JCO Global Oncology最新文献

Purpose: We studied the prevalence of somatic mutations in EGFR, KRAS, BRAF, and NRAS among Brazilian patients with early-stage non-small cell lung cancer (NSCLC). We also explored the association between these mutations and clinicopathologic characteristics.

Methods: We screened 557 patients diagnosed with NSCLC who underwent EGFR, KRAS, BRAF, and NRAS gene sequencing by next-generation sequencing (NGS) or RT-PCR (EGFR only) between 2021 and 2023. We analyzed the frequency of mutations in these genes and their association with clinical characteristics among 399 patients with early-stage nonsquamous NSCLC.

Results: Among 399 patients with early-stage nonsquamous NSCLC included in the analysis, we identified mutations in 218 (54.6%), totaling 224. The median age was 67 years, and most were female (58.9%). The most frequently mutated genes were EGFR and KRAS. Actionable genomic alterations were found in 137 cases, representing 34.3% of the entire cohort and 62.8% of patients with mutations. In cases with actionable mutations identified by NGS, EGFR mutations accounted for 68.0%, followed by KRAS (27.3%) and BRAF (4.7%). We found a significant association between histologic subtype and grade, as well as between tumor T stage and histologic subtype. A higher frequency of EGFR mutations was observed among females. We noted an association between mutated EGFR and the lepidic subtype, mutated KRAS and the mucinous/colloid subtype, and between the nonmutated genotype and the solid/micropapillary subtype.

Conclusion: This study provides an overview of the genomic landscape of early-stage nonsquamous NSCLC in Brazilian patients. The high prevalence of mutations observed in our cohort underscores the importance of genomic testing in this setting, enabling selection of patients suitable for targeted approved therapies or clinical trials.

Purpose: Breast cancer (BC) is a significant health challenge in Nigeria, exacerbated by early onset, advanced-stage diagnosis, and high prevalence of triple-negative tumors. Access to genetic testing and counseling is scarce, with minimal capacity for hereditary cancer services. Despite these barriers, there is strong interest in expanding care to include genetic testing and improve understanding of familial risk. The purpose of this study was to develop and assess the effectiveness of a BC genetics education program for Nigerian health care providers (HCPs).

Methods: A multidisciplinary international team developed a four-module hybrid education program combining asynchronous online learning and an in-person didactic session. Invitations were circulated to HCPs in tertiary hospitals across Nigeria. Knowledge improvement was assessed using standardized pre- and postmodule tests.

Results: Thirty-one physicians and nurses participated. All online modules had significant knowledge improvement, with the largest score increases in BRCA1/2 genetic counseling (mean change, 1.9 [95% CI, 1.3 to 2.5]; P < .001) and BRCA1/2 clinical management (mean change, 1.6 [95% CI, 1.2 to 2.1]; P < .001). The subsequent in-person workshop had additional, albeit smaller, module increases. Aggregated analysis showed a 23.0% increase in knowledge after the online training (P < .001), with a further 10.1% gain after the in-person workshop (P = .007). Overall knowledge improved from 45.0% at baseline to 87.0% post-training, representing a 43.0% absolute gain (P < .001).

Conclusion: This hybrid training program significantly improved provider knowledge of hereditary BC genetics in Nigeria and offers a scalable, culturally tailored model for expanding BC genetic services in low-resource settings. While promising, the modest sample size and limited follow-up warrant further evaluation and broader rollout to confirm long-term effectiveness.

Purpose: The International Agency for Research on Cancer and St Jude Children's Research Hospital established Targeting Childhood Cancer through the Global Initiative for Cancer Registry Development, a collaboration to accelerate change in childhood cancer registration in selected countries. We summarize the overall situation of the first 5-year implementation period highlighting key commonalities and challenges encountered.

Methods: Following the Global Initiative for Cancer Registry Development model, Georgia, Mexico, South Africa, and Vietnam were selected as implementation sites. We established a team per country, assessed the general and childhood cancer registration situation, and implemented targeted support via online meetings and site visits. Multimodal situational assessments were organized in four domains: Context, Governance, Procedures, and Dissemination. Key challenges were identified in each domain and mapped to critical attributes for evaluating surveillance systems.

