Liquid biopsy in clinical outcomes and detection of T790M mutation in metastatic non-small cell lung cancer after progression to EGFR-TKI.

BACKGROUND: Liquid biopsy (LB) is used to detect epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) and has been demonstrated to have prognostic and predictive value. OBJECTIVE: To associate the rates of EGFR and T790M mutations detected by LB during disease progression after first- or second-generation EGFR-TKIs with clinical characteristics and survival outcomes. METHODS: From January 2018 to December 2021, 295 patients with advanced EGFR mutant (EGFRm) NSCLC treated with first- or second-generation EGFR-TKIs were retrospectively analyzed. LB was collected at the time of progression. The frequency of EGFRT790M mutations, overall survival (OS), and the clinical characteristics associated with LB positivity were determined. RESULTS: The prevalence of EGFRT790M mutation detected using LB was 44%. In patients with negative vs. positive LB, the median OS was 45.0 months vs. 25.0 months (p= 0.0001), respectively. Patients with a T790M mutation receiving osimertinib had a median OS of 44 months (95% CI [33.05-54.99]). Clinical characteristics associated with positive LB at progression extra-thoracic involvement, > 3 metastatic sites, and bone metastases. CONCLUSIONS: Our findings showed that LB positivity was associated with worse survival outcomes and specific clinical characteristics. This study also confirmed the feasibility and detection rate of T790M mutation in a Latin American population.

Perilesional edema diameter associated with brain metastases as a predictive factor of response to radiotherapy in non-small cell lung cancer.

Background: Different prognostic scales exist in patients with brain metastasis, particularly in lung cancer. The Graded Prognostic Assessment for lung cancer using molecular markers (Lung-molGPA index) for brain metastases is a powerful prognostic tool that effectively identifies patients at different risks. However, these scales do not include perilesional edema diameter (PED) associated with brain metastasis. Current evidence suggests that PED might compromise the delivery and efficacy of radiotherapy to treat BM. This study explored the association between radiotherapy efficacy, PED extent, and gross tumor diameter (GTD). Aim: The aim of this study was to evaluate the intracranial response (iORR), intracranial progression-free survival (iPFS), and overall survival (OS) according to the extent of PED and GT. Methods: Out of 114 patients with BM at baseline or throughout the disease, 65 were eligible for the response assessment. The GTD and PED sum were measured at BM diagnosis and after radiotherapy treatment. According to a receiver operating characteristic (ROC) curve analysis, cutoff values were set at 27 mm and 17 mm for PED and GT, respectively. Results: Minor PED was independently associated with a better iORR [78.8% vs. 50%, OR 3.71 (95% CI 1.26-10.99); p = 0.018] to brain radiotherapy. Median iPFS was significantly shorter in patients with major PED [6.9 vs. 11.8 months, HR 2.9 (95% CI 1.7-4.4); p < 0.001] independently of other prognostic variables like the Lung-molGPA and GTD. A major PED also negatively impacted the median OS [18.4 vs. 7.9 months, HR 2.1 (95% CI 1.4-3.3); p = 0.001]. Conclusion: Higher PED was associated with an increased risk of intracranial progression and a lesser probability of responding to brain radiotherapy in patients with metastatic lung cancer. We encourage prospective studies to confirm our findings.

Factors associated with the evaluation of geriatric assessment (GA) domains by oncology specialists in Mexico.

The use of geriatric assessment (GA) by oncology specialists in Mexico is low. We aimed to explore factors associated with the evaluation of individual GA domains by Mexican oncology specialists. We performed an exploratory analysis of a sequential explanatory mixed-methods study consisting of an online cross-sectional survey of Mexican oncology specialists and follow-up interviews on the use of GA in cancer care. For each GA domain, we performed multivariable logistic regression analyses with the frequency of evaluation of the domains as the dependent variable (dichotomised as never/rarely/sometimes versus most of the time/always). A p-value <0.05 was considered significant. Qualitative data from the interviews were analysed inductively. Of 196 respondents, 62% were male, 50% were surgical oncologists, 51% took care of >10 patients per day and 61.7% had access to a geriatrician. Self-perceived confidence in managing common geriatric conditions was associated with the evaluation of specific GA domains. For instance, self-perceived confidence in managing dementia (OR 2.72; 95% CI 1.42-5.51, p = 0.008) was associated with cognition evaluation, while for evaluation of falls, self-perceived confidence in evaluation of falls (OR 6.31; 95% CI 3.19-12.46, p < 0.001) was significantly associated. Follow-up interviews showed quality and appropriateness of evaluations may not be ideal: in many cases, physicians do not use guideline-recommended tools. For example, evaluation of cognition is commonly performed through non-validated methods which may miss the detection of patients with an impairment in this domain, partly due to limitations in knowledge and time to use recommended tools. In conclusion, self-perceived confidence in evaluating and managing common situations in older adults was associated with the evaluation of GA domains as part of everyday practice in a sample of oncology specialists in Mexico. This analysis supports the use of educational interventions to boost knowledge and confidence regarding the proper use of validated GA tools among oncology specialists.

