The increasing adoption of targeted therapies over chemotherapy has made randomized controlled trials (RCT) with chemotherapy increasingly challenging in advanced NSCLC with actionable genomic alterations (AGA), particularly for rare subgroups. Contemporary chemotherapy outcomes specific to AGAs are lacking despite growing reliance on single-arm studies and external-control analyses. We sought to establish first-line platinum-doublet chemotherapy outcomes in advanced NSCLC with AGAs using data from RCTs.

We extracted objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) data from Phase 2/3 RCTs. Individual patient-level data were reconstructed from Kaplan-Meier curves to pool and compare PFS and OS across AGAs.

Twenty-two RCTs (n = 2132) were included. Across most AGAs, platinum-doublet chemotherapy produced similar outcomes-pooled ORRs ranging from 28.7 to 39.0% and median PFS from 6.0 to 7.3 months. Pairwise comparisons showed better ORR/PFS for RET fusion (one trial with control arm-chemotherapy/pembrolizumab) and shorter OS for KRAS mutation versus other AGAs (logrank P<.001). Detailed pooled ORR and median PFS and OS were: ALK rearrangement (n = 461)-ORR 39.0% (95% CI 25.8-52.2), PFS 7.0 months (6.8-7.2), OS 43.0 months (32.2-inestimable); common EGFR mutation (n = 1038)-ORR 28.7% (22.3-35.1), PFS 6.0 months (5.7-6.3), OS 27.4 months (26.1-29.3); uncommon EGFR mutation (n = 61)-ORR 35.1% (12.6-57.7), PFS 6.7 months (5.2-8.4), OS 29.5 months (13.3-inestimable); EGFR exon 20 insertion (n = 330)-ORR 38.3% (21.7-55.0), PFS 7.3 months (6.9-8.6), OS 30.1 months (29.1-inestimable); KRAS mutation (n = 140)-ORR 21.7% (12.4-30.9), PFS 6.2 months (4.7-6.9), OS 10.8 months (8.8-12.7); RET fusion (n = 102)-ORR 65.0% (54.5-75.5), PFS 11.4 months (8.9-16.9), OS not available.

Platinum-doublet chemotherapy yields remarkably consistent ORR and PFS across most advanced NSCLC with AGAs. These data provide contemporary molecularly defined benchmarks that may support interpretation of single-arm studies, development of external-control analyses, and future trial design in this rare population.

Persistent gastrointestinal symptoms are common after esophagectomy or gastrectomy, which frequently co-occur and significantly decrease quality of life. This study aimed to identify gastrointestinal symptom profiles over the first-year post-surgery and to explore changes over time.

Patients diagnosed between 2013 and 2024 who underwent esophagectomy or gastrectomy for nonmetastatic esophageal or gastric cancer were selected. Longitudinal self-reported gastrointestinal symptom data were linked to patient and tumor characteristics. K-means clustering based on symptom severity scores was performed at baseline and at every three months up to 12 months postoperatively. Generalized Linear Mixed Models assessed associations between patient characteristics and symptom profiles.

Among 1462 patients who underwent esophagectomy and 434 who underwent gastrectomy, three symptom severity profiles, mild, moderate, and severe, were identified for each period. These profiles reflected increasing symptom severity rather than distinct symptom patterns. The mild symptom profile was the most common (esophagectomy: 42.5 ~ 60.5%; gastrectomy: 53.9 ~ 73.5% across time periods). Most patients remained in the same profile over time. Amongst others, female sex (esophagectomy: OR = 1.67; 95% CI:1.30-2.14, gastrectomy: OR = 1.54; 95% CI:1.07-2.23) and receiving neoadjuvant chemotherapy (esophagectomy: OR = 1.91; 95% CI:1.22-2.99, gastrectomy: OR = 2.39; 95% CI:1.55-3.67) were associated with a higher likelihood of moderate/severe symptom profile.

Three stable gastrointestinal symptom severity profiles were identified during the first postoperative year, supporting risk-stratified monitoring after upper gastrointestinal cancer surgery. Early identification of patients at risk for persistent moderate-to-severe gastrointestinal symptoms may facilitate timely supportive care and improve survivorship outcomes.

