Japanese journal of clinical oncology最新文献

Objective: Esophageal cancer is one of the most lethal cancers worldwide. Previous studies have shown that reduced skeletal and respiratory muscle strength is correlated with increased postoperative complications. This study investigated the relationship between hand grip strength (HGS) and respiratory muscle strength assessed as peak expiratory flow (PEF) rate. We also examined the association of these factors with long-term prognosis in patients who had undergone radical esophagectomy for esophageal cancer.

Methods: We reviewed 392 patients who underwent radical subtotal esophagectomy from 2007 to 2023. HGS and PEF rate were measured preoperatively. Data analysis included univariable and multivariable Cox regression to identify prognostic factors for overall survival (OS).

Results: During a median follow-up of 36 months, 171 patients died, with 68.1% of deaths attributable to the primary disease. Because a weak correlation was observed between HGS and PEF rate (r = 0.353), separate multivariate analyses were performed for each factor to investigate their relationship to prognosis. Multivariable analysis identified PEF rate as an independent prognostic factor for OS (HR 0.991, 95% CI 0.984-0.999; P = .028), along with clinical stage (HR 1.345, 95% CI 1.188-1.521; P < .001), age (HR 1.026, 95% CI 1.007-1.046; P = .008), and surgical approach (open vs. minimally invasive; HR 0.674, 95% CI 0.490-0.928; P = .015). HGS was also identified as an independent prognostic factor for OS (HR 0.974, 95% CI 0.955-0.994; P = .012) along with clinical stage (HR 1.321, 95% CI 1.168-1.495; P < .001).

Conclusions: HGS and PEF rate are independent predictors of OS after esophagectomy.

Background: Fluorescence cystoscopy (FL) using 5-aminolevulinic acid (ALA) enhances the detection of urothelial carcinoma compared to white-light endoscopy (WL). The location of bladder tumors may affect the diagnostic performance of FL; however, this issue has been underexplored. We analyzed the diagnostic performance of FL compared with that of WL across different bladder regions.

Methods: Between 2018 and 2021, 181 patients with non-muscle-invasive bladder cancer who underwent FL-guided transurethral resection of bladder tumors (TURBT) using oral ALA were identified. During TURBT, WL and FL findings were recorded separately, and samples were collected. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for detecting urothelial carcinoma in each method were analyzed.

Results: The median patient age was 72 years, and 122 patients (85%) were male. Among the 526 collected tissues, 66, 106, and 35 were diagnosed as pTis, pTa, and pT1 urothelial carcinomas, respectively, and 319 lesions were benign. The sensitivity, specificity, PPV, and NPV of FL and WL were 91.8%, 58.3%, 58.8%, and 91.6% and 76.3%, 69.3%, 61.7%, and 81.9%, respectively. In the sensitivity analysis across different regions, the sensitivities of FL/WL in the posterior and lateral walls were 100/76.6% and 92.6/79.0%, respectively, and FL was superior (P < .001 and P = .003, respectively), whereas no advantages of FL were observed in the other regions.

Conclusions: FL presented a higher sensitivity than WL at the posterior and lateral walls but failed to show superiority in the other regions.

Objective: To identify pretreatment factors associated with developing primary resistance to nivolumab plus ipilimumab therapy in patients with advanced renal cell carcinoma (RCC).

Methods: We retrospectively reviewed the clinical characteristics, laboratory data, and tumor-related factors in patients with advanced RCC who initiated nivolumab plus ipilimumab as first-line therapy between January 2018 and July 2021. Primary resistance was defined as radiographic or clinical progression within 3 months of treatment initiation. Cases with suspected pseudoprogression were excluded.

Results: Eighty-nine patients met the inclusion criteria; 23 exhibited primary resistance. Univariate analysis identified the following significant predictive factors: body mass index (P = .006), lymph node metastasis (P = .021), sarcomatoid differentiation (P = .035), solitary metastatic organ (P = .051), liver metastasis (P = .056), and serum lactate dehydrogenase (LDH) (P = .094). Receiver operating characteristic curve analysis determined an LDH cutoff value of 174 U/L, which was significantly associated with primary resistance (P = .029). Considering the number of primary resistance cases, multivariable analysis incorporated three candidate variables (lymph node metastasis, sarcomatoid differentiation, and LDH ≥ 174 U/L) and identified sarcomatoid differentiation (odds ratio, 4.264; 95% confidence interval (CI), 1.299-14.825; P = .017) and LDH ≥ 174 U/L (odds ratio, 3.634; 95% CI, 1.143-13.770; P = .028) as independent predictors of primary resistance.

Conclusions: Sarcomatoid differentiation on pretreatment biopsy or elevated serum LDH before treatment initiation may predict primary resistance to nivolumab plus ipilimumab therapy in patients with advanced RCC. Alternative regimens should be considered in such cases, particularly for patients who are likely to experience rapid disease progression or for whom the occurrence of P-res is not clinically acceptable.

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.

