JCO Global Oncology最新文献

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.

Purpose: Surgical pathology services are essential for breast cancer (BC) diagnosis and treatment. Building capacity in immunohistochemistry (IHC) is urgently needed in sub-Saharan Africa. Here, we analyze the implementation process and results from launching manual IHC in a tertiary cancer center in southern Ethiopia between 2021 and 2024.

Materials and methods: A phased implementation approach was used. We reviewed the facilities that sent surgical specimen, preanalytical variables, and clinicopathologic characteristics. The distribution of BC phenotype was compared with reports in the country as an implementation metric.

Results: A total of 125 surgical specimens underwent manual IHC. Specimen came from 21 facilities, one 500 km away. Of the total 125 cases, 68% (n = 85) were missing information on specimen cold ischemia time and 60% (n = 50) were missing fixation time in formalin. Of the 32% with cold ischemia time reported, the median time was 20 minutes (range, 1-60 minutes). Of the 40% cases reporting fixation time, the median duration was 72 hours (range, 24-192). The median age of BC was 38 years. The majority (66%) were estrogen receptor (ER) positive. Of the 70 with Ki-67 staining, 39% were low; 61.4% high. Thirteen cases were stained for HER2neu. A significant association was observed with ER and Ki-67 expression.

Conclusion: A manual IHC program for BC was established in a tertiary hospital in southern Ethiopia. The service reached facilities up to 500 km away. Facilities that reported the cold ischemia and formalin time have met standards of care. The median age of BC was 38 years, and two-third were hormone positive, consistent with other reports in the country. Future work will include more regional training on preanalytical variables and developing capacity to evaluate HER2neu 2+ equivocal cases.

Despite accounting for over 8% of the global population and bearing a growing cancer burden, Latin America (LATAM) contributes <2% of global oncology trial activity and scientific output. Beyond funding and operational challenges, the region continues to face a lack of sustained academic investment to build a research ecosystem that complements industry-led trials. Drawing on recent data and institutional experience, this review analyzes the current landscape of cancer clinical trials in LATAM, highlighting both structural challenges and emerging opportunities. We examine the region's dual reliance on industry-led studies and fragile academic ecosystems, and assess how regulatory asymmetries, uneven infrastructure, and limited access to biobanks, registries, and protected research time constrain investigator-led innovation. Yet, the region's high patient adherence, urban concentration, cost-efficiency, and growing cooperative research networks position it to play a more strategic role in global cancer research. We outline a series of actionable priorities, including the creation of a regional funding mechanism (Latin American Cancer Research for Equity Fund), regulatory convergence, and investments in workforce development and research equity that could reshape LATAM from a peripheral implementer into an active contributor and generator of contextually relevant oncology evidence.

Purpose: Cervical cancer is the second most commonly diagnosed cancer and one of the leading causes of death in women. The objective of the current review was to synthesize the available evidence on the association between male circumcision and risk of cervical cancer in females.

Methods: We searched PubMed, Cochrane, CancerLit, Google Scholar, medRxiv, bioRxiv, UpToDate, TRIP database, and the ProQuest Dissertations and Theses Global databases to identify relevant articles. We considered research studies that assessed male circumcision status and cervical cancer in females for inclusion. The risk-of-bias assessment was performed using the Newcastle-Ottawa scales. We estimated summary measures of effect and 95% CIs for the odds of developing cervical dysplasia, carcinoma in situ, or invasive cervical cancer in females based on the circumcision status of their male partners.

Results: We identified 380 potentially eligible records through systematic database searches. After excluding 278 records on the basis of title and abstract screening, 102 full-text records were assessed for eligibility. We included 19 studies in the final analysis. The risk-of-bias assessment revealed a low risk across 10 records. Male circumcision was associated with decreased odds of cervical cancer (odds ratio [OR], 0.65 [95% CI, 0.53 to 0.79]). Circumcision was also associated with decreased odds of developing Invasive cervical cancer (OR, 0.71 [95% CI, 0.51 to 0.99]), cervical dysplasia (OR, 0.65 [95% CI, 0.45 to 0.92]), and carcinoma in situ cervix (OR, 0.67 [95% CI, 0.50 to 0.90]).

Conclusion: Male circumcision has been found to be associated with lower odds of developing various cervical lesions, suggesting its prophylactic potential. Understanding the effects of male circumcision on human papillomavirus (HPV) infection would have important implications for studies of HPV transmission, leading to a better understanding of the pathogenesis of cervical cancer.

Purpose: Data on long-term time trends in the incidence of cancer are an invaluable resource for tracking the evolution of the disease in populations, but they are very scarce in Africa. The Zimbabwe National Cancer Registry of Harare can report on the evolution of the cancer epidemic over a 30-year period.

Methods: Trends in age-standardized incidence rates in the Black (African) population (males and females) are reported for six cancers of the GI tract (oral cavity plus oropharynx, esophagus, stomach, colon plus rectum, liver, and pancreas).

Results: There has been a steady increase in the incidence of colorectal cancer, at about 2.5% annually, in both sexes, whereas liver cancer has declined, rather more rapidly in males (3.6% annually) than in females (3% annually). Although the incidence is much lower, cancers of the oral cavity and oropharynx have increased in both sexes (3.5% annually in males, 2.8% [nonsignificant] in females). The incidence of stomach cancer has risen over the period, although significantly so only in the most recent decade (2010-2019), before which there had been a slight decline in rates. While esophageal cancer has declined in incidence in men (1.8% annually), it has increased in women (2.4% annually), with adenocarcinomas comprising an increasing proportion (although still less common than squamous cell carcinomas). There has been no significant trend in the incidence of pancreatic cancer.

Conclusion: While some of these trends are related to population-level changes in lifestyles and exposure to environmental factors (such as hepatitis viruses and aflatoxins), the reasons for other changes in incidence are more obscure. While some may be in part due to improvements in diagnostic techniques (endoscopy and imaging), others merit further investigation.