Secondary findings of cancer patients who have undergone cancer precision medicine have been reported; however, cascade test outcomes have not yet been reported in Japan. This study aimed to evaluate the uptake of genetic medicine in cancer patients with germline pathogenic variants (GPVs) and cascade test in their relatives in Japan. Referral to genetic counseling, incidence of secondary findings [presumed GPVs (PGPVs) and GPVs], and uptake of confirmative germline testing and cascade test were retrospectively analyzed in 862 patients who underwent comprehensive genomic profiling testing in June 2019 and December 2023, using the institutional criteria of cascade test eligibility. Among the 852 patients who underwent tumor-only tests, 95 (11.2%) displayed PGPVs, 54 (6.3%) visited genetic counseling, 34 (4.0%) undertook germline testing, and 22 (2.6%) showed GPVs. One GPV was detected in 10 tumor/normal-paired tests. The 23 detected GPVs included BRCA2 [10], BRCA1 [6], APC [1], ATM [1], BAP1 [1], CDK4 [1], CDKN2A [1], MSH2 [1], and RAD51C [1]. The 23 patients with GPVs had 43 relatives eligible for cascade test and 22 non-eligible relatives (including 9 young relatives aged 14-34years). Cascade test was performed in 30 (69.8%) of the 43 eligible relatives, and GPVs were detected in 10 (33.3%). The median interval between GPV disclosure and cascade test was 50days (range: 6-304days). The uptake level of cascade test can be acceptable. Hospitals need to maintain contact with the young untested relatives until they have achieved sufficient growth to undertake cascade test.

Psychoeducational and relaxation-based interventions have been shown to reduce caregiver burden; however, limited evidence exists regarding the effectiveness of combined interventions delivered via mobile health (mHealth) in resource-limited settings. This study aimed to evaluate the combined effects of mHealth-based psychoeducation and the Benson Relaxation Technique (BRT) on caregiver burden among female informal caregivers of patients with cancer. A prospective, open-ended, randomized controlled trial (1:1 allocation) was conducted from October 2024 to March 2025. In total, 102 female caregivers were randomly assigned to either the intervention or control group. Validated Bangla versions of the Zarit Burden Interview, Hospital Anxiety and Depression Scale, and WHO - Quality of Life - Brief (WHOQOL-BREF) were administered at baseline, three months, and six months. Data were analyzed using repeated-measures analysis of variance under the intention-to-treat principle. The intervention group demonstrated significant reductions in caregiver burden (F=58.4, P<.001), anxiety (F=34.9, P<.001), and depression (F=34.9, P<.001) over six months, compared to the control group. Significant group × time interactions were observed for overall quality of life (QOL) (P<.001) and across physical (P<.001), psychological (P<.001), social (P=.004), and environmental (P<.001) domains. The combined mHealth psychoeducation and BRT intervention significantly reduced caregiver burden and psychological distress, and improved QOL among female caregivers of patients with cancer. This culturally adaptable, low-cost, technology-enabled approach offers a promising strategy to support caregiver needs in low- and middle-income countries where psychosocial services are limited.