Disentangling the role of micronutrients in gastric cancer (GC) is challenging and results are inconsistent to date. We investigated associations of dietary intake of B vitamins with GC in a pooled analysis of international studies.

We included orifinal data from 13 case-control studies of GC from the Stomach Cancer Pooling Project. Data were harmonized and study-specific quartiles of dietary intake of the B1 (thiamine), B2 (riboflavin), B3 (niacin) and B6 (pyridoxine) were created. We calculated odds ratios (OR) of associations between each B vitamin with GC and the corresponding 95% confidence intervals (CI) through logistic regression models adjusted for major risk factors. We then pooled study-specific ORs using random effect meta-analysis. Stratified analyses were conducted by sex, histologic type and anatomical site. Secondary analyses were further adjusted for Helicobacter pylori (Hp) infection, alcohol, meat and vegetables and fruit intake.

The study population included 5252 GC cases and 11,397 controls. We observed the following associations for one-quartile increase of dietary vitamin intake: B1, OR = 0.93 (95% CI = 0.88-0.97); B2, OR=0.97 (95% CI = 0.93-1.02); B3, OR = 0.95 (95% CI = 0.90-1.00); B6, OR = 0.86 (95% CI = 0.82-0.91); we observed an interaction between B1 and sex, with beneficil effect in men for the highest quartile of intake (p = 0.009). Main results were confirmed when further adjusting for Hp. When accounting for alcohol, meat and vegetables and fruit intakes, the associations were weakened or no more apparent. No heterogeneity was found between cardia and non-cardia GC; B2 was directly associated with diffuse but not intestinal GC (p = 0.03).

Dietary intake of B1 and B6 vitamins might reduce the risk of GC. Studies with homogeneous method of micronutrients assessment and adjustments are needed to confirm our results.

To examine how the co-occurrence of behavioral and psychosocial factors (depression, cigarette smoking, heavy alcohol use, and polydrug use) is associated with lung cancer incidence, we included 3,554 sexual minority men (SMM) from the Multicenter AIDS Cohort Study (MACS), 1996-2022, with assessments every 6 months. We used Cox proportional hazards models to examine the cumulative relationships of these factors with lung cancer incidence. We identified a positive dose-response relationship between the number of these factors and lung cancer incidence. Compared to men with no factors, those with two (aHR= 3.80, 95% Cl [1.46, 9.86]) and three or more (aHR = 8.33, 95% Cl [2.20, 31.60]) had increased lungcancer risk. Men living with HIV were more affected by these factors than men without HIV. Our findings highlight the need for prevention and treatment for depression and substance use when assessing lung cancer risk among SMM, which may inform strategies to reduce lung cancer incidence.

The current prognostic assessment of hilar cholangiocarcinoma (hCCA) relies heavily on postoperative pathological parameters, which limit preoperative clinical decision-making. This study aimed to develop and validate a decision tree-based prognostic model for risk stratification among patients with resectable hCCA using preoperative biomarkers.

A bicentric retrospective analysis was conducted on patients who underwent curative resection for hCCA. The decision tree model was developed in a training cohort and validated in an independent cohort. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS).

Among 435 patients (training cohort: 305 patients; validation cohort: 130 patients), multivariate analysis identified a carbohydrate antigen 19-9 level of ≥37 U/mL (hazard ratio [HR], 1.96 [95% CI, 1.24-3.08]), a carbohydrate antigen 12-5 level of ≥35 U/mL (HR, 2.62 [95% CI, 1.78-3.85]), and a C-reactive protein level of ≥5 mg/L (HR, 1.79 [95% CI, 1.31-2.45]) as independent predictors for survival and recurrence. The decision tree model was used to stratify patients into low- and high-risk groups with significantly different outcomes. In the training cohort, compared with high-risk patients, low-risk patients demonstrated superior 3-year OS (23.0% vs 56.1%, respectively) and RFS (21.9% vs 40.5%, respectively) (both P <.0001). The model maintained robust performance in the validation cohort.

