Int. J. Cancer [JOURNAL]
Sun
200 papers
Population-Based First Estimates of the Effect of HPV Vaccination in Three Italian Areas Covered by Organised Cervical Screening.
Armaroli P, Zappa M, Giorgi Rossi P … +12 more , Carozzi FM, Rizzolo R, Visioli CB, De Marco L, Bisanzi S, Del Mistro A, Iossa A, Bonelli L, Venturino E, Camussi E, Viti J, Ronco G
Int J Cancer · 2026 May · PMID 42084786 · Publisher ↗
In Italy, the first women invited for HPV vaccination at 15-16 years reached the age for cervical screening (25 years) in 2018. The real-world vaccination impact was evaluated. Women born in 1993-1996 invited for organis...
In Italy, the first women invited for HPV vaccination at 15-16 years reached the age for cervical screening (25 years) in 2018. The real-world vaccination impact was evaluated. Women born in 1993-1996 invited for organised cervical screening in three Italian areas in 2018-2022 were eligible. After informed consent, they were tested for high-risk HPV and genotyped. Positives, triaged by cytology, were immediately referred to colposcopy if ASCUS+ (irrespective of genotyping); otherwise, recalled for cytology after 3 years. We estimated the relative (vaccinated with ≥ 2 doses vs. unvaccinated women) infection prevalence of three groups of genotypes: HPV16/18, HPV31/33/45 and HPV 35, 39, 51, 52, 56, 58, 59, 66, 68 ('non-vaccine preventable') and the relative positive predictive value (PPV) for histology-based CIN2+ detected at immediate colposcopy. Of 14,346 enrolled women, 34% had no vaccination, 66% ≥ 2 doses. The relative infection prevalence was 0.05 (0.03-0.10) for HPV16/18 without non-vaccine genotypes, 1.36 (1.23-1.50) for non-vaccine genotypes without HPV16/18 infections and 0.06 (0.03-0.12) for co-infections by both groups. The relative PPV for CIN2+ was very high (4.09; 1.40-12.01) in vaccinated women co-infected by HPV16/18 and non-vaccine types (4/9 vs. 7/84 cases) but reduced to zero in case of stand-alone HPV16/18 infections (0/12 vs. 15/117 cases). The CIN2+ relative detection in women infected only by non-vaccine types was 1.57 (0.87-2.82). The increase in infections and high-grade CIN from the pool of all non-vaccine genotypes requires further research (including pooling of data) to be confirmed with longer follow-up and on a larger study population.
Late and Durable Minimal Residual Disease Response Predicts Favorable Outcomes in Newly Diagnosed Multiple Myeloma.
Zhou J, Yan W, Liu Y … +10 more , Cui J, Xu J, Li Y, Du C, Deng S, Sui W, Xu Y, Li X, Qiu L, An G
Int J Cancer · 2026 Aug · PMID 42083445 · Publisher ↗
Minimal residual disease (MRD) negativity is a well-established prognostic marker in multiple myeloma (MM), yet the clinical relevance of MRD response timing and duration remains unclear, particularly in real-world setti...
Minimal residual disease (MRD) negativity is a well-established prognostic marker in multiple myeloma (MM), yet the clinical relevance of MRD response timing and duration remains unclear, particularly in real-world settings. We retrospectively analyzed 1048 newly diagnosed MM patients from the National Longitudinal Cohort of Hematological Diseases in China (NICHE) between 2012 and 2023, with a total of 5406 MRD assessments. A longer time to best MRD response (> 6 months) was significantly associated with improved progression-free and overall survival, especially among those with persistent MRD positivity but stable low-level disease burden. Early responders were more likely to exhibit high tumor burden and high-risk cytogenetic abnormalities. Notably, a prolonged MRD duration (≥ 36 months) predicted favorable outcomes regardless of MRD negativity status. Integrating response timing and duration identified a "Late + Durable" MRD pattern consistently associated with the best prognosis, even in patients with persistent MRD positivity, high-risk cytogenetics, or without ASCT. These findings highlight the prognostic significance of longitudinal MRD monitoring beyond single-timepoint assessments. A slow but durable MRD response may overcome adverse biological features and support individualized risk stratification, therapeutic decisions, and long-term disease monitoring in MM.
Targeting ERα Coregulator Networks to Overcome Endocrine Resistance in ER+ Breast Cancer.
Bar M, Widłak W, Vydra N
Int J Cancer · 2026 May · PMID 42083279 · Publisher ↗
Breast cancer (BC) is the most commonly diagnosed tumor among women worldwide. Approximately 70% of cases are estrogen receptor-positive (ER+), whose growth is driven by estrogen signaling. Endocrine therapies targeting...
Breast cancer (BC) is the most commonly diagnosed tumor among women worldwide. Approximately 70% of cases are estrogen receptor-positive (ER+), whose growth is driven by estrogen signaling. Endocrine therapies targeting ER signaling are the common treatment for ER+ disease; however, both intrinsic and acquired endocrine resistance continue to be a major clinical challenge. A growing body of evidence indicates that multiple coregulators influence ER recruitment to its genomic binding sites and tumor growth. Their aberrant expression can promote ligand-independent ER activation and attenuate the effectiveness of ER-targeted therapies. Consequently, targeting ERα coregulators has emerged as a promising therapeutic strategy to overcome endocrine resistance. In this review, we synthesize current evidence defining the roles of ERα coregulators in endocrine resistance, critically assess their therapeutic potential, and provide prioritization guidance for clinical development. A deeper understanding of the molecular mechanisms underpinning endocrine resistance is essential to improve treatment outcomes for patients with ER+ BC.
