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.

Re-irradiation in patients with progressive or recurrent brain metastases from extracranial solid tumors: A novel prognostic index.

BACKGROUND: Most studies evaluating factors associated with the survival of patients with brain metastases (BM) have focused on patients with newly diagnosed BM. This study aimed to identify prognostic factors associated with survival after brain re-irradiation in order to develop a new prognostic index. METHODS: This 5-year retrospective study included patients treated with repeat-radiotherapy for recurrent BM at the "Instituto Nacional de Cancerología" of Mexico between 2015 and 2019. Significant variables in the multivariate Cox regression analysis were used to create the brain re-irradiation index (BRI). Survival and group comparisons were performed using the Kaplan-Meier method and the log-rank test. RESULTS: Fifty-seven patients receiving brain re-irradiation were identified. Most patients were women (75.4%) with a mean age at BM diagnosis of 51.4 years. Lung and breast cancer were the most prevalent neoplasms (43.9% each). Independent prognostic factors for shorter survival after re-irradiation were: Age >50 years (hazard ratio [HR]:2.5 [95% confidence interval [CI], 1.1-5.8]; p = 0.026), uncontrolled primary tumor (HR:5.5 [95% CI, 2.2-13.5]; p < 0.001), lesion size >20 mm (4.6 [95% CI, 1.7-12.2]; p = 0.002), and an interval <12 months between radiation treatments (HR:4.3 [95% CI, 1.7-10.6]; p = 0.001). Median survival (MS) after re-irradiation was 14.6 months (95% CI, 8.2-20.9).MS of patients stratified according to the BRI score was 17.38, 10.34, and 2.82 months, with significant differences between all groups. CONCLUSIONS: The new BRI can be easily implemented for the prognostic classification of cancer patients with progressive or recurrent BM from extracranial solid tumors.

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.

Radiation oncology in Mexico: Current status according to Mexico's Radiation Oncology Certification Board.

AIM: Describe the results of the first national census of radiotherapy in Mexico in order to make a situational diagnosis of radiotherapy availability, offer more accurate information to radiation oncologists, and promote an adequate scientific based investment for the country. BACKGROUND: According to the Organisation for Economic Co-operation and Development (OECD), the density of radiotherapy (RT) machines per million habitants in Mexico is approximately 1.7-1.8. Other international organizations such as DIRAC-IAEA report 1.15 per million habitants. National organizations collect data indirectly and previous surveys had a low accrual rate (32.5%). Therefore, a precise census is required. MATERIAL AND METHODS: The Mexican Radiation Oncology Certification Board (CMRO for its acronym in Spanish) conducted a nationwide census from January through November 2019. Gathered information was combined with CMRO database for sociodemographic information and human resources. RESULTS: The study included 103 RT centers [95.1% answered the survey], with a median of 2 centers by state (ranging from 0 in Tlaxcala to 20 in Mexico City) and with a report of only 1 center in 11 states (34.4%). Fifty-six (54.3%) of the centers are public. Fourteen centers (13.6%) have residency-training programs. The total number of RT machines is 162 [141 clinical and linear accelerators (87%) and 21 radionuclide units (13%)] with a median of 3 machines by state (0 in Tlaxcala to 46 in Mexico City) and with ≤3 machines in 18 states (56.25%). The overall calculated density of RT machines per million habitants is 1.32, varying from 0 in Tlaxcala to 5.16 in Mexico City. The density of linear and clinical accelerators per million population is 1.19. The total number of brachytherapy units is 66, with a median of 1 center with brachytherapy unit per state and 29 states with ≤3 centers with a brachytherapy unit (90.6%). Thirty-seven brachytherapy units (56.1%) have automated afterload high-dose rate. The overall rate of brachytherapy units per million inhabitants is 0.55, varying from 0 in 5 states (15.6%), 0.1-0.49 in 8 states (25%), 0.5-0.99 in 13 states (40.6%), 1-1.49 in 5 states (15.6%) and 1.5-1.99 in Mexico City (3.1%). The Mexican CMRO has 368 radiation oncologists certified (99 women and 269 men), of whom only 346 remain as an active part of Mexico's workforce. CONCLUSIONS: This is the first time the CMRO conducts a national census for a radiotherapy diagnostic situation in Mexico. The country currently holds a density of clinical and linear accelerators of 1.19 per million habitants. Brachytherapy density is 0.55 devices per million habitants, and 57% of radiotherapy centers have brachytherapy units.

Locoregional control and toxicity after pleurectomy/decortication and intensity-modulated pleural radiation therapy in patients with malignant pleural mesothelioma.

