International Journal of Clinical Oncology最新文献

Background: The implementation of cancer precision medicine in Japan is deeply intertwined with insurance reimbursement policies and requires case-by-case reviews by Molecular Tumor Boards (MTBs), which impose considerable operational burdens on healthcare facilities. The extensive preparation and review times required by MTBs hinder their ability to efficiently assess comprehensive genomic profiling (CGP) test results. Despite attempts to optimize MTB operations, significant challenges remain. This study aims to evaluate the effectiveness of QA Commons, an artificial intelligence-driven system designed to improve treatment planning using CGP analysis. QA Commons utilizes a comprehensive knowledge base of drugs, regulatory approvals, and clinical trials linked to genetic biomarkers, thereby enabling the delivery of consistent and standardized treatment recommendations. Initial assessments revealed that the QA Commons' recommendations closely matched the ideal treatment recommendations (consensus annotations), outperforming the average results of MTBs at Cancer Genomic Medicine Core Hospitals.

Methods: A clinical performance evaluation study will be conducted by comparing the QA Commons' treatment recommendations with those of the Academia Assembly, which includes medical professionals from the Cancer Genomic Medicine Core and Hub Hospitals. One hundred cases selected from the "Registry of the Academia Assembly," based on defined inclusion and exclusion criteria, will be analyzed to assess the concordance of recommendations.

Conclusion: The expected outcomes suggest that QA Commons could reduce the workload of MTB members, standardize the quality of MTB discussions, and provide consistent outcomes in repeated patient consultations. In addition, the global expansion of QA Commons could promote worldwide adoption of Japan's pioneering precision oncology system.

Background: The standard for robotic para-aortic lymphadenectomy has not been fully established. Para-aortic lymphadenectomy performed by sharing the same ports with pelvic procedures, a procedure known as dual-docking surgery, can be performed using the latest robotic system. We prospectively examined the ability of standardized dual-docking robotic surgery in endometrial cancer patients.

Methods: This study prospectively verified the feasibility and safety of dual-docking robotic surgeries performed between March 2017 and December 2021. The laterally placed ports were aligned with the umbilicus. Primary outcome was the surgical completion rate; secondary outcomes were blood loss, operative time, unexpected port placement, conversion, complications, length of hospital stay, and survival.

Results: Most patients (14/15, 93%) underwent surgery using our methods without additional port placements, and one patient was converted to laparotomy. Median blood loss was 162 mL (range: 20-685 mL). Median operative time was 183 and 206 min in the upper and lower abdomen. Median number of resected para-aortic lymph nodes was 19 (range: 6-29), and pelvic lymph nodes was 28 (range: 15-42). Although there was no difficulty in moving the forceps intraoperatively, major complications including vessel injury, and pelvic abscesses were observed. The lateral ports could be placed 6-10 cm apart in patients with any range of body type.

Conclusion: Dual-docking surgery for endometrial cancer has the potential to be a standard procedure for robotic endometrial cancer surgery, although a greater number of cases are needed to acquire proficiency.

Background and objective: Lymph node metastasis (LNM) in soft tissue sarcoma (STS) of the extremities is relatively rare. We aimed to evaluate the prognosis and the survival of patients with LNM and correlate them to the pattern of metastasis.

Methods: A retrospective study of patients diagnosed with STS of the extremities from 2015 to 2019.

Results: 111/1506 patients (7.4%) had LNM. Nodal metastasis was correlated significantly with old age, advanced tumor stages, high-grade tumors, presence of Lymphovascular invasion (LVI), and resection margins <  = 2 cm. Metachronous LNM was documented in 96 patients (86.5%) and synchronous LNM in 15 patients (13.5%). The 6-year overall survival (OS) was 36.3% for those with LNM and 52.9% for those without LNM. The 6-year disease-free survival (DFS) was 5.7% for those with LNM and 32.6% for those without LNM. Metachronus pattern of LNM showed a significantly poorer outcome regarding 6-year OS and DFS than the synchronous pattern.

