Japanese journal of clinical oncology最新文献

Background: Risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) are preventive options for women with hereditary breast and ovarian cancer (HBOC). The Japanese national medical insurance began covering RRM and RRSO for patients with HBOC in April 2020.

Methods: We retrospectively analyzed 59 individuals with pathogenic germline variants (PGVs) from 55 families diagnosed with HBOC between 2010 and 2024 to assess the prevalence of RRM and RRSO after April 2020.

Results: The median age at diagnosis was 50 years. Ten individuals (16.9%) were diagnosed before April 2020, whereas 49 (83.1%) were diagnosed afterward. PGVs included BRCA1 (28 individuals) and BRCA2 (31 individuals). The most common cancer was breast cancer (74.6%), followed by ovarian (13.6%), and pancreatic cancer (3.3%); 15.3% had no cancer history. RRM was performed in 19 of 41 individuals (46.3%), with the highest rate observed among BRCA1 PGV individuals (55.0%). RRSO was conducted in 30 of 41 individuals (73.1%), with higher rates among BRCA1 and BRCA2 PGV individuals. None of the individuals without a history of breast and/or ovarian cancer underwent these procedures. The median age was 50 for RRM and 49 for RRSO. Most surgeries (64.7% for RRM and 76.0% for RRSO) occurred within a year of genetic testing. Multivariate analysis showed that breast cancer history was strongly associated with RRM.

Conclusions: National insurance coverage has enhanced access to genetic testing and preventive surgeries, with 46.3% and 73.1% undergoing RRM and RRSO, respectively. However, individuals without a cancer history remain underrepresented.

Background: Salivary gland cancer (SGC) is rare and has various histological types. This rarity and heterogeneity have hindered elucidation of the therapeutic contribution of systemic therapy, including immune checkpoint inhibitors, to recurrent or metastatic SGC (RM-SGC). The purpose of this trial was to investigate the efficacy and safety of nivolumab for platinum-refractory RM-SGC.

Methods: This phase II trial for platinum-refractory RM-SGC was conducted at nine centers. Nivolumab 240 mg was administered intravenously every 2 weeks. The primary endpoint was the objective response rate (ORR), and secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.

Results: Twenty-four patients were enrolled between March 2018 and January 2022. The main histological types were salivary duct carcinoma (n = 10), adenoid cystic carcinoma (n = 6), and adenocarcinoma not otherwise specified (n = 5). The ORR was 8.3% (2/24, 80% CI, 2.2-20.6), with two partial responses in patients with salivary duct carcinoma. The DCR was 29.2% (7/24), while all of the other 17 patients (70.8%) showed progressive disease on first disease evaluation at 12 weeks. With a median follow-up of 21.2 months, median PFS and OS were 3.0 months (95% CI, 2.8-3.2) and 25.0 months (95% CI, 10.9-39.1), respectively. There were no new safety concerns with nivolumab monotherapy.

Conclusions: This phase II trial of nivolumab for patients with platinum-refractory RM-SGC did not meet its primary endpoint of ORR. Although nivolumab may be worth further development in salivary duct carcinoma, these results may raise concerns over nivolumab monotherapy for RM-SGC.

Background: Germline pathogenic variants (GPVs) in cancer predisposition genes increase cancer risk, but their population-level prevalence in Japan remains unclear.

Aim: To estimate the prevalence of GPV carriers of hereditary cancer predisposition syndromes (HCPSs) in the Japanese population.

Data source and methods: A cross-sectional analysis of the Tohoku Medical Megabank Organization datasets was conducted to assess allele frequencies of rare GPVs, estimate carrier prevalence, and describe variant distribution.

Results: The cumulative allele frequency of rare GPVs of cancer predisposing genes was 1.47% for autosomal dominant and 3.20% for autosomal recessive diseases. The estimated prevalence of GPV carriers was 2.90% (1 in 35 individuals) and 0.10% (1 in 977 individuals) for autosomal dominant HCPSs and autosomal recessive HCPSs, respectively; ~6.19% of the population (1 in 16 individuals) were carriers. Variant types differed across genes, and hotspot variants had a significant impact on allele frequencies. Moreover, 47 structural variants (0.28%) having the potential to cause structural disruption were identified.

