Japanese journal of clinical oncology最新文献

Immune checkpoint inhibitors (ICIs) can induce diverse immune-related adverse events (irAEs), but pan-airway mucosal involvement is rare and may mimic common infectious laryngopharyngitis. A 76-year-old woman receiving long-term pembrolizumab for lung squamous cell carcinoma developed asthma-like symptoms ~1 year after treatment initiation, which were partially controlled with inhaled corticosteroid. Approximately 3 years after pembrolizumab initiation, she presented with persistent hoarseness and sore throat. Laryngoscopy showed diffuse erythema and a characteristic cobblestone-like appearance of the pharyngeal and laryngeal mucosa, and chest computed tomography revealed diffuse thickening of the tracheal and bronchial walls. Bronchoscopy demonstrated continuous mucosal inflammation extending from the bronchi to the larynx. Biopsies from both the larynx and trachea revealed identical dense CD8-positive T-cell infiltration without granulomatous changes, consistent with ICI-induced mucositis. Her symptoms and endoscopic and radiologic abnormalities resolved after discontinuation of pembrolizumab and initiation of oral prednisolone, and steroids were successfully tapered without recurrence. This case highlights a rare but clinically important pattern of ICI-induced pan-airway mucositis, in which lower-airway inflammation may be initially attenuated by inhaled steroids and later become evident after extension to the upper airway; such airway irAEs should be considered in ICI-treated patients presenting with persistent or atypical upper-airway symptoms.

Rectal cancer management has increasingly shifted toward organ-preserving strategies that aim to maintain oncologic control while preserving bowel, urinary, and sexual functions. Although radical surgery remains highly effective, its substantial long-term functional morbidity underscores the need for less invasive, risk-adapted approaches. This review summarizes current evidence and emerging directions in organ-preserving treatment for rectal cancer, with a particular focus on the evolving role of endoscopists in patient selection, treatment decision making, endoscopic treatment, and post-treatment surveillance. Recent advances in risk stratification have improved the potential for more accurate patient selection. Refined histopathological risk criteria, predictive nomograms, artificial intelligence-based models, and emerging liquid biopsy biomarkers, such as circulating tumour DNA, are being explored to better estimate the risk of lymph node metastasis after endoscopic resection. In parallel, novel endoscopic techniques, such as peranal endoscopic myectomy and endoscopic intermuscular dissection, have expanded the technical feasibility of en bloc resection for challenging rectal lesions. Local excision followed by adjuvant chemoradiotherapy represents a promising investigational strategy, with ongoing trials, such as TESAR and JCOG1612 (RESCUE), that are expected to clarify its safety and efficacy. Total neoadjuvant therapy has become a central treatment paradigm for locally advanced rectal cancer, achieving higher pathological complete response rates and improved disease-related outcomes compared with conventional neoadjuvant chemoradiotherapy. Additionally, non-operative management (watch-and-wait) after total neoadjuvant therapy, supported by prospective trials and international registries, has established a strong evidence base for organ preservation in carefully selected patients. In molecularly selected patients with mismatch repair-deficient or microsatellite instability-high tumours, immune checkpoint inhibitor-based therapy has emerged as a promising organ-preserving strategy, although current evidence remains limited to early-phase prospective studies. Despite these advances, optimal patient selection and long-term oncologic safety remain under investigation. Further prospective studies and international collaboration are needed to establish robust evidence and optimize the implementation of organ-preserving strategies in rectal cancer.

Background: Enfortumab vedotin (EV) exhibited superior efficacy in the EV-301 trial; however, real-world outcomes stratified by trial eligibility criteria remain unclear. We evaluated the real-world efficacy of EV in Japanese patients with metastatic urothelial carcinoma (mUC) via EV-301 eligibility stratification and restricted mean survival time (RMST) analysis.

Methods: This multicenter retrospective study analyzed 115 Japanese mUC patients treated with EV following platinum-based chemotherapy and immune checkpoint inhibitors. Patients were categorized as eligible (n = 81, 70.4%) or ineligible (n = 34, 29.6%) based on EV-301 criteria. The primary endpoint was overall survival (OS) evaluated via RMST at multiple time points. Reconstructed individual patient data from EV-301 enabled comparative analysis, with Bayesian power prior methodology integrating evidence sources.