Postmastectomy radiation Therapy (PMRT) reduces locoregional recurrence (LRR) and breast cancer mortality in patients with ≥4 positive lymph nodes. However, evidence supporting PMRT in patients with 1-3 positive nodes remains limited. While the 2014 Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analysis demonstrated benefit in this population, the constituent trials preceded current standard practices including sentinel lymph node biopsy, contemporary systemic therapies, and modern radiation therapy techniques. This analysis examines the applicability of EBCTCG findings to current clinical practice. Historical trials reported elevated LRR rates, potentially attributable to inadequate axillary staging and suboptimal systemic therapy regimens such as cyclophosphamide, methotrexate, and fluorouracil. Contemporary studies demonstrate substantially lower LRR rates in comparable patients managed without PMRT, particularly those with favorable tumor characteristics. Current adjuvant therapies-including anthracyclines, taxanes, trastuzumab, endocrine agents, and targeted therapies such as abemaciclib and olaparib-have markedly reduced recurrence risk. Retrospective analyses yield conflicting results regarding PMRT efficacy, while randomized trials (SUPREMO, TAILOR RT) seek to refine treatment indications. Contemporary practice should not universally recommend PMRT for intermediate-risk patients (1-3 nodes); instead, individualized risk assessment is warranted. The role of PMRT remains undefined in patients without axillary lymph node dissection or those achieving pathologic complete response following neoadjuvant therapy. Clinical decision-making must consider treatment benefits relative to potential late toxicities and reconstructive complications. Personalized, evidence-based approaches informed by emerging trial data represent the optimal strategy for patient management.

Background: Ewing sarcoma (ES) is a malignant type of bone and soft tissue tumor with EWSR1-ETS gene fusions as the primary driver alteration. Incidence is higher in White populations compared to Black and Asian populations. Researchers use next-generation sequencing to identify alterations as potential therapeutic targets. We compared the data from the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets in the USA with the data from Center for Cancer Genomics and Advanced Therapeutics in Japan.

Methods: We sequenced tumor DNA from 81 ES samples using the FoundationOne® CDx for multigene panel testing. Genetic alterations were interpreted via the Cancer Knowledge Database (CKDB) and potentially actionable alterations were classified into levels A-F.

Results: Analysis of 81 ES samples revealed 556 mutations in 197 genes and 126 copy-number alterations in 58 genes. Potentially actionable alterations were detected in 10 patients (12.3%) at CKDB levels A or C. STAG2 mutations accounted for 3.7%, TP53 mutations for 17.3%, and CDKN2A deletions for 13.6%. There was no significant difference in overall survival after genomic profiling test enrollment for STAG2 and TP53 mutations (P = .663 and P = .767), but those with CDKN2A and CDKN2B deletions had poor prognosis (P = .024 and P = .012).

Conclusion: Compared to previous reports, Japanese ES cases showed lower STAG2 and higher TP53 mutation frequencies. CDKN2A and CDKN2B deletions may serve as prognostic biomarkers indicating unfavorable outcomes.

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.

The ARASENS trial demonstrated a significant overall survival (OS) benefit for a triplet regimen in metastatic castration-sensitive prostate cancer (mCSPC). We aimed to determine whether this benefit is synergistic or additive. Using a mathematical model of independent drug action and published data from the ARASENS and ARANOTE, we compared the observed OS of the triplet regimen to a predicted OS curve. Reconstructed individual patient data were compared using a Cox model. The observed OS was statistically superior to the predicted OS (hazard ratio [HR] 0.82, 95% CI 0.68-0.99; P = .047), indicating a clinical benefit ~18% greater than the expected additive effect. To address confounding by subsequent therapies, we analyzed time to initial subsequent anticancer therapy, which showed an even more pronounced greater-than-additive benefit (HR 0.57, 95% CI 0.44-0.74; P < .001). These findings suggest the triplet regimen provides an early therapeutic advantage that exceeds additive expectations, supporting an upfront combination strategy in mCSPC.

Objectives: This article aims to describe the newly developed Japanese practice guidelines for psychological distress of adult individuals with cancer who have elevated levels of psychological distress.

Methods: We conducted systematic reviews and Delphi consensus rounds to determine the levels of certainty of evidence and strength of recommendation.

Results: In our proposed flow of care, all individuals with cancer should initially be provided with general support, comprising supportive communication, detection of psychological distress, attendance to their needs, and differentiating physical conditions that mimic psychological distress. If a patient still has significant psychological distress despite such support, more specific care for psychological distress should be considered. Collaborative care has strong evidence base and is strongly recommended. Evidence for psychotherapy for psychological distress and fear of cancer recurrence is moderate to strong, however, recommendations for these interventions were weakened because of the heterogeneity of interventions and lack of formal training system. Evidence of pharmacotherapy was weak. Thus, anxiolytics are weakly recommended only for short term and should be accompanied with psychosocial support. Antidepressants are weakly recommended when a patient is diagnosed with depression. Early specialized palliative care, care for caregivers and peer support are not recommended as a sole means to alleviate psychological distress, due to the scarce supporting evidence. Provision of these interventions is not hindered when they aim to improve the outcomes other than psychological distress, such as quality of life, symptom burden and self-efficacy.

Discussion: New practice guidelines for psychological distress of adult individuals with cancer have been developed.