A comprehensive characterization of the spectrum of MUTYH germline pathogenic variants in Latin America.

MUTYH-Associated Polyposis (MAP) is caused by biallelic pathogenic germline variants in the MUTYH gene. However, individuals harboring monoallelic MUTYH pathogenic variants in the presence of a positive family history have been reported to have a twofold increased risk of colorectal cancer (CRC) and extra colonic cancers. Our aim was to characterize the spectrum of monoallelic and biallelic germline MUTYH pathogenic variants in Latin American patients and to describe their clinical and genetic characteristics. Patients were identified from eight high-risk genetic cancer centers of five Latin American countries. Statistical analysis was performed using the two-sided P test using the Vassarstats statistical tools. Statistical significance was set at a p value ≤ 0.05. Of the 105 unrelated patients with cancer or colorectal polyposis, 84.8% and 15.2% carried pathogenic monoallelic and biallelic MUTYH variants, respectively. The most common pathogenic variants were p.Gly396Asp and p.Tyr179Cys (55% and 23%, respectively). The mean age at first diagnosis was 48.29 years (range 31-71) and 49.90 years (range 27-87) in biallelic and monoallelic MUTYH patients, respectively. CRC was the only cancer diagnosed in patients with biallelic MUTYH pathogenic variants (75%), while breast cancer (46.1%) was more common than CRC (24.7%) in individuals with monoallelic MUTYH pathogenic variants. We reported a high frequency of European founder variants in our diverse population. Some phenotypic differences from current studies were identified, such as a higher breast cancer burden in monoallelic carriers and a complete absence of extra-colon tumors in biallelic patients.

Supervivencia global y supervivencia libre de recaída bioquímica en pacientes con cáncer de próstata tratados con radioterapia de intensidad modulada (IMRT) en el Instituto Nacional de Cancerología / Global survival and biochemical relapse-free survival in patients with prostate cancer treated with intensity modulated radiotherapy (IMRT) at the National Cancer Institute

Resumen Introducción: En 2018 el cáncer de próstata presentó el segundo lugar en incidencia a nivel mundial. Con el avance en la tecnología y la aparición de la radioterapia de intensidad modulada (IMRT), se ha logrado disminuir dosis a tejido sano sin reducir la cobertura del volumen objetivo, permitiendo menor morbilidad asociada por la radioterapia y la posibilidad de escalar la dosis del tratamiento. El objetivo del estudio fue mostrar los resultados en supervivencia global y supervivencia libre de recaída bioquímica en el Instituto Nacional de Cancerología de Colombia (INC) en los paciente diagnosticados con cáncer de próstata tratados con radioterapia de intensidad modulada (IMRT). Materiales y métodos: La revisión retrospectiva incluyó 98 pacientes, mayores de 40 años con cáncer de próstata, sin evidencia de enfermedad metastásica, tratados con IMRT entre 2008 - 2015, independiente de la supresión androgénica. La dosis administrada de radioterapia varió según su riesgo basado en la clasificación D´Amico. Hallazgos: La mediana de edad fue de 68,5 años, dentro de los cuales 16 pacientes (16%) se catalogaron de bajo riesgo, 33 (34 %) de riesgo intermedio y 49 (50 %) de riesgo alto. La dosis media de radioterapia recibida fue de 75,8 Gy. La supervivencia libre de recaída bioquímica a 5 años fue del 78,6 % y la supervivencia global fue 98 %. Conclusión: En pacientes con cáncer de próstata de alto riesgo, la IMRT es una alternativa efectiva y segura, con una supervivencia global a 5 años del 98% y con un adecuado perfil dosimétrico a los órganos a riesgo.

