Japanese journal of clinical oncology最新文献

Fibroblast growth factor receptor 2 (FGFR2) gene fusions are detected in 10%-16% of cholangiocarcinomas but are rarely detected in other solid tumours. Herein, we report the case of a 59-year-old woman with stage IVB gastric cancer (UICC 8th edition) characterized by FGFR2-TRIM44 fusion and FGFR2 amplification. Her tumour progressed despite multiple lines of standard chemotherapy. Plasma ctDNA analysis revealed these alterations, and pemigatinib was recommended by an expert panel. Treatment led to a remarkable clinical and radiological response, and she remained on pemigatinib with stable symptoms for 5 months. According to the C-CAT database, FGFR2 amplification was identified in 4.9%, while FGFR2 fusions were identified in only 0.26% of 3116 oesophagogastric adenocarcinomas, with FGFR2-TRIM44 fusions detected in just 0.064%, including our case. Targeted therapies based on genomic information are limited in the treatment of advanced gastric cancer. Thus, this case suggests that pemigatinib may represent a promising targeted therapy option for patients with advanced gastric cancer harbouring FGFR2 alterations.

Objectives: Pancreatic cancer frequently presents with tumor necrosis, which may influence the success of comprehensive genomic profiling in endoscopic ultrasound-guided tissue acquisition specimens. This study aimed to evaluate the relationship between tumor necrosis and comprehensive genomic profiling success.

Methods: This single-center retrospective study enrolled patients diagnosed with pancreatic cancer via endoscopic ultrasound-guided tissue acquisition, whose tissue samples were submitted for FoundationOne® CDx analysis between November 2019 and November 2023. Based on the FoundationOne® CDx report, a 'passed' result indicated successful analysis. Histological type, tumor quantity, and necrosis were evaluated as pathological factors. Univariable and multivariable analyses were conducted to identify factors associated with successful FoundationOne® CDx.

Results: Among 109 patients included in this study, the overall success rate of FoundationOne® CDx analysis was 67.9%. Extensive tumor necrosis (>50%) was significantly associated with a lower success rate of FoundationOne CDx analysis (28.6% [>50%] vs. 70.6% [≤50%], P = 0.034). Among the 83 cases that met the quantity criteria for FoundationOne® CDx analysis, the success rate was significantly lower in cases with extensive necrosis (>50%) than in those with limited necrosis (40% [2/5] vs. 83% [65/78]; P = 0.036). Multivariate analysis identified extensive necrosis (odds ratio [OR] 0.09, P = 0.015), samples that met the quantity criteria for FoundationOne® CDx analysis (OR 14.90, P < 0.0001), and pancreatic ductal adenocarcinoma histology (OR 4.21, P = 0.038) as significant factors influencing the success of FoundationOne® CDx analysis.

Conclusions: Extensive tumor necrosis observed on pathological examination is associated with a lower success rate of FoundationOne® CDx analysis in pancreatic cancer.

Local therapy is not considered a standard treatment option for patients with high-volume metastatic prostate cancer. Our research group's previous retrospective study indicated potential benefits of local radiotherapy (LRT) for some high-volume metastatic prostate cancer patients, but prospective studies have yet to confirm these findings. We have thus planned a multicenter, open-label, randomized controlled phase III trial to confirm the efficacy of adding LRT to systemic hormonal therapy with androgen deprivation therapy plus an androgen receptor pathway inhibitor in a population of high-volume metastatic prostate cancer patients for whom the hormonal therapy is effective for 6 months. The primary endpoint is failure-free survival, defined as the time from randomization to prostate-specific antigen progression, radiological progression, clinical progression, or death from any cause. We aim to enroll 360 patients from 56 institutions over a 4-year period. This trial is registered at the Japan Registry of Clinical Trials (study no. jRCT1031220676).

Background: Androgen receptor signaling inhibitors (ARSIs) have become the standard treatment for metastatic castration-sensitive prostate cancer (mCSPC). While visceral metastases, including lung metastases (LMs), are considered poor prognostic factors, their impact on clinical outcomes in mCSPC remains unclear. This study aimed to evaluate the prognostic significance of LM in mCSPC patients treated with ARSI-based doublet therapy.

Methods: This retrospective study analyzed a multi-institutional cohort of 453 mCSPC patients treated with ARSIa-based doublet therapy.

Results: The median overall survival (OS) and time to castration resistance (TTCR) were 80 and 41 months, respectively, with a median follow-up of 20 months. The total cohort included 117 patients (25.8%) with LM and 336 patients (74.2%) without LM. LATITUDE high-risk and CHAARTED high-volume criteria classified 380 patients (83.9%) and 356 patients (78.6%), respectively. Although not statistically significant, OS and TTCR showed a trend toward better outcomes in the LM group compared to the non-LM group in LATITUDE high-risk (n = 380: P = .097 for OS and P = .104 for TTCR) and CHAARTED high-volume (n = 356: P = .064 for OS and P = .086 for TTCR). In the propensity score matching cohort (n = 218 and n = 206 for LATITUDE and CHAARTED criteria, respectively), OS and TTCR remained comparable between the LM and non-LM groups.

Conclusions: LM does not appear to be related to OS or TTCR in mCSPC patients treated with ARSI-based doublet therapy, indicating that its prognostic value may need to be reevaluated.

