Cancer[JOURNAL]

BACKGROUND: The optimal timing of resection for colorectal liver metastases (CRLM) after systemic therapy remains unclear. This study evaluated the impact of time-to-surgery (TTS) on postoperative morbidity and oncologic... BACKGROUND: The optimal timing of resection for colorectal liver metastases (CRLM) after systemic therapy remains unclear. This study evaluated the impact of time-to-surgery (TTS) on postoperative morbidity and oncologic outcomes. METHODS: In this retrospective cohort (2018-2022) from a German high-volume hepatobiliary center, 159 patients underwent hepatic resection for CRLM following systemic therapy. Patients were stratified by TTS ≤ 41 versus ≥ 42 days. The primary endpoint was clinically meaningful postoperative morbidity (Comprehensive Complication Index ≥ 30). Secondary endpoints included liver-specific recurrence-free survival (RFS) and overall survival (OS). Multivariable regression, Cox proportional-hazards models, and prespecified subgroup analyses were performed. RESULTS: CCI ≥ 30 occurred in 48.7% of patients with shorter TTS versus 31.3% with longer TTS (P = 0.023). After multivariable adjustment, TTS ≥ 42 days was independently associated with lower odds of postoperative morbidity (OR 0.355; 95% CI 0.127-0.992; P = 0.048). In the subgroup of major hepatectomies, TTS ≥ 42 days demonstrated an even more pronounced protective effect (OR 0.069; 95% CI 0.006-0.778; P = 0.031). However, TTS ≥ 42 days was not independently associated with liver-specific RFS or OS. CONCLUSION: Delaying surgery to ≥ 6 weeks after neoadjuvant systemic therapy was associated with significantly reduced postoperative morbidity without evidence of impaired early oncologic outcomes among patients who ultimately underwent resection. These findings support consideration of a prolonged interval before complex hepatectomy while highlighting the need for prospective validation.

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Perioperative NLR/PLR dynamic phenotypes and prediction of postoperative recurrence in locally advanced gastric cancer: a retrospective cohort study.

Wu Y, Zhou J, Li S … +2 more , Xuan Y, Cai D

BMC Cancer · 2026 Jun · PMID 42380878 · Full text

BACKGROUND: Systemic inflammation plays a critical role in tumor progression and postoperative recurrence in gastric cancer. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are readily acc... BACKGROUND: Systemic inflammation plays a critical role in tumor progression and postoperative recurrence in gastric cancer. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are readily accessible biomarkers of systemic inflammatory and immune responses, but their dynamic changes around surgery remain underexplored. This study aimed to assess the prognostic value of principal component-derived phenotypes based on perioperative NLR and PLR-specifically, principal component 1 (PC1; preoperative inflammatory burden) and principal component 2 (PC2; postoperative inflammatory recovery dynamics)-for predicting disease-free survival (DFS) in patients with locally advanced gastric cancer (LAGC). METHODS: We retrospectively analyzed data from 375 patients with LAGC who underwent radical gastrectomy at the Affiliated Hospital of Jiangnan University between January 2018 and December 2022, with follow-up through March 2025. NLR and PLR were measured one week before and one month after surgery. Principal component analysis (PCA) was applied to derive two independent inflammatory phenotypes (PC1 and PC2). These components, together with T stage, N stage, and preoperative carcinoembryonic antigen (CEA), were incorporated into a Cox proportional hazards regression model, and internal validation was performed using bootstrap resampling (1000 times). Model performance was evaluated using Kaplan-Meier survival analysis, log-rank testing, and time-dependent receiver operating characteristic (ROC) curve analysis. RESULTS: PCA identified two independent components: PC1 (preoperative inflammatory burden; variance explained 40.24%) and PC2 (postoperative inflammatory recovery; variance explained 36.16%). Multivariate Cox regression revealed that N stage, T stage, preoperative carcinoembryonic antigen (CEA), PC1, and PC2 were independent predictors of DFS (all p < 0.05). Stratified analysis demonstrated that patients with the "Dual-High" phenotype (high PC1 and high PC2) had a markedly shorter median DFS (13.1 months) compared with those with the "Dual-Low" phenotype (74.6 months; p < 0.001). Internal validation showed good discriminative ability of the model (bias-corrected concordance index [C-index] = 0.762), and time-dependent ROC curves indicated stable predictive performance at 12, 36, and 60 months postoperatively. CONCLUSIONS: PCA-derived perioperative inflammatory phenotypes effectively stratify recurrence risk in LAGC. The "Dual-High" phenotype indicates poor prognosis, and combining these phenotypes with T stage, N stage, and preoperative CEA enhances individualized postoperative surveillance and adjuvant therapy decision-making.

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NT5E promotes colorectal cancer progression and correlates with PD-L1 expression: evidence from multi-omics analysis, clinical samples, and cellular functional assays.