Abstract Background: In 2018, prostate cancer ranked second in incidence worldwide. Advances in technology and the appearance of intensity-modulated radiotherapy, have made it possible to reduce doses to healthy tissue without reducing the coverage of the target volume, thus allowing lower morbidity associated with adiotherapy and the possibility of scaling the treatment dose. The aim of the study was to present the results in overall survival and biochemical relapse-free survival at the Colombian National Cancer Institute (INC) in patients diagnosed with non-metastatic prostate cáncer treated with intensity-modulated radiotherapy (IMRT). Material and methods: The retrospective review included 98 patients over 40 years of age with prostate cancer, without evidence of metastatic disease, treated with IMRT between 2008 and 2015 irrespective of androgenic suppression. The administered dose of radiotherapy varied according to their risk based on the D'Amico classification. Results: The median age was 68.5 years, and of the total of 98 patients, 16 (16%) were classified as low risk, 33 (33%) as intermediate risk, and 49 (50%) as high risk. The mean dose of radiation therapy received was 75.8 Gy. Biochemical relapse-free survival at 5 years was 78.6%, and overall survival was 98%. Conclusions: In patients with high-risk prostate cancer, IMRT is an effective and safe alternative, with an overall 5-year survival of 98%, and an adequate dosimetric profile for at-risk organs.

Radioterapia de salvamento para pacientes con cáncer de próstata: experiencia en el Instituto Nacional de Cancerología / Salvage radiotherapy for prostate-specific antigen relapse after radical prostatectomy for prostate cancer: experience at the Instituto Nacional de Cancerología

Objetivo: describir la experiencia con radioterapia de salvamento en pacientes que presentaron recaída bioquímica, posterior a una prostatectomía radical, en el Instituto Nacional de Cancerología (INC). Métodos: estudio observacional retrospectivo tipo serie de casos. Se recolectaron los casos atendidos entre 2003 y 2007. Se describió la información mediante estadística descriptiva, empleando frecuencias relativas, así como medidas de tendencia central y de dispersión. Se describió la supervivencia libre de enfermedad. Resultados: un total de 40 pacientes que recibieron radioterapia de salvamento por recaída bioquímica fueron incluidos. La recaída posprostatectomía se presentó antes de dos años en el 65% de los pacientes. La mediana de PSA prerradioterapia en el presente estudio fue de 0,9 ng/ml. El 87,5% de los pacientes fueron tratados con radioterapia conformacional 3D. El 97,5% de los pacientes recibieron una dosis total de 66 Gy. La supervivencia libre de enfermedad según la clasificación de riesgo de la enfermedad fue de 2,29 años, con una mediana de seguimiento de 28,5 meses. Dos pacientes presentaron recaída bioquímica posterior a la radioterapia de salvamento. Conclusiones: la radioterapia de salvamento se muestra como una intervención apropiada en pacientes con cáncer de próstata que presentaron recaída bioquímica después de prostatectomía radical; el 94% de los pacientes tratados con radioterapia de rescate en el INC entre 2003 y 2007 están libres de recaída.

Objective: To describe a National Cancer Institute (NCI) study on rescue radiotherapy carried out among patients who had biochemical relapse following radical prostatectomy. Methods: A retrospective, observational study was performed on cases treated from 2003 to 2007; descriptive statistics, using relative frequency as well as measures of central tendency and dispersion, were used to analyze information. Disease free survival was described. Results: A total of 40 patients who underwent rescue radiotherapy for biochemical relapse were included in the study. Post-prostatectomy relapse occurred within 2 years in 65% of patients. Median pre-radiotherapy PSA was 0.9ng/ml. 3D conformational radiotherapy was used to treat 87.5% of cases; 97.5% of patients received a total dose of 66 Gy. In accordance with disease risk classification, disease free survival was 2.29 years, with 28.5 months median follow-up. Two patients had biochemical relapse following rescue radiotherapy. Conclusions: Rescue radiotherapy has been shown to be an appropriate intervention for prostate cancer patients with biochemical relapse following radical prostatectomy; 94% of patients treated with rescue radiotherapy at the NCI from 2003 to 2007 are relapse free.