Japanese journal of clinical oncology最新文献

Background: Financial toxicity (FT) arises from the economic burden of cancer treatment and is associated with reduced quality of life and worse survival. However, its association with socioeconomic and financial factors among Japanese cancer patients has not been fully elucidated.

Methods: Between October 2023 and May 2024, a cross-sectional study was conducted among adult cancer patients undergoing chemotherapy for at least two months at two cancer centers in Japan. Patients receiving public assistance or who had participated in clinical trials were excluded. FT was assessed using the Comprehensive Score for Financial Toxicity (COST). Lower COST scores indicate higher FT. Associations between COST score and clinical, demographic, socioeconomic, and financial factors were analyzed using univariable linear regression.

Results: Of 258 patients invited, 245 responded, and 203 (78.7%) were analyzed. The median age was 62 years, and the most common primary tumor sites were head and neck (22.7%), colorectal (12.3%), and lung (11.3%). The median COST score was 22 (range: 2-41), with FT (COST <26) observed in 69.0% of patients. The use of coping strategies (β: -3.09; P = .03) and having debts or loans (β: -3.23; P = .04) were significantly associated with lower COST scores. Higher education (β: 3.61; P = .02), household annual income ≥14 million JPY (β: 8.44; P = .02), and savings of 10-12 million JPY (β: 9.99; P = .003) were associated with higher COST scores.

Conclusion: In this study, 69.0% of Japanese cancer patients experienced FT. The identified socioeconomic and financial factors may help clinicians detect patients at risk of financial vulnerability.

Background: Human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC) presents significant therapeutic challenges due to its molecular heterogeneity. Previous studies suggest that immune checkpoint inhibitors (ICIs) may enhance the efficacy of subsequent HER2-targeted therapy. However, evidence suggesting an optimal sequence for nivolumab and trastuzumab deruxtecan (T-DXd) treatment is limited. This exploratory analysis of EN-DEAVOR evaluated the effectiveness and safety of administering T-DXd relative to the timing of prior ICI administration.

Methods: This study assessed real-world outcomes of T-DXd in patients with HER2-positive AGC stratified by prior ICI exposure: within 2 months of nivolumab (Group A), >2 months (Group B), and no prior nivolumab (Group C). The primary effectiveness endpoints included real-world progression-free survival (rwPFS) and objective response rate (ORR). Safety endpoints included grade ≥ 3 adverse events (AEs).

Results: Among 311 eligible patients, Group A showed the longest median rwPFS (n = 63; 6.9 months) compared with Group B (n = 63; 4.6 months) and Group C (n = 185; 4.2 months). The risk of progression was significantly lower in Group A compared with Group B (hazard ratio [95% confidence interval]: 0.6 [0.4-0.9]; P = .0074). ORR was numerically highest in Group A (54.9%) versus Group B (30.8%) and Group C (43.4%). More patients in Group B (58.7%) experienced grade ≥ 3 AEs than in Group A (50.8%) and Group C (43.8%). No new safety signals were observed.

Conclusions: Initiating T-DXd within 2 months post-ICI may enhance therapeutic efficacy in HER2-positive AGC without affecting safety, supporting a potential sequencing option after ICI therapy.

This study examined recent international trends in age-standardized mortality for all cancers combined and major cancer types, comparing Japan with selected countries (Australia, Canada, the Republic of Korea (Korea), the United Kingdom, and the United States of America) using the latest available national data (from 1980 through the early 2020s). Overall cancer mortality in Japan continued to decline at a pace similar to that of other high-income countries. Marked reductions were observed for stomach and liver cancers in Japan, which historically had high mortality. These declines narrowed international differences, and mortality from female liver cancer in Japan has now fallen below levels in Western countries. Stomach cancer mortality rates have been continuously decreasing in Japan, while the pace was slower than that of Korea. In contrast to those decreasing cancers, Japan showed persistently high mortality for colorectal, pancreatic, and cervical cancers. Mortality from male lung cancer and female breast cancer in Japan declined only slowly or continued to rise, resulting in levels approaching those in Western countries. The decline in liver cancer is considered an effect of measures against hepatitis B and C, and could serve as an international model. The decrease in stomach cancer is also one of Japan's progressive movements, but comparisons with Korea indicate challenges remain in secondary prevention. Strengthened primary and secondary prevention are urgently needed for colorectal, lung, female breast, and cervical cancers, which have not shown a clear decreasing tendency in Japan.

