Japanese journal of clinical oncology最新文献

Immune checkpoint blockades (ICBs), particularly PD-1 pathway blockades, have significantly improved outcomes in advanced renal cell carcinoma (RCC). However, long-term ICB therapy imposes substantial financial and toxicity burdens. Retrospective data suggest that treatment responses plateau around 24 weeks, and some patients maintain disease control even after ICB pause. We initiated a multi-institutional, open-label, randomized controlled trial to confirm the non-inferiority of pausing PD-1 pathway blockade to its continuous administration in patients with advanced clear cell RCC without disease progression. The primary endpoint is overall survival and the secondary endpoint includes time to failure of strategy, progression-free survival, and adverse events. Conducted by the Urologic Oncology Study Group of the Japan Clinical Oncology Group (JCOG), this phase III trial was approved by Certified Review Board in February 2020, with patient enrollment beginning in July 2020. The trial is registered in the Japan Registry for Clinical Trials (JCOG1905; jRCT1031200071).

Background: Pazopanib is used to treat relapsed and refractory sarcomas. Pazopanib's role in pediatric, adolescent, and young adult populations remains unestablished.

Methods: To assess pazopanib's utility, we analyzed retrospectively collected data from pediatric (0-14 years) and adolescent and young adult (15-39 years) patients diagnosed with relapsed or refractory sarcomas who received pazopanib.

Results: We assessed data from 21 patients (10 pediatric, 11 adolescent, and young adult). Their diagnoses included osteosarcoma (n = 11), rhabdomyosarcoma (n = 4), alveolar soft part sarcoma (n = 5), and leiomyosarcoma (n = 1). Thirteen (62%) patients presented with metastatic disease at the initial diagnosis. Patients had received a median of three prior chemotherapy regimens (range: 0-6). The median duration of pazopanib treatment was 3.5 months (range: 1-12) for pediatric patients and 4 months (range: 1-83) for adolescents and young adults. Nine patients (five adolescents and young adults) discontinued pazopanib owing to disease progression, and two discontinued owing to adverse events (pneumothorax). We observed seven cases of stable disease (four adolescents and young adults) and 12 of progressive disease (six adolescents and young adults) after ~3 months. The median survival following pazopanib initiation was 7.8, 4.8, and 12.4 months for overall, pediatric, and adolescent and young adult patients, respectively.

Conclusions: In a small cohort of children and adolescent and young adult patients with heavily pretreated relapsed or refractory sarcoma, pazopanib may be a feasible option. Further research on optimal therapeutic timing and the target population for pazopanib's indication is required.

Background: Extended waiting periods between cancer diagnosis and treatment initiation may impact patients' quality of life and prognosis. However, few studies have examined the current situation in Japan and the factors influencing these waiting periods.

Methods: This study included individuals with gastric cancer (n = 1956), colorectal cancer (n = 2843), lung cancer (n = 3309), and female breast cancer (n = 3172) diagnosed in 2016-17 at 19 facilities in the Hokushin region of Japan. The proportion of patients who waited over 30 days for each cancer type was calculated. Multilevel logistic regression analysis was used to examine the association between waiting over 30 days and patient and facility characteristics.

Results: The proportions of patients who waited over 30 days were 53.7% for gastric cancer, 42.8% for colorectal cancer, 50.5% for lung cancer, and 75.7% for female breast cancer. Among lung cancer patients, elderly patients showed a higher proportion of waiting over 30 days compared to younger patients. Patients at medical institutions with a large number of hospital beds showed higher proportions of waiting over 30 days across multiple cancer types.

Conclusion: In the Hokushin region, patients who waited over 30 days are prevalent among female patients with breast cancer compared to other cancer types, and among older adults with lung cancer compared to younger lung cancer patients, as well as in medical institutions with a large number of hospital beds across cancer types. Hence, efforts to reduce this number are needed.

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.

Introduction: Enfortumab vedotin plus pembrolizumab (EVP) has shown promising efficacy in locally advanced or metastatic urothelial carcinoma (la/mUC), but real-world data in Japanese patients are limited. We assessed the safety and early efficacy of EVP, with a focus on cutaneous adverse events (AEs).

Methods: We retrospectively analyzed 48 Japanese patients with la/mUC treated with first-line EVP at 12 centers between November 2024 and March 2025. Clinical data, AEs, and tumor responses were collected. Cutaneous AEs were evaluated for onset, severity, and management. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Results: The patients' median age was 76 years, and 89.6% were cisplatin-ineligible. All patients experienced treatment-related AEs, with 39.6% having grade ≥3 events. Cutaneous AEs occurred in 60.4%, including 18.8% with grade ≥3 rash and two cases of Stevens-Johnson syndrome. The median time to discontinuation due to AEs was 14 days. The overall response rate was 39.6%, and the disease control rate was 69%, rising to 87% among 38 evaluable patients.

Conclusion: EVP demonstrated favorable early efficacy in Japanese patients but was associated with frequent early discontinuation due to AEs, particularly cutaneous toxicity. Early skin care and interdisciplinary management are essential. These findings support EVP use while emphasizing AE management and patient-centered care.

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.

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.