Japanese journal of clinical oncology最新文献

Background: The JAVELIN Bladder 100 trial established avelumab maintenance as standard care for advanced urothelial carcinoma (UC). However, Asian (n = 147) and Japanese (n = 73) subgroups showed non-significant results with wide confidence intervals, as expected given limited sample sizes. We sought to provide complementary insights using Bayesian methods that quantify probability of treatment benefit.

Methods: We performed Bayesian reanalysis using published data from JAVELIN Bladder 100. The global trial data (n = 700; HR = 0.76, 95% CI: 0.63-0.91) informed prior distributions across four scenarios: neutral prior (no borrowing), conservative borrowing (prior SD = 2 × Standard Error [SE]), moderate borrowing (prior SD = 1.5 × SE), and strong borrowing (prior SD = SE). Posterior distributions were derived using normal-normal conjugate updating.

Results: For the Asian cohort, posterior mean hazard ratios ranged from 0.754-0.758 across borrowing scenarios, with probability of benefit P(HR < 1) ranging from 85.5% (neutral) to 99.9% (strong). The Japanese cohort showed posterior mean HRs of 0.763-0.828, with P(HR < 1) ranging from 71.9% (neutral) to 99.9% (strong). Under moderate borrowing, both cohorts achieved credible intervals excluding 1.0 (Asian: 0.591-0.966; Japanese: 0.594-0.990). Probability of clinically meaningful benefit P(HR < 0.8) reached 67.5% in Asian and 62.7% in Japanese patients.

Conclusions: While statistical limitations exist regarding the non-independence of data sources and dominance of global information, the high probabilities of benefit across all analytical scenarios support the use of avelumab in these populations. These findings illustrate both the utility and limitations of Bayesian methods in interpreting underpowered regional subgroups, supporting equitable access to effective cancer therapies.

Background: Psychoeducational and relaxation-based interventions have been shown to reduce caregiver burden; however, limited evidence exists regarding the effectiveness of combined interventions delivered via mobile health (mHealth) in resource-limited settings. This study aimed to evaluate the combined effects of mHealth-based psychoeducation and the Benson Relaxation Technique (BRT) on caregiver burden among female informal caregivers of patients with cancer.

Methods: A prospective, open-ended, randomized controlled trial (1:1 allocation) was conducted from October 2024 to March 2025. In total, 102 female caregivers were randomly assigned to either the intervention or control group. Validated Bangla versions of the Zarit Burden Interview, Hospital Anxiety and Depression Scale, and WHO - Quality of Life - Brief (WHOQOL-BREF) were administered at baseline, three months, and six months. Data were analyzed using repeated-measures analysis of variance under the intention-to-treat principle.

Results: The intervention group demonstrated significant reductions in caregiver burden (F = 58.4, P < .001), anxiety (F = 34.9, P < .001), and depression (F = 34.9, P < .001) over six months, compared to the control group. Significant group × time interactions were observed for overall quality of life (QOL) (P < .001) and across physical (P < .001), psychological (P < .001), social (P = .004), and environmental (P < .001) domains.

Conclusion: The combined mHealth psychoeducation and BRT intervention significantly reduced caregiver burden and psychological distress, and improved QOL among female caregivers of patients with cancer. This culturally adaptable, low-cost, technology-enabled approach offers a promising strategy to support caregiver needs in low- and middle-income countries where psychosocial services are limited.

Background: For patients suffering from intractable cancer pain, which cannot be sufficiently relieved even with strong opioid analgesics, methadone is recommended in Japan. However, the real-world data on the efficacy and safety of methadone for intractable pain in patients with lung cancer remain scarce in clinical setting. The aim of this clinical study was to investigate the efficacy and safety of methadone for intractable pain in advanced lung cancer patients.

Methods: All the cases of advanced lung cancer patients who were administered methadone for intractable pain at the Shizuoka Cancer Center between September 2014 and December 2022 were extracted, and their medical information in the electronic medical records were examined. We investigated pain intensity in Numeric Rating Score (NRS) on the day before and 5 days after the initiation of methadone administration, when methadone blood levels were expected to reach a plateau. In addition, the adverse events possibly caused by methadone were also investigated.

Results and conclusions: Methadone was prescribed for intractable pain in 37 patients with advanced lung cancer during the study period. The leading cause of intractable pain was bone metastasis (including invasion). Both the pain intensity in NRS and the number of rescue doses were significantly reduced by the introduction of methadone (P < .001). In only two patients, methadone was discontinued due to the side effects thought to be caused by this drug. The results of this study indicated the favorable efficacy and safety profile of methadone for intractable pain in patients with advanced lung cancer.

