International Journal of Clinical Oncology最新文献

Background: Surgery for inferior vena cava tumor thrombus (IVC-TT) in patients with renal cell carcinoma (RCC) is highly invasive and is associated with perioperative mortality. This study aimed to assess the efficacy of presurgical systemic therapy (PT) on perioperative outcomes in RCC patients with IVC-TT.

Methods: A total of 68 patients with right-sided RCC and level ≥ II IVC-TT were included in this study. The tumor response to PT was investigated, and we compared surgical outcomes and perioperative complications between patients with PT (n = 23) and those who underwent immediate surgical resection (non-PT, n = 45).

Results: In the PT group, while 15 patients were treated with tyrosine kinase inhibitors (TKIs) alone, a combination of immune-oncology (IO) therapy and TKIs (IO + TKI) was used in 8 patients. Eleven of 23 (47.8%) patients in the PT group showed a reduction in the level of TT. PT significantly reduced the operation time, intraoperative blood loss, the need for extracorporeal circulation, the incidence of grade ≥ III perioperative complications, and the duration of hospitalization after surgery.

Conclusion: Our findings suggest that PT may be effective in reducing surgical invasiveness in RCC patients with IVC-TT. Further prospective studies are needed to identify the optimal drug regimen for PT and to clarify its survival benefits.

Background: This study investigated the characteristics of prostate-specific antigen (PSA) dynamics when androgen receptor signaling inhibitor (ARSI), or vintage agent (bicalutamide) was used for patients with metastatic hormone-sensitive prostate cancer (mHSPC).

Patients and methods: A total of 213 mHSPC patients from each of the ARSI and bicalutamide groups treated between 2015 and 2022 were selected from multiple institutions using propensity score-matched analysis to align backgrounds. PSA progression-free survival (PFS) and overall survival (OS) were assessed. PSA level at 3 months, PSA nadir level, and time to PSA nadir were examined to analyze of PSA kinetics.

Results: ARSI treatment significantly improved PSA PFS compared to bicalutamide (P = 0.0063), although no significant difference in OS was seen (P = 0.3134). No significant differences were observed between treatment groups in median PSA levels at 3 months (1.47 vs 0.52 ng/ml, P = 0.3042) or PSA nadir levels (0.263 vs 0.1345 ng/ml, P = 0.1228). Bicalutamide treatment demonstrated longer time to nadir than ARSI in progression-free cases (median: 243 vs 213.5 days, P = 0.0003). Survival tree analysis found that PSA nadir ≤ 1.5 ng/ml and time to nadir ≥ 145 days were the optimal cut-offs for best stratifying OS with bicalutamide, while PSA nadir ≤ 0.45 ng/ml and time to nadir ≥ 70 days were optimal with ARSI.

Conclusion: No significant differences in PSA response was seen between groups; however, distinct optimal cut-offs were demonstrated for PSA nadir and time to nadir. The present findings will be useful for optimal PSA monitoring for mHSPC patients and for early identification of poor-prognosis populations.

Background: In a global phase I/II study (GO29781; NCT02500407), single-agent mosunetuzumab had a manageable safety profile and induced durable complete responses in patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma, including in patients with R/R follicular lymphoma (FL). In this analysis, the efficacy and safety of mosunetuzumab monotherapy were evaluated in an expansion cohort, FLMOON-1, in Japanese patients with R/R FL who had received  ≥ 2 prior lines of therapy in a phase I study (JO40295, jRCT2080223801).

Methods: Mosunetuzumab was administered intravenously at the recommended phase II dose (with cycle 1 step-up dosing) for eight cycles or up to 17 cycles, or until disease progression or unacceptable toxicity. The pre-specified primary endpoint was Independent Review Facility (IRF)-assessed complete response rate (CRR; as best overall response). Secondary objectives included investigator (INV)-assessed CRR, INV- and IRF-assessed objective response rate (ORR), and safety.