Background: EMPOWER-Lung 1 and EMPOWER-Lung 3 (phase 3 studies) demonstrated survival benefits for cemiplimab with/without chemotherapy in global (non-Japanese) patients with advanced non-small cell lung cancer (aNSCLC). This single-arm dose-expansion study assessed safety, tolerability, pharmacokinetics, and efficacy of first-line cemiplimab (350 mg intravenous every 3 weeks) as monotherapy/with chemotherapy in Japanese patients with aNSCLC.

Methods: The primary objectives were safety, tolerability, and pharmacokinetics of cemiplimab as monotherapy/with chemotherapy. Secondary objectives included immunogenicity, tumor response (objective response rate [ORR], and duration of response [DOR]). Patients whose tumors expressed programmed cell death-ligand 1 (PD-L1) ≥50% on tumor cells received cemiplimab monotherapy (Cohort A; n = 60, safety; n = 50, efficacy). Patients whose tumors expressed any level of PD-L1 received cemiplimab plus four cycles of chemotherapy (Cohort C; n = 50).

Results: Safety results were generally consistent with the known safety profile of cemiplimab. Treatment-emergent adverse events (grade ≥3) were experienced by 51.7% (31/60) in patients receiving cemiplimab monotherapy (Cohort A) and 68.0% (34/50) in those receiving cemiplimab + chemotherapy (Cohort C). Pharmacokinetic results were similar across both cohorts. In Cohort A patients with centrally confirmed PD-L1 ≥50%, ORR was 60.0% (30/50) with an observed DOR of 2.1-42.5 months. In Cohort C, ORR was 42.0% (21/50) with an observed DOR of 2.3-20.7 months. Immunogenicity was low in both cohorts.

Conclusion: Cemiplimab demonstrated efficacy in Japanese patients as monotherapy for PD-L1 ≥50% and with chemotherapy irrespective of PD-L1 expression. Overall, cemiplimab demonstrated a favorable benefit-risk profile in Japanese patients.

Objective: Esophageal cancer is one of the most lethal cancers worldwide. Previous studies have shown that reduced skeletal and respiratory muscle strength is correlated with increased postoperative complications. This study investigated the relationship between hand grip strength (HGS) and respiratory muscle strength assessed as peak expiratory flow (PEF) rate. We also examined the association of these factors with long-term prognosis in patients who had undergone radical esophagectomy for esophageal cancer.

Methods: We reviewed 392 patients who underwent radical subtotal esophagectomy from 2007 to 2023. HGS and PEF rate were measured preoperatively. Data analysis included univariable and multivariable Cox regression to identify prognostic factors for overall survival (OS).

Results: During a median follow-up of 36 months, 171 patients died, with 68.1% of deaths attributable to the primary disease. Because a weak correlation was observed between HGS and PEF rate (r = 0.353), separate multivariate analyses were performed for each factor to investigate their relationship to prognosis. Multivariable analysis identified PEF rate as an independent prognostic factor for OS (HR 0.991, 95% CI 0.984-0.999; P = .028), along with clinical stage (HR 1.345, 95% CI 1.188-1.521; P < .001), age (HR 1.026, 95% CI 1.007-1.046; P = .008), and surgical approach (open vs. minimally invasive; HR 0.674, 95% CI 0.490-0.928; P = .015). HGS was also identified as an independent prognostic factor for OS (HR 0.974, 95% CI 0.955-0.994; P = .012) along with clinical stage (HR 1.321, 95% CI 1.168-1.495; P < .001).

Conclusions: HGS and PEF rate are independent predictors of OS after esophagectomy.

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.

Objective: To identify pretreatment factors associated with developing primary resistance to nivolumab plus ipilimumab therapy in patients with advanced renal cell carcinoma (RCC).

Methods: We retrospectively reviewed the clinical characteristics, laboratory data, and tumor-related factors in patients with advanced RCC who initiated nivolumab plus ipilimumab as first-line therapy between January 2018 and July 2021. Primary resistance was defined as radiographic or clinical progression within 3 months of treatment initiation. Cases with suspected pseudoprogression were excluded.

Results: Eighty-nine patients met the inclusion criteria; 23 exhibited primary resistance. Univariate analysis identified the following significant predictive factors: body mass index (P = .006), lymph node metastasis (P = .021), sarcomatoid differentiation (P = .035), solitary metastatic organ (P = .051), liver metastasis (P = .056), and serum lactate dehydrogenase (LDH) (P = .094). Receiver operating characteristic curve analysis determined an LDH cutoff value of 174 U/L, which was significantly associated with primary resistance (P = .029). Considering the number of primary resistance cases, multivariable analysis incorporated three candidate variables (lymph node metastasis, sarcomatoid differentiation, and LDH ≥ 174 U/L) and identified sarcomatoid differentiation (odds ratio, 4.264; 95% confidence interval (CI), 1.299-14.825; P = .017) and LDH ≥ 174 U/L (odds ratio, 3.634; 95% CI, 1.143-13.770; P = .028) as independent predictors of primary resistance.

Conclusions: Sarcomatoid differentiation on pretreatment biopsy or elevated serum LDH before treatment initiation may predict primary resistance to nivolumab plus ipilimumab therapy in patients with advanced RCC. Alternative regimens should be considered in such cases, particularly for patients who are likely to experience rapid disease progression or for whom the occurrence of P-res is not clinically acceptable.

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.