Wu W, Cheng C, Yang T … +2 more , Meng W, Wang Y

BMC Cancer · 2026 Jun · PMID 42380875 · Full text

BACKGROUND: Extracellular 5'-nucleotidase (NT5E/CD73) plays a pivotal role in the tumor immune microenvironment by catalysing the production of adenosine. This study aims to evaluate the expression and function of NT5E i... BACKGROUND: Extracellular 5'-nucleotidase (NT5E/CD73) plays a pivotal role in the tumor immune microenvironment by catalysing the production of adenosine. This study aims to evaluate the expression and function of NT5E in colorectal cancer progression, and to explore its potential as a novel biomarker and for associated immunotherapy. METHODS: Genomic alterations, prognostic significance, and immune landscape of NT5E were analyzed using cBioPortal, Kaplan‑Meier Plotter, the cancer genome atlas(TCGA)and the Human Protein Atlas. Following siRNA‑mediated knockdown in HCT116 cells, proliferation, migration, and invasion were assessed. NT5E and PD‑L1 expression were examined in 40 paired colorectal cancer specimens by qRT‑PCR. The regulatory relationship between PD‑L1 and NT5E was further validated in vitro. RESULTS: NT5E alterations were identified in 5.17% of CRC patients, primarily manifested as high mRNA expression and amplification. Elevated NT5E expression was significantly correlated with poorer overall survival and relapse‑free survival, particularly in patients with advanced stage, CMS1 (Consensus Molecular Subtypes 1), CMS4, and high microsatellite instability (MSI-H) subtypes. Gene set enrichment analysis revealed enrichment of purine metabolism, sphingolipid signaling, focal adhesion, and T cell receptor signaling pathways in NT5E‑high tumors. NT5E expression was positively correlated with helper T cells, macrophages, and mast cells, while negatively correlated with NK CD56dim cells. A significant positive correlation was observed between NT5E and PD‑L1, HAVCR2, and TIGIT. In clinical specimens, NT5E was upregulated in 65% of colorectal cancer tissues and positively associated with lymph node metastasis and PD‑L1 expression. In vitro experiments demonstrated that NT5E knockdown suppressed the proliferation, migration, and invasion of colorectal cancer cells, and confirmed that PD‑L1 regulates NT5E expression in colon cancer cells. CONCLUSION: NT5E accelerates disease progression by promoting malignant biological behaviors in colorectal cancer and synergistically shaping an immunosuppressive microenvironment with PD-L1. Its overexpression constitutes an independent adverse prognostic factor. This discovery offers novel insights for anti-PD-1/PD-L1 combination immunotherapy.

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Optimized chemotherapy sequence for metastatic pancreatic ductal adenocarcinoma patients: FOLFIRINOX followed by Gemcitabine plus nab-paclitaxel.

Del Campo-Pedrosa R, Martín-Carnicero A, González-Marcos A … +1 more , Martínez A

BMC Cancer · 2026 Jun · PMID 42380871 · Full text

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers, usually diagnosed at late stages, at which point the best option is palliative chemotherapy. Several treatment sequences are currently... BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers, usually diagnosed at late stages, at which point the best option is palliative chemotherapy. Several treatment sequences are currently used in the clinic, but the optimal sequence is unknown. METHODS: Retrospectively, 168 PDAC patients treated at a Spanish hospital (single-center study) with either FOLFIRINOX, Gemcitabine (GEM) or Gemcitabine plus nab-paclitaxel (GEM-NABP) as first-line of chemotherapy were studied. Of them, 80 patients received second-line treatment with either GEM- or 5FU-based drugs. Survival analysis was calculated by Kaplan-Meier curves, log-rank test and hazards ratios by univariate and multivariate Cox regression. RESULTS: GEM-NABP and FOLFIRINOX presented similar survival outcomes for first-line treatment, and both were better than GEM alone, although FOLFIRINOX presented higher toxicity than GEM-NABP. However, the best second-line option was application of GEM-based drugs after FOLFIRINOX first-line, which offered a better survival and lower toxicity than 5FU-based treatments after GEM-NABP. Specifically, within the most frequent second-line therapies in our cohort, GEM-NABP outperformed FOLFOX6. Thus, individuals that received FOLFIRINOX followed by GEM-NABP treatment presented better outcomes. CONCLUSIONS: In patients deemed eligible for multiple lines of chemotherapy, initiating treatment with FOLFIRINOX followed by a GEM-NABP regimen may represent a beneficial therapeutic sequence for metastatic PDAC, as opposed to the alternative approach of starting with GEM-NABP followed by a 5FU-based regimen.

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Exercise and nutritional prehabilitation in gastrointestinal cancer patients: prospective controlled trial assessing feasibility, safety and effects on quality of life.

Assenbaum L, Pahl A, Baumann FT … +5 more , Weiß C, Bertz H, Seifert G, Neeff H, Greil C