Modifying factors of PD-L1 expression on tumor cells in advanced non-small-cell lung cancer.

BACKGROUND: Programmed death ligand-1 (PD-L1) expression predicts immunotherapy utility in nononcogenic addictive lung adenocarcinoma (ADC). However, its reproducibility and reliability may be compromised outside clinical trials. This study aimed to evaluate factors associated with PD-L1 expression in lung ADC. METHODS: This observational study assessed 547 tumor samples with advanced lung ADC from January 2016 to December 2020 in a single cancer institution. Tumor samples were stained by at least one approved PD-L1 clone, SP263 (Ventana) or 22C3 (Dako), and stratified in tumor proportion score (TPS) <1%, 1-49%, or ≥50%. RESULTS: Of all the tumor samples, positive PD-L1 staining was higher in poorly differentiated tumors (67.3% vs. 32.7%, p < 0.001). Analytical factors associated with a PD-L1 high expression (TPS ≥ 50%) were the SP263 clone (19.6% vs. 8.2%, p < 0.001), time of archival tumor tissue <12 months (15.3% vs. 3.8%, p = 0.024), whenever the analysis was performed in the most recent years (2019-2020) (19.0% vs. 8.3%, p < 0.001), and whenever the analysis was performed by pathologists in the academic setting (Instituto Nacional de Cancerologia, INCan) (19.9% vs. 11.9%, p = 0.001). In the molecular analysis, EGFR wild-type tumors had an increased proportion of PD-L1 positive and PD-L1 high cases (60.2% vs. 47.9%, p = 0.006 and 17.4% vs.8.5%, p = 0.004). A moderate correlation (r = 0.69) in the PD-L1 TPS% was observed between the two different settings (INCan vs. external laboratories). CONCLUSION: Clinicopathological factors were associated with an increased PD-L1 positivity rate. These differences were significant in the PD-L1 high group and associated with the academic setting, the SPS263 clone, time of archival tumor tissue <12 months, and a more recent period in the PD-L1 analysis.

Guía de Práctica Clínica para el diagnóstico temprano y la referencia oportuna del cáncer de pulmón.

OBJETIVO: Proporcionar recomendaciones para la detección temprana de pacientes con alto riesgo de desarrollar cáncer de pulmón (CP) en el primer nivel de atención y su referencia oportuna. Material y métodos. Se realizó una búsqueda detallada de la evidencia científica disponible para responder las preguntas de investigación clínica y se utilizó el Panel Delphi modificado para lograr un consenso entre expertos. RESULTADOS: Se generaron 14 recomendaciones siguiendo los estándares de una GPC. Conclusión. El CP representa un problema de salud pública en México; por ello, esta guía establece recomendaciones que apoyan la toma de decisiones sobre la detección precoz y la referencia de pacientes con sospecha de CP en el primer nivel de atención.

Barriers and Facilitators for the Implementation of Geriatric Oncology Principles in Mexico: A Mixed-Methods Study.

PURPOSE: There is limited information regarding the use of the geriatric assessment (GA) for older adults with cancer in developing countries. We aimed to describe geriatric oncology practice among Mexican oncology professionals and to identify barriers and facilitators for the implementation of GA into the routine care of older adults with cancer in Mexico. METHODS: We conducted an explanatory sequential mixed-methods study. We administered an online survey to cancer specialists in Mexico about the routine use of GA and barriers for its use. We then conducted online semistructured interviews with survey respondents selected by their use of GA, expanding on barriers and facilitators for performing GA. Descriptive statistical analyses were performed for quantitative data; qualitative data were analyzed inductively through thematic analysis. We developed joint displays to integrate quantitative/qualitative results. RESULTS: We obtained 196 survey responses: 37 physicians (18.9%) reported routinely performing a GA. Medical oncologists (P = .002) and physicians seeing ≤ 10 patients/day (P = .010) were more likely to use GA. The most frequent barriers for GA use were lack of qualified personnel (49%), limited knowledge (43.9%), and insufficient time (37.2%). In the interviews (n = 22), the limited availability of geriatricians was commonly mentioned. Respondents highlighted the lack of geriatric oncology knowledge among cancer specialists and geriatricians. Saturation of oncology services and a lack of effective referral pathways for GA were also common issues. Facilitators included availability of geriatricians, system/administrative facilitators, presence of a multidisciplinary team, and availability of geriatric oncology education. CONCLUSION: The routine use of geriatric oncology principles in Mexico is limited by the availability of qualified personnel and by insufficient knowledge. An educational intervention could improve the implementation of GA in cancer care.