This novel biomarker-based decision tree model effectively stratified patients with resectable hCCA into distinct prognostic groups. By integrating readily available preoperative parameters, this practical tool could facilitate personalized treatment strategies and improve surgical decision-making.

Incidental gallbladder cancer (iGBC) after laparoscopic cholecystectomy (LC) remains clinically relevant, and preoperative recognition may be especially difficult in acute cholecystitis (AC). We reviewed iGBC cases diagnosed after LC and descriptively compared cases with and without AC.

We retrospectively reviewed 2572 consecutive LCs performed between January 2013 and November 2025. After excluding patients with preoperatively detected gallbladder polyps or suspected malignancy, 2224 patients were analyzed (AC, n = 663; non-AC, n = 1561). The denominator cohort was used to estimate iGBC incidence, and clinicopathologic details were reviewed for the 12 iGBC cases.

Twelve patients (0.54%) had iGBC. The incidence was numerically higher in the AC group than in the non-AC group (0.90% vs. 0.38%; p = 0.201), but the difference was not statistically significant. Among 11 patients with evaluable T stage, nine had T2 or deeper disease, and flat-type morphology predominated. Bile leakage occurred in two AC cases, subtotal cholecystectomy was required in one AC case and peritoneal dissemination developed in one AC case. Because only 12 iGBC cases were identified, causal interpretation was not possible.

iGBC was uncommon after LC and was numerically, but not significantly, more frequent in patients with AC. These findings should be regarded as hypothesis-generating. Surgeons should maintain awareness of occult malignancy during LC for AC and should minimize uncontrolled bile contamination when bailout procedures are unavoidable.

Breast cancer is the most commonly diagnosed cancer among women worldwide and a leading cause of cancer-related mortality. Survival varies across regions, with most deaths occurring in low- and middle-income countries due to limited early detection and treatment access. This study aimed to estimate the 5-year survival rate and identify determinants of decreased survival among patients with breast cancer in Africa.

A systematic review of only retrospective cohort studies was conducted using PubMed, Hinari, EMBASE, Google Scholar, African Journals Online, African Index Medicus and Web of Science. The literature search was conducted for a 1-month duration (1-30 November 2024). We included all available articles without restriction on publication date to ensure a comprehensive review. Methodological quality was assessed using the Newcastle-Ottawa 2016 Critical Appraisal Checklist. Publication bias was evaluated using funnel plots and Egger's test, and heterogeneity was assessed with the I² test. Data were analysed with Stata V.17.

55 articles with 19 577 participants from 19 countries were included; 37 studies (4622 participants) were used to estimate pooled 5-year survival. The pooled 5-year survival rate of patients with breast cancer in Africa was 40.38% (95% CI 33.92 to 46.83%). Reduced survival was strongly associated with tumour characteristics, including tumour stage >2 (HR 3.06, 95% CI 2.02 to 4.09), negative oestrogen receptor status (HR 2.52, 95% CI 1.89 to 3.15), tumour size >5 cm (HR 1.62, 95% CI 1.48 to 1.76), positive nodal status (HR 1.64, 95% CI 1.58 to 1.70) and higher histological grade (HR 1.26, 95% CI 1.22 to 1.29). Treatment-related factors such as single-agent chemotherapy (HR 1.78, 95% CI 1.04 to 2.53) and patient-related factors, including comorbidities (HR 1.45, 95% CI 1.40 to 1.50) and illiteracy (HR 6.54, 95% CI 4.39 to 8.69), were also associated with reduced survival.

This study reveals a critically low 5-year survival rate of 40.4% for breast cancer in Africa. Poor survival is linked to advanced tumour features, suboptimal treatment and patient-related factors, with comorbidities and illiteracy being the strongest patient-related factors. These results highlight the urgent need for integrated strategies focused on early diagnosis, public education, equitable access to multimodal therapies and systematic management of comorbidities across the continent.

CRD420261387399.

