Japanese journal of clinical oncology最新文献

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).

Objective: Dasatinib was approved for treating pediatric patients with philadelphia chromosome-positive chronic myeloid leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia. While its efficacy has been proven, comprehensive safety data in pediatric populations remain limited. This study utilizes data from the food and drug administration adverse event reporting system (FAERS) to evaluate and characterize adverse events (AEs) reported in pediatric patients treated with dasatinib.

Methods: Data from the FAERS between 2014 Q1 and 2024 Q4 were analyzed. Disproportionality analysis was performed to identify AEs reported in pediatric patients treated with dasatinib.

Results: A total of 382 pediatric cases involving dasatinib were reported. The most frequent system organ classes included general disorders and administration site conditions, injury, poisoning, and procedural complications, and gastrointestinal disorders. Notably, previously unreported AEs such as hemorrhagic enterocolitis, lymphoid tissue hyperplasia, hydrocephalus, and hemorrhagic cystitis were identified, raising potential new safety concerns. Additionally, instances of off-label use were observed, particularly in regions where dasatinib is not recommended for pediatric patients, underscoring the importance of vigilant AEs monitoring to ensure patient safety.

Conclusion: This study highlights the need for enhanced pharmacovigilance and proactive monitoring in pediatric patients receiving dasatinib to ensure treatment safety and improve clinical outcomes, and provides supporting evidence for the safe use of dasatinib in pediatric populations.

Background: The impact of the starting dose of tyrosine kinase inhibitors (TKIs) following combination therapy of immune checkpoint inhibitors with TKIs (i.e. IO-TKI) for advanced renal cell carcinoma (RCC) remains unclear.

Methods: We retrospectively evaluated clinical data from 155 patients treated with first-line IO-TKI for RCC. Patients were categorized into full-dose and reduced-dose groups based on their starting dose of TKIs. Effectiveness and safety profiles were compared between groups.

Results: A reduced starting dose was administered to 52 patients (34%). These patients were older (P = 0.0137) and received pembrolizumab plus axitinib more frequently, while lenvatinib plus pembrolizumab was less used (P = 0.0258) compared to the full-dose group. Progression-free survival and overall survival did not significantly differ between the full-dose and reduced-dose groups (P = 0.202 and P = 0.309, respectively). Although the objective response rate appeared higher in the full-dose group, the difference was not statistically significant after adjusting for other covariates (P = 0.0588). Safety profiles were comparable, with no significant differences in TKI dose reduction, drug interruption or discontinuation, or glucocorticoids use (P > 0.05). However, adverse events of grade ≥3 were more frequent in the full-dose group, although not statistically significant (P = 0.121).

Conclusion: The starting dose of TKIs did not significantly impact clinical outcomes following IO-TKI for RCC. These findings suggest a potential for the optimization of the starting dose of TKIs; however, prospective studies are warranted to confirm these findings.

Background: This study aimed to investigate the risk factors and prognostic impact of regional lymph node metastasis (RLNM) in patients with bone sarcoma.

Methods: This retrospective study analyzed data from a Japanese registry of patients with bone sarcoma (2006-19). Disease-specific overall survival was estimated using the Kaplan-Meier method. A Cox regression model was used to identify risk factors for RLNM and prognostic factors.

Results: Among 5064 patients, 157 (3.1%) had RLNM. The incidence varied by histological subtype: 7.6% in Ewing sarcoma, 3.1% in osteosarcoma, 1.6% in chondrosarcoma, and 5.2% in undifferentiated pleomorphic sarcoma. Higher rates were observed in rare subtypes, including mesenchymal chondrosarcoma (12.9%) and dedifferentiated chondrosarcomas (10.3%). Risk factors for RLNM included older age, tumor size (>8 cm) (P = .02), distant metastasis at diagnosis (P < .0001), skip metastasis (P < .0001), and histological subtype (e.g. Ewing sarcoma and dedifferentiated chondrosarcoma). RLNM was associated with poor prognosis (HR 1.69, 95% CI: 1.35-2.1, P < .0001), with isolated RLNM conferring survival outcomes equivalent to those with distant metastasis. Among RLNM cases, skip metastasis was the only significant independent predictor of poor prognosis (HR 2.41, 95% CI: 1.35-4.30, P = .003).

