JCO Global Oncology最新文献

Purpose: Small cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy characterized by poor prognosis. The ADRIATIC trial demonstrated significant survival benefits with durvalumab as maintenance therapy for limited-stage SCLC (LS-SCLC). However, the high cost of durvalumab necessitates an evaluation of its cost-effectiveness.

Methods: A partitioned survival model was developed to assess the cost-effectiveness of durvalumab consolidation therapy compared with the standard of care (SOC). The model comprised three mutually exclusive health states: progression-free survival (PFS), progression of disease (POD)/metastasis, and death. Incremental cost-effectiveness ratio (ICER) was calculated as cost per quality-adjusted life year (QALY) gained, with a willingness-to-pay (WTP) threshold of $150,000 in US dollars (USD)/QALY. One-way and probabilistic sensitivity analyses were conducted. Analysis for POD was also stratified into intrathoracic, extrathoracic, and CNS.

Results: Durvalumab improved overall survival (OS) to 66.1 months and PFS to 40.2 months, compared with 57.8 and 31.8 months for SOC, respectively. The total cost of durvalumab was $163,722 USD versus $25,816 USD for placebo, resulting in an incremental cost of $137,905 USD. Durvalumab provided an incremental QALY gain of 0.36 years, yielding an ICER of $383,069 USD/QALY, exceeding WTP. On stratification, durvalumab in patients with extrathoracic progression nearly met WTP (ICER, $151,137 USD).

Conclusion: Durvalumab remains cost-prohibitive for the overall cohort, exceeding acceptable thresholds despite favorable outcomes. Subgroup analysis, however, indicates that selective use in patients with extrathoracic progression may enhance cost-effectiveness. Overcoming economic barriers will be essential for the sustainable integration of immunotherapy into routine care.

Purpose: For children with ALL in low- and middle-income countries (LMICs), treatment regimen adaptation based on local contexts is often necessary. However, the clinical impact of such modifications is poorly understood. The purpose of this study is to examine pediatric ALL treatment regimens used in LMICs, assess for patterns in adaptation to identify common barriers affecting global delivery of ALL care, and describe the breadth of outcomes.

Methods: Using the PRISMA guidelines, a systematic review was conducted, across seven databases, of ALL regimens use in LMICs in 2000-2021, documenting the geographic distribution of treatment backbone adoption, regimen modifications, and outcomes. Article characteristics were summarized using descriptive statistics.

Results: Of 13,900 articles, 125 met abstraction criteria. Data spanned 36 countries (6.4% low-income, 43.2% lower-middle-income, 50.4% upper-middle-income) and 163 regimens, of which 138 (84.6%) referenced a high-income ALL collaborative group regimen as a backbone. Sixty-four percent of regimens (n = 104) were adapted. Individual modifications (n = 390) were consolidated into 73 distinct regimen changes; reduction/omission of high-dose methotrexate, observed in 30 modified regimens (28.8%), was the most common. Implementation challenges, such as drug access and cost, were cited more frequently than toxicity as the rationale for modification; however, implementation outcomes (eg, feasibility, cost) were only measured in 6.4% of articles. Across all outcomes, 5-year overall survival was higher with modified versus unmodified regimens (P = .030).

Conclusion: Although implementation barriers are primary drivers of ALL regimen adaptations globally, the paucity of reported implementation outcomes represents a methodological gap in the literature. Incorporating implementation science methods and frameworks is critical for the timely and effective delivery of innovative treatment regimens across resource settings.

Purpose: This study investigates the interplay between T-cell receptor (TCR) immune characteristics and microbiome profiles to explore the relationship between immune diversity and microbial composition in cervical samples from Ethiopia.

Methods: Cervical specimens were collected from patients at Tikur Anbessa Specialized Hospital in Addis Ababa, and rural Butajira, south-central Ethiopia. Patient data, including age, human papillomavirus status, pathology, and TCR immune characteristics, were analyzed with a focus on the interactions between TCR profiles and microbiome compositions in malignant samples.

Results: Three distinct TCR profiles were identified: Group 1 (TCR active) exhibited features of active immune engagement, including high diversity, clonal expansion, and repertoire richness. Group 2 (TCR restricted) showed reduced TCR diversity and expansion, suggesting a restricted repertoire. Group 3 (TCR balanced) had moderate diversity and clonal activity. TCR repertoire groups were linked with microbial diversity, with Group 1 (TCR active) showing the highest number of microbes (high operational taxonomic units and microbial diversity). Maximum TCR clonal expansion positivity associated with microbial richness, while Group 3 (TCR balanced) was linked to reduced microbial alpha diversity. Taxonomic analysis revealed specific organisms enriched in TCR repertoire group.

