Eribulin is an approved treatment option for soft tissue sarcomas (STSs) in Japan; however, real-world data regarding its safety, efficacy, and optimal dosing strategies across heterogeneous patient populations remain limited. Thus, this study aimed to evaluate clinical outcomes, treatment tolerability, and prognostic factors in patients with STS treated with eribulin. We retrospectively reviewed 50 patients with STS who received eribulin at a single institution between 2018 and 2024. Clinical variables, dosing schedules, tumor responses, survival outcomes, and adverse events (AEs) were analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method; group comparisons were performed with the log-rank test. The cohort had a median age of 66 years, and eribulin was administered as first-line therapy in 24 patients. The disease control rate was 62%; one patient achieved complete response and one achieved partial response. Median PFS and OS were 4 and 19 months, respectively. Hematologic toxicities were the most common Grade ≥3 AEs, with no treatment-related cardiac events observed. Dose modifications included a bi-weekly schedule or a regimen consisting of two administrations followed by a 2-week rest period with pegfilgrastim support. No treatment discontinuations due to AEs occurred in either reduced-intensity schedule; the latter regimen demonstrated the longest treatment duration. Survival outcomes were comparable across age groups, treatment lines, histological subtypes, and tumor locations. Patients aged ≥70 years achieved a median OS of 16 months, generally consistent with previously reported outcomes in elderly sarcoma populations. Eribulin demonstrated favorable tolerability and durable disease control across diverse patient subgroups, including elderly and comorbid patients who are often ineligible for anthracycline therapy. Although no significant prognostic factors were identified, bi-weekly dosing and two-administration/2-week rest schedules were feasible, with the latter offering the advantage of pegfilgrastim support. These findings support the integration of eribulin into individualized treatment strategies for advanced STS and highlight the need for prospective studies to refine patient selection and optimize dosing approaches.

This study assessed the safety and effectiveness of selpercatinib, a selective rearranged during transfection (RET) kinase inhibitor, in patients with RET fusion-positive non-small cell lung cancer (NSCLC) in real-world clinical practice in Japan. This single-arm, multicenter, prospective observational study included patients with RET fusion-positive NSCLC who received at least one dose of selpercatinib between February 2022 and October 2023. Data were extracted from medical records and entered into an electronic data capture (eDC) system. Safety (adverse events [AEs] and AEs of special interest [AESIs]) and effectiveness (tumor response, overall survival [OS]) were assessed over 12months. Among 243 patients (median age: 67years; 56% females), AEs occurred in 86.0% of patients, with Grade≥3 AEs in 48.1% and serious AEs (SAEs) in 24.7%. The most common AEs (≥10%) included hypertension (23.5%), abnormal hepatic function (21.0%), rash (11.1%), aspartate aminotransferase increase (10.3%), and diarrhea (10.3%). AEs led to treatment modifications, including dose interruption (54.7%), dose reduction (14.8%), and discontinuation (6.2%). AESIs included liver injury (44.0%), hypertension-related events (23.9%), and hypersensitivity (MedDRA preferred term; 9.9%). The overall response rate was 58.8%, comprising complete response in 4.5% and partial response in 54.3% of patients. Median OS was not reached; the 12-month survival rate was 80.9% (95% CI, 74.9-85.6). Real-world data showed selpercatinib to be effective in patients with RET fusion-positive NSCLC in Japan, with a favorable safety profile and no new safety concerns.