Skeletal Muscle Metastasis in Patients With SMARCA4-Deficient Thoracic Tumors: A Retrospective Cohort Study.
Chen X, Shi M, Yang Y … +10 more , Zhang L, Liu T, Xiao B, Mo S, Ma Y, Chen G, Zhou T, Yang Y, Lin Z, Zhao Y
Int J Cancer · 2026 May · PMID 42083275 · Publisher ↗
SMARCA4-deficient thoracic tumor (SDTT) is a malignant tumor with a poor prognosis that often presents with distant metastases at the time of clinical diagnosis. Skeletal muscle metastasis is a rare subtype of metastasis...
SMARCA4-deficient thoracic tumor (SDTT) is a malignant tumor with a poor prognosis that often presents with distant metastases at the time of clinical diagnosis. Skeletal muscle metastasis is a rare subtype of metastasis patterns, and there are limited studies about SDTT metastasis in skeletal muscle. Herein, we retrospectively analyzed the data of stage IV patients diagnosed with SDTT from May 2009 to June 2024. The clinical and genomic data, imaging features, and treatment information were collected. As a result, the study included 145 patients with metastatic SDTT, 17 with skeletal muscle metastases, and 128 without. The rate of skeletal muscle metastasis in SDTTs was 11.7%. Multivariate Cox regression analysis showed that skeletal muscle metastases (p = 0.014, hazard ratio 95% confidence interval [HR 95% CI] [2.90, 1.25-6.75]) and first-line chemoimmunotherapy (p < 0.001, HR 95% CI [0.31, 0.17-0.56]) were independent prognostic variables. Furthermore, patients with skeletal muscle metastases had a significantly shorter median overall survival (OS) than those without (13.20 vs. 18.6 months, p = 0.021) in metastatic SDTTs. The mutation rate of STK11 and KRAS was higher in the skeletal muscle metastasis group (62.50% vs. 15.52%, p = 0.008; 50.00% vs. 8.62%, p = 0.009). In conclusion, SDTTs exhibited a high rate of skeletal muscle metastases. Skeletal muscle metastases and first-line chemoimmunotherapy were independent prognostic factors for OS in SDTTs.
Associations of Outdoor Air Pollution With Incidence of Cancers Other Than Lung Cancer in a Large US Prospective Cohort.
Diver WR, Teras LR, Deubler EL … +2 more , Patel AV, Turner MC
Int J Cancer · 2026 May · PMID 42071337 · Publisher ↗
Outdoor air pollution, including particulate matter (PM), is a Group 1 carcinogen based on evidence for lung cancer; however, evidence for other cancers is limited. Further research on cancer incidence rather than mortal...
Outdoor air pollution, including particulate matter (PM), is a Group 1 carcinogen based on evidence for lung cancer; however, evidence for other cancers is limited. Further research on cancer incidence rather than mortality endpoints is needed as well as examinations in non-smokers. In the Cancer Prevention Study-II Nutrition Cohort, annual predictions of particulate and gaseous pollutant concentrations were assigned to residential addresses. Extended Cox regression estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations of pre-diagnosis pollutants with risk of all incident non-lung cancers and 20 cancer sites with detailed adjustment for confounding variables. There were 28,008 incident cancers identified among the 108,002 participants followed from 1992 to 2017. There were no statistically significant associations with fine particulates (PM) overall or among never smokers. There were elevated HRs with coarse particulates (PM) for uterine and cervical cancer incidence, though CIs were wide, and an association with ER- breast cancers (HR = 1.16; 95% CI 1.03-1.30). There were also weak positive associations of gaseous pollutants in never smokers with colorectal cancer (sulfur dioxide HR = 1.08; 95% CI 1.01-1.16), kidney cancer (carbon monoxide HR = 1.17; 95% CI 1.00-1.37), and melanoma of the skin (ozone HR = 1.11; 95% CI 0.99-1.25). Overall, these findings indicate few positive associations of ambient air pollutants with cancer incidence beyond lung cancer. The observed associations were low magnitude and stronger in never smokers. Larger pooled studies are needed to validate these associations with rare subtypes and non-smokers, and cancer survival research is needed to clarify differences in mortality and incidence studies.
Higher Daytime Light Exposure Predicts Lower Risk of Gastrointestinal Cancer Incidence and Mortality.
Mei X, Wang W, Zheng N … +12 more , Luo T, Xu J, Chan NY, Wang J, Liang YY, Ai S, Liu Y, Tan X, Benedict C, Wing YK, Zhang J, Feng H
Int J Cancer · 2026 May · PMID 42071269 · Publisher ↗
Daytime light exposure is essential for health, primarily by synchronizing tissue and cellular-level clocks with the external light/dark cycle. Insufficient exposure may disrupt circadian alignment and contribute to adve...