Results: The scope, modalities, and coverage of cancer registration across countries vary in important ways; only South Africa has a specific childhood cancer registry. Not all registries in the four countries included nonmalignant tumors of the CNS, reported cancers using the childhood cancer-specific system International Childhood Cancer Classification third edition, or reported any survival information. Common challenges identified in all four countries included irregular financial support, instability in personnel, and difficulties in access and data sharing; none had an advisory committee. These challenges affect sustainability and data quality.

Conclusion: Partnerships are valuable to accelerate change but take time to consolidate before impact is observed. Childhood cancer surveillance needs definitive support as a key component of the WHO Global Initiative for Childhood Cancer.

Purpose: One crucial use of telemedicine that is underreported is its role in providing health services in conflict-affected zones. The aim of this report is to describe the process and challenges of implementing a telemedicine-based radiation oncology (RO) clinic in a war zone in southern Lebanon, and to assess its effectiveness in providing care to patients with cancer residing in this unsafe, resource-limited area.

Methods: After the outbreak of the Lebanese-Israeli war in October 2023, we had to shift our RO clinic in Nabatieh Governmental Hospital to an exclusively remote clinic without on-site physicians. Consultations, treatment planning, and follow-ups were conducted virtually by physicians at the American University of Beirut Medical Center. Patient data and imaging were shared electronically between both hospitals, and treatment was administered locally by trained staff.

Results: From October 2023 to September 2024, 669 new patient consultations were completed remotely. Despite infrastructure limitations, including lack of electronic health records and occasional connectivity issues, we developed a model to ensure care continuity was largely maintained for the local patients with cancer.

Conclusion: Telemedicine can serve as a tool for delivering cancer care in times of war, improving access and equity for underprivileged groups in the face of severe logistical and infrastructural challenges.

Purpose: Risk/treatment stratification for children with neuroblastoma (NB) relies on clinical, histologic, and genomic factors. However, most children with cancer live in low- and middle-income countries (LMIC), where access to advanced methods for stratification is limited. To address this unmet need, we developed a novel risk/treatment classification, the Adaptive Clinical Neuroblastoma Risk Groups (ACNRG) using clinical prognostic biomarkers.

Patients and methods: A survival tree regression analysis of the International Neuroblastoma Risk Group (INRG) Data Commons (N = 14,501, diagnosed 1990-2014) was performed using univariate Cox regression models (age, International Neuroblastoma Staging System, serum lactate dehydrogenase [LDH], and serum ferritin) of event-free survival (EFS), separately for test and validation sets. Within each terminal node of the survival tree, the proportion of patients by initial treatment assignment and outcome achieved on that treatment were used to subjectively assign risk/treatment intensity (low-, intermediate-, and high-risk). For additional validation, the ACNRG was descriptively compared with INRG classification. Guidelines were developed for determining INRGs Staging System (INRGSS) in LMIC, using the minimum essential versus optimal imaging/biopsy procedures.

Results: Twelve statistically, clinically significant unique pretreatment risk groups of INRGSS/age/LDH/ferritin were identified (5-year EFS): low-L1/any/any/any (92% ± 0.5%); intermediate-L2/<18 months/<1,400/any (88% ± 1%), MS/any/<1,400/any (86% ± 1.5%), M/<12 months/<1,400/any (76% ± 2.3%); intermediate/high-L2/<18 months/≥1,400/any (73% ± 4.7%), L2/≥18 months/<1,400/<30 (68% ± 3.4%), L2/≥18 months/<1,400/≥30 (59% ± 3.7%), MS/any/≥1,400/any (52% ± 6.3%); high-L2/≥18 months/≥1,400/any (46% ± 4.7%), M/12-18 months/<1,400/any (64% ± 4.1%), M/<18 months/≥1,400/any (60% ± 1.6%), M/≥18 months/any/any (28% ± 0.8%). The concordance and discordance rates of ACNRG versus INRG were 86.6% and 13.4%, respectively (n = 8,152 nonmissing-data intersection).

Conclusion: The ACNRG classification, using easily obtained clinical markers, is highly prognostic. The ACNRG could transform risk and treatment stratification, improve accuracy of treatment intensity decisions, and potentially improve outcome, for the large number of children with NB in LMIC. Prospective validation of the ACNRG classification is planned in a pilot trial.

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.