International Journal of Clinical Oncology最新文献

Objective: Non-small cell lung cancer (NSCLC) represents over 80% of lung cancer cases. Neoadjuvant therapy (NAT) improves overall survival (OS) of NSCLC patients. We explored clinicopathological significance of pre- and post-NAT CD47 and PD-L1 (SP142) changes [ΔCD47, ΔPD-L1 (SP142)] in stage IIIA-N2 NSCLC patients.

Methods: Totally 137 stage IIIA-N2 NSCLC patients underwent post-NAT surgery were selected, with tissues and clinical data collected. CD47 and PD-L1 (SP142) were determined by RT-qPCR and immunohistochemistry, with their relationships with chemotherapy efficacy and the tumor regression grade (TRG) score analyzed. The predictive value of CD47 and PD-L1 (SP142) for poor prognosis and their effects on OS and progression-free survival (PFS), and independent risk factors (IRFs) for poor 5-year prognosis were analyzed by receiver operating characteristic, Kaplan-Meier curves, and COX univariate/multivariate regression models.

Results: Post-NAT CD47 and PD-L1 (SP142) were reduced in stage IIIA-N2 NSCLC patients. Higher ΔCD47 and ΔPD-L1 correlated with worse chemotherapy efficacy. Post-NAT ΔCD47 and ΔPD-L1 (SP142) were reduced in patients with major pathological response. ΔCD47 and ΔPD-L1 positively correlated with TRG scores. Elevated ΔCD47, ΔPD-L1 (SP142) were IRFs for poor prognosis in NSCLC patients. The area under the curve of ΔCD47, ΔPD-L1 (SP142) and their combination for predicting NSCLC poor prognosis were separately 0.801, 0.797 and 0.891. Elevated ΔCD47 and ΔPD-L1 (SP142) shortened OS, PFS, and increased mortality risk in patients.

Conclusions: Post-NAT CD47 and PD-L1 (SP142) levels were reduced in IIIA-N2 NSCLC patients. ΔCD47 and ΔPD-L1 (SP142) levels linked to clinicopathological characteristics and predicted prognosis.

Background: In Japan, approximately 1 million individuals are newly diagnosed with cancer each year, and 56,000 patients have children under 18 years old. Children of patients with cancer face many challenges, and many parents struggle with how and when to talk to their children about their illness.

Methods: This retrospective study involved patients with cancer who consulted child life specialists (CLS) for their children at a cancer center between January and December 2021. Patients' demographic and clinical information, their children's ages, and consultation topics were extracted from medical records.

Results: In total, 138 patients consulted CLS regarding concerns about their children. Most patients were women in their 40 s, with breast cancer as the most common diagnosis (46%). Consultations mainly occurred at diagnosis (43%) or during primary treatment (36%). Issues related to children aged 7-12 years were the most common. Of 294 consultation topics analyzed, the most common topic was how and when to tell children about treatment details and schedules (17%). Emotional support for children was a major concern among patients with recurrent diseases. Patients with breast cancer most often sought advice on discussing physical changes, whereas patients with gastrointestinal and gynecological cancers prioritized communication about diagnosis.

Conclusions: Patients with cancer that have minor children have diverse and complex concerns. Our findings highlight the importance of integrating psychosocial support services in standard oncology care to address families' unique needs. Tailored interventions, particularly for school-aged children, and ongoing support throughout the disease trajectory are essential to improve family outcomes.

Background: Pimitespib is a first-in-class heat shock protein 90 (HSP90) inhibitor, approved in Japan for the treatment of advanced gastrointestinal stromal tumors (GIST). This study aimed to characterize the incidence and time course of adverse drug reactions (ADRs) associated with pimitespib.

Methods: This was a post hoc analysis of pooled safety data from a phase 1 (NCT02965885), phase 2 (jRCT2080223127), and phase 3 (jRCT2080224033) study of pimitespib in patients with advanced GIST. The present analysis included Japanese study participants who received oral pimitespib 160 mg once daily for 5 days followed by 2 days' rest per week in 21-day cycles. Pooled safety outcomes included the incidence and severity of ADRs; ADRs leading to treatment modifications or discontinuation; and the time to ADR onset and resolution.

Results: In total, 119 patients were included. ADRs were reported in 114 patients (95.8%); gastrointestinal ADRs were most common (99 patients [83.2%]; most often diarrhea [75.6%]) and ocular ADRs occurred in 26 patients (21.8%; most often night blindness [11.8%]). Median time to first onset of any gastrointestinal ADR was 3.0 days; the outcome of gastrointestinal ADRs was recovered/recovering in 61 patients (61.6%), with a median time to resolution of 44.0 days. Median time to first onset of any ocular ADR was 19.0 days; ocular ADRs were recovered/recovering in 20 patients (76.9%), with a median time to resolution of 21.0 days.