Daytime light exposure is essential for health, primarily by synchronizing tissue and cellular-level clocks with the external light/dark cycle. Insufficient exposure may disrupt circadian alignment and contribute to adverse outcomes, including cancer. Given the high prevalence of gastrointestinal cancer, we conducted a prospective cohort study of 89,069 participants with objectively measured daytime light intensity and duration. Cox proportional hazards models were used to evaluate associations with gastrointestinal cancer incidence and mortality. Over a median follow-up of 8.8 years (804,111 person-years), 1692 gastrointestinal cancer cases were recorded, of which 891 were fatal. Higher mean levels of daytime light (≥ 1916 lux between 7:30-20:30, based on the 80% cut-off) were associated with lower risk of gastrointestinal cancer incidence (Hazard Ratio [HR]: 0.87, 95% confidence interval [CI]: 0.76-0.99, p = 0.04) and mortality (HR = 0.76, 95% CI: 0.63-0.93, p = 0.008), particularly for pancreatic cancer incidence (HR = 0.58, 95% CI: 0.40-0.85, p = 0.005) and mortality (HR = 0.47, 95% CI: 0.30-0.73, p = 0.001). Daytime light exposure ≥ 2.4 h (≥ 5000 lux between 7:30 and 20:30, which is often used as a chronotherapeutic threshold) was associated with a lower risk of pancreatic cancer incidence and mortality. Predictive ability of daytime light metrics exceeded that of sleep quality, diet, depression, and alcohol consumption. Higher daytime light exposure was associated with lower risks of gastrointestinal cancer incidence and mortality, especially for pancreatic cancer, indicating a potential protective effect that warrants further investigation in prevention and prognostic contexts.
Combination of Lenvatinib and Antibiotics: A Potential Approach to Enhance Sensitivity in Differentiated Thyroid Cancer.
Ablinger C, Huber-Cantonati P, Weber DD … +11 more , Pichler S, Schischkow G, Garcia-Miralles M, Pirich C, Rendl G, Kiener T, Felder T, Geroldinger M, Terkola R, Kofler B, Pachmayr J
Int J Cancer · 2026 May · PMID 42068240 · Publisher ↗
Approved in 2015 for radioiodine-refractory differentiated thyroid carcinoma (RR-DTC), the multikinase inhibitor lenvatinib has demonstrated substantial efficacy; nevertheless, severe adverse effects, intrinsic resistanc...
Approved in 2015 for radioiodine-refractory differentiated thyroid carcinoma (RR-DTC), the multikinase inhibitor lenvatinib has demonstrated substantial efficacy; nevertheless, severe adverse effects, intrinsic resistance or development of acquired resistance often limit its use. A novel approach to sensitize tumor cells to therapy is the administration of antibiotics that target mitochondrial metabolism. We analyzed the effects of a combination of lenvatinib with the tetracycline-class antibiotics tigecycline and eravacycline in DTC cells with reduced response to lenvatinib and explored the underlying mechanism of action. Cell viability was quantified after treatment with either single agents or combination therapies consisting of lenvatinib with tigecycline or eravacycline. Baseline oxidative metabolism and drug-induced changes in oxygen consumption rate were measured. Three-dimensional spheroid cultures were used to better mimic the in vivo tumor milieu. Apoptosis was assessed by caspase-3/7 activity, and expression of apoptosis-related proteins was elucidated by immunoblotting. We found that combining lenvatinib with tigecycline or eravacycline resulted in stronger reductions in 2D and 3D cell viability compared to single-agent treatments in K1 DTC cells, which show limited lenvatinib responsiveness. Both combination therapies markedly impaired mitochondrial respiration, accompanied by down-regulation of anti-apoptotic Bcl-2 family members, activation of caspase-3/7, and cleavage of Poly (ADP-ribose) polymerase (PARP), which are hallmarks of apoptosis. Although limited to in vitro models and subject to pharmacological limitations, our findings provide a mechanistic proof-of-concept that mitochondria-targeting antibiotics may enhance lenvatinib responsiveness in a DTC cell line.
Derivation and Validation of a Predictive Model for Advanced Colorectal Neoplasia Among Average-Risk Adults in China.
Liu Y, Liu Y, Feng Y … +4 more , Liu B, Yan W, Zhang N, Lu Y
Int J Cancer · 2026 May · PMID 42063357 · Publisher ↗
As the burden of colorectal cancer (CRC) continues to rise and current screening methods have limitations in efficiency and accuracy, there is an urgent need particularly in China and other large populations to develop a...
As the burden of colorectal cancer (CRC) continues to rise and current screening methods have limitations in efficiency and accuracy, there is an urgent need particularly in China and other large populations to develop and validate precision risk prediction models based on individual risk factors with improved discrimination and generalizability to optimize the allocation of screening resources. Asymptomatic individuals aged 40-74 years were recruited from multiple hospitals in China, between January 2024 and May 2025. All participants completed a standardized questionnaire, physical measurements, and colonoscopy. A multivariable logistic regression model was derived to predict the risk of advanced colorectal neoplasia (AN), and a scoring system was derived from regression coefficients. Model performance was evaluated using discrimination, calibration, and risk stratification ability. Among 9617 participants, 673 AN cases were identified. The final model included six variables: age, gender, smoking, drinking, chronic appendicitis, and hypertension. The model demonstrated acceptable discriminatory ability (c-statistics: 0.656 internal validation) and good calibration. A scoring system (range: 0-37) classified individuals into low-, intermediate-, and high-risk groups. AN prevalence for each group was 3.46%, 6.25%, and 11.48%, respectively. The number needed to screen (NNS) improved significantly from 28.9 in the low-risk group to 8.7 in the high-risk group. The prediction model and scoring system developed enable effective risk stratification and are suitable for individualized assessment prior to colonoscopy in resource-limited settings, thereby improving screening efficiency.