Conclusion: Variations in TCR profiles are linked to distinct microbial environments in cervical cancer with greater microbial richness in patients with greater maximum productive frequency. These findings underscore the interplay between TCR diversity, microbiome composition, and malignancy, offering insights into the potential implications for microbiome-targeted therapies and prognostic biomarkers in cervical cancer.

Purpose: This study aims to assess the rate of histopathologic diagnostic discordances between the local reviewer in each country of the Sarcoma European and Latin-American Network (SELNET) consortium and expert soft tissue and bone pathologists present in the SELNET network and to evaluate the causes of discrepancies.

Materials and methods: Histologic diagnosis at the local center of each country from the SELNET consortium and its relative agreement with the revised diagnosis of expert pathologists from the SELNET pathologist network were evaluated in 347 cases of bone or soft tissue tumors over 3 years.

Results: Diagnostic concordance was observed in 296 cases (85.3% with a Cohen's κ = 0.84, P < .001), whereas in the remaining 51 cases (14.7%), diagnostic discordance was observed. In 19 of 51 cases, the discordance was considered major because it was related to a significant change in clinical management. Minor histologic discordances were observed in the remaining 32 cases. The most frequent reason for diagnostic discordances was incorrect morphologic interpretation and/or the unavailability of key diagnostic immunohistochemical markers (41.2%), or the unavailability of molecular testing to confirm morphologic and immunohistochemical data (21.6%). Incorrect interpretations of morphologic features alone occurred in 37.2% of cases.

Conclusion: A diagnostic agreement of 85.3% was obtained between the original diagnosis in each country of the SELNET consortium and the expert pathologist of the network. Morphologic assessment of tumors, the use of newer immunohistochemical markers, and molecular analysis on a limited number of cases were found to be useful in correcting discrepancies.

Purpose: Gestational trophoblastic neoplasia (GTN) is a highly curable malignancy classified using the International Federation of Gynecology and Obstetrics (FIGO)/WHO scoring system into low-risk (score 0-6) and high-risk (score ≥ 7) categories. Although single-agent chemotherapy is standard for low-risk GTN, patients with FIGO scores of 5-6 exhibit disproportionately high rates of chemoresistance, raising concerns about current classification and treatment strategies.

Methods: This retrospective analytic study included 162 patients with low-risk GTN treated at a tertiary referral center in Saudi Arabia from 1980 to 2021. Patients were stratified into FIGO score subgroups (0-4 v 5-6), and data on demographics, treatment regimens, outcomes, and chemoresistance were collected. The primary outcome was resistance to first-line chemotherapy. Multivariable logistic regression identified independent predictors of chemoresistance.

Results: The median patient age was 35 years, with 64.8% age 40 years and younger. Hydatidiform mole was the most common antecedent pregnancy (88.9%), and 30.9% had FIGO scores of 5-6. First-line treatment included single-agent chemotherapy (74.7%) and multiagent regimens (25.3%). Although all patients achieved complete remission, 26.5% exhibited chemoresistance to first-line treatment, significantly associated with treatment before the year 2000, higher FIGO scores, and single-agent chemotherapy. On multivariable analysis, FIGO scores of 5-6 (odds ratio [OR], 2.6; P = .02) and single-agent chemotherapy (OR, 0.11; P = .007) were independent predictors of resistance. β-human chorionic gonadotropin (hCG) level was the only FIGO component independently linked to chemoresistance. Relapse occurred in 5.4% of cases.

Conclusion: Patients with FIGO scores of 5-6 and high β-hCG levels had increased resistance to first-line therapy. β-hCG was the strongest independent predictor. These findings highlight the need to reassess treatment strategies for this subgroup.

Purpose: Delays in presentation, diagnosis, and treatment present common challenges in breast cancer care in Ethiopia. However, few interventions have been implemented aimed at addressing the issue in the country. To tackle this problem, we conducted a situational assessment to gather general information on the health care infrastructure and workforce and to explore the potential opportunities and challenges for implementing clinical breast examination (CBE) and patient navigation (PN) intervention in Ethiopia.

Methods: A qualitative study was conducted at six general hospitals. A total of 18 in-depth interviews and nine focus group discussions were conducted based on the Consolidated Framework for Implementation Research (CFIR) approach with regional health officials, medical directors, clinical staff, eligible women, and breast cancer survivors. The data were deductively coded and thematically analyzed.