Zolbetuximab combined with fluoropyrimidine-oxaliplatin chemotherapy has demonstrated clinical benefit in CLDN18.2-positive, HER2-negative advanced gastric and gastroesophageal junction adenocarcinoma (GC/GEJC). In clinical practice, however, gastrointestinal toxicity and serum albumin decline are frequently encountered during treatment, and the relationship between early albumin kinetics and antitumor efficacy remains unclear. We conducted a single-center retrospective exploratory study of patients with unresectable or recurrent CLDN18.2-positive GC/GEJC treated with zolbetuximab-based chemotherapy between July 2024 and August 2025. Tumor response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in patients with measurable disease. The objective response rate (ORR) and early tumor shrinkage (ETS ≥20%) were assessed. Serum albumin kinetics were analyzed using baseline albumin, landmark nadir albumin measured at or immediately before the first radiological evaluation, and relative change in albumin from baseline (ΔAlb). Associations between albumin metrics and tumor response were explored using exploratory analyses, including continuous-variable modeling. Relative dose intensity and chemotherapy backbone (CAPOX vs FOLFOX) were also descriptively examined. Among 38 eligible patients, 24 had measurable disease and were evaluable for RECIST-based response. Partial response was observed in 18 patients, yielding an ORR of 75.0% (95% CI, 55.1-88.0). Early tumor shrinkage ≥20% was achieved in a proportion of evaluable cases. Baseline serum albumin showed a moderate positive correlation with landmark nadir albumin (Spearman's ρ=0.35, P=.030) and with ΔAlb (ρ=0.52, P=.0007), indicating that patients with higher baseline albumin tended to experience greater absolute albumin decline. Neither landmark nadir albumin nor ΔAlb was significantly associated with the ORR or ETS. Early reductions in serum albumin were frequently observed during initial treatment cycles but did not correspond to impaired tumor response. In this real-world exploratory cohort, zolbetuximab-based chemotherapy achieved objective tumor responses consistent with prior clinical trials. Early serum albumin decline was not associated with inferior tumor response. These findings suggest that early albumin decline should not be interpreted as a surrogate marker of treatment failure or reduced antitumor efficacy but rather as a treatment-related physiological change. Prospective studies are warranted to clarify the clinical implications of albumin dynamics and optimize supportive care during anti-CLDN18.2 therapy.

Nuclear protein in testis (NUT) carcinoma is an extremely rare and aggressive malignancy characterized by NUTM1 gene rearrangement. It frequently develops in the lungs or the head and neck region as a poorly differentiated squamous cell carcinoma. The prognosis is generally poor and particularly dismal in cases with a pulmonary origin. Given the lack of an established standard treatment and the rapid disease progression, recently, immune checkpoint inhibitors (ICIs) have attracted attention, particularly in combination with platinum-based chemotherapy. We report a case series of four patients with pulmonary NUT carcinoma who received ICI-containing regimens as first-line therapy. Three patients received ICIs in combination with platinum-based chemotherapy and showed transient tumor shrinkage, although all ultimately experienced disease progression and died. One patient received ICI monotherapy owing to poor performance status and showed no clinical response. The median progression-free and overall survival were 53 and 108days, respectively. Given the limited treatment options for NUT carcinoma, a combination of ICIs with platinum-based chemotherapy may represent a potential first-line treatment option. However, their efficacy remains limited.

To identify independent prognostic factors for recurrence and develop a practical risk stratification system in patients with clinical T1 (cT1) clear-cell renal cell carcinoma (ccRCC) following curative-intent surgery. This retrospective multi-institutional study analyzed 1081 consecutive patients with cT1N0M0 ccRCC who underwent partial or radical nephrectomy at 14 Japanese tertiary centers (2016-21). We evaluated six established prognostic factors based on prior literature: pathological T3 upstaging, tumor size, nuclear grade, tumor necrosis, surgical approach, and venous invasion. Cox proportional hazards regression was performed to identify independent predictors of recurrence-free survival. During a median follow-up of 48months, 66 patients (6.1%) developed recurrence. Multivariable Cox regression identified two independent prognostic factors: pathological T3 upstaging (HR 4.67, 95% CI 2.40-9.08, P <.001) and tumor necrosis (HR 2.51, 95% CI 1.22-5.13, P =.012). Tumor size showed borderline significance (HR 1.22 per cm, 95% CI 1.00-1.49, P =.055). Based on the significant factors, patients were stratified into low-risk (91.1%, no upstaging/necrosis) and high-risk (8.9%, upstaging or necrosis present) groups with recurrence rates of 4.3% and 25.0%, respectively (log-rank P <.001). The 5-year recurrence-free survival rates were 95.2% and 73.4% for low- and high-risk groups, respectively. Pathological T3 upstaging and tumor necrosis were identified as the only independent predictors of recurrence in cT1 ccRCC. This simplified two-tier risk stratification effectively distinguishes a small high-risk subset (9% of patients) with 25% recurrence rate from the low-risk majority, enabling tailored surveillance strategies and appropriate selection for adjuvant therapy trials.