Results: At the data cutoff (October 13, 2023), 19 patients (median age 72 years) were evaluated. The IRF-assessed CRR and ORR were 68.4% and 78.9%, respectively; the INV-assessed CRR and ORR were 63.2% and 84.2%, respectively. Grade 3-4 adverse events (AEs) were observed in 89.5% of patients, with a low incidence of AEs leading to mosunetuzumab discontinuation (10.5%) and one fatal AE unrelated to mosunetuzumab. Cytokine release syndrome occurred in 47.4% of patients and were mostly Grade 1 in severity.

Conclusion: These findings indicate mosunetuzumab has a consistent efficacy and manageable safety profile in Japanese patients with R/R FL compared with previously reported data from the global phase I/II study.

Background: Effective management with second-line therapy with the lenvatinib + pembrolizumab regimen for patients with advanced endometrial cancer is necessary.

Methods: This retrospective study enrolled patients with endometrial cancer treated with the lenvatinib + pembrolizumab regimen. We evaluated progression-free survival (PFS), overall survival (OS), safety for patients non-eligible for the KEYNOTE775 trial, aged ≥65 years, or with ECOG performance status 1-2.

Results: Forty-five patients were analyzed: 21 (47%) were aged ˃ 65 years, 16 (36%) had performance status 1-2, and 15 (33%) were non-eligible for KEYNOTE775 trial participation. Overall, the median PFS was 8.5 months (95% confidence interval [CI] 4.6-12.4), and the median OS was 15.6 months (95% CI 9.4-NA). Median PFS was significantly shorter in patients not eligible for KEYNOTE775 participation and with performance status 1-2. The median OS was significantly shorter in patients with performance status 1-2. Grade ˃3 adverse events (AEs) occurred in 78% of patients who received the lenvatinib + pembrolizumab regimen. AEs resulted in lenvatinib dose reductions in 35 patients (78%) and lenvatinib and pembrolizumab discontinuation in 3 (7%) and 5 (11%), respectively. The median time to the first lenvatinib dose reduction was 1.5 (0.92-2.3) months in all patients and was significantly shorter in patients aged >65 years.

Conclusions: The current regimen has favorable efficacy and manageable safety with appropriate dose reduction of lenvatinib in the real world. However, the efficacy may be inferior in patients with performance status 1 or 2, heavily treated patients, and those with organ dysfunction. The current treatment status should reflect real-world data relative to the medical environment and management.

Background: Methylation of microRNA (miRNA) promoters associated with diseases is a common epigenetic mechanism in the development of various human cancers. However, its relationship with prognosis in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to explore the association between the methylation level of has-miR-3665 promoter and prognosis in ESCC.

Methods: Human miRNA data were downloaded from miRbase, and we identified CpG islands of these human miRNAs by genomics browser analysis. MiRNA methylation levels were detected by methylation-specific high-resolution melting. Gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to explore the molecular mechanism of hsa-miR-3665. Cox regression analysis was used to investigate prognostic factors. The overall survival rate was predicted by a nomogram.

Results: We found that 88 human miRNAs had promoter methylatio, of which 15 miRNAs were found to be epigenetically regulated in ESCC cells compared with their normal counterparts, including hsa-miR-3665. Meanwhile, hsa-miR-3665 expression was significantly lower in ESCC tumour tissue than in adjacent tissue (P = 0.03). GO and KEGG analyses demonstrated that the target genes are involved in protein transport, transcription regulator activity, MAPK and RAS signaling pathway. High hsa-miR-3665 promoter methylation levels were associated with a poor prognosis (HR = 3.89, 95% CI 1.11 ~ 13.55). Moreover, a nomogram incorporating the hsa-miR-3665 methylation level and clinical factors presented a good performance for predicting survival in the training and validation tests, with C-indices of 0.748 and 0.751, respectively.

Conclusions: High hsa-miR-3665 promoter methylation levels may be a potential biomarker for the progression of ESCC.