Lymphovascular invasion (LVI) is an established adverse prognostic factor in urothelial carcinoma; however, prior studies have rarely distinguished lymphatic vessel invasion (LymVI) from blood vessel invasion (BVI). We investigated the prevalence and prognostic significance of LymVI and BVI in upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNUx), and assessed their associations with clinicopathological characteristics and metastatic patterns. We retrospectively analyzed 455 patients who underwent RNUx at Jikei University Hospital and six affiliated centers between 2012 and 2021. LVI subtype was assessed using hematoxylin-eosin staining, supplemented by D2-40, CD31, and Elastica van Gieson staining when required. Patients were categorized into four groups: no LVI, LymVI only, BVI only, and combined LymVI+BVI. Outcomes included non-urothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Kaplan-Meier methods and Cox regression analyses were used to evaluate prognostic associations. LVI subtypes were distributed as follows: no LVI (65.1%), LymVI only (9.9%), BVI only (7.7%), and combined LymVI+BVI (17.4%). Higher pathological T and N stages were observed progressively across these groups (P<0.001). BVI only and combined LymVI+BVI were independent predictors of inferior NUTRFS (HR 4.52 and 5.01), OS (HR 2.46 and 2.73), and CSS (HR 2.85 and 4.06), whereas isolated LymVI did not significantly affect outcomes. Hematogenous metastases to the lung, liver, and bone were significantly more frequent in patients with BVI or combined LVI. Distinguishing BVI from LymVI provides refined prognostic stratification in UTUC. BVI, alone or combined with LymVI, is strongly associated with adverse survival and increased hematogenous dissemination, while isolated LymVI has limited prognostic impact. Routine pathological subclassification of vascular invasion may improve postoperative risk assessment and guide adjuvant treatment decisions.

Although pivotal trials have demonstrated the superiority of triplet therapy over androgen deprivation therapy (ADT)-docetaxel doublet therapy, direct comparisons between triplet and androgen receptor pathway inhibitor (ARPI)-ADT doublet therapy remain lacking in real-world practice. This study evaluated the comparative efficacy and safety of triplet versus ARPI-doublet therapy in patients with metastatic castration-sensitive prostate cancer (mCSPC). A total of 837 patients with de novo mCSPC treated between February 2018 and April 2025 were included: 121 received triplet therapy (darolutamide plus docetaxel with ADT), and 716 received ARPI-doublet therapy (abiraterone acetate, enzalutamide, or apalutamide with ADT). The primary endpoint was castration-resistant prostate cancer-free survival (CRPC-FS), and the secondary endpoints were progression-free survival 2 (PFS2) and treatment-related adverse events (TRAEs). Propensity score-based inverse probability of treatment weighting (IPTW) and multiple sensitivity analyses adjusted for baseline imbalances. The median follow-up was 24months. In the IPTW-adjusted analysis, triplet therapy significantly improved CRPC-FS compared with ARPI-doublet therapy (hazard ratio 0.52, 95% confidence interval 0.39-0.68; P<.001). Subgroup analysis demonstrated consistent benefits in patients with high-volume disease, while no CRPC events occurred in the low-volume subgroup. Sensitivity analyses using propensity score matching and truncated IPTW confirmed the robustness of these findings. Cancer-specific and overall survival were not assessable because of limited follow-up and few events in the triplet cohort. Regarding safety, triplet therapy was associated with higher rates of grade≥3 TRAEs (48.8% vs 8.7%), mainly hematologic toxicities. Triplet therapy significantly prolonged CRPC-FS compared with ARPI-doublet therapy in patients with de novo mCSPC, particularly among those with high-volume disease. However, this benefit was accompanied by higher toxicity, underscoring the need to balance efficacy with safety. Longer follow-up is required to determine impacts on PFS2, cancer-specific survival, and overall survival.

Multiple cancers occur in the same individual, such as hereditary breast and ovarian cancer (HBOC) syndrome and Lynch syndrome. Here, we report a patient with HBOC syndrome who developed four different cancer types (pancreatic cancer, right lung adenocarcinoma, prostate cancer, and left lung adenocarcinoma) within a relatively short period of 6.5years. In HBOC syndrome, the lung adenocarcinoma is rare, and the tumors were initially suspected to be lung metastases from pancreatic cancer, respectively. The pathological analysis results in each of the three lesions were inconsistent. A whole-exome analysis was performed on all three tumors using next-generation sequencing (NGS). The results showed that many of the deletion mutations found in pancreatic cancer were not present in other lung tumors. Homologous recombination is required for the repair of deletion mutations, but this function is impaired in HBOC syndrome. Deletions occurring in the primary tumor are irreversible and should be inherited in metastatic lesions. Therefore, we hypothesized that these three cancers arose independently, that each lung tumor was a primary tumor rather than a metastasis of pancreatic cancer, and that their resection would be curative. This assumption was reasonable, as no new lesions were observed in a 10-year follow-up study since the onset of pancreatic cancer. Tracking genetic traits using NGS helps understand the origins and progression of malignant tumors.

