International Journal of Clinical Oncology最新文献

Background: Pimitespib, an oral heat shock protein 90 inhibitor, significantly prolonged progression-free survival in patients with advanced gastrointestinal stromal tumors (GIST) in CHAPTER-GIST-301 study. This expanded access program was conducted to evaluate the safety and efficacy of pimitespib in Japanese patients with advanced GIST.

Methods: This multicenter, open-label, single-arm study was conducted in patients (≥ 20 years) with histologically confirmed GIST who had been previously treated with imatinib, sunitinib and regorafenib and had an Eastern Cooperative Oncology Group performance status of 0-1. Patients received pimitespib 160 mg/day for five days, followed by a 2-day rest, in 21-day cycles.

Results: Between February and August 2022, 23 patients were enrolled (median age 59.0 years). Over a median pimitespib treatment duration of 81.0 days, adverse events occurred in 22 patients (95.7%). The most common adverse events were diarrhea (73.9%), nausea (39.1%) and increased blood creatinine (30.4%). Serious adverse events occurred in two patients (tumor hemorrhage and tumor pain); neither was related to pimitespib. One patient had grade 3 diarrhea that was considered treatment-related. Four patients (17.4%) had eye disorders, all of which were grade 1 and treatment-related. The median progression-free survival was 4.2 months (95% confidence interval [CI] 1.9-6.2), the overall response rate was 0% (95% CI 0-16.1) and the disease control rate was 66.7% (95% CI 43.0-85.4).

Conclusions: Pimitespib was well tolerated and effective in patients with advanced GIST in real-world practice in Japan. No new safety signals were identified.

Trial registration: jRCT2031210526 registered 1 February 2022.

Background: Fertility preservation for patients with cancer or other diseases who receive gonadotoxic treatment has gained importance as cancer survival rates increase. In Japan, a database for registering all fertility preservation patients, named the Japan Oncofertility Registry (JOFR), was established in 2018. This study aimed to analyze recent trends in fertility preservation in Japan utilizing data from the JOFR.

Methods: Data was extracted from the JOFR for patients who consulted fertility preservation teams until May 2024. A descriptive analysis was conducted to examine trends in patient demographics, cancer types, fertility preservation treatments, complications, and outcomes. The data covered the period from diagnosis to fertility preservation and subsequent usage or disposal of frozen specimens.

Results: A total of 11,510 patients were recorded, with 9491 undergoing fertility preservation treatments. The number of patients increased steadily after 2006. After 2021, the number of female patients was much higher than the number of male patients. The most common primary diseases were breast cancer among women and testicular tumors and leukemia among men. There were some complications including ovarian hyperstimulation syndrome (5.0%), bleeding (0.12%), and infections (0.05%) for women. Seven hundred and sixty clinical pregnancies were recorded, with 440 using preserved specimens. The discard rate was 16.3% for men and 3.7% for women.

Conclusion: The study highlights recent trends in the growing number of cases undergoing fertility preservation in Japan. It also identifies several issues to be solved in fertility preservation in Japan, regarding its efficacy and safety, as well as the medical provision system.

Background: This study aimed to identify differentially expressed genes (DEGs) that are associated with hepatocarcinogenesis and metastasis in hepatocellular carcinoma (HCC) and to explore their value in predicting overall survival (OS). The methods used included bioinformatics analysis of gene expression datasets and in vitro experiments using HCC cell lines.

Methods: Gene expression profiles from metastatic and non-metastatic liver cancer specimens were analyzed using the limma R package. Functional enrichment was performed using Metascape. A prognostic 5-gene signature was constructed using the LASSO algorithm based on TCGA-LIHC data. Kaplan-Meier survival analysis assessed the association of these genes with clinical outcomes (DFI, DSS, OS, and PFS). In vitro, Huh7 and Hep3B cells were transfected with shRNA for SPP1 knockdown. Cell viability was measured with CCK-8 assays, and migration was assessed with Transwell and wound-healing assays. Protein expression was evaluated via western blotting.

Results: The analysis of gene expression profiles led to the identification of 11 DEGs associated with immune response, phagocytosis, and cell migration. From these DEGs, the LASSO algorithm identified a 5-DEG signature (MASP1, MASP2, MUC1, TREM1, and SPP1) that was predictive of OS in liver cancer patients. Among the five genes, SPP1 was the most upregulated in cancer samples and was significantly associated with poorer outcomes, including DFI, DSS, OS, and PFS. In vitro experiments confirmed that SPP1 knockdown in Huh7 and Hep3B cells significantly inhibited cancer cell viability and migration. Western blot analysis showed alterations in key proteins, with a reduction in vimentin and Ki-67 and an increase in E-cadherin following SPP1 knockdown.

Conclusion: This study highlights the pivotal effect of SPP1 on HCC development and underscores its potential as a biomarker for the OS of liver cancer patients. The identified DEGs may serve as predictive markers for OS and potential therapeutic targets for HCC treatment.

