BACKGROUND:To evaluate the dissemination and real-world implementation of recommendations from the 5th Edition of the Japanese Esophageal Cancer Practice Guidelines and to inform development of the upcoming 6th Edition, the Guideline Committee of the Japanese Esophageal Society conducted a nationwide Quality Indicator (QI) survey in Japan. METHODS:A nationwide, cross-sectional, web-based questionnaire survey was distributed to 381 certified institutions participating in the 2023 National Registry of Esophageal Cancer in Japan. Conducted in November 2024, the survey covered six domains-epidemiology, surgery, endoscopy, chemotherapy, radiation therapy, and pathology-reflecting key recommendations of the 5th Edition. Responses were summarized descriptively at the institutional level. RESULTS:Valid responses were obtained from 190 institutions (49.9%). Smoking cessation guidance was implemented in more than 90% of institutions, and over 90% also provided guidance on alcohol abstinence or moderation, although complete alcohol abstinence was less uniformly recommended. Minimally invasive, including robot-assisted, esophagectomy was adopted by over 90% of institutions. The proportion of institutions performing prophylactic cervical lymph node dissection varied by tumor location and stage, reflecting contemporary staging concepts. The DCF regimen was the predominant neoadjuvant therapy for stage II/III disease (94.7%), and immune checkpoint inhibitor-based chemotherapy was widely used for unresectable or recurrent disease. Advanced endoscopic diagnostic modalities, including magnifying and image-enhanced endoscopy, were widely adopted. CONCLUSIONS:This nationwide QI survey demonstrates broad adherence to guideline-based multidisciplinary management of esophageal cancer in Japan and provides an evidence base for refining recommendations in the 6th Edition of the Japanese Esophageal Cancer Practice Guidelines.
BACKGROUND: Japan Clinical Oncology Group (JCOG) defined gastric cancer (GC) with bulky lymph node (Bulky N) and/or para-aortic lymph node (PAN) as extensive lymph node metastasis (ELM), and has developed neoadjuvant chemotherapy followed by D2 gastrectomy with PAN dissection (PAND) through three phase II trials using different regimens (JCOG0001: irinotecan/cisplatin, JCOG0405: cisplatin/S-1, JCOG1002: docetaxel/cisplatin/S-1). However, whether PAND provides survival benefit remains uncertain. METHODS: The therapeutic value index was investigated using integrated data from JCOG0001, JCOG0405, and JCOG1002. Patients were classified into Bulky N group (only bulky N without PAN) and PAN group (PAN regardless of bulky N) based on the clinical diagnosis. The index was calculated by multiplication of incidence of metastasis and percentage 5-year relapse-free survival (5yRFS) of patients with metastasis for each lymph node area. RESULTS: A total of 122 patients were analyzed (Bulky N group: 68, PAN group: 54). In Bulky N group, the proportion of metastasis/5yRFS/index in the PAN area was 15.2%/30.0%/4.5 (JCOG0001: 27.8%/20.0%/5.6, JCOG0405: 13.6%/33.3%/4.5, JCOG1002: 7.7%/50.0%/3.8). The proportion of metastasis decreased across trials. In PAN group, the proportion of metastasis/5yRFS/index in the PAN area was 44.4%/4.2%/1.9 (JCOG0001: 81.3%/7.7%/6.3, JCOG0405: 30.0%/0.0%/0.0, JCOG1002: 27.8%/0.0%/0.0). Notably, the indices of the recent two trials were zero. CONCLUSIONS: PAND may retain a potential role in the Bulky N group, whereas its benefit appears limited in the PAN group. Decreasing trends in PAN metastasis and therapeutic value were observed in both groups. Given the distinct characteristics of these subgroups, the omission of PAND should be determined through separate future validation.
Lynch syndrome (LS) is an autosomal-dominant hereditary disorder caused by germline pathogenic variants in mismatch repair (MMR) genes, predisposing individuals to multiple malignancies. In Japan, universal screening for LS, such as through microsatellite instability (MSI) testing, is not widely implemented. Moreover, MMR genetic testing is not covered by insurance, often leading to missed diagnoses. We present a rare case of a 72-year-old woman with LS who developed nine metachronous cancers over 35 years, including colorectal, endometrial, gastric, breast, and skin cancers, one of the highest numbers reported in a single patient. She had a family history of cancer. MSI testing of colorectal cancer tissues revealed MSI-high status; therefore, LS was suspected. The definitive diagnosis was established through germline genetic testing, which identified pathogenic MLH1 variants. Each cancer was treated with curative resection. The patient remained disease-free for 3.8 years after her most recent skin cancer surgery. This case underscores the importance of early detection, systematic surveillance, and timely intervention in achieving long-term survival in patients with LS. It highlights the potential for early diagnosis, optimal management, and improved outcomes through comprehensive cross-organ monitoring and emphasizes the need for expanded LS screening, including MMR genetic testing.