BMC Cancer · 2026 Jun · PMID 42380848 · Full text

BACKGROUND: Perioperative morbidity in gastrointestinal (GI) cancers is closely associated with reduced physical fitness and impaired nutritional status. While prehabilitation has been shown to improve outcomes in patien... BACKGROUND: Perioperative morbidity in gastrointestinal (GI) cancers is closely associated with reduced physical fitness and impaired nutritional status. While prehabilitation has been shown to improve outcomes in patients with colorectal cancer (CRC), it is not yet standard of care and remains underexplored in other GI malignancies. This study evaluates the feasibility, safety, and preliminary effectiveness of a supervised moderate-to-high intensity exercise program combined with nutritional counseling in a cohort of GI cancer patients scheduled for surgery. METHODS: In a prospective, two-arm, controlled trial, patients scheduled for GI cancer surgery were assigned to a prehabilitation program (2-3 sessions/week ≥ 3 weeks, endurance and resistance training with nutritional counseling) or usual care. Primary endpoints were feasibility (eligibility, recruitment, acceptance, retention, adherence) and safety (adverse events). Secondary endpoint was quality of life (QoL; EORTC QLQ-C30 global score, SF-36 physical and mental health component scores, PCS, MCS), assessed at baseline (t0), presurgery (t1), hospital discharge (t2), and 12-week follow-up (t3). RESULTS: Among the 400 patients assessed for eligibility, 36% met the eligibility criteria. Of those approached, 41% consented to participate, resulting in an overall recruitment rate of 27% (n = 38). Of the recruited patients, 84% completed the study (n = 32; prehabilitation = 17; usual care = 15; mean age 63.5 years, range 38-85; ICD-10 C15-C26). Participants attended 95% of the planned sessions (8.1 ± 3.6) within a mean of 30 days (SD ± 16) and completed 59% at the target intensity. Nutritional counseling was provided to 94% of the patients. No intervention-related serious adverse events occurred. A modest improvement in PCS was observed in the prehabilitation group at t1 (+ 4.25 points), although this finding reached statistical significance only in the one-tailed analysis. No between-group differences were observed for global QoL or MCS. CONCLUSION: Multimodal prehabilitation combining supervised moderate-to-high intensity exercise with nutritional counseling is feasible and safe in a real-world GI cancer population. Recruitment and achievement of prescribed training intensity remain key challenges. Preliminary findings indicate short-term benefits for physical health, supporting further investigations in larger randomized trials. TRIAL REGISTRATION: DRKS00028728; prospectively registered 05/05/2022.

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Immune-related adverse events with cancer clinical benefits: a systematic review and meta-analysis.

Li Z, Sun Q, Yang X … +8 more , Ni J, Zhang Y, Wang J, Ding K, Wang G, Yang H, Yu Q, Li Y

BMC Cancer · 2026 Jun · PMID 42380824 · Full text

BACKGROUND: Growing research have reported an association of the occurrence of immune-related adverse events (irAEs) and clinical benefits in patients with immune checkpoint inhibitors (ICIs) treatments, but the findings... BACKGROUND: Growing research have reported an association of the occurrence of immune-related adverse events (irAEs) and clinical benefits in patients with immune checkpoint inhibitors (ICIs) treatments, but the findings remain controversial. The aim of this study is to identify whether the incidence of irAEs and their subtypes undergoing ICIs treatment is associated with enhanced efficacy and survival benefits in all solid tumors. METHODS: Cochrane Library, Embase, PubMed and Web of Science databases were searched from database inception and December 31, 2023. Two reviewers independently extracted data and reviewed the quality items using the Newcastle-Ottawa Scale criteria, and resolved any discrepancies by consensus discussion with third reviewer. We performed the systematic review and meta-analysis in compliance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis and Meta-analysis of Observational Studies in Epidemiology. The main outcomes were irAEs incidence, objective response rate (ORR), overall survival (OS) and progression-free survival (PFS). Subgroup and sensitivity analyses were performed. RESULTS: A total of 184 articles involving a total of 63,780 patients met the inclusion criteria. The pooled incidence of irAEs in this meta-analysis was 37.3% (95%CI: 34.4%-40.3%). The occurrence of irAEs was associated with increased ORR (RR, 2.32 [95%CI, 2.02-2.67]; I = 80.1%; P < 0.001), and pooled ORRs in irAE+ versus irAE- patients were 39.4% (95%CI: 35.4%-43.5%) versus 16.2% (95%CI: 13.5%-19.4%). Besides, irAEs development presented better weighted average OS (20.03 months versus 10.83 months), and associated with longer OS (HR, 0.55 [95%CI, 0.51-0.59]; I = 70.4%; P < 0.001). Similar finding in PFS, weighted average PFS in irAEs patients was 9.73 months versus 4.15 months in without irAEs patients, and irAEs occurrence improved PFS (HR, 0.58 [95%CI, 0.53-0.63]; I = 50.8%; P < 0.001) compared with those who did not. CONCLUSIONS: The intimate association was observed between the development of irAEs and increased response rate and improved survival benefits in patients who treated with ICIs, and may have useful prognostic value in ICIs therapy.

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Comprehensive CYP2D6 genotyping improves phenotype classification and highlights methodological pitfalls in tamoxifen-treated breast cancer.