BACKGROUND: Treatment of malignant pleural mesothelioma (MPM) represents a major challenge for oncologists. Multimodality treatment, which generally involves induction chemotherapy, surgery and radiotherapy have recently shown promising results. The aim of this study was to evaluate the locoregional control and toxicity of intensity modulated radiotherapy (IMRT) after pleurectomy and decortication (P/D) as part of trimodality therapy for patients with locally advanced MPM. METHODS: We prospectively analyzed data from 20 patients with MPM treated at a single tertiary-care institution. Initially every patient received induction chemotherapy with platinum-based chemotherapy. After chemotherapy, patients without progression underwent P/D, and if feasible, hemi-thoracic IMRT was administered at a planned dose of 50.4-54 Gy in 28-30 fractions and treated with 9-11 noncoplanar fields. RESULTS: A total of 15 of the 20 enrolled patients underwent P/D followed by IMRT to the hemi-thoracic cavity. The median total radiotherapy dose was 48.7 Gy (23.4-54 Gy). Radiation pneumonitis (RP) developed in nine patients (60%), and of these, two patients (13.3%) experienced G3 or G4 RP. The estimated locoregional-relapse-free survival at two years was 75.9%, and the main pattern of recurrence was distant (72.7%). For the entire cohort median follow-up was 22.7 months, median progression-free survival was 18.9 months and median overall survival 23.6 months. CONCLUSIONS: Platinum-based chemotherapy followed by lung-sparing surgery (P/D) and IMRT is a feasible and safe treatment modality that yields acceptable locoregional control in patients with locally advanced MPM; however, these results should be corroborated in larger studies.

The importance of image guided radiotherapy in small cell lung cancer: Case report and review of literature.

AIM: Describe the anatomical changes and tumor displacement due to a rapid response of a patient's small cell lung cancer (SCLC) during definitive chemoradiotherapy (CRT). BACKGROUND: The treatment for SCLC is based on CRT. If interfractional changes during RT are incorrectly assessed they might compromise adequate coverage of the tumor or increase dose to organs at risk. Image guided RT with cone-beam computed tomography (CBCT) allows to identify daily treatment variations. MATERIAL AND METHODS: Describe a SCLC case with rapid changes in size, shape and location of the primary tumor during RT. CASE REPORT: A 62-year-old woman was diagnosed with SCLC with complete obstruction of the anterior and lingular bronchi and incomplete left thorax expansion due to a 12 × 15 cm mass. During CRT (45 Gy in 1.5 Gy per fraction, twice daily) the patient presented rapid tumor response, leading to resolution of bronchi obstruction and hemithorax expansion. Tumor shifted up to 4 cm from its original position. The identification of variations led to two new simulations and planning in a 3-week treatment course. CONCLUSIONS: The complete radiological response was possible due to systematic monitoring of the tumor during CRT. We recommend frequent on-site image verification. Daily CBCT should be considered with pretreatment tumor obstruction, pleural effusion, atelectasis, large volumes or radiosensitive histology that might resolve early and rapidly and could lead to a miss of the tumor or increased toxicity. Further research should be made in replanning effect in coverage of microscopic disease since it increases uncertainty in this scenario.

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.

Advanced Squamous Cell Carcinoma of the Head and Neck: The Current Role of Cetuximab.

We review clinical trials of squamous cell carcinoma of the head and neck (SCCHN) to address the current and potential uses of cetuximab (CTX). PubMed was reviewed to identify papers published between 2010 and 2016. The search terms used were "cetuximab" and "head and neck cancer." A total of 634 articles were identified. Phase II or III studies with CTX in patients with advanced SCCHN without treatment or with recurrent/metastatic tumors were selected. Forty-six registries were obtained. Information was critically reviewed and relevant information presented. As definitive treatment of advanced squamous cells carcinomas and as palliative treatment of recurrent/metastatic disease, CTX alone or associated with chemotherapy and/or radiotherapy is an alternative to chemoradiotherapy because of its distinct and favorable toxicity profile.

Cetuximab concomitant with gemcitabine and radiotherapy in advanced squamous cell carcinomas of upper aerodigestive tract: a pilot study.

