi...
This single-center retrospective study evaluated radiation pneumonitis (RP) in 209 treatment-naive EGFR-mutant non-small cell lung cancer (NSCLC) patients receiving first-line third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) plus thoracic radiotherapy (TRT), with concurrent defined as any overlap of ≥ 1 day between EGFR-TKI and TRT, at Shandong Cancer Hospital and Institute between January 2019 and September 2024, excluding concurrent chemotherapy and anti-angiogenic therapy. RP was diagnosed by chest computed tomography (CT), clinical symptoms, and irradiated field concordance, while infectious pneumonia and tumor progression were excluded by laboratory tests and serial imaging. Grade ≥ 2 RP occurred in 43.54% of patients (22.01% grade 2, 21.53% grade 3; no grade 4/5 RP), with osimertinib showing the highest rates of grade ≥ 2 and grade 3 RP, followed by aumolertinib and furmonertinib. For grade ≥ 2 RP, patients receiving aumolertinib or furmonertinib had a lower observed risk than those receiving osimertinib, while ipsilateral lung V5 ≥ 35.93% and gross tumor volume (GTV) ≥ 12.62 mL were independent risk factors. For grade 3 RP, an inverse association between smoking history and RP risk was observed, whereas ipsilateral lung V30 ≥ 24.61% and GTV ≥ 14.56 mL were associated with increased risk. Median progression-free survival (PFS) was 26.70 months, with no significant difference among the three TKIs. In this cohort, first-line third-generation EGFR-TKI plus TRT was associated with frequent but generally manageable RP. TKI type, ipsilateral lung V5/V30, and GTV were key predictors of RP, although the dosimetric thresholds and drug-specific differences identified in this cohort require external validation.
Epigenetic Markers of Cell Division and Ageing in Relation to Breast Cancer Survival.
Li L, Zarean E, Li DL … +8 more , Zhu Y, Li S, Makalic E, McLean C, Giles GG, Milne RL, Southey MC, Dugué PA
Int J Cancer · 2026 Jun · PMID 42363768 · Publisher ↗
Breast cancer remains a major challenge to public health. Biomarkers may be useful to improve prediction of breast cancer survival. Several epigenetic markers of cell division and ageing based on DNA methylation have bee...
Breast cancer remains a major challenge to public health. Biomarkers may be useful to improve prediction of breast cancer survival. Several epigenetic markers of cell division and ageing based on DNA methylation have been proposed. In this study, we measured these epigenetic markers in breast tumours and assessed their prognostic value. We used genome-wide DNA methylation data measured in 1992 breast cancer tumours from the Melbourne Collaborative Cohort Study and publicly available datasets. We calculated four markers of cell division (epiTOC2, stemTOC, MiAge and CellDRIFT), two markers of chronological age (Horvath age and BTEC), and four markers of biological age (PhenoAge, GrimAge, MRscore and DunedinPACE). Cox regression models were used to assess the associations of age-adjusted epigenetic markers with 5-year overall survival, with adjustment for clinical variables. Effect modification by estrogen receptor (ER) status and molecular subtype was also investigated. After adjustment for age and stratification by study, higher levels of cell division markers were associated with poorer survival (e.g., epiTOC2: per one-standard-deviation increase, hazard ratio [HR] = 1.14, 95% CI: 1.03-1.27), whereas higher chronological age markers were linked to better prognosis (e.g., Horvath age: HR = 0.70, 95% CI: 0.61-0.82). Epigenetic markers of biological age showed variable associations. These associations were partly explained by the main clinicopathological variables at diagnosis and varied across subtypes. Our study revealed associations of several epigenetic markers with breast cancer survival. The associations were quite weak, suggesting these markers may have limited prognostic value. The varying associations observed among subtypes may reflect underlying biological differences that should be further investigated.
Herpes Zoster as a Marker of Occult Malignancy in Older Adults: A Real-World Cohort Study.
Lai SW, Liao KF
Int J Cancer · 2026 Jun · PMID 42360816 · Publisher ↗
This study aimed to evaluate whether herpes zoster (HZ) is associated with an increased short-term probability of newly diagnosed cancer in older adults, and to determine whether HZ may serve as an early clinical marker...