We evaluated the significance of spread through alveolar space (STAS) as a predictor of cancer recurrence in epidermal growth factor receptor (EGFR)-mutated pathological stage IA lung adenocarcinomas. Between 2011 and 2020, data from 856 patients with surgically resected pathological stage IA EGFR-mutated lung adenocarcinoma were evaluated to investigate the oncological and prognostic roles based on the presence of STAS. The cumulative incidence of recurrence (CIR) was estimated using the Fine-Gray test. Survival outcomes were assessed using Kaplan-Meier analysis and log-rank tests. Seventy patients (8.2%) were STAS-positive, demonstrating a higher proportion of larger tumor size, lymphovascular invasion, nonlepidic predominant lesions, and the Ex19 subtype (P < .001). Postoperative cancer recurrence was significantly higher in the STAS-positive group (total: 18.6% vs. 5.7%, P < .001; locoregional: 10.0% vs. 3.8%, P = .015; distant: 15.7% vs. 3.7%, P < .001). Both CIR and recurrence-free survival (RFS) differed significantly according to the presence of STAS (5y-CIR: 14.4% vs. 4.2%, P < .001; 5y-RFS: 83.2% vs. 91.8%, P = .001). Multivariate analysis revealed that the presence of STAS (P = .028), lymphovascular invasion (P = .020), pathologic tumor size (P = .036), and absence of a lepidic component (P < .001) were independent significant factors for CIR. When combined with STAS, these factors further increased recurrence prediction (STAS and absence of a lepidic component, 5y-CIR: 26.8% vs. 4.0%, P < .001; STAS and larger tumor size, 18.1% vs. 4.3%, P < .001; STAS and lymphovascular invasion, 27.1% vs. 4.5%, P < .001). STAS is an important risk factor for predicting postoperative cancer recurrence in EGFR-mutated pathological stage IA lung adenocarcinomas.

Residual or recurrent esophageal squamous cell carcinoma (ESCC) after definitive chemoradiotherapy (CRT) is a therapeutic challenge. Salvage surgery is invasive, and endoscopic resection is limited by radiation-induced fibrosis. Argon plasma coagulation (APC) and photodynamic therapy (PDT) are less invasive salvage options, however their role in depth-oriented organ-preserving strategies remains unclear. We analyzed 52 consecutive patients with residual or recurrent ycT1-2 ESCC who underwent CRT. APC is indicated for ycT1a lesions, and PDT is indicated for ycT1b-T2 lesions, with flexibility. We evaluated the survival rates, adverse events, and predictors of local failure. Thirteen patients underwent APC, and 39 underwent PDT. The overall local complete response rate was 78.8% (92.3% APC and 74.3% PDT). During a median follow-up of 24.7months (range, 1.9-110.5months), the 2-year overall survival, progression-free survival, disease-specific survival, and esophagectomy-free survival rates were 82.8%, 44.0%, 86.7%, and 75.9%, respectively. Adverse events occurred in 30.8% of APC patients and 41.0% of PDT patients, all of which were manageable without treatment-related mortality. Multivariate analysis identified ycT2 stage (hazard ratio [HR]: 9.61, 95% confidence interval [CI]: 1.04-88.55, P=.04) and tumor location in the upper thoracic esophagus (HR 3.48, 95% CI 1.02-11.85; P=.04) as independent predictors of local failure. A salvage endoscopic strategy applying APC for ycT1a and PDT for ycT1b-T2, with flexibility based on tumor depth, is feasible, safe, and effective. Tailoring treatment to invasion depth may optimize organ preservation and local control in residual or recurrent ESCC after CRT.