Alkebbeh L, Berndt A, Oberkanins C … +3 more , Kenj M, Kriegshäuser G, Youssef LA

BMC Cancer · 2026 Jul · PMID 42380819 · Full text

BACKGROUND: The clinical utility of CYP2D6 genotyping in predicting tamoxifen outcomes remains controversial, partly due to incomplete allele coverage and limited assessment of copy number variation (CNV). We aimed to ex... BACKGROUND: The clinical utility of CYP2D6 genotyping in predicting tamoxifen outcomes remains controversial, partly due to incomplete allele coverage and limited assessment of copy number variation (CNV). We aimed to expand CYP2D6 genetic profiling in Syrian breast cancer patients and to reassess phenotype classification and its clinical relevance. METHODS: In this retrospective cohort of estrogen receptor-positive breast cancer patients treated with adjuvant tamoxifen, CYP2D6 genotyping was performed using a test strip-based assay complemented by semi-quantitative PCR for CNV detection. Selected results were validated by next-generation sequencing (NGS). Diplotypes were translated into activity scores to assign metabolizer phenotypes. Disease-free survival (DFS) was evaluated using time-to-event analyses. RESULTS: Expanded CYP2D6 profiling, incorporating broader allele coverage and CNV analysis, led to metabolizer phenotype reclassification in 19% of patients. NGS identified primer-binding region variants responsible for allele drop-out in conventional assays. No significant association between CYP2D6 phenotype and DFS was observed in the overall cohort. However, exploratory stage-specific analyses suggested shorter DFS among patients with reduced CYP2D6 activity in Stage II disease (HR = 3.59; 95% CI 2.34-67.48), although estimates were imprecise due to small subgroup size. CONCLUSIONS: Comprehensive CYP2D6 profiling improves phenotype assignment and highlights methodological pitfalls that may contribute to inconsistencies in pharmacogenetic studies. While no definitive association with clinical outcomes was observed in the overall cohort, these findings underscore the importance of analytically robust genotyping strategies and warrant validation in larger, prospectively designed cohorts, and highlight the importance of comprehensive genotyping strategies in resolving inconsistencies across pharmacogenetic studies.

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Comparative efficacy of postoperative adjuvant chemoradiotherapy versus no chemoradiotherapy in the treatment of pancreatic adenocarcinoma.

Ren B, Guo Q, Ma J … +7 more , Zhu W, Wang Y, Feng Z, Shen Y, Zhu Y, Xie L, Peng Q

BMC Cancer · 2026 Jun · PMID 42380817 · Full text

BACKGROUND: The benefit of adjuvant chemoradiotherapy (CRT) for pancreatic adenocarcinoma (PAAD) is debated. This study aimed to elucidate the impact of adjuvant CRT on survival outcomes. METHODS: We searched major medic... BACKGROUND: The benefit of adjuvant chemoradiotherapy (CRT) for pancreatic adenocarcinoma (PAAD) is debated. This study aimed to elucidate the impact of adjuvant CRT on survival outcomes. METHODS: We searched major medical databases for clinical and retrospective studies comparing postoperative CRT vs. no CRT in PAAD. Data were synthesized using RevMan 5.4 and Stata 17.0 software. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for overall survival (OS), local recurrence, and distant metastasis. RESULTS: Our analysis included 19 studies involving 4,581 patients. Adjuvant CRT was associated with a significant improvement in 2-year OS compared to no CRT (OR = 0.63, 95% CI: 0.53-0.76, P < 0.001). This benefit was consistent in subgroup analyses compared to chemotherapy alone (OR = 0.54, P = 0.0003) and the observation group (OR = 0.61, P < 0.001). The 5-year OS analysis showed a non-significant trend favoring CRT (OR = 0.66, 95% CI: 0.43-1.02, P = 0.06). In subgroup analyses, CRT was associated with a significant survival benefit compared with observation alone (OR = 0.67, 95% CI: 0.47-0.97, P = 0.03), but not compared with chemotherapy alone (OR = 0.57, 95% CI: 0.06-5.46, P = 0.62). Notably, patients with high-risk features, including lymph node-positive (2-year OS: OR = 0.47, P < 0.001; 5-year OS: OR = 0.53, P < 0.001) and margin-positive disease (2-year OS: OR = 0.45, P < 0.001), derived substantial survival benefits from CRT. Furthermore, CRT was significantly associated with reduced local recurrence rates (OR = 0.27, P = 0.008) but did not affect the incidence of distant metastasis (OR = 1.11, P = 0.72). CONCLUSIONS: This study shows that adjuvant CRT significantly improves 2-year OS and local tumor control in resected PAAD, especially for patients with lymph node metastasis. However, its effect on long-term (5-year) survival is limited, and it was not associated with distant metastasis. These findings support the selective use of adjuvant CRT for local control in high-risk patient subgroups, such as those with positive lymph nodes or positive surgical margins. Further research is needed to prospectively validate these findings and identify patients most likely to benefit.

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Artificial intelligence for cervical cancer screening and diagnosis using Pap smear images: a systematic review.

