Lung cancer remains the leading cause of cancer-related mortality worldwide, and cigarette smoking is its predominant factor. However, genetic biomarkers contributing to susceptibility, particularly within cell-cycle regulatory genes such as cyclin dependent kinase inhibitor 1B (CDKN1B), remain incompletely identified. The study aimed to investigate the contribution of CDKN1B rs34330 and rs2066827 polymorphisms to lung cancer risk, and to evaluate their interaction with smoking behavior in a Taiwanese cohort.

The CDKN1B genotypes of 358 lung cancer patients and 716 healthy controls were determined using polymerase chain reaction-restriction fragment length polymorphism methodology. Genotypic and allelic distributions were compared using chi-square tests, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Stratified analyses were performed according to smoking status.

No significant association was observed between CT (OR=1.20, 95%CI=0.87-1.66, p=0.2928) or TT (OR=1.26, 95%CI=0.87-1.83, p=0.2656) rs34330 genotypes and lung cancer risk. Similarly, in dominant (OR=1.22, 95%CI=0.90-1.66, p=0.2302) and recessive models (OR=1.11, 95%CI=0.82-1.49, p=0.5576), no significant association were found. Allelic analysis confirmed no difference for rs34330 T allele (p=0.2654) or rs2066827 G allele (p=0.8868). However, among smokers, rs34330 TT genotype carriers exhibited significantly elevated lung cancer risk (OR=1.59, 95%CI=1.05-2.42, p=0.0372), persisting after adjustment for age and sex (OR=1.64, 95%CI=1.07-2.36). This is not found among non-smokers.

Although CDKN1B polymorphisms are not independently associated with lung cancer susceptibility, rs34330 may interact with cigarette smoking to elevate its risk. These findings suggest a potential gene-environment interaction influencing smoking-related lung carcinogenesis and warrant further validation in larger multi-ethnic populations.

Cervical cancer (CC) remains one of the most common malignancies worldwide, particularly in low-resource countries. Expression of programmed death-ligand 1 (PD-L1) has emerged as an immune-related biomarker with predictive and potential prognostic relevance in several cancer types. However, its prognostic role in CC remains unclear. This study investigated the clinicopathological and prognostic significance of tumoral PD-L1 expression in CC.

This monocentric retrospective study included 113 patients diagnosed with invasive CC at the University Hospital Bonn between 2002 and 2016. Clinical and histopathological data were obtained from patient records, and immunohistochemical analyses were performed on tissue microarrays for PD-L1 [evaluated by Tumor Proportion Score (TPS) and Combined Positive Score (CPS)], p16, p53, Ki-67, and estrogen and progesterone receptors.

PD-L1 expression was positive by TPS in 15.9% and CPS by 54.9% of cases. No significant association was found between PD-L1 expression and most clinicopathological parameters. In univariate analysis, increasing age was associated with worse overall survival (OS) and showed a trend towards reduced progression-free survival (PFS). Advanced International Federation of Gynecology and Obstetrics (FIGO) stage was associated with reduced PFS and OS. The presence of distant metastases was associated with worse OS but had no impact on PFS. Primary surgical treatment was associated with improved PFS and OS. Progesterone receptor positivity correlated with improved PFS. In multivariate analysis, PD-L1 positivity by CPS was independently associated with improved OS, whereas PD-L1 positivity by TPS was not. FIGO stage remained the dominant prognostic factor for OS.

Tumoral PD-L1 expression, assessed by CPS, is an independent favorable prognostic factor for OS in CC, whereas TPS-based assessment lacked prognostic impact. CPS scoring may therefore provide superior biological and prognostic insight into PD-L1-related immune activity in CC.

Docetaxel, cisplatin, and 5-fluorouracil (DCF) have been established as a standard neoadjuvant chemotherapy regimen for resectable esophageal squamous cell carcinoma (ESCC); however, the substantial toxicity of this regimen may limit its use in clinical practice. Therefore, a biweekly divided-dose DCF regimen (Bi-DCF) has been developed to improve tolerability while maintaining dose intensity. This study aimed to evaluate the safety and feasibility of preoperative Bi-DCF in a real-world clinical setting.