Conclusions: This analysis suggests that most ADRs associated with pimitespib are manageable and reversible, thus supporting its use in patients with advanced GIST.

Background: Gastric cancer (GC) is a prevalent malignancy with a substantial impact on public health. Muscle quality and function may serve as predictors of poor clinical outcomes in GC. The aim of this updated meta-analysis was to evaluate the prognostic significance of hand grip strength (HGS) in patients undergoing gastrectomy for GC.

Methods: A comprehensive literature search was conducted in PubMed, EMBASE, and Cochrane CENTRAL till August 2023, using keyword combinations of "hand grip strength", "gastric resection", and "gastrectomy". Eligible studies were those focused on outcomes of GC patients undergoing gastrectomy, with a comparison of preoperative HGS. The primary outcome was overall survival (OS); postoperative complications were assessed as a secondary outcome. Newcastle-Ottawa scale was used for quality assessment.

Results: Nine studies involving 3,496 patients met our inclusion criteria, conducted primarily in China and Japan. A low HGS was significantly associated with worse OS (pooled adjusted hazard ratio [HR] = 2.29, 95% confidence interval [CI] 1.47-3.57) and increased postoperative complications (pooled adjusted odds ratio [OR] = 1.91, 95% CI 1.55-2.36). Sensitivity analysis confirmed the robustness of the results.

Conclusions: This meta-analysis highlights the prognostic relevance of preoperative HGS in GC patients undergoing gastrectomy. The findings strongly link low HGS to decreased OS and postoperative complications risk. This relationship suggests the potential of HGS as a valuable marker for a preoperative risk assessment and stratification.

Objective: Combination therapy with enfortumab vedotin (EV) and pembrolizumab has shown superior overall survival (OS) compared to platinum-based chemotherapy in advanced urothelial carcinoma (UC). Given the expanding landscape of first-line treatments, understanding site-specific effectiveness is vital for developing individualized strategies.

Methods: We conducted a retrospective analysis of 225 patients with advanced UC treated between April 2009 and August 2024. Systemic therapy efficacy was assessed in relation to metastatic site, focusing on site-specific responses. Patients were classified into three treatment periods (chemotherapy period [April 2009-June 2017; P1], pembrolizumab period [July 2017-December 2020; P2], and avelumab and EV period [January 2021-August 2024; P3]). Within each period, patients were stratified by metastatic pattern-lymph node-only, liver, or other-and OS was analyzed accordingly.

Results: The objective response rates for chemotherapy, pembrolizumab, avelumab, and EV were 41%, 23%, 20%, and 46%, respectively. Lymph node and pulmonary metastases exhibited favorable responses across all treatment modalities, whereas bone metastases consistently responded poorly. Notably, EV exhibited substantial activity against liver metastases. Median OS improved over successive treatment periods (P1: 14 months; P2: 16 months; P3: 26 months). However, patients with liver metastases experienced no meaningful OS improvement (P1: 9.5 months; P2: 9.2 months; P3: 8 months), with 54% of these patients not receiving EV.

Conclusions: Sequential therapies may offer a survival benefit in selected patients. EV plus pembrolizumab may be particularly beneficial in patients with rapidly progressive disease such as those with liver metastases, warranting further investigation in real-world settings.

Background: Cervical cancer remains a major health problem, and HPV-independent subtypes such as gastric-type adenocarcinoma carry dismal outcomes. Although immune checkpoint inhibitors (ICIs) have improved survival in large trials, their real-world effectiveness including HPV-independent tumors is not well established.

Methods: We conducted a retrospective multicenter study of two surrogate cohorts representing refractory cervical cancer: patients treated with bevacizumab (Bev-cohort, n = 65) and those undergoing comprehensive genomic profiling (CGP-cohort, n = 42). Early ICI administration was evaluated using landmark analysis (Bev: 180 days; CGP: 6 months), with differences in restricted mean survival time (ΔRMST) as the primary endpoint. Multivariable Cox models adjusting for stage, histology, and treatment interval were performed as secondary analyses. Exploratory analyses assessed HPV and molecular status for associations with ICI response.