Esmailzadeh A, Rashki Kemmak A, Rasoulian A … +2 more , Alizadeh Tabatabaei FS, Mazaheri Habibi MR

BMC Cancer · 2026 Jun · PMID 42380812 · Full text

BACKGROUND: Cervical cancer continues to be the second most prevalent type of cancer in women globally, especially in the less developed areas. Among several screening methods Pap test, more popularly known as the Papani... BACKGROUND: Cervical cancer continues to be the second most prevalent type of cancer in women globally, especially in the less developed areas. Among several screening methods Pap test, more popularly known as the Papanicolaou test or Pap smear, is one of the most efficient ones for the early detection of this type of cancer. AI has recently made possible the large-scale screening of the whole process. This whole thing has been done in order to increase the early detection rates, which is the long-term aim of reducing the number of cases and deaths that are due to cervical cancer. OBJECTIVE: This systematic review aimed to investigate the role of artificial intelligence in the diagnosis of cervical cancer based on Pap smear results. METHODS: A comprehensive search was conducted in PubMed, Web of Science, Scopus, Cochrane Library, and Google Scholar from database inception to January 2025, with the final search update performed on January 30, 2025. The search strategy was designed using relevant keywords and their synonyms related to "artificial intelligence," "diagnosis," and "cervical cancer."This review included only the English-language studies that had investigated the application of AI in the diagnosis of cervical cancer using Pap test data. The titles and abstracts were initially reviewed by two independent reviewers, and subsequently, full-text assessment was carried out. Data extraction followed the use of standardized forms that collected information on study title, country, number of participants, study purposes, AI technique, error rate, accuracy, and performance outcomes. RESULTS: The initial search identified 844 studies, of which 22 met the inclusion criteria and were included in the final analysis. Most studies reported that AI-based algorithms improved the accuracy and efficiency of cervical cancer detection using Pap smear images. Deep learning and machine learning approaches demonstrated high diagnostic performance, with several studies reporting accuracy rates above 90%. CONCLUSION: AI-based approaches show considerable potential for improving the accuracy and timeliness of cervical cancer diagnosis using Pap smear analysis. However, further high-quality studies are required to validate these tools and support their integration into clinical practice.

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Priority setting for the implementation of effective interventions for cancer prevention through collaboration among patients, the public and researchers in Japan.

Yamaguchi M, Nishihara M, Kaji Y … +8 more , Yamashita M, Odawara M, Saito J, Mimura A, Yamaki C, Inoue M, Nakayama T, Shimazu T

BMC Cancer · 2026 Jun · PMID 42380796 · Full text

BACKGROUND: Despite the availability of effective interventions for cancer prevention, Japan faces substantial evidence-practice gaps, such as in the low utilization of smoking cessation treatments, HPV vaccination, and... BACKGROUND: Despite the availability of effective interventions for cancer prevention, Japan faces substantial evidence-practice gaps, such as in the low utilization of smoking cessation treatments, HPV vaccination, and cancer screening. Implementation research plays a critical role in bridging this gap by promoting the uptake of effective interventions in real-world settings. Globally, however, prioritization of the implementation of these various interventions remains unclear. To address this need, we conducted a structured priority-setting exercise using the CHNRI method and incorporating perspectives from diverse stakeholders, including citizens. METHODS: We conducted a four-phase research prioritization process using the CHNRI method to identify which effective interventions for cancer prevention should be prioritized for implementation in Japan. The process included listing effective interventions for cancer prevention, surveying stakeholders, conducting a web-based survey among researchers, and calculating priority scores. RESULTS: Among 215 invited researchers, 92 (42.8%) and 67 (31.2%) researchers responded to the first and second surveys, respectively. In both surveys, physicians accounted for the largest proportion of respondents. Across both surveys, HPV vaccination for females, cervical cancer screening, fecal occult blood testing (FOBT), mammography, and tobacco control policies were identified as top priorities. CONCLUSIONS: Priorities for implementing effective interventions for cancer prevention were set through collaboration with researchers and citizens, providing a foundation for future research and progress.

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Association between comorbidities and major adverse cardiovascular events in patients undergoing immune checkpoint blockade.

Daetwyler E, Jauch A, Aeschlimann N … +4 more , Rommers N, Kasenda B, Zippelius A, Kuster GM

BMC Cancer · 2026 Jun · PMID 42374316 · Full text

BACKGROUND: Cancer patients have an increased risk for cardiovascular diseases (CVDs). Conflicting information exists regarding whether cancer treatment with immune checkpoint inhibitors (ICIs) itself increases the risk... BACKGROUND: Cancer patients have an increased risk for cardiovascular diseases (CVDs). Conflicting information exists regarding whether cancer treatment with immune checkpoint inhibitors (ICIs) itself increases the risk for CVDs. We therefore assessed the incidence of major adverse cardiovascular events (MACE) in cancer patients treated with versus without ICIs. METHODS: One hundred fifty-eight and 163 cancer patients, treated with and without ICIs respectively, were compared. The primary endpoint was the incidence of MACE, defined as acute coronary syndrome, ischemic stroke, transient ischemic attack, new or worsening coronary artery disease or peripheral arterial occlusive disease, or cardiovascular death. We used Cox proportional hazard models and competing risk models (death), adjusted for age, sex and comorbidities (Charlson Comorbidity index, CCI) to investigate the cause-specific association between ICI-treatment and MACE. RESULTS: Over a median follow-up of 30.6 months, 37 MACE occurred. The overall incidence of MACE was 14.0% in patients with and 9.3% in patients without ICI-treatment. In the multivariate analysis CCI was significantly associated with MACE (HR 1.19, 95% CI [1.03, 1.37]), whereas no association was found for ICI-treatment (HR 1.12, 95% CI [0.56, 2.22]). Competing risk analysis showed no treatment associations. CCI was associated with non-cardiovascular mortality. CONCLUSIONS: We did not observe statistical evidence of an association between ICI treatment and MACE. There is evidence that a higher comorbidity burden is associated with MACE. Comorbidities are clearly associated with non-cardiovascular mortality in cancer patients. Further prospective studies are required to investigate whether treating comorbidities and optimizing cardiovascular risk factors result in improved outcomes among cancer patients.