Radical lobectomy, proposed as a curative treatment for lung cancer in 1960, has long been regarded as the standard surgical approach. The findings of two phase III randomized controlled trials comparing limited resection versus lobectomy for non-small cell lung cancer (NSCLC) ≤2 cm have challenged the long-standing evidence supporting lobectomy as the universal surgical option for all patients with lung cancer. The Japanese clinical oncology group (JCOG) and West Japan Oncology Group (WJOG) (JCOG0802/WJOG4607L) demonstrated both the non-inferiority and superiority of segmentectomy, while the Cancer and Leukemia Group B trial (CALGB140503) conducted by the Alliance for Clinical Trials in Oncology in North America, confirmed the non-inferiority of limited resection, including wedge resection for NSCLC measuring ≤2 cm. As both trials demonstrated non-inferiority of limited resection in NSCLC ≤2 cm, their results are often summarized together. However, patient background, radiological findings, prognosis, and extent of resection differ significantly between the two trials and should be interpreted with caution. Previous trials have demonstrated that preserving lung parenchyma helps maintain pulmonary function and improves patient prognosis by enabling appropriate management of subsequent malignancy or other diseases. Limited resection, including segmentectomy, is currently the standard of care for early-stage NSCLC. The JCOG and WJOG are conducting trials to determine whether the indications for limited resection can be expanded to include patients with NSCLC >2 cm or those with stage I NSCLC. This review article outlines the results of previous trials, provides an overview of ongoing trials, and discusses prospects for limited resection.

Definitive chemoradiotherapy (CRT) is a treatment strategy for localized esophageal squamous cell carcinoma (ESCC). Herein, we aimed to evaluate clinical outcomes of definitive CRT for ESCC. We reviewed 127 patients who received definitive CRT for localized ESCC at our institution between January 2004 and December 2022. All patients received elective nodal irradiation with concurrent chemotherapy, primarily comprising cisplatin and 5-fluorouracil, during radiotherapy. Seventeen patients (13%) received intensity-modulated radiation therapy (IMRT) only, and 16 patients (13%) were treated with IMRT as a boost. The median total dose was 61.4Gy. Approximately 80% of the patients had clinical stage III or higher disease. We analyzed overall survival (OS), progression-free survival (PFS), locoregional recurrence rate (LRR), prognostic factors, and adverse events. The median follow-up period was 13months for all patients and 22months for survivors. The 2-year OS, PFS, and LRR were 40.4%, 27.1%, and 30.8%, respectively. The overall complete response rate was 40.2%. On multivariate analysis, clinical stage 0-III (non-T4) (P<.001) and the use of IMRT (P=.034) were significantly associated with better OS. Pulmonary toxicity was significantly lower in the IMRT group (P=.049). IMRT for localized ESCC may improve prognosis and reduce pulmonary toxicity.

The Geriatric-8 (G8) is used for the functional status of older adult patients with cancer. However, its role in treatment decision-making for gynecological malignancies has not been established. We retrospectively analyzed the data of 180 women aged ≥75years with gynecological malignancies who underwent initial treatment at our institution between January 2019 and December 2023. Pre-treatment G8 scores were assessed and patients were categorized as fit (G8>14) or frail (G8≤14). Associations between the G8 score and patient background, disease characteristics, treatment options, and treatment tolerability were examined. Of the 180 women, 53 (29.4%) were classified as fit and 127 (70.6%) as frail. Frail patients required long-term care (P=.008) and used anticoagulants more frequently than fit patients (P=.019). Median G8 scores were highest in endometrial cancer (14) and lowest in vulvar cancer (10). Best supportive care (8) and neoadjuvant chemotherapy (10) had lower G8 scores than surgery and concurrent chemoradiotherapy (14) (P<.001). Postoperative complications occurred in 10/96 surgical cases; these cases had lower scores than those without complications (12 vs. 14, P=.044). During chemotherapy, median scores were lower in women with ≥ grade 3 (12 vs. 14, P=.008) and grade≥4 adverse events (10 vs. 14, P=.002). The G8 score is associated with patient background, cancer type, and treatment options, and is associated with treatment tolerability in women aged ≥75years with gynecological malignancies.