Conclusions: Allele frequency analysis of rare GPVs of cancer predisposition genes offered valuable insight into the prevalence of GPV carriers of HCPSs in the Japanese population. Hotspot variants may represent founder mutations within specific ethnic groups, and their presence or absence could affect gene-specific allele frequencies.

Background: Amrubicin monotherapy has been used in Japan for patients with refractory, relapsed, small cell lung cancer (SCLC). However, the clinical guidelines do not specify a recommended initial dose for elderly patients. This retrospective study aimed to explore the appropriate initial dose of amrubicin for elderly patients with refractory, relapsed SCLC.

Methods: This study included elderly patients (aged ≥70 years) with refractory, relapsed SCLC who received amrubicin monotherapy at Nagoya City University Hospital between April 2009 and March 2023. Patients were divided into two groups based on the initial dose: the low-dose group (<40 mg/m2) and the high-dose group (≥40 mg/m2).

Results: Forty-seven patients were included, thirty-eight in the low-dose group and nine in the high-dose group. Median progression-free survival was significantly longer in the low-dose group than in the high-dose group (3.64 vs. 1.5 months, P = 0.04), whereas overall survival was not significantly different (10.18 vs. 8.18 months, P = 0.58). Febrile neutropenia occurred in seven patients. Treatment discontinuation due to adverse events was more frequent in the high-dose group (44.4%) than in the low-dose group (13.5%). Non-infectious adverse events such as interstitial pneumonia, arrhythmia, and myocardial infarction were observed in five patients who discontinued treatment.

Conclusions: Both hematological and non-infectious adverse events may have contributed to shorter progression-free survival in the high-dose group. Low-dose administration, granulocyte colony-stimulating factor support, and close monitoring for non-infectious toxicities may be important in elderly patients.

Introduction: Breast-conserving therapy involves breast-conserving surgery (BCS) with sentinel node (SN) biopsy, followed by whole-breast irradiation (WBI). As a de-escalating strategy, partial-breast irradiation (PBI) has been implemented in SN-negative patients. In contrast, postoperative WBI with regional nodal irradiation (RNI) has replaced axillary clearance in SN-positive patients. This study evaluates the oncological outcomes of these SN-based strategies in Japanese patients.

Patients and methods: This retrospective study included clinical node-negative patients who underwent BCS with SN biopsy between January 2016 and November 2024. Perioperative PBI using multicatheter interstitial brachytherapy (MIB) was administered to patients with pN0(sn) or pN1mi(sn) disease, whereas WBI with RNI was administered to those with pN+(sn) disease. Oncological outcomes were assessed based on locoregional recurrence (LRR), distant recurrence (DR), and overall survival (OS).

Results: Among 828 patients, 694 (83.8%) received MIB-PBI and 134 (16.2%) underwent WBI alone. Based on SN status, 649 (78.4%) patients received MIB-PBI, 114 (13.8%) underwent WBI alone, and 65 (7.8%) underwent WBI with RNI. After a median follow-up of 54 months, there was no significant difference in 5-year LRR-free survival (97.5% vs 97.1% vs 97.0%; p = 0.78); however, significant differences were observed in DR-free (99.6% vs 98.4% vs 93.6%; p < 0.001) and OS (99.4% vs 98.4% vs 93.6%; p < 0.001) among the MIB-PBI, WBI alone, and WBI with RNI groups, respectively.

Discussion: Despite the limitations of a retrospective design, a small sample size, and a relatively short follow-up period, SN-based de-escalating strategies, including perioperative MIB-PBI and RNI, demonstrated favorable oncological outcomes.

Background: Treatment of unresectable salivary gland cancers is challenging. This multicenter, retrospective study aimed to evaluate the treatment outcomes of definitive radiotherapy, with or without chemotherapy, for locally advanced, unresectable, salivary gland cancers.

Methods: A total of 27 patients with unresectable salivary gland cancers who underwent concurrent chemoradiotherapy or radiotherapy with curative intent between 2012 and 2022 at 13 hospitals in northern Japan were included in this study. Overall survival (OS) and progression-free survival (PFS) were assessed, and factors affecting OS and PFS were identified through univariate and multivariate Cox regression analyses. The variables evaluated included age, sex, primary site, histological type, clinical T and N status, clinical stage, treatment type, and radiation type.

