National Clinical Practice Guidelines for the management of non-small cell lung cancer in early, locally advanced and metastatic stages. Extended version. / Guía de Práctica Clínica Nacional para el manejo del cáncer de pulmón de células no pequeñas en estadios tempranos, localmente avanzados y metastásicos.

OBJECTIVE: Lung cancer is one the leading causes of mortality worldwide. Symptomatic manifestations of the disease generally occur in the advanced-stage setting, and therefore an important number of patients have advanced or metastatic disease by the time they are diagnosed. This situation contributes to a poor prognosis in the treatment of lung cancer. Evidencebased clinical recommendations are of great value to support decision-making for daily practice, and thus improving health care quality and patient outcomes. MATERIALS AND METHODS: This document was an initiative of the Mexican Society of Oncology (SMEO) in collaboration with Mexican Center of Clinical Excellence (Cenetec) according to Interna- tional Standards. Such standards included those described by the IOM, NICE, SIGN and GI-N. An interdisciplinary Guideline Development Group (GDG) was put together which included medical oncologists, surgical oncologistsc, radiation therapists, and methodologists with expertise in critical appraisal, sys- tematic reviews and clinical practice guidelines development. RESULTS: 62 clinical questions were agreed among members of the GDG. With the evidence identified from systematic reviews, the GDG developed clinical recommendations using a Modified Delphi Panel technique. Patients' representatives validated them. CONCLUSIONS: These Clinical Practice Guideline aims to support the shared decision-making process for patients with different stages of non-small cell lung cancer. Our goal is to improve health-care quality on these patients.

OBJETIVO: El cáncer de pulmón es una de las principales causas de mortalidad alrededor del mundo. Su historia natural, con la manifestación de síntomas en etapas avanzadas y el retraso en su diagnóstico hacen que una gran proporción de pacientes se diagnostiquen en estadios tardíos de la enfermedad, lo que hace muy complicado el tratamiento exitoso de la misma. De esto deriva la importancia de dar origen a recomendaciones basadas en evidencia para soportar la toma de decisiones clínicas por parte de los grupos interdisicplinarios que se encargan del manejo de este padecimiento. MATERIAL Y MÉTODOS: Este documento se desarrolló por parte de la Sociedad Mexicana de Oncología en colaboración con el Centro Nacional de Excelencia Tec- nológica de México (Cenetec) a través de la dirección de integración de Guías de Práctica Clínica en cumplimiento a estándares internacionales como los descritos por el Ins- tituto de Medicina de EUA (IOM, por sus siglas en inglés), el Instituto de Excelencia Clínica de Gran Bretaña (NICE, por sus siglas en inglés), la Red Colegiada para el Desarrollo de Guías de Escocia (SIGN, por sus siglas en inglés), la Red Internacional de Guías (G-I-N, por sus siglas en inglés); entre otros. Se integró en representación de la Sociedad Mexicana de Oncología un Grupo de Desarrollo de la Guía (GDG) de manera interdisciplinaria, considerando oncólogos médicos, cirujanos oncólogos, cirujanos de tórax, radio-oncólogos, y metodólogos con experiencia en revisiones sistemáticas de la literatura y guías de práctica clínica. RESULTADOS: Se consensuaron 62 preguntas cllínicas que abarcaron lo establecido previamente por el GDG en el documento de alcances de la Guía. Se identificó la evidencia científica que responde a cada una de estas preguntas clínicas y se evaluó críticamente la misma, antes de ser incorporada en el cuerpo de evidencia de la Guía. El GDG acordó mediante la técnica de consenso formal de expertos Panel Delphi la redacción final de las recomendaciones clínicas. C. CONCLUSIONES: Esta Guía de Práctica Clínica pretende proveer recomendaciones clínicas para el manejo de los distintos estadios de la enfermedad y que asistan en el proceso de toma de decisiones compartida. El GDG espera que esta guía contribuya a mejorar la calidad de la atención clínica en las pacientes con cáncer de pulmón de células no pequeñas.