Background: To evaluate the current state of hereditary cancer syndrome management in patients with ovarian and endometrial cancer and to identify the barriers to uptake of genetic testing.

Methods: We conducted a cross-sectional multicenter study at five regional cancer centers in Japan, including 229 patients with ovarian cancer and 454 with endometrial cancer treated between January 2021 and December 2022. We assessed the proportion of patients who received information about hereditary cancer syndromes from gynecologists, underwent genetic counseling with genetic experts, and completed genetic testing; in addition, we explored the barriers to testing uptake.

Results: Among patients with ovarian cancer, 152 (66.4%) received information about hereditary cancer syndromes from their gynecologists, with 61 (26.6%) subsequently receiving genetic counseling and 58 (25.3%) undergoing genetic testing. By contrast, patients with endometrial cancer demonstrated markedly lower rates: only 76 (16.7%) received initial information, 22 (5.3%) accessed genetic counseling, and 13 (2.9%) completed genetic testing. Among patients who received information about hereditary cancer syndromes from their gynecologists, 38% with ovarian cancer and 14% with endometrial cancer underwent genetic testing. Among patients identified as high-risk for hereditary cancer syndromes through tumor profiling, 27.6% (8/29) with ovarian cancer and 70.6% (12/17) with endometrial cancer did not undergo genetic testing. Patient disinterest was the primary barrier to genetic testing among high-risk individuals.

Conclusions: The barriers to uptake of genetic testing arise primarily from inadequate provider communication and patient disinterest in hereditary cancer syndromes.

Purpose: Prostate-specific membrane antigen radioligand therapy (PSMA RLT) improves survival in metastatic castration-resistant prostate cancer (mCRPC). However, evidence in Japanese cohorts is limited. We evaluated the safety and efficacy of PSMA RLT in Japanese patients with mCRPC.

Materials and methods: We retrospectively analyzed 82 Japanese patients with mCRPC treated with PSMA RLT between 2018 and 2024 in Australia. PSMA RLT included Lutetium-177, Actinium-225, or Terbium-161 conjugated PSMA ligands, following PSMA Positron Emission Tomography / Computed Tomography confirmation of target expression. Endpoints were prostate-specific antigen (PSA) response (≥50% decline), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TrAEs). Cox proportional hazards regression identified prognostic factors for survival.

Results: Thirty-one patients (38%) achieved a PSA response. Median PFS and OS were 4 and 20 months, respectively. While no significant difference was observed in >50% PSA decline, >80% decline was significantly higher in chemo-naïve patients (43% vs. 7.4%, P < .001), with longer PFS (8 vs. 3 months, P = .006) and OS (not reached vs. 11 months, P < .001). On multivariable analysis, poorer performance status and prior chemotherapy were independent factors for worse OS. TrAEs of any grade occurred in 49 patients (60%), most commonly fatigue. Grade ≥ 3 TrAEs occurred in 15%, with no treatment-related deaths.

Conclusion: PSMA RLT provided meaningful clinical benefit with favorable tolerability in Japanese patients with mCRPC, especially those without prior chemotherapy. Early integration of PSMA RLT may offer additional therapeutic advantages.

Background: Immune checkpoint inhibitors (ICI) have recently been developed and launched in Japan, at the same time, soaring national healthcare costs have become one of the major social issues. We investigated the volume of prescriptions and the drug costs of ICIs using National Database (NDB) open data.

Methods: This is a retrospective cohort study; we used aggregate data between fiscal year (FY)2015 and FY2022 (April 2015-March 2023) from the NDB. The drugs of interest included nivolumab, ipilimumab, pembrolizumab, avelumab, atezolizumab, and durvalumab. Findings are presented as descriptive statistics.

Results: Since the introduction of ICIs, prescription volume of all ICIs increased overtime. Overall ICI drug costs increased from 16 898 million yen in FY2015 to 419 615 million yen in FY2022; the total of ICI drug costs from FY2015 to FY2022 was over 1 793 billion yen. For each drug, >70% of drug costs were generally for patients aged 65 years or older. In addition, total drug costs tended to increase over the years among those aged 75 and over.

Conclusions: Drug costs for ICIs are significantly increasing despite the Japanese government's frequent efforts to reduce ICI drug prices. The elderly population made up a particularly high proportion of those burdened with the higher costs. Healthcare economic policies are warranted to ensure efficient distribution of budgetary resources.

Background: Anthracycline (A) and taxane (T)-based therapies improve breast cancer survival, with guidelines strongly recommending these regimens and dose-dense approaches. However, the real-world maintenance of optimal dose intensity, a critical prognostic factor, remains unclear. We aimed to clarify the current treatment situation regarding relative dose intensity (RDI), with a secondary focus on safety.