Adverse Health Events in Chronic Myeloid Leukaemia Patients Treated With Tyrosine Kinase Inhibitors 2009-2019: A Real-World Study From the UK's Haematological Malignancy Research Network.
Kane E, Smith A, Howell D … +5 more , Cargo C, Rothwell K, Green S, Patmore R, Roman E
Int J Cancer · 2026 Apr · PMID 42057558 · Publisher ↗
Outcomes among patients with chronic myeloid leukaemia (CML) improved markedly when tyrosine kinase inhibitors (TKIs) were introduced into routine clinical practice around the turn of the century. Nonetheless, adverse ev...
Outcomes among patients with chronic myeloid leukaemia (CML) improved markedly when tyrosine kinase inhibitors (TKIs) were introduced into routine clinical practice around the turn of the century. Nonetheless, adverse events still occur, survival remains suboptimal and the long-term health impact of the disease and its treatment is poorly understood. Using data from an established UK population-based cohort of haematological malignancies, we compared the morbidity of 411 CML patients treated with TKIs 2009-2019 to that of individually age- and sex-matched general population-based controls (n = 4099). Over the course of follow-up (to March 2021, median 5.3, interquartile range 3.0-8.2 years), patients were more likely than controls to die from cardiovascular or respiratory diseases; Hazard Ratios of 1.9, 95% Confidence Interval, 95% CI = 1.2-2.8 and 2.4, 95% CI 1.2-4.9 respectively. Hospital admissions for cardiovascular or respiratory conditions were similarly elevated; HR = 1.6, 95% CI 1.3-1.9; HR = 2.3, 95% CI 1.6-3.4 respectively. The risk of a cardiovascular admission varied over time; being increased in the first year (HR = 2.4, 95% CI 1.5-3.8), and then again 5 years or more after starting TKI therapy (HR = 2.3, 95% CI 1.5-3.6); no increase was evident in the intervening years (HR = 1.1, 95% CI 0.8-1.7). While not related to excess mortality, admissions for infections and gastrointestinal conditions occurred more frequently among cases than controls; the increased risk remaining largely constant over the course of follow-up. In the era of TKIs, these real-world analyses revealed that CML patients are at increased risk of severe cardiovascular events several years after starting treatment, and that admission for infections and gastrointestinal conditions are raised throughout.
Chemotherapy-Induced Nausea and Vomiting in Early Breast Cancer Patients Receiving Adjuvant Chemotherapy With Fluorouracil, Epirubicin, Cyclophosphamide Followed by Docetaxel Versus an Anthracycline-Free Regimen With Docetaxel, Cyclophosphamide-Results From a Randomized Clinical Trial.
Hörner M, Schäffler H, Häberle L … +14 more , Goossens C, Pfister K, Leinert E, Veselinovic K, Brucker SY, Köhler U, Heinrich G, Schneeweiss A, Beckmann MW, Fasching PA, Janni W, Rack B, Heublein S, Ziegler P
Int J Cancer · 2026 Apr · PMID 42056728 · Publisher ↗
Chemotherapy-induced nausea and vomiting (CINV) remains an important side effect despite new antiemetic drugs. This study tried to understand the occurrence of CINV in patients receiving two different chemotherapy regime...
Chemotherapy-induced nausea and vomiting (CINV) remains an important side effect despite new antiemetic drugs. This study tried to understand the occurrence of CINV in patients receiving two different chemotherapy regimens. As part of the randomized controlled clinical trial SUCCESS C (NCT00847444), 1582 of the 3463 patients completed CINV diaries. Patients were randomized to receive either chemotherapy with FEC (5-fluorouracil, epirubicin, cyclophosphamide followed by docetaxel) or TC (docetaxel, cyclophosphamide). CINV was evaluated hourly using a specially designed questionnaire. Endpoints of the study were complete response (no emesis) and total control (no nausea and no emesis) and were assessed with Kaplan-Meier curves and Cox regression analyses over three chemotherapy cycles. Eight hundred fourteen patients received FEC and 768 received TC; patients and tumor characteristics were similar in both groups. Patients receiving FEC had significantly more nausea and vomiting, with the main difference in the first 12 h. In the first cycle, the 0-12-h nausea/emesis-free rates were 70%/41% for FEC and 91/76% for TC. By 24 h after chemotherapy, the rates were 65%/33% (FEC) and 85%/60% (TC). The differences were similar in cycles 2 and 3. The detailed analysis of CINV in the study is unique and paves the way for modern CINV analysis of new therapeutics such as antibody-drug conjugates.
Targeting HIF as a Promising Approach to Synergize With Immune Checkpoint Inhibitors.