Background: Parotid gland carcinoma (PGC) is rare and prognostic evidence is limited, making preoperative risk stratification challenging. We evaluated the prognostic relevance of pretreatment skeletal muscle mass measured on routine cervical magnetic resonance imaging.

Methods: We retrospectively analyzed 58 patients with histopathologically confirmed PGC treated between 1991 and 2024. Cervical skeletal muscle mass was quantified as the C3 skeletal muscle index (C3SMI) using axial T2-weighted magnetic resonance imaging (MRI) at the C3 level. Overall survival (OS) and recurrence-free survival (RFS) were assessed using Kaplan-Meier analysis and Cox proportional hazards models.

Results: Low C3SMI was significantly associated with worse OS and RFS on Kaplan-Meier analysis. In multivariable Cox models restricted to pretreatment variables, low C3SMI remained an independent predictor of shorter OS and RFS. In addition, low C3SMI was significantly associated with adverse pathological features, including high-grade histology, perineural invasion, extracapsular extension, and lymphovascular invasion.

Conclusions: MRI-derived C3SMI is an independent prognostic biomarker for survival and recurrence in PGC and correlates with pathological aggressiveness. Because C3SMI can be obtained from standard preoperative cervical MRI without additional imaging or radiation exposure, it may provide a practical tool for preoperative risk stratification and treatment planning in patients with PGC.

Background: Evidence regarding treatment outcomes of third-line systemic therapy after failure of immune checkpoint inhibitor (ICI) combinations and subsequent VEGFR-TKIs in advanced renal cell carcinoma (RCC) remains limited.

Methods: We retrospectively evaluated clinical data from 35 patients with advanced RCC who received third-line therapy following ICI-based first-line regimens and subsequent VEGFR-TKIs. Treatment effectiveness and safety during third-line therapy were assessed.

Results: The most frequently administered first-line, second-line, and third-line drugs were nivolumab plus ipilimumab (n = 25, 71%), axitinib (n = 21, 60%), and cabozantinib (n = 15, 43%), respectively. Clear-cell histology was observed in 23 patients (66%), and 14 patients (40%) were classified as International Metastatic RCC Database Consortium poor risk. Median progression-free survival (PFS) and overall survival (OS) from third-line therapy initiation were 7.43 and 15.2 months, respectively, with an objective response rate of 11%. Clear-cell histology (hazard ratio [HR] 0.30, p = 0.0131) and Karnofsky Performance Status ≥80% (HR 0.27, P = .0157) were associated with longer OS after multivariable adjustment. Grade ≥ 3 adverse events occurred in 13 patients (37%). Dose reduction, treatment interruption, and treatment discontinuation were required in 14 (40%), 14 (40%), and 5 (14%) patients, respectively. In the subgroup receiving the most common treatment sequence-first-line nivolumab plus ipilimumab followed by VEGFR-TKIs (n = 25)-median PFS and OS were 10.3 and 17.3 months, respectively.

Conclusion: Third-line systemic therapy following ICI combinations and sequential VEGFR-TKIs shows feasible clinical effectiveness and manageable toxicity in real-world patients with advanced RCC.

Background: Megaprosthetic reconstruction has become the standard method for resecting bone and soft tissue tumors. However, the long-term functional outcomes and complications have not yet been sufficiently investigated. This study aimed to address a gap in the literature by analyzing patients who underwent tumor prosthesis of the hip or knee and were followed up for over 30 years.

Methods: We retrospectively analyzed 10 patients who underwent megaprosthetic reconstruction of the hip or knee between 1986 and 1995 at two institutions in Japan, with a minimum follow-up of 30 years. Patient characteristics, complications, reoperation, and Musculoskeletal Tumor Society (MSTS) scores were reviewed. The long-term risks of reoperation, major revision, and deep infection were assessed.

Results: This study included seven distal femoral, two proximal femoral, and one proximal tibial reconstructions (median age at surgery, 22 years). Histologically, the tumors were predominantly osteosarcomas (n = 7). Eight of the 10 patients (80%) developed complications, with a median of 1.5 reoperations (range, 1-5). Major revisions occurred in five patients, including four with stem fractures and two with deep infections. The median overall reoperation-free survival was 16.2 years (95% confidence interval, 2.4-24.2). At the final follow-up, all patients remained ambulatory, and the median MSTS score was 75.0% (range, 53.3-96.7).