This retrospective single-institution study included 63 patients with ESCC who had received preoperative Bi-DCF between January 2016 and December 2020. Patients were stratified by age (≤75 years and ≥76 years), and age-based comparisons were performed as exploratory analyses. The primary endpoint was the incidence of grade ≥3 adverse events. Secondary endpoints included treatment feasibility, as assessed by the average relative dose intensity (ARDI), surgical outcomes, pathological responses, and recurrence-free survival (RFS).

Grade ≥3 adverse events occurred in 44.4% of patients. Non-hematological toxicities were generally infrequent, and severe renal dysfunction occurred in only two patients. No treatment-related mortality occurred. In exploratory analyses, no apparent differences in the incidence of grade ≥3 adverse events were observed between age groups. The median ARDI was 100% (range=33.3-100%) in the overall cohort and was maintained across age groups. Exploratory analyses did not demonstrate clear differences in RFS between age groups; however, these findings should be interpreted with caution because of the limited number of elderly patients.

Biweekly divided-dose DCF appears to be a feasible and tolerable neoadjuvant regimen for ESCC, with preserved dose intensity and acceptable perioperative outcomes in a real-world clinical setting. This regimen may represent a practical alternative for selected patients who are not suitable candidates for standard-dose DCF, although prospective validation in larger cohorts is warranted.

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rising. Despite the better prognosis of HPV-associated disease, treatment protocols do not yet differentiate by HPV status. In patients with lateralized OPSCC with suspected ipsilateral lymph node metastases (LNM), contralateral neck management remains controversial. This study evaluated the necessity of elective contralateral neck dissection (ND) in patients with OPSCC.

Clinical and pathological data from patients treated surgically for OPSCC between 2000 and 2023 with bilateral ND at a single tumor center were analyzed retrospectively. Tumor stage was classified according to the 7^th and 8^th editions of the UICC tumor classification. All imaging studies were re-evaluated by the same board-certified senior radiologist to ensure consistency. Tumor laterality (lateral vs. crossing the midline) and LNM were classified. Radiological findings were correlated with histopathological results.

A total of 124 patients out of 467 were included (80.6% male; mean age 56.6 years). Tonsillar and base-of-tongue carcinomas accounted for 67.7% and 27.4% of cases respectively. In lateralized OPSCC (n=69), radiologically suspected LNM were present in 66 patients (sensitivity 95.6%), while contralateral occult LNM were confirmed histologically in only one case (1.4%, pT3 base of tongue carcinoma). In contrast, tumors extending/crossing the midline showed contralateral LNM in 47 of 55 patients (sensitivity 97.9%, specificity 42.9%). Survival was significantly lower in patients with contralateral metastases (p=0.046).

Elective contralateral ND appears unnecessary in most lateralized OPSCC without radiological evidence of contralateral metastasis. Precise preoperative imaging reliably identifies candidates for unilateral ND.

The therapeutic landscape for advanced renal cell carcinoma (aRCC) has improved significantly, leading to extended treatment durations. Because many patients receiving systemic therapy are older adults, optimizing treatment and supportive care across age groups is critical. This study aimed to clarify age-related differences in unmet needs and specific concerns among patients with aRCC.

We retrospectively reviewed 83 patients who initiated first-line systemic therapy for aRCC. Patients were divided into an older group (>70 years; n=39) and a younger group (≤70 years; n=44). Data regarding symptoms, concerns, physical and psychological distress, and treatment preferences at treatment initiation were extracted from interview sheets and compared between the groups.

No significant differences were observed between the age groups regarding the severity of physical or psychological distress, or the prevalence of physical symptoms. However, younger patients reported significantly greater concerns regarding "work" (p<0.01) and tended to have more "financial issues" (p=0.054) than older patients. Half of the younger patients (50%) were willing to pursue further treatment with severe side effects if standard therapy became difficult, compared to 36% of older patients (p=0.461).