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Pre-operative proton versus photon-based chemoradiotherapy as an addition to best systemic therapy in the management of oesophageal cancer: protocol for the UK multi-centre randomised phase 2 PROTIEUS study.

Radhakrishna G, Jones CM, Bleaney CW … +21 more , Blackshaw J, Blencowe N, Brand D, Clarke CS, Gwynne S, Hava N, King A, Lewis GJ, Lopes A, Mak KM, Miles E, Mukherjee S, Nicholas O, Rashid M, Owczarczyk K, Shiu KK, Smyth E, Tattum J, Underwood T, Veiga C, Hawkins MA

BMC Cancer · 2026 Jun · PMID 42374301 · Full text

BACKGROUND: Oesophageal cancer is a major cause of morbidity and mortality. Around 40% of patients present with locally advanced disease. Outcomes are poor, with 5-year survival of around 50% for locally advanced oesopha... BACKGROUND: Oesophageal cancer is a major cause of morbidity and mortality. Around 40% of patients present with locally advanced disease. Outcomes are poor, with 5-year survival of around 50% for locally advanced oesophageal adenocarcinoma (OAC) and 60% for oesophageal squamous cell carcinoma (OSCC). Over a fifth of recurrences are locoregional. These may be reduced by the addition of chemoradiotherapy (CRT) to best pre-operative systemic anti-cancer therapy (SACT). However, photon-based CRT is associated with a higher frequency of complications than chemotherapy alone. This study will explore whether, in patients with locally advanced OAC and OSCC managed with hypofractionated CRT following best pre-operative systemic therapy, the use of proton beam therapy (PBT) reduces post-operative complications when compared with photon-based treatment. METHODS/DESIGN: PROTIEUS is an investigator-initiated randomised multi-centre phase 2 trial aiming to recruit 170 patients with locally advanced OAC (n = 130) or OSCC (n = 40) from the UK National Health Service. Patients with locally advanced cT ≥ 2, N0-2 non-metastatic disease are eligible for inclusion and will be randomised 1:1 to receive 40.05 Gy (RBE) in 15 fractions over three weeks using either PBT or intensity modulated/rotational arc photon radiotherapy. All patients will receive three one-week cycles of concurrent intravenous carboplatin/paclitaxel. CRT will be delivered following best pre-operative SACT. The primary endpoint is the rate of severe post-operative complications within 90 days post-surgery (grade 3 or higher Clavien-Dindo classification and CTCAE v5.0). Secondary endpoints relate to efficacy (pathological complete response and clear resection margin rate, disease-free and overall survival), tolerability (completion of planned CRT regime, time to and completion of adjuvant therapy), morbidity (long-term quality of life measures) and health economics (cost-effectiveness analyses using EQ-5D-5 L and resource use assessments). DISCUSSION: There is a need to improve local control in OAC and OSCC. Given only modest gains with perioperative immune checkpoint inhibition and a disease landscape in which there are few targets for precision or personalised therapies, there are limited options to achieve further gains across the disease population using SACT. This study will therefore determine which of PBT or photon-based pre-operative CRT is the most tolerable and least toxic for integration into existing systemic treatment paradigms. TRIAL REGISTRATION: https://doi.org/10.1186/ISRCTN50098578.

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The prognostic significance of pretreatment systemic immune-inflammation index and prognostic nutritional index in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

Yang X, Fu P, Liu H

BMC Cancer · 2026 Jun · PMID 42374297 · Full text

BACKGROUND: Systemic immune-inflammation index (SII) and Prognostic nutritional index (PNI) are emerging inflammation-related indicators that have previously been linked to prognosis of cancer patients, but the results h... BACKGROUND: Systemic immune-inflammation index (SII) and Prognostic nutritional index (PNI) are emerging inflammation-related indicators that have previously been linked to prognosis of cancer patients, but the results have been inconsistent. This meta-analysis aims to review and report the latest data regarding the prognostic value of the SII and PNI in cancer patients treated with immune checkpoint inhibitors (ICIs). METHODS: We searched the relevant literature in PubMed, Cochrane Library, and Embase databases from inception to February 15, 2026. Meta-analyses were performed for overall survival (OS) and progression-free survival (PFS) to assess the prognostic role of SII and PNI in cancer patients treated with ICIs. The pooled OS and PFS were estimated using hazard ratios (HR) with 95% confidence intervals (95% CI) by the random-effects model. Subgroup analysis was also conducted to investigate the correlation between indicators and study features. RESULTS: A total of 27 studies comprising 4000 patients treated with ICIs were included in this meta-analysis. In terms of the results based on multivariate analysis, the pooled results revealed that high SII level was an unfavorable predictor for OS (HR = 2.42, 95% CI = 1.88-3.10) and PFS (HR = 1.99, 95% CI = 1.36-2.90). In addition, lower level of PNI was correlated with worse OS (HR = 2.28, 95% CI = 1.68-3.08), as well as PFS (HR = 1.84, 95% CI = 1.56-2.17). Furthermore, subgroup analysis was conducted, and we found similar conclusions. CONCLUSION: Our findings support SII and PNI as promising biomarkers for adequately studied cancer types, but extending them to all malignancies requires prospective validation in less-studied cancers.