Conclusions: LNM significantly negatively predicts OS and DFS in the extremities' STS. In particular, the metachronous pattern of LNM indicates a grave prognosis as these patients are supposed to harbor an occult LNM at presentation and were not subjected to lymphadenectomy at their initial primary treatment surgery. Therefore, seeking a valid noninvasive diagnostic tool such as sentinel lymph node biopsy to detect nodal metastasis is necessary.

Background: This study aimed to evaluate the efficacy of androgen receptor signaling inhibitors (ARSIs) combined with androgen deprivation therapy (ADT) for treating castration-sensitive metastatic prostate cancer in Japanese patients, focusing on the effects on time to the development of castration-resistant prostate cancer (CRPC) and overall survival (OS).

Methods: This retrospective muti-institutional analysis included 332 patients diagnosed with metastatic prostate cancer in Japan between 2018 and 2023. The patients were categorized into two groups: patients receiving ADT combined with ARSI (ARSI group) and those receiving ADT alone or with bicalutamide (ADT group). Data on demographics, treatments, and outcomes were compared using the Kaplan-Meier method with propensity score matching.

Results: We found an increasing trend in ARSI use over time. The median time to CRPC was significantly longer in the ARSI group than in the ADT group (47.1 vs. 15.2 months, p < 0.001); however, no significant differences in OS were observed before or after propensity score matching. The 1-year-survival rate of patients in the ARSI group tended to be higher than that of patients in the ADT group in subgroups with high tumor volume (96.1% vs. 85.0%) and high Gleason grade (98.1% vs. 85.9%).

Conclusions: Adding ARSI to ADT extended the time to CRPC but did not significantly affect OS. However, it potentially suppressed the short-term risk of death in high-risk subgroups. This study highlights the need for further research to explore the characteristics of Japanese patients with metastatic prostate cancer in whom upfront ARSIs are effective.

The efficacy of molecularly targeted agents has been established in advanced lung cancer, and their indications have recently expanded to include perioperative treatment of resectable lung cancer. For epidermal growth factor receptor (EGFR) mutation-positive patients, postoperative adjuvant therapy with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) is available in Japan following the results of the ADAURA trial. In addition to EGFR-TKIs, postoperative adjuvant therapy with TKIs targeting anaplastic lymphoma kinase (ALK) and rearranged during transfection (RET) is expected to be established. On the other hand, because adjuvant chemotherapy is ineffective in patients who have been completely cured of cancer through surgery alone, the balance between efficacy and adverse effects must be considered, and further studies will be needed to determine the necessary and sufficient dosage and the appropriate duration of administration. In addition, the cost of adjuvant chemotherapy has recently become an issue that cannot be overlooked. Therefore, it will be imperative to develop biomarkers to effectively narrow down the patients who benefit from adjuvant chemotherapy.

Background: Osteosarcoma, the most common primary bone malignancy, has a complex genetic basis and two incidence peaks. In younger patients, the standard treatment involves wide surgical resection combined with adjuvant chemotherapy; however, the role of chemotherapy in elderly patients remains controversial. The aims of this study were to investigate genetic differences between younger and elderly patients with osteosarcoma and to identify genetic signatures associated with chemotherapy response.

Methods: Genetic alterations were analyzed using cancer genome profiling data for 204 patients with osteosarcoma obtained from the Center for Cancer Genomics and Advanced Therapeutics.

Results: The mutation spectrum was consistent with previous results for osteosarcoma. CCNE1, MCL1, MYC, and RB1 alterations were significantly associated with a younger age, while CDK4, CDKN2A, CDKN2B, H3F3A, KMT2D, MDM2, RAC1, and SETD2 alterations were significantly associated with an older age. Age, unsupervised clustering of gene alterations, and MYC amplifications were significantly associated with the response to ifosfamide. Notably, both clustered mutation signatures and MYC amplification were correlated with age.

Conclusions: These findings suggest that distinct oncogenic mechanisms contribute to differential sensitivity to chemotherapy in younger and elderly patients. Cancer genome profiling may aid in chemotherapy selection, and its early implementation is recommended to optimize treatment strategies.

Background: In Japan, since 2014, new treatments such as androgen receptor signaling inhibitors and cabazitaxel have become applicable for metastatic castration-resistant prostate cancer (mCRPC), leading to dramatic changes in treatment options.

