Japanese journal of clinical oncology最新文献

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: Fluorescence cystoscopy (FL) using 5-aminolevulinic acid (ALA) enhances the detection of urothelial carcinoma compared to white-light endoscopy (WL). The location of bladder tumors may affect the diagnostic performance of FL; however, this issue has been underexplored. We analyzed the diagnostic performance of FL compared with that of WL across different bladder regions.

Methods: Between 2018 and 2021, 181 patients with non-muscle-invasive bladder cancer who underwent FL-guided transurethral resection of bladder tumors (TURBT) using oral ALA were identified. During TURBT, WL and FL findings were recorded separately, and samples were collected. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for detecting urothelial carcinoma in each method were analyzed.

Results: The median patient age was 72 years, and 122 patients (85%) were male. Among the 526 collected tissues, 66, 106, and 35 were diagnosed as pTis, pTa, and pT1 urothelial carcinomas, respectively, and 319 lesions were benign. The sensitivity, specificity, PPV, and NPV of FL and WL were 91.8%, 58.3%, 58.8%, and 91.6% and 76.3%, 69.3%, 61.7%, and 81.9%, respectively. In the sensitivity analysis across different regions, the sensitivities of FL/WL in the posterior and lateral walls were 100/76.6% and 92.6/79.0%, respectively, and FL was superior (P < .001 and P = .003, respectively), whereas no advantages of FL were observed in the other regions.

Conclusions: FL presented a higher sensitivity than WL at the posterior and lateral walls but failed to show superiority in the other regions.

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.

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.

Background: Ewing sarcoma (ES) is a malignant type of bone and soft tissue tumor with EWSR1-ETS gene fusions as the primary driver alteration. Incidence is higher in White populations compared to Black and Asian populations. Researchers use next-generation sequencing to identify alterations as potential therapeutic targets. We compared the data from the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets in the USA with the data from Center for Cancer Genomics and Advanced Therapeutics in Japan.

Methods: We sequenced tumor DNA from 81 ES samples using the FoundationOne® CDx for multigene panel testing. Genetic alterations were interpreted via the Cancer Knowledge Database (CKDB) and potentially actionable alterations were classified into levels A-F.

Results: Analysis of 81 ES samples revealed 556 mutations in 197 genes and 126 copy-number alterations in 58 genes. Potentially actionable alterations were detected in 10 patients (12.3%) at CKDB levels A or C. STAG2 mutations accounted for 3.7%, TP53 mutations for 17.3%, and CDKN2A deletions for 13.6%. There was no significant difference in overall survival after genomic profiling test enrollment for STAG2 and TP53 mutations (P = .663 and P = .767), but those with CDKN2A and CDKN2B deletions had poor prognosis (P = .024 and P = .012).

Conclusion: Compared to previous reports, Japanese ES cases showed lower STAG2 and higher TP53 mutation frequencies. CDKN2A and CDKN2B deletions may serve as prognostic biomarkers indicating unfavorable outcomes.