Conclusions: The incidence of RLNM in bone sarcomas varies by histological subtype. Risk factors include older age, tumor size, distant metastasis, skip metastasis, and histological subtype. Isolated RLNM has a prognosis comparable to that of distant metastases, and skip metastasis is a significant negative prognostic factor.

Background: Pelvic lymph node dissection in intermediate- or high-risk localized prostate cancer is important for detecting or eliminating lymph node metastases. This study evaluates the effectiveness of extended pelvic lymph node dissection (ePLND) for high-risk prostate cancer.

Methods: We identified 275 patients who underwent robot-assisted radical prostatectomy for high- or very high-risk prostate cancer, as defined by the National Comprehensive Cancer Network risk categories, at two centers between May 2013 and March 2021. Using propensity score matching, 61 patients from each group were compared between the no ePLND and ePLND groups. Console time, estimated blood loss, surgery-related complications, and biochemical recurrence (BCR) rates were compared between the groups. Multivariate analysis was used to identify independent predictors of BCR.

Results: The ePLND group had longer operative and console times and greater blood loss compared with the no ePLND group (P < .01). Intraoperative surgery-related complications were also more frequent in the ePLND group (P = .01); however, no significant difference was observed in postoperative surgery-related complications (P = .28). The median follow-up period was 60 months; BCR rates were not different between the groups (P = .12). However, in a sub-analysis limited to very high-risk cases, the BCR in the no ePLND group was significantly higher than in the ePLND group (P = .01). Multivariate analysis identified pathologic T stage ≥3 and lymphovascular invasion as independent predictors of BCR, whereas ePLND was not associated with BCR.

Conclusions: In this study, ePLND for high- or very high-risk prostate cancer did not improve BCR. However, it may improve BCR in very high-risk prostate cancer.

Background: Osteosarcoma is the most common primary malignant bone tumor. Although previous studies reported genetic differences between younger and older patients, comprehensive nationwide data remain scarce. This study aimed to describe age-related differences in demographics, treatment, and survival using Japan's Bone and Soft Tissue Tumor (BSTT) Registry.

Methods: We retrospectively analyzed 3446 osteosarcoma cases recorded in the BSTT Registry from 2006 to 2022. Patient demographics, tumor characteristics, treatment modalities, and outcomes were examined, with a focus on differences across age groups.

Results: The cohort showed a slight male predominance (57%) and bimodal age distribution peaking at 10-19 and 70-79 years. The proportion of patients aged ≥60 years increased from 16% (2006-2012) to 19% (2013-2022). The femur (46%) was the most common tumor site, but spine or pelvis involvement was more frequent in elderly patients. Nodal and distant metastases were more common in older adults (5% vs 2%, and 26% vs 17%, respectively). Patients aged <60 underwent surgery and chemotherapy more often (79% and 83%) compared to those aged ≥60 (61% and 47%). The 5-year disease-specific survival (DSS) rate was 64% overall, but markedly lower in the elderly (40%) than younger patients (70%). Key prognostic factors included histologic grade, metastasis status, tumor size, location, and surgical margins. DSS was slightly worse in recent years, though not statistically significant (P = 0.080).

Conclusions: This nationwide analysis highlights age-associated disparities in osteosarcoma care in Japan. Older patients receive less aggressive treatment and have poorer outcomes. These findings may inform healthcare planning in aging societies globally.

Level of evidence: Prognostic studies, Level III.