Results: Eligible patients exhibited significantly higher OS than ineligible ones (HR 2.19, 95% CI 1.24-3.89, P = .009). RMST analysis at 12 months revealed OS of 9.65 months (95% CI 8.67-10.63) and 7.11 months (4.79-9.44) in eligible and ineligible patients, respectively. Significant RMST differences were observed between the eligible and ineligible groups at 6 months (1.18 months, P = .017) and 12 months (2.54 months, P = .049). Bayesian analysis with moderate borrowing (α = 0.5) revealed posterior RMST of 9.40 months (95% credible intervals 8.80-9.98) at 12 months. Eligible patients showed comparable RMST outcomes to EV-301 trial participants, with no significant differences.

Conclusions: EV exhibited real-world efficacy in Japanese mUC patients comparable to the eligible patients' outcomes in the EV-301 trial. Ineligible patients showed statistically inferior outcomes.

Background: Bevacizumab (BEV) is commonly used to treat unresectable or metastatic colorectal cancer; however, it is associated with delayed wound healing. This study aimed to assess whether administration of BEV within 14 days after central venous (CV) port placement was associated with an increased incidence of delayed wound healing complications.

Methods: This retrospective cohort study included patients with unresectable or metastatic colorectal cancer who underwent CV port placement between January 2017 and January 2023. The primary outcome was the incidence of wound-healing complications within 90 days. The incidence of complications was examined in 29 patients who received BEV within 8 weeks prior to CV port placement.

Results: Data on 264 matched patient pairs, selected from 778 eligible patients, were included in the analysis. Wound healing complications occurred in 4/264 patients (1.5%; 95% confidence interval [CI], 0.4%-4.0%) in the BEV group and 3/264 patients (1.1%; 95% CI, 0.2%-3.4%) in the non-BEV group, a nonsignificant difference (P > .99). Additionally, no wound-healing events were observed among the 29 patients who received BEV before CV port placement; however, this finding should be interpreted with caution because of the limited sample size.

Conclusions: Administration of BEV before and after CV port placement does not significantly increase the risk of delayed wound healing complications. These findings suggest that the risk of delayed wound healing associated with peri-CV port administration of BEV appears to be low in this specific clinical setting; however, this should be interpreted with caution and does not constitute definitive proof of safety.

Background: Comprehensive biomarker testing is mandatory for advanced non-small cell lung cancer (NSCLC). Pleural effusion cell blocks are a minimally invasive alternative to biopsy. The AmoyDx pan lung cancer (PLC) polymerase chain reaction panel is a sensitive multiplex assay; however, its performance using pleural cell-block specimens with low tumor-cell content remains largely unexplored.

Methods: We conducted a retrospective study of 30 patients with advanced NSCLC and having known driver mutations, whose pleural effusion cell blocks were tested using the AmoyDx PLC panel at Kanagawa Cancer Center between 2021 and 2023. Tumor content was quantified using thyroid transcription factor 1 immunohistochemistry. DNA and RNA quality were assessed, and the panel results were compared with those of other molecular assays.

Results: The AmoyDx PLC panel achieved a detection success rate of 96.7% (29/30), with a sole discordant case owing to the absence of malignant cells. The concordance in confirmed malignant cases was 100%. Notably, the panel detected target mutations in specimens with tumor contents well below the recommended threshold. High detection performance was observed even when the nucleic acid concentrations were suboptimal or the purity levels were outside the reference range. The median tumor content was 8.5% (range, 0.2%-88.2%), with 74% samples below the 20% threshold.

Conclusions: Pleural effusion cell blocks are a practical and reliable alternative for molecular testing of advanced NSCLC when biopsy is not feasible. The high sensitivity of the AmoyDx PLC panel even for specimens with low tumor cell content underscores its potential clinical utility.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Background: 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.

Methods: 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 12 months.

Results: Among 243 patients (median age: 67 years; 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).

Conclusions: 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.

Background: 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).

Methods: 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.

Results: The median follow-up was 24 months. 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.

Conclusion: 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 6.5 years. 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.