Background: Financial toxicity impacts the treatment choices, daily life, and health-related quality of life (HRQoL) of cancer patients. We investigated future variations in financial toxicity and HRQoL of patients with gynecologic cancer, evaluated using the COmprehensive Score for financial Toxicity (COST) questionnaire.

Methods: This multicenter study enrolled patients with gynecologic cancer incurring co-payments for anti-cancer drug treatment for over 2 months. Questionnaires were administered at baseline and at the end of follow-up. Patients completed the COST, EORTC-QLQ-C30, EORTC-QLQ-OV28, EORTC-QLQ-CX24, EORTC-QLQ-EN24, and EQ-5D-5L. Paired t-tests were used to compare the initial and follow-up responses. Spearman's rank test was used to examine correlations between COST and HRQoL scores.

Results: Ninety-one patients (ovarian, 40; cervical, 18; endometrial, 33) completed the questionnaires at baseline and follow-up. The mean COST score was not significantly different between baseline and end of follow-up (19.56 ± 6.63 and 19.97 ± 7.47, respectively; p = 0.439). Significant correlations were found between COST scores and emotional functioning (r = 0.251, p = 0.023), cognitive functioning (r = 0.254, p = 0.020), and financial difficulties (r = - 0.298, p = 0.006), attitude toward disease/treatment (r = 0.356, p = 0.033), poor body image (r = - 0.362, p = 0.042), back and pelvis pain (r = - 0.451, p = 0.010), and taste change (r = - 0.359, p = 0.040).

Conclusions: During anticancer drug therapy for gynecologic cancer, the COST score remained stable and did not correlate with overall HRQoL, although higher scores were associated with worse HRQoL for specific functions and symptoms.

Background: For prostate cancer (PCa) in the elderly, including patients ≥ 80 years, the safety of robot-assisted radical prostatectomy (RARP) is controversial. We aimed to evaluate the effect of aging on the postoperative complication rates after RARP.

Methods: This cohort study used a database of patients who had undergone RARP at 25 different institutes. We divided the cohort into four age groups (< 70, 70-74, 75-79, and ≥ 80 years). The complication rates after RARP in the 70-74, 75-79, and ≥ 80 year group were compared using the < 70 year group serving as the control group by applying the inverse probability of treatment weighting (IPTW)-adjusted regression analysis.

Results: A total of 8055 patients were evaluated. The postoperative complication rates were 8.8%, 9.7%, 9.6%, and 10.0% in the < 70, 71-74, 75-79, and ≥ 80 age groups, respectively. In IPTW-adjusted analyses, the risk of overall complications (< 70 vs. 70-74 year group: OR = 1.09 [95% CI 0.92-1.29]; < 70 vs. 75-79 year group: OR = 1.09 [95% CI 0.88-1.37], and < 70 vs. ≥ 80 year group: OR = 2.21 [95% CI 0.92-5.32]) did not change with increasing age. There was no significant increase in risk for any complication category, such as bowel dysfunction, symptomatic lymphocele, or bacterial infection, between the < 70 and ≥ 80 age groups.

Conclusion: Our findings showed that, in appropriately selected patients, the risk of complications after RARP did not increase with age, even at 75 or 80 years.

Background: The expenses related to fertility preservation or subsequent assisted reproductive treatments are significant for adolescents and young adult patients in Japan's current healthcare system. With fertility preservation becoming more widespread in developed countries, it is expected that these costs will be covered by insurance or subsidies. It is critical for patients, healthcare providers, and the government to know the costs that patients will be responsible for. In Japan, the costs of fertility preservation and subsequent assisted reproductive technology are not covered by insurance, but patients can apply for subsidies from the local and central governments if certain conditions are met. Presently, the above-mentioned costs, as well as the amount paid by the patient, vary by facility. Therefore, it is essential to ensure patients' continued access to necessary medical care despite the associated costs.