Background: In chemotherapy for unresectable advanced pancreatic cancer (UPC), the clinical utility of pre-treatment health assessment questionnaires, EuroQoL 5-Dimension 5-Level (EQ-5D-5L) and G8, is unknown. This study aimed to fill this gap.

Methods: This multicenter, prospective, observational study investigated the association of EQ-5D-5L and G8 with the clinical outcomes of first-line gemcitabine plus nab-paclitaxel (GnP) for UPC. Differences in survival were analyzed using the log-rank test, and multivariate analyses were performed using the Cox proportional hazards model.

Results: Between April 2022 and September 2023, 60 patients were enrolled, and their data were analyzed. When patients were classified into two groups using the median EQ-5D-5L utility value (0.824), progression-free survival (PFS) and overall survival (OS) were significantly longer in patients with high EQ-5D-5L utility values than in those with low utility values (median PFS 7.0 vs. 4.7 months, P < 0.01; median OS 12 vs. 8.0 months, P = 0.023). Such differences were not observed in the EQ-5D-5L Visual Analog Scale or G8 scores. There was no association between the occurrence of severe adverse events and EQ-5D-5L or G8 scores. Multivariate analyses showed that high EQ-5D-5L utility value (≥ 0.824), high albumin (≥ 3.8 g/dl), and low carcinoembryonic antigen (CEA) (< 5.4 ng/mL) were preferable independent efficacy predictors for PFS and also independent prognostic factors for OS.

Conclusion: Pre-treatment EQ-5D-5L utility value, along with albumin and CEA, was an independent efficacy predictor and prognostic factor in patients with UPC treated with first-line GnP. Their usefulness should be validated in future studies.

Background: Early tumor shrinkage (ETS) and depth of response (DpR) are early indicators of survival in patients with metastatic colorectal cancer (mCRC) undergoing anti-epidermal growth factor receptor monoclonal antibody treatment. However, their relevance in v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E mutant (MT) mCRC remains unclear. In this study, we evaluate the association between ETS/DpR and clinical outcomes in BRAF V600E MT mCRC.

Patients and methods: Patients with mCRC who were diagnosed with BRAF V600E MT and treated with first-line chemotherapy between June 2011 and March 2023 at a single cancer institute were enrolled. The association between ETS/DpR and clinical outcomes in patients with at least one target lesion was assessed. The cutoff value for ETS and DpR was set at 20% and 25%. Multivariate analysis of factors affecting progression-free survival (PFS) and overall survival (OS) was conducted.

Results: In total, 54 patients with BRAF V600E MT mCRC exhibited at least one target lesion. Patients with ETS and DpR were 24 (44.4%) and 27 (50%), respectively. Moreover, median PFS and OS were 7.5 and 17.1 months, respectively. Patients with ETS exhibited longer PFS and tended toward longer OS than those without ETS. Similarly, patients with DpR exhibited longer PFS and OS than those without DpR. Multivariate analysis confirmed a significant association between DpR and longer PFS and OS.

Conclusion: ETS and DpR could serve as early surrogate markers of clinical outcomes in patients with BRAF V600E MT mCRC treated with first-line chemotherapy.

Background: One of the most serious adverse events associated with trastuzumab treatment is cardiac dysfunction, including congestive heart failure. Therefore, regular cardiac screening with echocardiography is commonly performed during trastuzumab treatment, although it is unclear for how long the patient will continue to be evaluated. We investigated the time to the occurrence of trastuzumab-induced cardiac dysfunction using the Japanese Adverse Drug Event Report (JADER) database. We examined the optimal duration of cardiac function evaluation in patients treated with trastuzumab.

Methods: This study used data registered between April 2004 and September 2023 in the JADER database. We investigated the time to onset of cardiotoxicity in patients treated with trastuzumab, trastuzumab emtansine, or trastuzumab deruxtecan. We considered the time to exclude outliers detected using the Smirnov-Grubbs test as the optimal follow-up duration for cardiac function tests.

Results: Of 868,478 patients who reported adverse drug events, 977 experienced cardiac dysfunctions among those treated with trastuzumab. A total of 375 patients were included in the analysis after excluding patients for whom the time to onset of cardiotoxicity was unknown or those who experienced cardiac dysfunction after receiving trastuzumab followed by anthracycline. The median time to cardiotoxicity was 4.5 months (range 0-100 months). However, ≥ 19 months after the start of trastuzumab administration was detected as an outlier in the target population (P = 0.036).

Conclusion: The duration of regular follow-up of cardiac function using echocardiography during anti-HER2 therapy can be 18 months from the start of treatment.

Background: Gastrointestinal endoscopy (GIE) performed by gastroenterologists is essential for the early detection of pharyngeal cancer. Human papillomavirus (HPV) is a significant cause of oropharyngeal squamous cell carcinoma (OPSCC). However, the prevalence of HPV-related OPSCC detected by GIE remains unclear.

Aim: This study aims to evaluate the differences in detection rates, patient characteristics, and treatment approaches between HPV-positive and HPV-negative OPSCCs, with a focus on the role of GIE in early diagnosis.