Conclusion: Despite the occurrence of frequent late complications, considerably long-term survivors following tumor endoprosthetic reconstruction in this small cohort were able to preserve ambulatory function for more than three decades, suggesting the effectiveness of this method while underscoring its lifelong risks and the necessity of long-term follow-up.

Objective: To evaluate the efficacy and safety of lenvatinib plus pembrolizumab (LP) for recurrent endometrial cancer, focusing on nonendometrioid histologic types such as carcinosarcoma and other rare variants.

Methods: Patients with recurrent endometrial cancer treated with LP at Jichi Medical University Hospital between December 2021 and August 2025 were retrospectively reviewed. Out of 26 patients, 15 had endometrioid carcinoma, whereas 11 had nonendometrioid carcinoma, specifically carcinosarcoma (n = 6), mesonephric-like adenocarcinoma (n = 2), dedifferentiated carcinoma (n = 1), mixed carcinoma (clear cell and endometrioid histology, n = 1), and clear cell carcinoma (n = 1). Clinical outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Prognostic factors for PFS were explored using Cox regression.

Results: The ORR and disease control rates, respectively, were 33.3% and 90.9% in nonendometrioid carcinoma, compared to 22.2% and 100% in endometrioid carcinoma. The median PFS was 6.2 months for nonendometrioid and 11.5 months for endometrioid carcinoma (hazard ratio [HR] 1.75, P = .295), while the median OS was 12.0 and 38.2 months, respectively (HR 2.41, P = .202). On multivariate analysis, histology, platinum-free interval, and eight-week relative dose intensity were not identified as independent prognostic factors. The most frequent AEs were hypertension (92.3%) and hypothyroidism (65.4%).

Conclusions: LP therapy demonstrated clinical activity in nonendometrioid carcinoma, including rare subtypes such as carcinosarcoma and mesonephric-like adenocarcinoma. Further accumulation of patients is warranted to validate its efficacy in these uncommon histologic types.

Objective: To evaluate the cost-effectiveness of treatment strategies for patients with breast cancer and bone metastasis (BM) developed with and without the involvement of a multidisciplinary BM cancer board.

Methods: In this single-center retrospective cohort study, we used previously published data and the data obtained from consecutive patients diagnosed with breast cancer and BM referred to the Tohoku University Hospital between July 2021 and May 2025. We developed a model combining a decision tree for the diagnosis and treatment phases of breast cancer and BM and a Markov model for long-term follow-up to evaluate the cost-effectiveness from a healthcare payer's perspective. The model included three health states: alive without skeletal-related event (SRE), alive with SRE, and death, with 1-month cycles. Effectiveness was measured in quality-adjusted life years. Deterministic and probabilistic sensitivity analyses were also performed.

Results: The strategy developed using BM cancer board inputs demonstrated superior cost-effectiveness; the incremental cost-effectiveness ratio was below the Japanese willingness-to-pay threshold of 5 million Japanese yen per quality-adjusted life year. Sensitivity analysis confirmed robustness of these results, with a tornado diagram identifying the key influential parameter: the probability of treatable BM in the BM cancer board strategy. In the probabilistic sensitivity analysis with 10 000 Monte Carlo simulations, more than half of the estimates fell below the willingness-to-pay threshold.

Conclusions: The treatment strategy developed by involving a BM cancer board is more cost-effective than that developed without involving such a board, justifying healthcare resource allocation for implementation of this board.

E7820, a sulphonamide-type anticancer agent, was developed to inhibit angiogenesis by suppressing integrin α2 expression. Although early-phase trials outside Japan established 100 mg/day as the maximum tolerated dose in monotherapy, no objective responses were observed, and further development was not planned. Subsequent studies revealed that E7820 promotes DCAF15-mediated degradation of the splicing factor RBM39 and acts as a molecular glue, providing a novel mechanism and rationale for clinical evaluation. Preclinical screening using patient-derived xenograft models demonstrated antitumour activity in biliary tract and endometrial cancers and in tumours with homologous recombination repair gene alterations. Based on these findings, the CIRCUS trial, a multicentre investigator-initiated phase I study, was initiated to assess the safety, tolerability, and preliminary efficacy of E7820 in Japanese patients with unresectable solid tumours. If the proof of concept is demonstrated in biomarker-defined cohorts, E7820 may be repositioned for selected patients, providing insights into the development of previously intractable compounds.