Results: In the Bev-cohort, 14 ICI-treated patients achieved significantly longer survival than 48 non-ICI patients (ΔRMST + 19.4 days at 180 days; + 56.2 days at 360 days). Multivariable Cox confirmed ICI as an independent predictor of survival (HR 0.15, 95%CI 0.01-0.69). In the CGP-cohort, 11 ICI-treated patients also experienced superior survival compared with 20 non-ICI patients (ΔRMST + 1.05 months at 6 months; + 2.33 months at 12 months). Among 36 ICI-treated cases overall, efficacy was not clearly associated with PD-L1 or tumor mutation burden status. Importantly, HPV-independent tumors, including gastric-type adenocarcinoma, demonstrated progression-free survival comparable to HPV-associated tumors.

Conclusion: ICIs improved survival in advanced refractory cervical cancer across two real-world cohorts. HPVI may respond favorably, but further studies are needed.

Background: Systematic pelvic and aortic lymphadenectomy in stage IIB-IVB patients with epithelial ovarian cancer, undergoing complete abdominal macroscopic resection with normal lymph nodes, was revealed to have no prognostic significance for survival in the LION trial. However, the proportion of patients with ovarian clear cell carcinoma (OCCC) in the LION trial was only 2.2%, so the significance of systematic retroperitoneal lymphadenectomy in patients with OCCC remains unclear.

Methods: We conducted an ancillary analysis of 619 patients enrolled in a randomized phase III trial (JGOG 3017) in patients with OCCC. Of these, 89 were stage IIB to IVB, underwent a complete macroscopic resection, and had no grossly enlarged lymph nodes intraoperatively. Patients were divided into two groups: group A with lymphadenectomy and group B without lymphadenectomy. The Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS) and the log-rank test and Cox proportional hazard model were used to compare the two groups.

Results: Among the 89 patients, 77 (86.5%) underwent a lymphadenectomy (group A), while 12 (13.5%) did not (group B). Three-year PFS were 62.3% in group A and 58.3% in group B (p = 0.7705). Three-year OS were 73.0% in group A and 65.6% in group B (p = 0.6346). No significant differences were observed between two groups.

Conclusion: This study did not demonstrate a definitive survival benefit from systematic lymphadenectomy in advanced OCCC patients with complete resection and clinically negative nodes. Given the small sample size, these results should be interpreted with caution and regarded as exploratory.

Background: Patients with advanced renal cell carcinoma (RCC) undergoing hemodialysis are often excluded from clinical trials. We aimed to evaluate real-world outcomes of first-line molecular targeted therapy (MTT) and immuno-oncology (IO) combination therapies in patients with advanced RCC receiving hemodialysis.

Methods: We retrospectively analyzed data from 88 patients undergoing hemodialysis who received first-line systemic therapy for advanced RCC at 18 institutions in Japan between 2008 and 2023. Patients were divided into three groups by first-line regimen: MTT (n = 53), IO-IO (n = 18), or IO-tyrosine kinase inhibitor (IO-TKI, n = 17). Treatment response, progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) were evaluated. Prognostic factors were identified using univariate and multivariate Cox regression analyses.

Results: The median PFS and OS were 3.9 and 18.9 months, respectively. The IO-IO and IO-TKI groups achieved significantly longer PFS than that in the MTT group (median PFS 3.5, 5.4, and 7.5 months, respectively; p = 0.003); OS did not differ significantly between the groups. Grade ≥ 3 TRAEs occurred in 30.2%, 33.3%, and 41.2% of the MTT, IO-IO, and IO-TKI groups, respectively. Multivariate analysis identified poor Eastern Cooperative Oncology Group performance status, longer hemodialysis duration (≥ 10 years), and first-line regimen as independent PFS predictors. International Metastatic RCC Database Consortium risk classification and hemodialysis duration independently predicted OS.

Conclusions: Systemic therapy, including IO-IO and IO-TKI regimens, demonstrated acceptable safety profiles for patients with advanced RCC undergoing hemodialysis. IO combination therapy significantly improved PFS, supporting its utility as a first-line treatment option.

Approximately 5% of all colorectal cancers have a strong genetic component and are classified as hereditary colorectal cancer (HCRC). Some of the unique features commonly seen in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics require different management approaches, including diagnosis, treatment or surveillance, from those used in the management of sporadic colorectal cancer. Accurate diagnosis of HCRC is essential because it enables targeted surveillance and risk reduction strategies that improve patient outcomes. Recent genetic advances revealed several causative genes for polyposis and non-polyposis syndromes. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) first published guidelines for the management of HCRC in 2012, with subsequent revisions every 4 years. The 2024 update to the JSCCR guidelines for HCRC was developed by meticulously reviewing evidence from systematic reviews and the consensus of the JSCCR HCRC Guidelines Committee, which includes representatives from patient advocacy groups for FAP and Lynch syndrome. These guidelines provide an up-to-date summary of HCRC, along with clinical recommendations for managing FAP and Lynch syndrome.