Results: From the five major domains of the CFIR, 17 constructs were developed from the narration of the stakeholders. Several factors were identified as opportunities for implementation: the presence of national breast cancer guidelines, a supportive environment from regional and Ministry of Health, experience of working with the community, teamwork experience, and the existence of a community health extension program. The challenges mentioned included a lack of adequate diagnostic facilities, security issues, limited cancer-trained professionals, staff turnover, negative perceptions about cancer in the community, staff workload, and the need for training and logistics.

Conclusion: The stakeholders recognized that implementing provider-initiated CBE and navigation is an acceptable and feasible initiative that can be performed in the study hospitals using the existing infrastructure and human resources. Collaboration, community engagement, continuous monitoring, and evaluation are vital for successful implementation.

Purpose: Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer represents a substantial proportion of breast cancer cases globally. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy are established first-line treatments in high-income settings, improving progression-free survival (PFS) and quality of life. However, access remains limited in low- and middle-income countries (LMICs) because of cost, infrastructure, and policy barriers.

Methods: We critically evaluated global challenges in CDK4/6 inhibitor implementation and assessed recent phase III data on tibremciclib plus fulvestrant in HR+/HER2-negative advanced breast cancer after prior endocrine therapy. Comparative analyses were conducted with landmark MONALEESA-3 and MONARCH-2 trials, focusing on study populations, outcomes, safety, and generalizability.

Results: The tibremciclib trial demonstrated a significant PFS benefit and high objective response rates in a single-country cohort without prior CDK4/6 inhibitor exposure. Overall survival (OS) data remain immature (19.7% maturity), and grade ≥3 toxicities-including neutropenia (15.2%), hypokalaemia (12.0%), and anemia (12.0%)-pose feasibility challenges in LMICs with limited monitoring capacity. Compared with ribociclib and abemaciclib trials, tibremciclib data are less generalizable because of narrow inclusion criteria and limited international representation. This highlights the need for future trials in more ethnically and geographically diverse populations, with extended OS and quality-of-life follow-up.

Conclusion: Tibremciclib shows promise as an additional CDK4/6 inhibitor; however, its global integration requires broader, more diverse clinical trials, robust safety and survival data, and strategies to mitigate toxicity risks. Bridging access gaps will require coordinated efforts across policy, infrastructure, and global partnerships to ensure equitable benefit from emerging therapies.

Purpose: Fever with neutropenia (FN) is a common complication of cancer treatment in children and is associated with high morbidity and mortality. Evidence-based clinical practice guidelines (CPGs) for FN aim to standardize care and thereby improve it, prioritize resources, and influence national policies. Despite the significant burden of childhood cancer in sub-Saharan Africa, current CPG fail to explicitly address certain conditions critical for our context. We developed a FN management CPG for pediatric cancer patients in sub-Saharan African countries.

Methods: The clinical guideline development process involved training of panelists (oncology specialists) in 10 sub-Saharan African countries on guideline development. The guideline was developed following the Grading of Recommendations, Assessment, Development and Evaluation approach. Question development by panelists, systematic review to evaluate evidence for itemized questions, and in-person voting for each recommendation were conducted. Classification of the decision to "recommend" or "not recommend" and the strength of recommendation (strong versus conditional) was decided by a simple majority among (>50%) the CPG panel members.

Results: Fifty-eight respondents representing 19 countries in the region participated in the question prioritization exercise. Fifteen panelists received training in evidence synthesis and guideline development. Twenty-five recommendations and two definitions intended for practice settings in sub-Saharan Africa were developed to address the management of pediatric FN.

Conclusion: This FN guideline developed by a multidisciplinary team incorporates regional considerations in treatment of FN and can serve as a tool for policymaking. The performance of guideline recommendations and associated outcomes should be monitored to improve FN outcomes in the region. The CPG development also highlights the need for more research efforts on the continent to generate evidence tailored to the local context.

Purpose: To describe the proportion of biopsy-proven gastric adenocarcinoma (GAC) that was surgically resected in South Africa (SA) and explore contributory factors for nonresection.

Methods: This was a national retrospective study of GAC from 2015 to 2020 in SA using data available from the National Cancer Registry. Risk factors for nonresection were modeled using logistic regression.

Results: 3,919 individuals had biopsy-proven GAC, and of these, 560 (13.4%) had a surgical resection. Black race (odds ratio [OR], 2.3; P < .001), female sex (OR, 1.3, P = .020), and being uninsured (OR, 3.7, P < .001) were associated with nonresection. Resection rates showed a nonlinear increasing trend over time.

Conclusion: The majority of GACs in SA were not resected, and race, sex, and health insurance status were associated with nonresection. Additional research to understand ways to mitigate barriers related to social determinants of health are needed to make cancer care more equitable in SA.