Older age was not associated with increased distress or a decreased willingness to pursue treatment. Because socioeconomic challenges represent a significant unmet need for younger patients, supportive care strategies should be carefully tailored to address these specific concerns.

The prognostic relevance of erythropoietin receptor (EPOR) expression in clear cell renal cell carcinoma (ccRCC) remains incompletely defined. We evaluated whether EPOR expression is associated with overall survival in The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma cohort (TCGA-KIRC) and whether this association persists after joint adjustment for erythropoietin (EPO) expression.

Transcriptomic and clinical data from TCGA-KIRC were analyzed. EPOR expression was modeled as a z-scored continuous variable. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival.

Higher EPOR expression was associated with worse overall survival in univariable analysis (HR=1.37, 95%CI=1.19-1.58, p<0.001) and remained independently associated with survival after adjustment for age and tumor stage, and in an exploratory joint model including EPO expression (HR=1.43, 95%CI=1.23-1.66, p<0.001). EPO was not associated with survival (HR=1.02, 95%CI=0.89-1.17, p=0.762).

Higher EPOR expression was independently associated with worse overall survival in ccRCC after adjustment for clinical covariates and EPO expression. These findings support further study of EPOR as a potential prognostic biomarker in ccRCC.

Enfortumab vedotin plus pembrolizumab (EVP) has become the standard first-line treatment for metastatic urothelial carcinoma (mUC); however, evidence regarding its use in very elderly patients remains limited. We evaluated the effectiveness and safety of EVP in patients aged ≥80 years with mUC.

This multicenter retrospective study included 60 patients with mUC treated with EVP at six institutions in Japan between September 2024 and March 2026. Patients were stratified into two groups according to age at treatment initiation: ≥80 years and <80 years. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (AEs). Continuous variables were compared using the Mann-Whitney U test, while categorical variables were analyzed using the chi-square test or Fisher's exact test. Survival outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test.

Of the 60 patients, 11 (18%) were aged ≥80 years and 49 (82%) were aged <80 years. The ORR was 60% in the ≥80-year group and 64% in the <80-year group (p=0.24), while the DCR was 80% and 84%, respectively (p=0.09). Median PFS was 8.5 months in the ≥80-year group and 12.1 months in the <80-year group (p=0.51). The 12-month OS rate was 50% and 84%, respectively (p=0.19). Grade ≥3 AEs occurred in 9% of older patients and 31% of younger patients (p=0.14).

EVP demonstrated comparable effectiveness and safety in patients aged ≥80 years with mUC. These findings suggest that advanced age alone should not preclude the use of EVP in carefully selected elderly patients.

In soft-tissue sarcoma (STS) of the extremities, radiotherapy (RT) is known to improve local control, overall survival (OS) and preserve extremity function. Whether RT should be applied pre- or postoperatively is still commonly discussed. This study aimed to gather data about the treatment reality at a certified sarcoma centre and investigate the impact of RT timing on local control, OS and progression-free survival (PFS).

This was a retrospective analysis of all patients who received curative RT for STS of the extremities between 2012 and 2022. Patients were identified using the ICD-10 diagnosis codes C49.1, C49.2 and C49.9. Patient-specific data, such as sex and relevant medical history, were collected. Tumour-specific data included histological subtype, staging, grading and location of the tumour. Therapy-specific data included the type and number of operations, postoperative complications, chemotherapy, RT, and acute and long-term toxicities. All cases were discussed pre-therapeutically in an entity-specific Interdisciplinary Tumour Board.

A total of 67 patients were included; 49 who received adjuvant RT were compared to 18 that received neoadjuvant RT. Mean follow-up was 17.83 months for the neoadjuvant RT cohort and 21.29 months for the adjuvant RT cohort. PFS for the neoadjuvant RT cohort averaged 25.7 months (range=5.2-52.7 months) compared to 15.1 months for the adjuvant RT cohort (range=0.8-51.1 months) (p=0.162). At 2 years, OS rates were 95.9% for patients treated with adjuvant RT and 94.4% for the neoadjuvant RT group.