Li S, Liu Y, Liu X … +10 more , Wang X, Li W, Song M, Fu N, Guo Y, Li Z, Zhang Q, Liang J, Wang L, Zhang B
Int J Cancer · 2026 Apr · PMID 42056724 · Publisher ↗
In solid tumors, hypoxia-inducible factor (HIF) is upregulated in various cell types within the tumor microenvironment (TME) due to hypoxia. In tumor cells, HIF signaling acts as a primary driver: it triggers metabolic r...
In solid tumors, hypoxia-inducible factor (HIF) is upregulated in various cell types within the tumor microenvironment (TME) due to hypoxia. In tumor cells, HIF signaling acts as a primary driver: it triggers metabolic reprogramming toward the Warburg effect and upregulates various angiogenic factors to support adaptation to hypoxia. Meanwhile, it promotes malignant progression by regulating cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), and extracellular matrix (ECM) remodeling. In immune cells, HIF signaling precisely regulates the abundance and function of various immune cell subsets, thereby establishing an immunosuppressive microenvironment that enables tumor cells to evade immune surveillance. Ultimately, HIF signaling in different cell types acts in concert and constitutes a key factor that attenuates the therapeutic efficacy of immune checkpoint inhibitors (ICIs). Over the decades of the development of HIF inhibitors, the antitumor effects of a large number of these agents have been validated in preclinical studies, with some having entered clinical trials or obtained clinical approval. Although only a small subset of HIF inhibitors has been verified to exert synergistic effects when combined with ICIs in experimental settings, it is undeniable that HIF inhibitors have emerged as a crucial "reserve force" for overcoming ICI resistance. Their potential in reshaping the immune microenvironment and enhancing the efficacy of ICIs provides a new direction for the immunotherapy of hypoxic solid tumors.
HPV-Related Cancers in Solid Organ Transplant Recipients: A Nationwide Danish Cohort Study.
Timm S, Skjøth F, Hansen TF … +5 more , Jensen LH, Holdgaard PC, Fokdal LU, Larsen TB, Soerensen MM
Int J Cancer · 2026 Apr · PMID 42051040 · Publisher ↗
Human papillomavirus (HPV) is a major cause of several epithelial cancers. Solid organ transplant recipients (SOTRs) are chronically immunosuppressed, but population-based estimates of HPV-related cancer risk across tran...
Human papillomavirus (HPV) is a major cause of several epithelial cancers. Solid organ transplant recipients (SOTRs) are chronically immunosuppressed, but population-based estimates of HPV-related cancer risk across transplanted organs and by sex remain limited. We conducted a nationwide, population-based cohort study including all SOTRs in Denmark from January 1, 2000, to December 31, 2023. Information on transplantation and cancer diagnoses was obtained from the Danish National Patient Registry. Each SOTR was matched with five population controls by age, sex, and birth cohort. Incidence rates and hazard ratios (HRs) for HPV-related cancers were estimated using Cox proportional hazards models, and cumulative incidence was calculated using the Aalen-Johansen method. The cohort comprised 6509 SOTRs and 32,545 matched controls, followed for a median of 7.8 years (IQR 3.8-13.1). The 10-year incidence rate of HPV-related cancers was higher among SOTRs than controls (0.10 [95% CI 0.08-0.14] vs. 0.04 [95% CI 0.03-0.05] per 100 person-years). The overall HR for any HPV-related cancer was 2.49 (95% CI 1.74-3.56) and was highest for anogenital cancers (HR 3.29; 95% CI 1.88-5.76). Relative risks were higher among women than men (HR 3.11 [95% CI 1.77-5.46] vs. 2.15 [95% CI 1.35-3.43]), with cumulative incidence indicating earlier onset among women. Solid organ transplant recipients experience a sustained two-to-three-fold increased risk of HPV-related cancers, with pronounced sex-specific differences. These findings provide robust population-level evidence of elevated long-term cancer risk in immunosuppressed individuals.
Real-World Outcomes of Nivolumab and Ipilimumab in Metastatic Melanoma as Third Line and Beyond.
Garitaonaindia Y, Petersen SK, Guldbrandt LM … +9 more , Borch TH, Ruhlmann CH, Friis RB, Luczak AA, Bastholt L, Schmidt H, Svane IM, Ellebaek E, Donia M
Int J Cancer · 2026 Apr · PMID 42050807 · Publisher ↗
Nivolumab plus ipilimumab has demonstrated activity after anti-PD-1 failure in advanced melanoma, but its effectiveness in later lines and as rechallenge remains unclear. We aimed to characterize outcomes of nivolumab/ip...
Nivolumab plus ipilimumab has demonstrated activity after anti-PD-1 failure in advanced melanoma, but its effectiveness in later lines and as rechallenge remains unclear. We aimed to characterize outcomes of nivolumab/ipilimumab administered in the third line or beyond. Using the Danish Metastatic Melanoma Database (DAMMED), we identified patients with metastatic melanoma (excluding uveal melanoma) treated with nivolumab/ipilimumab after at least two prior lines of therapy, including adjuvant treatment, between 2017 and 2024. Baseline characteristics, prior treatments, and clinical outcomes were collected. Seventy-three patients were included (median age 57.8 years), of whom 47.9% had brain metastases. Most had progressed on anti-PD-1-based therapy (93.2%); 32.9% had prior exposure to anti-CTLA-4, and 84.9% had received BRAF/MEK inhibitors. Nivolumab/ipilimumab was administered as third-line therapy in 71.2%. After a median follow-up of 27.6 months, the overall response rate was 23.3% (12.5% with prior anti-CTLA-4 exposure vs. 28.6% without). Median duration of response was 19.4 months (95% CI, 14.5-NR). Median PFS was 2.7 months (95% CI, 2.4-5.7) and median OS was 9.6 months (95% CI, 6.5-20.1). In conclusion, in heavily pretreated melanoma, nivolumab/ipilimumab induces durable responses in a minority of patients, with reduced efficacy after prior anti-CTLA-4 exposure.