Accurate prognostic information is crucial for guiding end-of-life (EOL) decision-making in advanced cancer care. Although the European Society for Medical Oncology (ESMO) recommends using clinicians' prediction of survival (CPS) as an initial reference, CPS alone often lacks precision. This review synthesizes current prognostic models and the dialog surrounding EOL survival prediction. For patients with an expected survival of months, several validated prognostic tools are available, including measures such as the Eastern Cooperative Oncology Group Performance Status, the modified Glasgow Prognostic Scale, and comprehensive models such as the Supportive and Palliative Care Indicator Tool and the adaptable prognosis prediction model. When survival is expected to be weeks, the Palliative Performance Scale serves as a key assessment tool, while models such as the Palliative Prognostic Index and Prognosis in Palliative Care Study models are helpful. In the final days of life, clinicians primarily rely on observable physical indicators, including decreased consciousness and specific breathing patterns, whereas the surprise question has demonstrated limited predictive utility in this context. While most patients with advanced cancer express a desire for prognostic information, cultural considerations-particularly in Asia-necessitate nuanced communication approaches. Serious illness conversations have been shown to improve patient well-being; however, further research is needed to optimize these discussions, address unfinished business, and promote equitable access to prognostic dialog, particularly for vulnerable populations. Enhancing prognostic communication is critical for facilitating shared decision-making and improving the quality of EOL care.

Background: This study aimed to investigate the prognostic risk factors for T1/2 major salivary gland cancer. Additionally, we sought to determine the impact of adjuvant radiotherapy, especially in low-grade cancer cases with clinicopathological adverse features.

Methods: A retrospective review of medical records for 93 patients who underwent surgery for T1/2 major salivary gland cancers between January 2000 and December 2024 was conducted. We evaluated clinicopathological adverse features as prognostic factors and compared 5-year disease-free survival (DFS) to determine the influence of adjuvant radiotherapy on prognosis in low-grade cancer cases exhibiting any histological adverse features.

Results: Lymphatic invasion was linked to reduced 5-year overall survival in patients with T1/2 major salivary gland cancers (hazard ratio [HR] = 8.563, 95% confidence interval [CI] = 1.202-60.996, P = .032). Regarding 5-year DFS, histological grade and positive nodal metastasis were pinpointed as detrimental prognostic factors (HR = 3.330, 95% CI = 1.023-10.842, P = .046; HR = 9.891, 95% CI = 1.520-64.355, P = .046, respectively). For low-grade cancers presenting with any clinicopathological adverse features, no significant difference was observed in 5-year DFS following adjuvant radiotherapy (86.8% vs. 93.8%, P = .781).

Conclusions: Lymphatic invasion, high histological grade, and positive nodal metastasis were determined as poor prognostic factors in T1/2 major salivary gland cancer. However, adjuvant radiotherapy did not significantly influence the prognosis in low-grade cancer cases with adverse features.

Background: Immune checkpoint inhibitors (ICIs) improve outcomes in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, some patients remain unresponsive to treatment, necessitating further investigation into optimal therapeutic strategies and prognostic biomarkers. This study aimed to evaluate the efficacy of various therapies and identify factors influencing overall survival (OS) in these patients.

Methods: We retrospectively analyzed 606 patients (517 men, 89 women; median age 68 years) treated at 13 head and neck cancer specialty facilities in Japan between January 2018 and December 2022. Associations between OS and variables, including age, sex, primary site, Eastern Cooperative Oncology Group performance status, estimated glomerular filtration rate, therapeutic target lesion, history of drug use in systemic chemotherapy, number of treatment lines, nondrug treatments, de novo metastasis, programmed death-ligand 1 combined positive score, and platinum resistance were statistically examined.

Results: Median OS was 14.2 months, and median progression-free survival was 5.0 months. Multivariate analysis identified poor OS in patients with oral cavity tumors and performance status 2-3, whereas ICI therapy and nondrug salvage interventions were associated with improved OS. ICI/non-ICI subgroup analysis revealed that ICI may have a limited effect on oral cancer. Additionally, our results indicated that a history of platinum therapy for R/M HNSCC may not affect the therapeutic efficacy of ICIs.

Conclusion: For patients with R/M HNSCC, further OS improvement may be achieved using ICIs or aggressive nondrug salvage therapy and by considering the use of chemotherapy other than ICI for patients with oral cancer or poor PS.