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Cutaneous and mucosal melanoma among the Palestinian population: a retrospective clinicopathological study with comparative regional context.

Salhi I, Bannoura S, Abedaljawwad O … +1 more , Salah Z

BMC Cancer · 2026 Jun · PMID 42374290 · Full text

BACKGROUND: Cutaneous and mucosal melanoma are biologically and clinically distinct malignancies whose epidemiology varies markedly across populations and skin phototypes. In Arab and other Eastern Mediterranean populati... BACKGROUND: Cutaneous and mucosal melanoma are biologically and clinically distinct malignancies whose epidemiology varies markedly across populations and skin phototypes. In Arab and other Eastern Mediterranean populations, melanoma is comparatively uncommon but is frequently diagnosed at an advanced stage and shows a relatively high proportion of acral and mucosal subtypes. Data describing melanoma in the Palestinian population are scarce. We characterised the clinicopathological profile of cutaneous and mucosal melanoma diagnosed at a large Palestinian diagnostic pathology service and placed the findings in a comparative regional context. METHODS: We performed a retrospective review of all histopathologically confirmed cases of cutaneous and mucosal melanoma reported at Medicare Diagnostic Laboratories, West Bank, Palestine, between May 2008 and May 2026. Demographic variables (age, sex), anatomical site, melanoma subtype, depth of invasion (Clark level), and, where recorded, Breslow thickness and American Joint Committee on Cancer (AJCC) stage were abstracted from pathology records. Diagnoses were confirmed on haematoxylin-eosin sections supported by immunohistochemistry (S100, SOX10, HMB-45, Melan-A). Repeat specimens were consolidated to the patient level, and findings were compared with published series from neighbouring countries. RESULTS: Fifty-seven patients with primary melanoma were identified, comprising 47 cutaneous (82.5%) and 10 mucosal (17.5%) tumours. The mean age at diagnosis was 59.5 +/- 17.0 years (range 10-87), and there was a slight female predominance (30 women, 52.6%; male-to-female ratio 0.90:1). Acral sites (sole, heel, plantar, and subungual regions) accounted for 15 of 47 cutaneous melanomas (31.9%), the most common single location, followed by the head and neck (14, 29.8%). Among mucosal tumours, the anorectum was the predominant site (6 of 10, 60%). A histological subtype was explicitly recorded in only 19 of 57 cases; within this limited subset the nodular pattern predominated (18 of 19), although the large proportion of cases without a stated subtype precludes firm conclusions about the true distribution of melanoma subtypes in this cohort. The Clark level was documented in 27 patients, of whom 26 (96.3%) had level IV-V (deep) invasion. A further 17 patients presented with metastatic melanoma deposits without a primary tumour in the archive. Melanoma in this Palestinian cohort was characterised by a slight female predominance, a high proportion of acral (31.9% of cutaneous) and mucosal (17.5% of all primary) tumours, a predominantly nodular phenotype among the subset of cases with a recorded subtype, and deep invasion at diagnosis. This profile mirrors patterns reported in neighbouring Arab and Eastern Mediterranean populations and contrasts with more lightly pigmented (Fitzpatrick I-II) Western populations. The findings underline the need for improved melanoma awareness, routine examination of acral and mucosal sites, and strengthened cancer registration in Palestine.

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Urologic malignancy in renal transplant recipients: Analysis of OPTN/UNOS data from 2000 to 2022.

Hao X, Ye C, Lai W … +17 more , Xu J, Wu Y, Sun Y, Pang H, Lv C, Lv K, Yang G, Wang J, Gao Y, Lu Y, Huang S, Luo Z, Dong J, Zhao M, Zhang X, Chen H, Yuan Q

BMC Cancer · 2026 Jun · PMID 42374287 · Full text

PURPOSE: The increasing incidence of urologic malignancy after renal transplantation (RT) has become a leading cause of recipient mortality. However, no recent analyses have been performed to identify the risk factors fo... PURPOSE: The increasing incidence of urologic malignancy after renal transplantation (RT) has become a leading cause of recipient mortality. However, no recent analyses have been performed to identify the risk factors for post-transplant urologic malignancy (PTUM) and to evaluate the effect of PTUM on RT outcomes. MATERIALS AND METHODS: This retrospective, population-based cohort study was based on Organ Procurement and Transplantation Network data. RESULTS: A total of 268,606 recipients underwent RT from January 2000 to December 2019 and met the inclusion criteria. Of these, 2,079 (0.77%), 1,983 (1.20% of male recipients), and 846 (0.32%) patients were diagnosed with renal cancer (RCa), prostate cancer (PCa), and bladder cancer (BCa), respectively, after RT. Urologic malignancy was a major cause of patient death after RT (RCa: 41.5%, PCa: 23.5%, BCa: 50.4%). The 5-year survival rates of the four groups ranking from best to worst were as follows: [95% confidence interval, lower value-upper value], PCa, 93.3% [92.2%-94.4%]; cancer-free, 87.2% [87.0%-87.3%]; RCa, 87.2% [85.8%-88.7%]; BCa, 81.0% [78.4%-83.7%] (P < 0.001 for all, except cancer-free vs. RCa, P = 1.00). CONCLUSIONS: The effects of PTUM on RT outcomes differ depending on the type of malignancy. Thus, a personalized approach to screening may be an appropriate strategy to address the multitude of complex issues that RT recipients encounter.