Methods: In this study, questionnaires were mailed to 186 certified fertility preservation facilities in Japan to assess patients who had undergone fertility preservation or assisted reproduction. The questionnaires were sent between October 27, 2023 and March 31, 2024, with 140 of the 186 facilities responding (response rate: 75.3%).

Results: Our findings show that approximately one-third of the costs was borne by the patients.

Conclusion: Given these circumstances, sustainable pricing and insurance coverage are necessary for both patients and facilities.

Background: Cutaneous melanoma (CM) is the most common type in Caucasians, while acral melanoma (AM) and mucosal melanoma (MM), which are resistant to immunotherapies and BRAF/MEK-targeted therapies, are more common in East Asians. Genomic profiling is essential for treating melanomas, but such data are lacking in Japan.

Methods: Comprehensive genomic profiling data compiled in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) were analyzed.

Results: A total of 380 melanomas was analyzed, including 136 CM, 46 AM, 168 MM, and 30 uveal melanoma (UM). MM included conjunctival, sinonasal, oral, esophageal, anorectal, and vulvovaginal melanomas. No significant difference in the median tumor mutational burden (TMB) of CM (3.39 mutations/megabase), AM (2.76), and MM (3.78) was the key finding. Microsatellite instability-high status was found in one case. BRAF V600E/K was found in only 45 patients (12%). Key driver mutations in CM were BRAF (38%), NRAS (21%), NF1 (8%), and KIT (10%), with frequent copy number alterations (CNAs) of CDKN2A, CDKN2B, and MYC. AM was characterized by altered KIT (30%), NRAS (26%), and NF1 (11%) and CDKN2A, CDKN2B, CDK4, MDM2, and CCND1 CNAs. MM was characterized by altered NRAS (24%), KIT (21%), and NF1 (17%) and MYC, KIT, and CDKN2A CNAs, with differences based on anatomical locations. UM bore GNAQ or GNA11 driver mutations (87%) and frequent mutations in SF3B1 or BAP1.

Conclusion: The distinct genomic profiling in Japanese patients, including lower TMB, compared to Caucasians, is associated with poorer treatment outcomes. This result underscores the need for more effective therapeutic agents.

Background: Previously reported results from phase III KEYNOTE-048 demonstrated similar or improved overall survival (OS) with pembrolizumab or pembrolizumab-chemotherapy versus cetuximab-chemotherapy (EXTREME) in Japanese patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We report results in Japanese patients from KEYNOTE-048 after 5 years of follow-up.

Methods: Patients with R/M HNSCC of the oropharynx, oral cavity, hypopharynx, or larynx were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or EXTREME. Primary endpoints were OS and progression-free survival. Efficacy was evaluated in the programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, PD-L1 CPS ≥ 1, and total Japanese populations.

Results: In Japan, 67 patients were enrolled (pembrolizumab, n = 23; pembrolizumab-chemotherapy, n = 25; EXTREME, n = 19). Median follow-up was 71.0 months (range, 61.2-81.5); data cutoff, February 21, 2022. 5-year OS rates with pembrolizumab versus EXTREME were 35.7% versus 12.5% (hazard ratio [HR] 0.38; 95% CI 0.13-1.05), 23.8% versus 12.5% (HR 0.70; 95% CI 0.34-1.45), and 30.4% versus 10.5% (HR 0.54; 95% CI 0.27-1.07) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. 5-year OS rates with pembrolizumab-chemotherapy versus EXTREME were 20.0% versus 14.3% (HR 0.79; 95% CI 0.27-2.33), 10.5% versus 14.3% (HR 1.18; 95% CI 0.56-2.48), and 8.0% versus 12.5% (HR 1.11; 95% CI 0.57-2.16) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively.

Conclusion: After 5 years of follow-up, pembrolizumab and pembrolizumab-chemotherapy showed long-term clinical benefits; results further support these treatments as first-line options for Japanese patients with R/M HNSCC.

Clinical trial registration: NCT02358031.