Mental Health Conditions and Incident Cancer: A Prospective Cohort Study of 402,255 UK Biobank Participants.
Amin MS, Parra-Soto S, Zhou Z … +6 more , Nakada S, Rochmawati ID, Celis-Morales C, Meligy N, Pell JP, Ho FK
Int J Cancer · 2026 Apr · PMID 42050794 · Publisher ↗
Mental health conditions (MHCs) affect both psychological health and biological systems and have also been linked to cancer risk. However, evidence from epidemiological studies regarding this link remains inconsistent. W...
Mental health conditions (MHCs) affect both psychological health and biological systems and have also been linked to cancer risk. However, evidence from epidemiological studies regarding this link remains inconsistent. We conducted a population-based prospective cohort study involving 402,255 UK Biobank participants to investigate the associations of five MHCs (depressive disorders [DD], anxiety disorders [AD], bipolar disorder [BD], schizophrenia [SZ] and post-traumatic stress disorder [PTSD]) with overall and site-specific cancer risk. Cox proportional hazard models were used, adjusting for sociodemographic, health-related and lifestyle confounders. Over a median follow-up of 13.4 years, 68,065 (17%) incident cancer cases were recorded. DD (HR 1.18; 95% CI 1.13-1.23), AD (HR: 1.17, 95% CI: 1.11-1.24) and BD (HR: 1.29, 95% CI: 1.11-1.51) were associated with increased overall cancer risk. No significant association was found for SZ and PTSD. The associations of DD (HR: 1.27, 95% CI: 1.18-1.35) and BD (HR: 1.54, 95% CI: 1.26-1.88) were only significant in men. AD and DD were positively associated with lung, blood and liver cancers, while AD was also associated with prostate cancer. A dose-response relationship was observed between depressive symptom severity and cancer risk. While we cannot assume causality, our finding suggests that diagnoses of MHCs could be useful for cancer risk stratification and prevention.
Indirect Comparison of Neoadjuvant Treatment Strategies for Muscle-Invasive Bladder Cancer: ddMVAC and Perioperative Durvalumab-Gemcitabine-Cisplatin Versus Gemcitabine-Cisplatin: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials.
Mangold MH, Baumann G, Wieland VLS … +10 more , Carl N, Renner LV, Studier-Fischer A, Menold H, Zschäbitz S, Wessels F, Westhoff N, Michel MS, Kowalewski KF, Haney-Aubert CM
Int J Cancer · 2026 Apr · PMID 42050770 · Publisher ↗
For cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC), neoadjuvant cisplatin-based chemotherapy (NAC) is standard of care. More intensive regimens such as dose-dens...
For cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC), neoadjuvant cisplatin-based chemotherapy (NAC) is standard of care. More intensive regimens such as dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (ddMVAC) and chemoimmunotherapy with durvalumab plus gemcitabine-cisplatin (D-GC) have shown superior outcomes. This network meta-analysis (NMA) compares the efficacy of ddMVAC, D-GC and GC and explores the efficacy thresholds for emerging therapy options, such as enfortumab vedotin plus pembrolizumab (EV-P), to surpass current standards. Following PROSPERO registration (CRD420251077606), systematic searches of PubMed, CENTRAL and Web of Science were conducted to March 2025. Randomised controlled trials (RCTs) comparing neoadjuvant regimens in cisplatin-eligible MIBC were included. A random-effects NMA was performed. Simulations explored hypothetical hazard ratios (HRs) for EV-P. Three RCTs were included. ddMVAC (HR 0.75, 95% CI 0.58-0.98; p = 0.034) and D-GC (HR 0.75, 95% CI 0.66-0.85; p < 0.001) improved overall survival (OS) versus GC, without differences between ddMVAC and D-GC (HR 0.99, 95% CI 0.75-1.33; p = 0.97). Both regimens improved progression-free survival. D-GC achieved higher pathological complete response (pCR) versus GC (OR 1.57, 95% CI 1.21-2.03; p < 0.001), whereas ddMVAC did not. No significant difference in pCR was found between ddMVAC and D-GC. Simulation-NMA suggested EV-P would need to achieve HR ≤ 0.45 versus GC to outperform ddMVAC and D-GC. Limitations include few trials and indirect comparisons. DdMVAC and D-GC improve survival compared with GC in neoadjuvant MIBC. Alternative therapeutic strategies must demonstrate substantial survival benefits to warrant replacing established neoadjuvant regimens.
Health Care Policy Implementation Trial of Primary Human Papillomavirus-Based Cervical Screening in Denmark.