Therapy-related myeloid neoplasms (t-MN) after chimeric antigen receptor (CAR) T-cell therapy occur with short latency, but whether they carry an independent survival disadvantage is unclear. We assembled a multicenter retrospective cohort of 399 adults with t-MN after CAR T-cell therapy (n=56), autologous hematopoietic cell transplantation (auto-HCT; n=98), or standard chemotherapy/radiation (n=245), and constructed a nearest-neighbor latency-matched cohort (n=220). Median latency was 15.2 months for post-CAR-T versus 38.0 and 30.0 months for post-auto-HCT and standard therapy (p<0.001). In the matched cohort, median overall survival (OS) was 9.1 months for post-CAR-T versus 16.9 and 18.7 months for post-auto-HCT and standard therapy (p=0.013). In multivariable Cox models, the hazard ratio for overall mortality was 1.98 (95% CI 1.33-2.94) for post-CAR-T and 0.99 (95% CI 0.74-1.32) for post-auto-HCT, each relative to standard therapy; The post-CAR-T estimate was 1.85 (95% CI 1.21-2.82) after adjustment for TP53 status and 2.15 (95% CI 1.23-3.76) in an era-restricted cohort with near-complete molecular data. TP53 variant allele frequency independently predicted OS (HR 1.14 per 10% increment, 95% CI 1.03-1.26). The hazard ratio for allogeneic HCT, modeled as a time-varying covariate, was 0.74 (95% CI 0.52-1.06). Post-CAR-T t-MN carries an independent survival disadvantage not explained by TP53 clone burden; allogeneic HCT remains the only potentially curative option.

Modern cancer diagnostics is heavily reliant on molecular data. Next-generation sequencing using liquid biopsy (LB) is primarily focused on identifying predictive and prognostic biomarkers to guide systemic therapy decision making. However, additional findings including genomic variants of possible or probable germline origin are detected in a significant minority of patients (3%-18%), with significant implications for patients and their families. Pretest information provision regarding both the purpose and potential benefits of the test and additional findings on LB varies in clinical practice, with little guidance for clinicians regarding the degree of detail required regarding possible additional findings. LB requires explicit disclosure of these aspects. Implementing a standardized, context-dependent approach to this discussion, with nationally standardized information provision tools, should be prioritized to enable patient-centered decision making regarding LB, without prioritizing the incidentalome over the primary purpose of the test-refining and optimizing treatment options.

The prognostic significance of multifocal and multicentric breast cancer (MMBC) with low tumor burden remains controversial, and adjuvant chemotherapy guidelines for these patients are lacking.

Female patients with cT1-T2 MMBC or unifocal breast cancer (UBC) diagnosed between 2010 and 2020 were identified from the SEER database. Propensity score matching (PSM) balanced baseline characteristics. Survival outcomes were evaluated using Kaplan-Meier and Cox proportional hazards models, with subgroup analyses stratified by tumor size in node-negative MMBC.

After PSM, 9,751 matched pairs of patients with MMBC and UBC were included. Analyses showed MMBC had significantly worse overall survival (OS) and breast cancer-specific survival (BCSS) than UBC (both P < .001). Multivariate Cox regression confirmed chemotherapy improved OS (hazard ratio [HR], 0.583 [95% CI, 0.522 to 0.652]) and BCSS (HR, 0.830 [95% CI, 0.702 to 0.980]) in MMBC. In eligible cases, 1,731 matched pairs with and without chemotherapy were identified. Subgroup analyses showed that in node-negative MMBC, chemotherapy improved OS only when tumors were ≥1 cm (tumor <1 cm: HR, 0.804 [95% CI, 0.506 to 1.275], P = .353; 1-2 cm: HR, 0.577 [95% CI, 0.414 to 0.806], P = .001; ≥2 cm: HR, 0.535 [95% CI, 0.399 to 0.717], P < .001).

MMBC predicts poorer survival than UBC. In node-negative MMBC, chemotherapy confers benefit only when tumor size is ≥1 cm, suggesting multifocality and multicentricity should guide chemotherapy decisions. Prospective studies are warranted to confirm findings and refine guidelines.