The phase III TALAPRO-2 trial showed that talazoparib plus enzalutamide significantly improves radiographic progression-free survival (rPFS) in patients with metastatic castration-resistant prostate cancer. In contrast, the Japanese subgroup (n=116) demonstrated non-significant results with wide confidence intervals, as expected, because of the limited sample size. We attempted to provide complementary insights using Bayesian methods to quantify the probability of treatment benefit. We performed a Bayesian analysis using published data from the TALAPRO-2 trial. Prior distributions were set across four scenarios based on global trial data: neutral prior (no borrowing), conservative borrowing (prior standard deviation [SD]=2×standard error [SE]), moderate borrowing (prior SD=1.5×SE), and strong borrowing (prior SD=SE). The posterior distributions for the Japanese subgroup were derived using normal-normal conjugate updating. The 'treatment effectiveness (hazard ratio [HR] < 1)' probability in Japanese all-comers reached 98% with conservative borrowing and>99% with moderate and strong borrowing. With moderate borrowing, the posterior mean HR was 0.67 (95% credible interval 0.50-0.89). In the homologous recombination repair-deficient subgroup, all borrowing scenarios excluded HR=1.0, with P(HR<1.0) exceeding 99%. Using Bayesian evidence synthesis with prespecified borrowing levels, the Japanese subgroup results were compatible in direction and magnitude with the overall TALAPRO-2 effect. These findings reduce uncertainty around local extrapolation; a dedicated randomized study would be required to establish efficacy independently in Japanese patients.

Patients undergoing curative surgery for upper gastrointestinal (UGI) cancers often experience substantial postoperative weight loss and reduction in muscle mass, one contributing factor being decreased ghrelin secretion following surgery. Anamorelin, a ghrelin receptor agonist, has been shown to improve appetite and increase lean body mass in patients with cancer cachexia; however, its efficacy in the postoperative setting has not been established. The CLEAR-UP study is a multicenter, open-label, randomized controlled trial designed to investigate the clinical effects of anamorelin in patients who have undergone curative resection for gastric or esophageal cancer. A total of 160 patients will be randomly assigned in a 1:1 ratio to receive either anamorelin (100mg orally once daily for 12weeks) or standard postoperative care without pharmacological intervention. Randomization will be stratified by cancer type (gastric vs. esophageal) and baseline body mass index (BMI <18.5 vs. ≥18.5). All patients will be followed for 48weeks. The primary endpoint is the percent change in lean body mass at 12weeks, assessed using multifrequency bioimpedance analysis. Secondary endpoints include changes in body weight, fat mass, muscle, and fat cross-sectional area on CT, muscle strength, appetite, quality of life, hormonal markers, nutritional indicators, and adverse events. This study aims to clarify the potential benefits of anamorelin in mitigating postoperative deterioration of body composition in patients with UGI cancer and to provide essential preliminary data to inform the design of future confirmatory trials.

Radical cystectomy (RC) remains the standard treatment for muscle-invasive bladder cancer (MIBC), but is highly invasive and may cause functional decline, especially among geriatric patients. This study evaluated age-stratified outcomes of RC through a nationwide, multi-institutional cohort in Japan. We analyzed 1867 patients with MIBC who underwent RC at 36 institutions, stratified into five age groups: <60, 60-69, 70-74, 75-79, and≥80years. The baseline characteristics, perioperative factors, and oncological outcomes were compared. Patients aged ≥80years had significantly worse overall survival (OS, P<.001), cancer-specific survival (CSS, P=.006), and disease-free survival (DFS, P=.004) after RC. Although preoperative clinical T stage was comparable (P=.22), patients aged ≥80years less frequently received neoadjuvant chemotherapy (NAC), and more often showed pathological extravesical extension and positive surgical margins (all P<.001). The incidence of grade≥3 complications and 30-day mortality were comparable, whereas 90-day mortality was higher in this group (P=.047). Multivariable Cox analysis confirmed age≥80years as an independent predictor for unfavorable OS (P<.001), CSS (P=.017), and DFS (P=.018). Among patients aged ≥80years, the use of NAC was associated with better OS (P=.033), particularly in those with Eastern Cooperative Oncology Group performance status of 0 (P=.015). Patients aged ≥80years had significantly worse oncological outcomes after RC. NAC may improve OS in selected older patients with good performance status.