Objective: This study aims to evaluate the impact of recent advancements in treatment options on the overall survival (OS) of patients diagnosed with de novo metastatic castration-sensitive prostate cancer (mCSPC) in Japan.

Methods: A retrospective analysis was conducted on 2450 Japanese men diagnosed with de novo mCSPC between 2008 and 2018. Patients were stratified into two groups based on the period of diagnosis: an earlier period (2008-2013) and a later period (2014-2018). OS was compared between earlier and later periods using Kaplan-Meier analysis in total and propensity score matched subpopulation as well as risk-stratified subgroups.

Results: Patients diagnosed in the later period exhibited significantly improved OS compared to those diagnosed in the earlier period. The risk score, calculated based on ISUP grade group, LDH levels, and ALP levels, was a poor prognostic factor. In the later period, compared to the earlier period, there was no improvement in OS in the favorable-risk group, but a significant improvement was observed in the poor-risk group.

Conclusion: It was suggested that the introduction of novel androgen receptor signaling inhibitors and chemotherapy treatment regimens since 2014 has led to improved survival outcomes for patients with de novo mCSPC, particularly those with poor-risk profiles. The findings highlight the impact of recent advancements in treatment on the prognosis of patients with metastatic prostate cancer in Japan.

Background: Treatment-related skin reactions (TRSRs) induced by enfortumab vedotin (EV) targeting nectin-4 are among the most common adverse events. However, their association with survival and treatment response is poorly understood.

Methods: We retrospectively identified patients who received EV from December 2021 to April 2023 at Nagoya University Hospital and its affiliated facilities and extracted clinical data from their medical records. We evaluated cancer-specific survival (CSS) and progression-free survival (PFS) as survival outcomes and overall response rate (ORR) and disease control rate (DCR) as treatment responses between patients with and without TRSRs.

Results: In total, 67 eligible patients were identified. Thirty-four patients experienced TRSRs, and the remaining 33 did not experience TRSRs. The median follow-up period was 8 months. Patients in the TRSRs group demonstrated significantly longer median CSS (15 vs. 8 months; p = 0.003) and median PFS (10 vs. 5 months; p < 0.001) than the non-TRSRs. Regarding treatment response, the patients in the TRSRs group showed a favorable, albeit nonsignificant, treatment response trend compared with those in the non-TRSRs group (ORR, 73.5% vs. 51.5%; p = 0.107; DCR, 91.2 % vs. 81.8%; p = 0.444).

Conclusions: Patients with TRSRs demonstrated more prolonged survival and superior treatment responses to EV treatment. The role of TRSR as a surrogate marker of EV's efficacy should be further explored in prospective and sufficiently powered studies.

Background: Febrile neutropenia (FN) is a recognised adverse event associated with chemotherapy. This study investigates the impact of atezolizumab, an immune checkpoint inhibitor, on the incidence of FN in patients with non-small cell lung cancer receiving concurrent chemotherapy in Japan.

Methods: This post-marketing database study was conducted using data from patients with non-small cell lung cancer provided by Medical Data Vision Co., Ltd. covering April 2008 to present. The primary outcome measured was FN incidence, and its causal association with atezolizumab use was examined by comparing the atezolizumab plus bevacizumab plus carboplatin plus paclitaxel [ABCP])-containing regimen to the BCP control group. The data period was from 1 September, 2015, to 31 December, 2021, including approval date of this drug, 21 December, 2018.

Results: The database identified 301 subjects for the ABCP regimen (exposure) group, 44 for the BCP regimen (cohort design control) group during the same period, and 207 for BCP regimen (historical cohort design control) group before the approval of atezolizumab. For historical cohort design, the incidence and adjusted incidence ratios of febrile neutropenia in the exposure group to the control group were 6.13 (95% CI 2.78-13.49) and 8.19 (95% CI 3.79-25.33), respectively. Sensitivity analysis showed FN occurred in 17% (52/301) of the exposure group, 4.5% (2/44) of the cohort design control group, and 3% (7/207) of the historical cohort design control group.

Conclusions: The incidence of FN was higher in the exposure group. Considering the study results, special caution is needed for FN occurrence in patients receiving atezolizumab.