Bonde J, Schroll JB, Pedersen BT … +10 more , Lynge E, Waldstrøm M, Viborg PH, Frandsen A, Andersen RH, Nielsen S, Schledermann D, Kristensen BK, Andersen B, National Danish Cervical Cancer Screening Steering Committee
Int J Cancer · 2026 Apr · PMID 42046158 · Publisher ↗
On mandate from the Danish Health Authority, a nationwide health care policy trial (HCP) of primary HPV screening for women aged 30-59 was initiated in 2021. The aim was to inform on the performance of HPV screening in c...
On mandate from the Danish Health Authority, a nationwide health care policy trial (HCP) of primary HPV screening for women aged 30-59 was initiated in 2021. The aim was to inform on the performance of HPV screening in comparison to existing cytology practice. The HCP trial included all Danish women between 30 and 59 years of age undergoing cervical cancer screening in 2021 (n = 178,323). Women with odd birthdays were screened with HPV screening (n = 91,517), while women born on even dates were screened with cytology (n = 86,806). The follow-up period was individually censored at 18 months from the screening date. Outcomes and intention-to-treat analysis are reported. Overall, 9.1% and 3.0% were HPV or cytology positive on the index sample. Referral to colposcopy upon index sample was 1.9% with HPV and 2.1% with cytology screening. Referral to retest after a positive HPV index sample result was 7.7 higher for HPV than cytology. Combining index and retest rounds, 6.3% women had colposcopy in the HPV arm (RR 1.28) versus 4,9% in the cytology arm. HPV screening detected both more disease ≥ CIN2 (RR 1.51) and ≥ CIN3 (RR1.35). The national-scale health care policy implementation trial showed that HPV-based cervical cancer screening increased detection of histologically defined disease compared to the previous policy of cytology-based screening for women 30-59 years of age. The HCP demonstrated the real-life effect of HPV-based screening over cytology-based screening in detection of disease, but also details what to be expected in terms of health care resource requirements.
Prognostic Value of Perioperative Anemia in Neurosurgical-Oncological Treatment of Spinal Metastases.
Janjic M, Khalafov L, Dittmer J … +11 more , Abedellatif SE, Lampmann T, Asoglu H, Jaber M, Alenezi H, Heimann M, Schneider M, Hamed M, Thudium M, Vatter H, Banat M
Int J Cancer · 2026 Apr · PMID 42043869 · Publisher ↗
Neurosurgical resection of spinal metastases is an established treatment option for selected patients with advanced malignancies. However, high perioperative morbidity and mortality may further compromise outcomes in thi...
Neurosurgical resection of spinal metastases is an established treatment option for selected patients with advanced malignancies. However, high perioperative morbidity and mortality may further compromise outcomes in this vulnerable population, emphasizing the need to identify modifiable prognostic factors. Perioperative anemia is common and clinically relevant, yet its impact in this setting remains insufficiently studied. This retrospective, single-center study included 279 patients who underwent surgical treatment for spinal metastases between 2013 and 2025. Patients were stratified into three groups based on perioperative hemoglobin levels. Multivariable logistic regression, Cox proportional hazards models, and Kaplan-Meier analyses were used to assess associations between perioperative hemoglobin levels and postoperative complications, local recurrence, recurrence-free survival, and mortality at 1 month and 1 year after surgery. Preoperative anemia was independently associated with an increased risk of hospital-acquired complications (odds ratio [OR] 2.31, 95% confidence interval [CI] 1.35-3.97, p = 0.002), while higher hemoglobin levels showed a protective effect. No significant association was found between perioperative hemoglobin levels and surgical complications (OR 0.73, 95% CI 0.36-1.51, p = 0.400). Postoperative hemoglobin levels and perioperative hemoglobin changes were not significantly associated with complications (OR 1.008, 95% CI 0.990-1.026, p = 0.389) or mortality. One-month and one-year mortality rates were lowest in patients without anemia and highest in those with severe anemia. Our data demonstrate that early identification and optimization of preoperative anemia may reduce postoperative complications and potentially improve survival outcomes in patients undergoing surgery for spinal metastases.
Blood-Based Circulating Tumor DNA Assays for Early Colorectal Cancer Detection: A Systematic Review of Performance in Asymptomatic Screening Populations.
Kahn CL, Rasmussen MW, Kleif J … +2 more , Pedersen IS, Therkildsen C
Int J Cancer · 2026 Aug · PMID 42043732 · Full text
Early detection of colorectal cancer (CRC) via population-based screening programs can reduce incidence and mortality. Current screening approaches are limited by cost, accessibility, compliance, and colonoscopy capacity...
Early detection of colorectal cancer (CRC) via population-based screening programs can reduce incidence and mortality. Current screening approaches are limited by cost, accessibility, compliance, and colonoscopy capacity. Blood-based screening of circulating tumor (ct) DNA may resolve some of these limitations. This systematic review evaluated the screening potential of blood-based ctDNA assays in asymptomatic screening populations. We systematically searched the PubMed database (final search June 20th, 2025) for studies detecting advanced adenomas (AAs) or CRC in asymptomatic cohorts, where a blood-based ctDNA assay had been evaluated with data on specificity, sensitivity, and/or AUC at early stages of disease. Newcastle-Ottowa scale was used for quality assessment. Only 20 studies of 454 unique hits met our inclusion criteria. Of these, 12 studies used assays targeting specific DNA alterations, while the remaining 8 studies used complex assays. Generally, comprehensive assays such as Shield, ColonSecure, and FMBT-CRC had the best performance for early-stage CRC detection with sensitivities of 71%-85% and specificities of 88%-90%. Despite being tested in a small cohort, the Coloscape assay was the only assay to reach sufficient AA detection with 59% sensitivity and 92% specificity. None of the reviewed ctDNA assays demonstrated sufficient sensitivities for both AA and early-stage CRC detection to be considered future screening tools. Screening tools based on ctDNA assays have not proved superior to fecal-based immunochemical test (FIT) yet. Future studies need to test ctDNA screening tools in large, prospective, asymptomatic cohorts emphasizing AA, and early-stage CRC.
