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.
BACKGROUND:First-line chemotherapy with maintenance therapy is expected to be well-tolerated and improve survival in patients with metastatic colorectal cancer (mCRC). This study evaluated the efficacy and safety of trifluridine/tipiracil (TAS-102) plus bevacizumab (Bev) as maintenance therapy for mCRC, omitting both oxaliplatin and fluoropyrimidines. MATERIALS AND METHODS:Patients with untreated mCRC initially received induction chemotherapy with fluoropyrimidine, oxaliplatin plus bevacizumab for 3-4 months. After achieving stable disease or better on imaging, 52 patients transitioned to maintenance therapy with TAS+Bev: TAS-102 (35 mg/m2, twice daily on days 1-5 and 8-12) plus Bev (5.0 mg/kg on Days 1 and 15, intravenously). Progression-free survival 1 (PFS1), defined as the time from the start of maintenance therapy to disease progression or death, was evaluated as the primary endpoint. RESULTS:The median cumulative dose of oxaliplatin during induction was 529 mg/m2. Median PFS1 during TAS+Bev maintenance was 8.7 months (95% CI: 5.5-12.3). The response rate and disease control rate during maintenance were 59.6% and 94.2%, respectively. Oxaliplatin reintroduction was feasible in 53.8% (28/52) of patient with a median total first-line chemotherapy duration was 16.2 months (95% CI: 14.5-20.6). Safety outcomes, including dose intensity and adverse events, were acceptable. CONCLUSION:This strategy of switching to first-line maintenance therapy with TAS+Bev demonstrated promising efficacy and safety. This strategy effectively avoided cumulative neurotoxicity, preserved quality of life and enabled reintroduction of oxaliplatin, suggesting it may represent a promising alternative strategy for patients ineligible for prolonged oxaliplatin-based treatment. Overall survival analysis is currently ongoing. [UMIN Trial ID: UMIN000031317].
We report a case of ALK-rearranged pulmonary large-cell neuroendocrine carcinoma (LCNEC) with brain metastases and radiologically suspected leptomeningeal involvement, successfully treated with first-line lorlatinib. A 58-year-old woman was diagnosed with LCNEC, and molecular testing revealed an EML4-ALK fusion. Lorlatinib achieved a partial response, with regression of the primary lesion, brain metastases, and suspected leptomeningeal lesions. Our literature review showed that ALK-positive LCNEC occurs more often in younger, female, and never- or light-smoking patients. In such cases, molecular testing should be actively pursued. In LCNEC harboring actionable driver alterations, molecularly guided treatment, as used for NSCLC, may be a reasonable option.
Introduction:The clinical and epidemiological features of spontaneous pneumomediastinum (SPM) have not been fully characterized, and no previous studies have investigated the association between the onset of SPM and meteorological factors. This study aimed to examine the features of pediatric SPM and to investigate the association between its onset and meteorological factors. Methods:The medical records of patients aged 1-18 years diagnosed with SPM between January 2012 and December 2023 were retrospectively reviewed. Meteorological data for the same 12-year period were extracted from the Japan Meteorological Agency website. Multivariable logistic regression analysis was performed to evaluate the association between the onset of SPM and monthly meteorological factors. Results:Overall, 39 SPM cases were identified, including 1 recurrence. Of these, 34 (87.2%) were male with a median age at onset of 15.0 years. The median body mass index of the 26 boys with available data was 19.0 kg/m2. The most common presenting complaint at the time of onset was chest pain, which was present in 23 (59.0%) individuals. Statistical analysis revealed a potential association between SPM onset and the monthly average ambient temperature (adjusted odds ratio 1.022; 95% confidence interval 1.010-1.035; p < 0.001). Conclusions:Patients diagnosed with SPM at the authors' hospital were predominantly adolescent boys with slim builds. We suggest that SPM should be considered as a differential diagnosis in cases of chest pain in slender adolescent boys. No clear association between the onset of SPM and meteorological parameters was identified; further studies using more robust methods are necessary.
