Japanese journal of clinical oncology最新文献

Peripheral T-cell lymphoma (PTCL) represents a heterogeneous group of lymphomas with a generally poor prognosis. With recent advances in our understanding of the cellular origins and genomic profiles of PTCL, lymphomas of follicular helper T-cell (TFH) origins with distinct markers and gene mutation profiles are categorized as a single entity, nodal TFH lymphomas-angioimmunoblastic type, follicular type, and not otherwise specified, in the fifth edition of the WHO classification. The standard treatment for PTCL has been CHOP or CHOP-like regimens for decades. The ECHELON-2 trial marked a significant advance in the treatment of PTCL by demonstrating significantly longer survival with BV-CHP than with CHOP for CD30-positive PTCL, establishing BV-CHP as the standard of care for this group of patients. However, attempts to integrate other novel agents into CHOP have largely been unsuccessful, primarily due to increased toxicity, and, thus, CHOP remains the standard treatment for CD30-negative PTCL. Upfront autologous stem cell transplantation is currently controversial, and ongoing randomized controlled trials are expected to clarify its role. With advances in our understanding of the molecular and genetic characteristics of PTCL and potential predictive biomarkers, the future development of treatment will focus on more stratified approaches, and ongoing trials are expected to provide further insights into optimizing these treatment strategies.

More than half of brain metastases (BMs) in patients with non-small cell lung cancer are diagnosed at the time of lung cancer diagnosis and are therefore potentially amenable to systemic treatment. Before the introduction of molecular targeting therapy, medical treatment was thought to be ineffective owing to the presence of the blood-brain barrier (BBB). However, the molecular activities of cancer cells in the central nervous system affect the brain microenvironment, changing the function of the BBB and blood-cerebrospinal fluid barrier, allowing drug delivery. In non-small cell lung cancer with driver gene mutations, BMs respond rapidly to molecular targeted drugs. Although the immune response is attenuated within BMs, it varies according to cancer type. In addition, the changes in immune response after immune checkpoint inhibitor administration vary from patient to patient. In treating BMs, which develop in the unique environment of the brain, it is particularly important to understand these pathologies and develop pathogenesis-based treatment strategies. Although drug therapy is effective against BMs, it is not curative, as BMs will eventually acquire resistance. In the era of molecular targeted agents, it is important to determine the most appropriate combination of treatments for each individual patient, taking into account the effectiveness of conventional local treatments and drug therapy, the presence of side effects, and the timing of their onset.

Purpose: Despite 4-6 cycles of first-line chemotherapy being recommended before the initiation of avelumab maintenance treatment, a non-negligible number of patients received <4 cycles of first-line chemotherapy due to adverse events or pre-existing comorbidities. We assessed the prognostic impact of the number of first-line chemotherapy cycles in patients with metastatic urothelial carcinoma (mUC) treated with avelumab maintenance.

Methods: In this multi-institutional study, data were collected from patients with mUC who received avelumab maintenance treatment following first-line chemotherapy. Patients were divided into those who received <4 cycles versus ≥4 cycles of first-line chemotherapy. Kaplan-Meier curves and Cox regression analysis were used to assess the association of chemotherapy cycle numbers with overall survival (OS) and cancer-specific survival (CSS).

Results: Of 91 patients included in this analysis, 17 (19%) underwent <4 cycles of chemotherapy. Patients with <4 cycles of first-line chemotherapy were less likely to receive carboplatin-containing chemotherapy compared with their counterparts (6% versus 39%). On multivariable Cox regression analyses adjusted for the effects of confounding factors, receiving <4 cycles of chemotherapy was significantly associated with worse OS and CSS (HR 2.85; P = .006 and HR 3.18; P = .005, respectively), which was confirmed by subgroup analysis focusing on patients with 1-6 cycles of chemotherapy. Cisplatin-based chemotherapy use was associated with better OS over carboplatin-based chemotherapy (HR 0.41; P = .033).

Conclusions: An inadequate number of first-line chemotherapy cycles was associated with poor survival outcomes. Four or more cycles of first-line platinum-based chemotherapy may be beneficial to ensure the efficacy of avelumab maintenance treatment in patients with mUC.

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.