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Timing and clinical burden of febrile neutropenia and treatment discontinuation during neoadjuvant chemotherapy.

Nakada K, Takada K, Gose A … +10 more , Nishimoto M, Nishikawa M, Kochi A, Watanabe C, Tauchi Y, Ogisawa K, Kinoshita H, Shibutani M, Morisaki T, Kashiwagi S

BMC Cancer · 2026 Jun · PMID 42374286 · Full text

BACKGROUND: Febrile neutropenia (FN) remains a major complication of neoadjuvant chemotherapy (NAC) and is a frequent cause of treatment disruption. However, FN is a heterogeneous clinical entity, and the impact of its t... BACKGROUND: Febrile neutropenia (FN) remains a major complication of neoadjuvant chemotherapy (NAC) and is a frequent cause of treatment disruption. However, FN is a heterogeneous clinical entity, and the impact of its timing and clinical severity on treatment continuity has not been fully elucidated. This study aimed to characterize the timing and clinical burden of FN and to clarify their associations with treatment discontinuation during NAC. METHODS: We retrospectively analyzed 137 consecutive patients with HER2-positive breast cancer who received NAC. FN timing was assessed by chemotherapy cycle and days from NAC initiation, with early FN defined a priori as FN occurring at cycle ≤ 2. FN severity was evaluated based on the requirement for hospitalization. Treatment discontinuation was defined as premature discontinuation of NAC due to chemotherapy-related adverse events; dose reductions or treatment delays without permanent discontinuation were not included in this endpoint. Logistic regression analyses were performed to identify factors associated with treatment discontinuation. RESULTS: FN occurred in 18 patients (13.1%). The median time to FN onset was 46 days (interquartile range, 19-112), with half of FN events occurring by cycle 2. Although FN events were evenly distributed across chemotherapy cycles, cumulative incidence analysis revealed early clustering on a time-based scale. Hospitalization was required in 50.0% of patients with FN. Treatment discontinuation occurred in 8.4% of patients without FN, 11.1% of patients with non-hospitalized FN, and 44.4% of patients with hospitalized FN. Exploratory multivariable analyses demonstrated that hospitalized FN was associated with treatment discontinuation after adjustment for age and host-related factors (odds ratio, 11.20-13.33 across models), whereas low body mass index and reduced renal function were not independent predictors. CONCLUSIONS: The impact of FN on treatment continuity during NAC appears to be determined by both its timing and clinical severity. FN requiring hospitalization, particularly when occurring early during NAC, was associated with an increased likelihood of treatment discontinuation. These findings underscore the importance of early identification and prevention of severe FN to optimize treatment delivery during neoadjuvant chemotherapy, while recognizing the statistical uncertainty inherent to the limited number of events.

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Reproductive factors and lung cancer risk in never-smoking women: a prospective cohort study.

Nie Y, Liang D, Jin Y … +9 more , Gao M, Li J, Wang S, Wu S, Shi J, Liu Y, Su X, Cui S, He Y

BMC Cancer · 2026 Jun · PMID 42374272 · Full text

BACKGROUND: The association between endogenous estrogen and lung cancer in never-smoking women remains unclear. This study investigated the associations of various reproductive factors, as proxies for cumulative estrogen... BACKGROUND: The association between endogenous estrogen and lung cancer in never-smoking women remains unclear. This study investigated the associations of various reproductive factors, as proxies for cumulative estrogen exposure, with lung cancer risk among never-smoking women from a lung cancer screening cohort. METHODS: Associations between reproductive factors and lung cancer risk were evaluated using multivariable logistic regression and restricted cubic splines. Mediation analysis assessed the mediating role of body mass index (BMI). Subgroup analyses were stratified by baseline characteristics. Robustness was verified through propensity score matching and inverse probability of treatment weighting. RESULTS: The study included 155,103 never-smoking women, identifying 657 incident lung cancer cases. Early menarche (< 13 years: OR, 1.41; 95% CI, 1.06-1.87), a shorter reproductive span (≤ 32 years: OR, 1.25; 95% CI, 1.02-1.54), and parity (≥ 1) (OR, 2.02; 95% CI, 1.16-3.52) were associated with increased risk. Later age at first birth (≥ 30 years) (OR, 0.63; 95% CI, 0.41-0.98) and a history of benign breast disease (OR, 0.64; 95% CI, 0.47-0.87) were inversely associated with lung cancer risk, with age at first birth showing a non-linear dose-response relationship. Mediation analyses suggested a potential role of BMI in these associations. Stratified analyses revealed significant effect modification by age, BMI, and clinical history. CONCLUSION: Reproductive factors are associated with lung cancer risk among never-smoking women. Integrating reproductive histories into routine lung cancer screening programs will facilitate more precise risk stratification.

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