After a median study follow-up of 36.6 months, first-line pembrolizumab plus chemotherapy numerically improved overall survival (OS) and progression-free survival (PFS) versus placebo plus chemotherapy in Japanese participants with advanced esophageal cancer in the phase 3 KEYNOTE-590 study. The 5-year follow-up is presented. Participants with previously untreated advanced esophageal cancer were randomly assigned 1:1 to pembrolizumab 200 mg or placebo every 3 weeks up to 35 cycles plus chemotherapy (cisplatin 80 mg/m2 and 5-fluorouracil 800 mg/m2/day). Primary end points were OS and PFS per RECIST v1.1 by investigator; objective response rate (ORR) and safety were secondary. The data cutoff date was July 10, 2023. In total, 141 of 794... participants were enrolled in Japan. Median study follow-up was 60.6 months (range, 53.8–69.7). Median OS was 17.7 months (95
Background:Gastric cancer (GC) with peritoneal dissemination remains a challenge with poor prognosis and limited treatment options. We aimed to compare solvent-based paclitaxel (sb-PTX) + ramucirumab (RAM) vs. nanoparticle-albumin-bound paclitaxel (nab-PTX) + RAM as second-line therapy for unresectable or recurrent GC with peritoneal dissemination. Methods:This prospective, randomised, open-label, multicentre phase 2 trial was conducted at 58 centres within the West Japan Oncology Group (WJOG) in Japan. Eligible participants were patients with histologically-confirmed GC with peritoneal dissemination refractory or intolerant to first-line therapy. Patients were randomised 1:1 to receive sb-PTX + RAM or nab-PTX + RAM. Primary endpoint was overall survival (OS); key secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), safety, and protocol-specified biomarker analyses including the assessment of stromal caveolin-1 (Cav-1) expression by immunohistochemistry on archival tumour specimens. The data cutoff for the analysis presented herein was January 27, 2021. This trial was registered in the Japan Registry of Clinical Trials (jRCTs031180022). Findings:Between Oct 1, 2018, and Jan 27, 2020, 105 patients were assigned to sb-PTX + RAM (n = 53) or nab-PTX + RAM (n = 52). Median follow-up was 18.1 months. Median OS was 8.1 months with sb-PTX + RAM and 7.2 months with nab-PTX + RAM (HR [nab-PTX + RAM vs. sb-PTX + RAM], 0.960; 95% CI, 0.621-1.484; P = 0.631). Median PFS was 5.1 vs. 3.9 months (HR [nab-PTX + RAM vs. sb-PTX + RAM], 0.965; 95% CI, 0.642-1.450; P = 0.893). ORR was 20.7% vs. 20.0% (P = 0.993), and DCR was 77.4% vs. 63.5% (P = 0.150), with sb-PTX + RAM and nab-PTX + RAM. Grade≥3 neuropathy occurred in 7.5% with sb-PTX + RAM and 17.6% with nab-PTX + RAM, and febrile neutropenia in 11.3% vs. 5.9%. In biomarker analysis, OS and PFS improved stepwise with increasing Cav-1 expression in patients receiving nab-PTX + RAM (P = 0.007, P = 0.012); no such association was observed with sb-PTX + RAM. Among patients with high stromal Cav-1 expression (IHC score 3+), nab-PTX + RAM showed some evidence of improved OS compared with sb-PTX + RAM (HR [nab-PTX + RAM vs. sb-PTX + RAM], 0.371; 95% CI, 0.130-1.060; P = 0.055). The interaction between Cav-1 expression and treatment arm showed a non-significant trend (HR for interaction, 0.364; 95% CI, 0.115-1.152; P = 0.086), consistent with this finding. Interpretation:Treatment with nab-PTX + RAM did not meet the prespecified threshold (HR < 0.90) for promising efficacy in patients with GC and peritoneal dissemination. High stromal Cav-1 expression was associated with improved efficacy of nab-PTX + RAM. Future studies should prospectively validate the predictive value of stromal Cav-1 in patients receiving nab-PTX + RAM. Funding:Taiho Pharmaceutical Co. Ltd.