Methods: We retrospectively analyzed 207 OPSCCs from 2018 to 2022, where HPV infection was diagnosed by p16 immunohistochemistry. We compared detection modalities and evaluated the proportion of lesions detected by GIE in both p16-positive and p16-negative cases.

Results: Out of the 207 patients, 92 (44.4%) were p16-positive. p16-positive cases had significantly lower rates of alcohol use, smoking, and history of esophageal or head/neck squamous cell carcinoma (all p < 0.001). Only 4.3% of p16-positive cases were detected by GIE, compared to 44.3% of p16-negative cases (p < 0.001). In addition, p16-positive patients were often diagnosed at advanced stages and underwent transoral resection less frequently (2.2% vs. 31.3%, p < 0.001). In cT1 cases, GIE and laryngoscopy revealed that p16-positive lesions were typically protruding and white to normal-colored, while p16-negative lesions were predominantly flat and erythematous.

Conclusions: HPV-related OPSCC cases are rarely detected by GIE, and few cases are treated with minimally invasive transoral resection. These findings highlight the need for enhanced detection strategies for HPV-positive OPSCC.

Background: In aging societies like Japan, the number of elderly bone sarcoma (BS) and soft-tissue sarcoma (STS) patients is increasing. However, these malignancies' behavior is incompletely understood. We investigated clinical features, treatment modalities, survival, and prognostic factors for elderly BS and STS patients using Japan's National Cancer Registry (NCR).

Methods: We identified data for 11,015 individuals ≥ 70 diagnosed with BS or STS in 2016-2019 by ICD-O-3 cancer topography and morphology codes and analyzed patient characteristics, disease information, initial diagnostic process, treatment, and prognosis.

Results: We analyzed 1072 BS cases and 9933 STS cases. There was no significant sex difference among BS or STS. The most common histological subtypes were chondrosarcoma (N = 310, 29%) and liposarcoma (N = 1533, 15%). Twelve percent of BS and 11% of STS patients had distant metastasis at first presentation. Forty-six percent of BS and 50% of STS patients underwent surgery. The number of patients > 80 who underwent surgery or had chemotherapy was significantly smaller than patients 70-79 (P < 0.001; P < 0.001). Three-year overall survival (OAS) was 46% among BS and 50% among STS patients. Adjusted analyses provided significant associations between OAS and age, histological subtype, treatment, and extent of disease in BS, and age, sex, histological subtype, tumor location, treatment, and extent of disease in STS.

Conclusions: This study featured elderly BS and STS patients, presenting epidemiology, clinical characteristics, treatment, and oncological outcomes based on the NCR. It gives clinicians valuable information to develop treatments for elderly BS and STS patients for future aging societies.

Lenvatinib is an orally available multi-tyrosine kinase inhibitor that mainly targets vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) signaling. These inhibitory activities of lenvatinib exhibit antitumor efficacy, mainly due to their repressive effects on angiogenesis. In addition, a recent non-clinical evaluation using mouse tumor models revealed that lenvatinib causes immunomodulatory effects, including activation of effector T-cells and regulation of tumor-associated macrophages (TAMs). Combined treatment with lenvatinib and anti-programmed cell death-1 antibody (anti-PD-1) resulted in enhanced antitumor activity relative to monotreatment with anti-PD-1 or lenvatinib. This review summarizes the antitumor mechanisms of lenvatinib and of lenvatinib plus anti-PD-1 combination therapy.

Background: To evaluate the efficacy and safety of diffusing alpha-emitter radiation therapy (DaRT) for recurrent head and neck cancer (rHNC) after radiotherapy.

Methods: This study was a multicenter prospective clinical trial. Eligibility criteria included all patients with biopsy-proven rHNC and history of radiotherapy. The efficacy of DaRT was evaluated in terms of tumor shrinkage after 10 weeks of DaRT seed implantation. To assess safety of DaRT, radioactivity levels in blood and urine were measured, and incidence and grade of adverse events (AEs) were evaluated.

Results: Between 2019 and 2021, DaRT was performed in 11 patients and completed in 10 patients with 11 tumors. The tumor sites included the tongue (n = 3), buccal mucosa (2), lips (2), floor of the mouth (1), soft palate (1), nose (1), and subcutaneous layer (1). Nine tumors were confirmed to be squamous cell carcinoma, and the remaining two tumors were basal cell carcinoma and neuroblastoma. Complete response (CR) and partial response (PR) were observed in three and six patients, respectively. The response rate was 81.8%. The maximum average radioactivity levels in blood and urine were 42.5 Bq/cm³ and 8.4 Bq/cm³, respectively, on the second day after implantation. Forty AEs were observed in all 11 patients, including 22 Grade 1 AEs, 16 Grade 2, and 2 Grade 3 (hypertension and seed remnants).

Conclusion: The initial response of rHNC after radiotherapy to DaRT was favorable, and the incidence and grade of AEs were acceptable, as compared to existing therapies.