Consolidative stereotactic ablative radiotherapy (SABR) to intrapulmonary lesions is associated with prolonged progression-free survival and overall survival in oligometastatic NSCLC patients: A prospective phase 2 study.

OBJECTIVES: Stereotactic Ablative Radiotherapy (SABR) has shown high rates of local control and prolonged survival in early-stage non-small cell lung cancer (NSCLC), though its role in oligometastatic disease is undefined. This study aimed to evaluate SABR as a local consolidative therapy (LCT) in oligometastatic NSCLC patients. METHODS: In this prospective, single-arm phase 2 trial, we sought to evaluate SABR in patients with stage IV NSCLC, with ≤ five lesions, including the primary tumor. Patients received initial systemic therapy according to international guidelines. Patients without progression after front-line therapy (two months of targeted therapy and ≥ four cycles of chemotherapy) were evaluated by an 18F-FDG-PET/CT to receive consolidative SABR (45-60 Gy in 3-5 fractions) to the primary and all intrapulmonary metastatic sites. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS) and toxicity. RESULTS: A total of 47 patients were included. Mean age was 58.9 years, 59.6 % were female, 87.2 % had adenocarcinoma histology, and the contralateral lung was the main site of metastases in 42.6 %. All patients received systemic front-line therapy, chemotherapy in 61.7 %, and a tyrosine kinase inhibitor (TKI) in 38.3 %. Disease control rate (DCR) and complete metabolic response (CMR) to SABR were 93.6 % and 70.2 %. Median PFS was 34.3 months (95 %CI; 31.1-38.8) for the total cohort; patients with a CMR had a median PFS of 53.9 monthsvs.31.9 months in those without CMR (p = 0.011). Median OS was not reached.Grade 1, 2, and 3 pneumonitis were observed in 79.5 % (31/39), 12.8 % (5/39) and 7.7 % (3/39), respectively. No grade ≥4 toxicities were observed. CONCLUSION: The use of SABR as LCT in oligometastatic NSCLC patients was well tolerated and showed favorable results regarding PFS and OS compared with historical data. The benefit was significantly higher in patients who reached a CMR as assessed by 18F-FDG-PET/CT.

Evaluation of non-small cell lung cancer by PET/CT with 64CuCl2: initial experience in humans.

Human copper transporter 1 (hCtr1) is the main transporter of copper which has been involved as an essential cofactor in biological processes and mechanisms of action for cisplatin and its analogues. Although expression of hCtr1 is present in all tissues that require copper, several studies have showed that levels of expression are highly variable between normal and neoplastic tissues. We evaluated the potential diagnostic of the 64CuCl2-PET/CT in patients with wild type non-small cell lung cancer (NSCLC). Eleven patients were included. Baseline 18F-FDG-PET/CT and 64CuCl2-PET/CT performed before to initiate treatment with platinum-based chemotherapy. 18F-FDG-PET/CT detected a total of 68 lesions in different corporal sites: lung (24), regional lymph node (30), distant non-bone metastases (17) and bone metastases (14). Of total, 73% demonstrated high focal uptake of 64CuCl2-PET/CT: 36% in primary tumor and 27% in lymph-nodes metastases. The detection-rates (DRs) was lower with 64CuCl2 PET/CT compared to 18F-FDG-PET/CT, however, these was not statistically significant (P = 0.108). A complete match was found in 2 patients. All patients were treated with platinum-based chemotherapy. According to RECIST 1.1 and PERCIST 1.0 criteria, most patients with highest uptake 64CuCl2-PET/CT presented partial response (mean 3 cycles) corroborated with 18F-FDG PET/CT. On the other hand, patients with very low uptake or faint uptake have progressive disease (3/16 patients). To our knowledge, this is the first study with 64CuCl2-PET/CT in-human in patients with NSCLC chemo-naïve. Our results may represent that 64CuCl2-PET/CT had a good ability for detect lesions. In addition, the 64CuCl2 uptake is based on the expression of Ctr1 transporters seeking to differentiate between those patients who may benefit from platinum-based therapy. More studies are necessary for confirm these findings.