Transcriptome-Based Classification of Resected Pancreatic Ductal Adenocarcinoma Enhances Prognostic Modelling Accuracy of Overall Survival Following Adjuvant Treatment.
Lansbergen MF, Lanting VR, Manoukian P … +18 more , Besselink MG, Kazemier G, de Hingh IHJT, Liem MSL, van Eijck CHJ, van der Harst E, de Meijer VE, van Dam RM, Stommel MWJ, Koster J, Tanck MWT, Fariña Sarasqueta A, Verheij J, Dijk F, Wilmink JW, Bijlsma MF, van Laarhoven HWM, Dutch Pancreatic Cancer Group
Int J Cancer · 2026 Apr · PMID 42041032 · Publisher ↗
In pancreatic ductal adenocarcinoma, patient outcomes after resection remain highly variable. Prognostic models are often inaccurate. Our study aimed to improve survival prediction by adding transcriptome-based classific...
In pancreatic ductal adenocarcinoma, patient outcomes after resection remain highly variable. Prognostic models are often inaccurate. Our study aimed to improve survival prediction by adding transcriptome-based classification to a validated prognostic model and applying it on a multicenter real-world cohort of fresh-frozen resection materials. RNA was sequenced if tumor cellularity was > 30%. The samples were classified using transcriptome-based classification. Survival differences between transcriptome-based subtypes were studied in patients treated with and without adjuvant chemotherapy. 25.6% of the patients received neoadjuvant treatment (NAT). Samples of 461 patients were collected, of which 118 samples underwent RNA sequencing. Of those, 39.0% had a basal-like subtype and 61.0% had a classical subtype. The basal-like subtype became dominant after NAT (63.3%, p = 0.004). Patients with a classical tumor survived longer than those with a basal-like tumor (median overall survival [OS]: 22.8 vs. 11.4 months; p < 0.001, in patients receiving adjuvant gemcitabine, and 10.7 vs. 5.4 months; p = 0.082, in patients without adjuvant treatment). In multivariable Cox regression, the classical subtype significantly associated with increased survival (hazard ratio = 0.38; p = 0.002) and adding transcriptome-based subtyping significantly improved the prognostic model (p = 0.002). Subtype and adjuvant treatment independently significantly associated with OS. Transcriptome-based subtyping significantly adds to clinical variables in survival prediction after surgery. The independent associations for subtype and adjuvant treatment with OS indicate that subtypes are prognostic, but not predictive for OS with adjuvant treatment. The provided prognostic information could potentially support treatment decisions and serve as stratification factor.
The Cancer Immunotherapy Thromboembolism Assessment: A Novel Score for Predicting Thromboembolic Events in Melanoma Patients Treated With Immune Checkpoint Inhibition.
Zell T, Kött J, Zimmermann N … +10 more , Ancker G, Bauer AT, Smit DJ, Geidel G, Gerwers JC, Renné T, Wohlfeil SA, Utikal J, Schneider SW, Gebhardt C
Int J Cancer · 2026 Apr · PMID 42041031 · Publisher ↗
Venous and arterial thromboembolic events (TEEs) represent a substantial threat for melanoma patients treated with immune checkpoint inhibition (ICI) and have a significant impact on quality of life, therapy outcome, and...
Venous and arterial thromboembolic events (TEEs) represent a substantial threat for melanoma patients treated with immune checkpoint inhibition (ICI) and have a significant impact on quality of life, therapy outcome, and survival. Existing risk assessment models for predicting TEE risk have been developed for other patient collectives and show poor performance in melanoma patients treated with ICI. In this cohort analysis, 358 AJCC stage III/IV melanoma patients treated with ICI between April 2013 and July 2024 at the University Skin Cancer Center Hamburg and the University Medical Center Mannheim were included. TEEs were recorded and classified as thrombosis including vein thrombosis, pulmonary embolism, stroke, or transient ischemic attack. Clinical and laboratory data were determined before the start and prospectively during the treatment. We identified elevated serum baseline D-Dimer (p = 0.0098) and elevated C-reactive protein (p = 0.0042) concentrations and measurable tumor burden (p = 0.0039) as main risk factors for the occurrence of TEE. For the final model, points were assigned for the Cancer Immunotherapy Thromboembolism Assessment (CITA) according to the impact of those variables using multiple logistic regression. The score was calculated for each patient. For the high-risk group, the negative predictive value (NPV) was 97.2%; sensitivity and specificity were 83.3% and 62%, respectively. The CITA risk score provides a simple and easily calculated risk assessment tool for stratifying melanoma patients based on their risk for TEE after ICI initiation, but prospective validation is needed before clinical use can be recommended.
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