Methods: In this retrospective observational study, we analyzed big data from the DATuM IDEA® electronic medical record database of the Japan Medical Association Medical Information Management Organization, collected from 1 206 955 individuals across 53 medical institutions throughout Japan over 57 months since 2019. We focused on women with primary breast cancer receiving adriamycin/cyclophosphamide (AC), epirubicin/cyclophosphamide (EC), or docetaxel/cyclophosphamide chemotherapy (TC).

Results: Analysis included 1989 women who received at least two courses of AC, EC, or TC perioperatively. Patients received 2-weekly adriamycin/cyclophosphamide (ddAC) (n = 207), 3-weekly AC (AC q3w) (n = 177), 2-weekly epirubicin/cyclophosphamide (ddEC) (n = 269), 3-weekly EC (EC q3w) (n = 684), and TC (n = 652). Pegfilgrastim was administered to 98% of ddAC/ddEC, 38% of AC q3w, 42% of EC q3w, and 74% of TC patients. Grade 4 neutropenia (incidences >20%) was observed in AC q3w patients aged ≥65 years (22.6%) and in TC patients of any age (27.6%). RDI remained >95% in all groups.

Conclusions: RDI was high in all groups. Clinicians should be cautious when administering AC q3w therapy owing to the high likelihood of patients developing Grade 4 neutropenia. For TC, a slightly lower pegfilgrastim administration rate and >20% Grade 4 neutropenia suggest the need for appropriate pegfilgrastim use.

Background: Postoperative delirium (POD) is a common and serious complication, especially among older adults. The economic burden of POD, particularly in patients undergoing highly invasive cancer resection who are at high risk of delirium, remains unclear. We aimed to clarify the economic burden of subsyndromal delirium (SSD) and severe delirium in this population.

Methods: We prospectively enrolled 281 adults undergoing highly invasive cancer resection and evaluated the impact of severe delirium and SSD diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and the Delirium Rating Scale-Revised-98 severity scale. The primary outcome was diagnosis procedure combination (DPC) costs. Propensity score matching was performed to estimate the effect of delirium within a background-matched cohort, and generalized estimating equations with two-way cluster-robust standard errors were applied at both matched-set and patient levels. Sensitivity analyses were performed using direct medical costs (fee-for-service [FFS]).

Results: Fifty-five patients (19.6%) developed severe delirium. DPC costs showed no significant mean difference, whereas total FFS costs were significantly higher in severe delirium (mean difference: US$2364, 95%CI: US$122 ~ US$4606). Component analyses indicated higher costs for prescriptions, infusions, wound-related procedures, and laboratory tests. SSD had no significant economic impact.

Conclusion: Severe postoperative delirium after highly invasive cancer resection was associated with increased FFS expenditures, particularly for prescriptions, infusions, wound care, and laboratory tests, whereas no significant differences were observed in DPC costs. Findings underscore the importance of preventing severe delirium.

Objective: The aim of this study was to compare survival and the incidence of complications between stereotactic body radiotherapy/proton beam therapy (SBRT/PBT) and sublobar resection for vulnerable elderly patients with clinical stage IA non-small cell lung cancer (NSCLC).

Methods: We included patients aged ≥75 years who underwent sublobar resection without mediastinal lymph node dissection or SBRT/PBT for solid predominant clinical stage IA non-small cell lung cancer measuring ≤3 cm in total size. Propensity score matching was used to reduce the selection bias. Complication and survival rates were compared between groups.

Results: Of the 119 included patients, 86 received stereotactic body radiotherapy (62 received X-ray radiotherapy and 24 received proton beam therapy), while 33 received sublobar resection (11 received segmentectomy and 22 received wedge resection). The SBRT/PBT group included significantly older patients (median: 82 vs. 79 years) and larger tumors (median: 18 vs. 16 mm) than did the surgery group. After propensity score matching, 24 patients were analysed in each group. The incidence of ≥Grade 2 complications was not significantly different between the two groups (12.5% vs. 29.1%; OR = 0.35, 95% CI: 0.08-1.55; P = 0.286). Moreover, there were no significant differences in overall and recurrence-free survival rates (OS: HR = 0.68; 95% CI: 0.31-1.50; P= 0.343; RFS: HR = 0.69; 95% CI: 0.33-1.46; P = 0.336, respectively) and the cumulative incidence of recurrence (sHR = 0.87; 95% CI: 0.31-2.40; P = 0.781).

Conclusions: For vulnerable elderly patients with NSCLC, SBRT/PBT may be comparable with sublobar resection in terms of patient survival and safety. Prospective randomized controlled trials are required to confirm these findings.