Results: Seven patients received concurrent chemoradiotherapy, and 20 patients received radiotherapy (6 photon, 11 proton, 3 heavy ion). With a median follow-up period of 28 months, the three-year OS and PFS rates for the 27 patients were 54.4% and 27.8%, respectively. Patients who received concurrent chemoradiotherapy had better PFS than those who received radiotherapy alone (HR 0.16, 95% CI 0.03-0.81, P = .026).

Conclusions: Definitive radiotherapy for locally advanced, unresectable, salivary gland cancers resulted in relatively good outcomes. Concurrent chemoradiotherapy was associated with better PFS than radiotherapy.

Objective: Ovarian cancer (OC), accounting for 3.4% of female cancer diagnoses and 4.8% of cancer-related deaths globally, faces high recurrence risks. We aimed to develop a nomogram integrating novel biomarkers to improve prognostic accuracy for OC patients.

Methods: Clinical data from 1342 OC patients at Chongqing University Cancer Hospital (2019-21) were analyzed. Multivariate Cox regression identified independent prognostic factors to construct the nomogram. Model performance was evaluated via the C-index, time-dependent area under the receiver operating characteristic curve, calibration curves, and decision curve analysis (DCA).

Results: The independent prognostic factors for OC in this study include the body mass index, International Federation of Gynecology and Obstetrics stage, differentiation, surgery, targeted therapy, hemoglobin, β2 microglobulin, neutrophil-to-lymphocyte ratio, interleukin-6, and keratin 19. In both the training and validation cohorts, the C-indexes were 0.756 (95% CI: 0.718-0.793) and 0.751 (95% CI: 0.697-0.805), respectively. The calibration curve demonstrated a high level of consistency between the predicted and observed probabilities. DCA confirmed that the nomogram model provided a higher net benefit.

Conclusions: This study established a prognostic nomogram for OC and validated it with rigorous statistical metrics. An online tool was developed to facilitate personalized treatment strategies, offering clinical utility for OC management.

Background: Insulin-like growth factors (IGFs) are potent mitogens and IGF-binding protein 3 (IGFBP3) can regulate IGF activity. To elucidate relationships between IGF-related molecules and risk of pancreatic cancer, we analyzed associations between serum levels of IGF1 and IGFBP3 and incidence of pancreatic cancer in a prospective, nested, case-control study within the Japan Collaborative Cohort study.

Methods: A baseline survey was conducted from 1988 to 1990, during which period blood samples were obtained from 39 242 subjects. Subjects who had been diagnosed with pancreatic cancer by 1997 were regarded as cases. Conditional logistic regression was used to estimate odds ratios (ORs) for the incidence of pancreatic cancer in relation to serum levels of IGF1 and IGFBP3.

Results: This analysis included 72 cases and 216 controls. Free IGFBP3 (estimated as IGFBP3-IGF1) was associated with the risk of pancreatic cancer (P for trends = 0.011), with the third tertile showing the highest risk (OR = 3.42, 95%CI = 1.31-8.91). None of total IGF1, free IGF1 (estimated as IGF1/IGFBP3), or total IGFBP3 were associated with risk of pancreatic cancer. This result remained unchanged in subanalyses of male, female, and older subjects (P for trends = 0.017, 0.030, and 0.007, respectively). When limiting analysis to participants followed for over 2 years, free IGFBP3 was associated with risk of pancreatic cancer (P for trends = 0.025).

Conclusions: Our findings suggest that free IGFBP3 is associated with the risk of pancreatic cancer.

Stereotactic body radiation therapy (SBRT) is a radiotherapy technique that has been widely adopted in clinical settings for lung cancer treatment since the 1990s. In this study, we reviewed the medical history and current standard techniques of SBRT. Previous clinical studies on lung cancer, including those conducted by Japan Clinical Oncology Group, have demonstrated high local control rates with acceptable toxicities. Current indications for SBRT include expanded inoperable peripheral lung cancer to include operable, central, or oligometastatic lung cancer. We also reviewed the past and ongoing international clinical trials.