PURPOSE: To explore the response and toxicity of advanced non-metastatic squamous cell carcinomas of upper aerodigestive tract (SCC-UADT) to a combination of cetuximab concomitant with gemcitabine and radiotherapy. METHODS: We managed patients with concomitant treatment of cetuximab (400 mg/m(2) as uploading dose, then 250 mg/m(2), IV) concomitant with gemcitabine (50 mg/m(2)) weekly for seven courses, and radiotherapy in classical fractionation until completion of 70 Gy. Primary endpoints were complete response (CR) to treatment and toxicity. We evaluated patients for toxicity on a weekly basis; evaluation of response included physical examination, endoscopy, computed tomography (CT) scan and biopsy when indicated, and was performed 6 weeks after completion of radiotherapy. Additional evaluations were done every 3 months to document disease status. Between November 2004 and November 2005, 20 patients were included. RESULTS: CR was 82.4%, overall response was 100%. Neck disease reached CR in 61.5% and partial in 38.5% of patients. The main toxicities were nausea, lymphopenia, neutropenia and mucositis. Grade 3 and 4 side effects were presented in 70.6% of patients, but mucositis, and lymphopenia without clinical repercussions, occurred in 88.2% of patients. Gastrostomy was required in 11.8% of patients to maintain nutrition. Radioepithelitis developed in 76.5%, but only three of these (23.1%) were grade III. Median overall survival was 53 months (range 6-55 months) and median progression-free survival has not yet been reached at the time of evaluation. CONCLUSIONS: Although toxicity is important, this approach has interesting activity and deserves further investigation.

Virus del papiloma humano: Marcador de respuesta a radioterapia/quimiorradioterapia en cáncer cervical / Human papilloma-virus: Marker of response to radiotherapy/chemoradiotherapy in cervical cancer / Papilomavírus humano: marcador de resposta à radioterapia / quimiorradioterapia em câncer de colo uterino

El cáncer cérvico-uterino (CaCU) representa el 6% de todas las neoplasias malignas en mujeres. Evidencia epidemiológica y molecular implican al virus del papiloma humano (VPH) en la etiopatogenia del CaCU y los genotipos más frecuentemente asociados son el 16 y 18 (VPH-16 y -18). La radioterapia (RT) y la quimiorradiación (RT-QT) son las dos modalidades de tratamiento primario para el CaCU, con tasas variables de resistencia o persistencia de la enfermedad. El objetivo de este trabajo fue estudiar, por primera vez, la respuesta tumoral antes, durante y después de la RT y la RT-QT y analizar la carga viral de VPH-16 y -18 en pacientes mexicanas con CaCU. Se obtuvieron muestras de tejido tumoral en pacientes con CaCU: antes, durante y después de la RT y RT-QT, se determinó el número de copias absolutas del VPH-16 o -18 y se estudió la respuesta en relación a la carga viral por PCR en tiempo real. La disminución de la carga viral de VPH para RT-QT y RT fue de 100 y 62%, respectivamente. Se observó una mejor respuesta con la modalidad de tratamiento combinado, por lo que se sugiere que la carga viral de VPH (-16 y -18) podría ser un potencial indicador para evaluar la respuesta de ambos tratamientos en el CaCU.

Cervical cancer (CaCU) represents 6% of all malignancies in women. Molecular and epidemiological evidence relate the human papilloma virus (HPV) with the pathogenesis of the CaCU genotypes, the most frequent genotypes being 16 and 18 ( VPH-16 and -18). Radiotherapy (RT) and chemoradiotherapy (ChRT) are the two primary treatment modalities for CaCU, with variable rates of resistance or persistence of the disease. The aim of this work was to study for the first time, the tumorai response before, duríng and after RT and RT-QT and analyze HPV-16 and -18 viral load in a Mexican population with CaCU. Samples of tumor tissue were collected from patients with CaCU: before, duríng and after RT and ChRT. The absolute number of HPV-16 or -18 copies was determined, and the response related with viral load in both treatments was studíed by real-time PCR-based in fluorescence. The percentage of decrease ín HPV viral load for ChRT and RT was 100% and 62%, respectívely With ChRT, the response was better than with RTalone. HPV (-16 and -18) viral load ís suggested to be a potentíal índícator to evalúate CaCU response in both treatments.

Hepatitis crónica C, VIH y síndrome de Sjögren: informe de un caso / Chronic C-hepatitis, AIDS and Sjögren syndrome: a case report

El síndrome de Sjögren es una linfoexocrinopatía autoinmune de etiología desconocida, que se presenta como 1) forma primaria o 2) asociada a diversas enfermedades autoinmunes. Diversos virus intervienen en su origen (Epptein-Barr, citomegalovirus, herpes simple, retrovirus). En fechas recientes se ha relacionado con el virus C de la hepatitis; también se ha descrito asociado a hepatitis crónica, cirrosis biliar primaria y a trombocitopenias autoinmunes. Presentamos el caso de un paciente con hepatitis crónica C, seropositivo al VIH que desarrolló síndrome de Sjögren