This study aimed to evaluate whether herpes zoster (HZ) is associated with an increased short-term probability of newly diagnosed cancer in older adults, and to determine whether HZ may serve as an early clinical marker of occult cancer. We conducted a retrospective cohort study using de-identified electronic health record data from the TriNetX Research Network (2006-2024). Adults aged 65-84 years with newly diagnosed HZ were compared with matched controls without HZ. Propensity score matching (1:1) was performed based on demographics and comorbidities. A 1-month lag period was applied to minimize detection bias. The primary outcome was any newly diagnosed cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models within the TriNetX platform. After propensity score matching and applying a 1-month lag period, 182,104 adults in the HZ group and 182,463 controls were included. During the 1-year follow-up, 4527 adults with HZ and 667 controls developed cancer, corresponding to cumulative incidences of 2.49% and 0.37%, respectively. HZ was associated with a higher probability of cancer diagnosis (HR 5.81; 95% CI, 5.35-6.30). In adults aged 65-84 years, HZ is associated with a higher likelihood of a new diagnosis of cancer within 1 year. These findings suggest that HZ may serve as a clinical marker of occult cancer. Further research is warranted to clarify underlying mechanisms and to evaluate whether targeted cancer surveillance following HZ could improve early cancer detection.
Obesity-Driven Early-Onset Colorectal Cancer: Mechanistic Insights and Emerging Clinical Implications.
Liu J, Lu J, Dai C … +1 more , Zhou Y
Int J Cancer · 2026 Jun · PMID 42360685 · Publisher ↗
Early-onset colorectal cancer (EOCRC), defined as colorectal cancer diagnosed before 50 years of age, has increased markedly over the past decades, especially in high-income settings. In parallel, obesity and related met...
Early-onset colorectal cancer (EOCRC), defined as colorectal cancer diagnosed before 50 years of age, has increased markedly over the past decades, especially in high-income settings. In parallel, obesity and related metabolic disturbances have become more common in both adults and younger populations, raising the possibility that excess adiposity contributes to the changing EOCRC burden. Epidemiological studies increasingly support this association, particularly for early-life adiposity and persistent metabolic dysfunction. Most EOCRC cases are sporadic, indicating that environmental and lifestyle-related exposures likely play a major role. Among these, obesity may be especially important because it links systemic metabolic stress with intestinal inflammation, microbial imbalance, and epigenetic change. However, the mechanisms through which obesity promotes early colorectal carcinogenesis are still not fully defined. In this review, we examine how obesity may shape EOCRC development across four interacting domains: chronic inflammation, metabolic reprogramming, gut microbiota dysbiosis, and epigenetic remodeling. We also discuss how these pathways may converge during early-life windows of susceptibility and consider their implications for risk identification, prevention, and early intervention in younger populations.
Targeted Therapy and Oral Chemotherapy as Maintenance Treatment in Pediatric Very-High-Risk and High-Risk Rhabdomyosarcoma: A Retrospective Study of Efficacy and Safety.
Mao L, Mai Y, Lu S … +12 more , Sun F, Wang J, Zhu J, Huang J, Song M, Zhang Y, Zhen Z, Wu Y, Lin X, Meng C, Zhang Y, Que Y
Int J Cancer · 2026 Jun · PMID 42360676 · Publisher ↗
Maintenance therapy (MT) and targeted drugs have improved the survival of patients with high-risk rhabdomyosarcoma (RMS) in clinical trials. However, there are limited data concerning targeted drugs and oral chemotherapy...
Maintenance therapy (MT) and targeted drugs have improved the survival of patients with high-risk rhabdomyosarcoma (RMS) in clinical trials. However, there are limited data concerning targeted drugs and oral chemotherapy for MT in pediatric patients with very-high-risk (VHR) and high-risk (HR) RMS. Here, we evaluated the safety and effectiveness of these regimens and aimed to identify circulating tumor DNA (ct-DNA) markers associated with prognosis. We retrospectively retrieved data for 102 pediatric patients with VHR or HR RMS who underwent MT at Sun Yat-sen University Cancer Center from January 2011 to March 2025 involving targeted drugs plus oral chemotherapy (subgroup 1); targeted drugs (subgroup 2); and oral chemotherapy (subgroup 3). Ct-DNA markers were examined throughout treatment and at follow-up. Subgroups 1 and 2 comprised 14 and seven VHR RMS patients, respectively, and subgroup 3 consisted of 39 VHR and 42 HR RMS patients. With a median follow-up of 32 months, no significant differences among subgroups in duration of remission (p = 0.56) or 2-year event-free survival (p = 0.78) were observed. PAX-FOXO1 fusion (p = 0.01), CDK4 mutation (p = 0.02), and TP53 mutation (p = 0.02) were independently associated with unfavorable duration of remission. No grade 3 or higher treatment-related adverse events were observed. MT with targeted drugs shows comparable efficacy in VHR and HR pediatric RMS patients, with manageable adverse reactions. Longitudinal ct-DNA testing could guide treatment decision-making and prognostic stratification for these patients.
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