STS is a heterogeneous and rare oncological entity and clear data on subtype-adapted therapy are still lacking. This study highlights the complexity and the influence of various factors on the choice of treatment approach and outcome, suggesting that neoadjuvant RT may be beneficial.

The number of elderly patients with gastric cancer (GC) is increasing in aging societies. However, the optimal surgical strategy for patients aged ≥80 years with advanced gastric cancer remains unclear because these patients often have frailty, sarcopenia, and multiple comorbidities. This study aimed to identify prognostic factors in patients aged ≥80 years with stage II-III GC who underwent gastrectomy.

This retrospective study included 57 patients aged ≥80 years with pathological stage II-III gastric cancer who underwent curative gastrectomy between January 2013 and March 2023. We evaluated clinicopathological factors, nutritional indices (PNI, CONUT score, GNRI, and skeletal muscle index), surgical factors, and postoperative outcomes. Overall survival (OS) and cancer-specific survival (CSS) were analyzed using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors were evaluated using the Cox proportional hazards model.

The median age was 83 years (range=80-93 years). Distal gastrectomy was performed in 43 patients, proximal gastrectomy in six, and total gastrectomy (TG) in eight. Severe postoperative complications (Clavien-Dindo ≥3) occurred in nine patients (15.8%). Univariate analysis identified BMI <18, CONUT score ≥5, TG, and severe postoperative complications as significant predictors of poor OS. TG was the only independent prognostic factor (hazard ratio=3.48; 95% confidence interval=1.20-10.1; p=0.0218), according to multivariate analysis. Kaplan-Meier analysis showed significantly worse OS in the TG group than in the nonTG group, while no significant difference in the CSS was observed.

Total gastrectomy was an independent predictor of poor OS in patients aged ≥80 years with stage II-III GC. These findings suggest that patient-related factors and surgical extent may influence the prognosis of very elderly patients.

Immune checkpoint inhibitors have improved outcomes in several malignancies; however, their efficacy remains limited in many solid tumors. Personalized cancer immunotherapy targeting tumor-specific neoantigens represents a promising strategy. We conducted an interim analysis to evaluate the tolerability and preliminary efficacy of neoantigen-pulsed dendritic cell (Neo-DC) vaccination in patients with advanced solid tumors.

Patients with histologically confirmed solid malignancy, Eastern Cooperative Oncology Group performance status 0-1, preserved organ function, and who also provided written informed consent were enrolled. Tumor-specific neoantigens were identified by applying next-generation sequencing of tumor tissue, and selected peptides with high predicted MHC class I/II affinity and sufficient expression levels were pulsed with autologous dendritic cells generated from peripheral blood mononuclear cells. Neo-DCs were administered every 2-3 weeks for up to six cycles, with additional doses permitted. Safety, clinical outcomes, overall survival (OS), and immune cell profiles were evaluated.

As of November 2025, 36 patients were registered, and 27 received Neo-DC vaccination and were evaluable. No treatment-related or immune-related adverse events (irAEs) of grade ≥2 were observed, and all irAEs were CTCAE grade 1. The disease control rate (complete response + partial response + stable disease) was 44.4%. The median OS was not reached at the time of analysis. The OS tended to be longer in patients achieving disease control, whereas concomitant chemotherapy showed a nonsignificant trend toward shorter survival. Immunophenotyping demonstrated a significant reduction in regulatory T cells after Neo-DC treatment.

Neoantigen-pulsed dendritic cell vaccination was well tolerated and showed encouraging signs of clinical activity in patients with solid tumors. Modulation of the immunosuppressive tumor microenvironment, reflected by the decreased count of regulatory T cells, may contribute to disease control. Further prospective studies are warranted.