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PURPOSE: This study aims to describe genomic characteristics of patients with metastatic prostate cancer (mPC). PATIENTS AND METHODS: This study is a retrospective, multicenter cohort study of patients with mPC and reports on genomic testing. Patients were included from 12 academic centers in five countries. RESULTS: A total of 349 patients with PC were included in this study. Most patients (209, 59.9%) were de novo metastatic. Genomic analysis was performed in 233 (66.6%) patients in the metastatic castration-resistant prostate cancer (mCRPC) setting, and only 115 (32.8%) patients had a tumor evaluation in the metastatic hormone sensitive prostate cancer scenario. The evaluation of somatic and/or germline mutations was performed through multigene panel analyses in 290 (83.09%) patients, and next-generation sequencing of BRCA1 and BRCA2 genes was performed in 59 (16.91%) patients. Analyzing the mCRPC subgroup, with a median follow-up of 15.6 months (IQR, 14-19.06), the median progression-free survival (PFS) was not reached (NR) and the PFS at 16 months was 58.7% (95% CI, 50.8 to 67.8). When comparing patients with BRCA mutations with those who are not BRCA-mutated in the mCRPC scenario, the median PFS was NR (95% CI, 14 to NR) and 26.3 months (95% CI, 16.7 to 36.5; P = .2), respectively. Two of six patients with BRCA mutations were treated with targeted therapies (poly-ADP-ribose polymerase inhibitors). CONCLUSION: Our study, to the best of our knowledge, represents one of the larger data sets for somatic testing in patients with PC in Latin America (LATAM). It adds valuable information to the growing body of knowledge about the genomic landscape of advanced PC in real-world daily practice scenarios in LATAM countries, which are not always well-represented in large-scale randomized clinical trials.
Asunto(s)
Genómica , Neoplasias de la Próstata Resistentes a la Castración , Humanos , Masculino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , América Latina/epidemiología , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/mortalidad , Secuenciación de Nucleótidos de Alto Rendimiento , Proteína BRCA2/genética , Mutación , Mutación de Línea GerminalRESUMEN
Background: Next-generation sequencing (NGS) has proven to be a key implementation to understanding biological pathways involved in cancer. In daily practice, the identification of somatic and germline mutations has allowed physicians to gather relevant information to make therapeutic decisions and benefit patients. Importantly, somatic mutations provide targeted opportunities for treatment and reveal resistance mechanisms to understand patients' tumour evolution. Scanty data in clinical trials and in a real-world setting is available regarding the utility of poly(ADP-ribose) polymerase inhibitors in pathogenic or likely-pathogenic somatic breast cancer gene 1/2 (BRCA1/2) mutations and/or germline or somatic Homologous Recombination-Related Gene mutations in advanced breast cancer (ABC). Case report: Here we report a real-life case of a 47-year-old postmenopausal woman with hormone receptor-positive (HR-positive) Epidermal growth factor receptor 2 (HER2)-negative metastatic BC that had poor response to classic therapeutic strategies for HR+/HER2- ABC. At this point, the possibility of using NGS to guide the treatment was decided in a Molecular Tumour Board (MTB), and the patient had a major response to talazoparib targeting a non-germline BRCA2 mutation. Conclusion: Undoubtedly, more information regarding the cost effectiveness of NGS is needed to develop adequate reimbursement policies for this technology. It should be highlighted that the generalisation of MTBs and the implementation of molecular screening programmes are greatly needed in our region to gain more knowledge of somatic mutations implicated in the Hispanic and Latin-American population with BC diagnosis. Recently presented results of randomised studies may support the evaluation of somatic mutations with NGS to find targeted therapies for ABC patients.
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A 68-year-old man, without a family history of cancer, was treated for primary cutaneous melanoma of the scalp. Two years later, a right lateral cervical lymph recurrence was observed and he was treated with lymphadenectomy and adjuvant nivolumab for 1 year. Four years from the initial melanoma diagnosis, a computer tomography scan showed a solid nodular lesion of 26 × 40 × 75 mm inside the previously known inguinoscrotal hernia. A new recurrence of melanoma was the most probable diagnosis and a right inguinal hernioplasty was performed. Notably, the histopathological examination revealed a mesenteric fibromatosis with the typical immunohistochemical pattern (strong nuclear staining of ß-catenin). Interestingly, this represents the first case of a patient with a mesenteric desmoid tumour presenting as an inguinal hernia masking a cutaneous melanoma recurrence.
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BACKGROUND: The role of the molecular tumour board (MTB) is to recommend personalised therapy for patients with cancer beyond standard-of-care treatment. A comprehensive molecular analysis of the tumour in a molecular pathology laboratory is important for all targeted therapies approaches. Here we report the 1-year experience of the Instituto Alexander Fleming Molecular Tumour Board. PATIENTS AND METHODS: The MTB of the Instituto Alexander Fleming was launched in December 2019 in a monthly meeting. In each interactive monthly session, five cases were presented and discussed by the members. These cases were referred by the treating oncologists. The MTB recommendations were sent to each physician individually, and to the rest of the meeting participants. This was discussed with the patients/families by the treating oncologist. The final decision to choose therapy was left to the treating physicians. Of the 32 patients presented at MTB, 28 (87.5%) had potentially actionable alterations and only 4 (12.5%) had no actionable mutation. Six (19%) patients received a local regulatory agency approved drug recommendation, nine (28%) patients received an off-label approval treatment recommendation and three (9%) patients did not receive the treatment due to access and reimbursement of the drug. CONCLUSION: In most of the cases evaluated, the MTB was able to provide treatment recommendations based on targetable genetic alterations. Molecular-guided extended personalised patient care is effective for a small but clinically significant proportion of patients in challenging clinical situations. We believe that the implementation of a MTB is feasible in the Latin America (LATAM) region.
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El objetivo fue analizar retrospectivamente, en pacientes con cáncer de cuello uterino localmente avanzado tratados en nuestro centro, el perfil de toxicidad de la radioterapia concurrente con platinos mono droga o combinados con gemcitabine y su impacto en el tratamiento. Estudio descriptivo, retrospectivo y observacional de pacientes con cáncer de cuello uterino localmente avanzado (estadios IIa/IVa) desde marzo de 2011 a febrero de 2016. Se analizaron características patológicas, dosis de tratamiento radiante y quimioterápico, así como toxicidades graves (GIII/IV) y su impacto en el tratamiento, observado como reducción o suspensión de dosis y/o split de radioterapia (RT). Se evaluaron 60 pacientes, edad mediana 47 años (17-75), 93% PS0-1. Histología: escamoso (89%) y adenocarcinoma (8%). Estadio IIb 24 (40%) y IIIb 16 (27%). Dosis de RT utilizada 5040cGy; 35 (58%) realizaron boost y 47 (78%) braquiterapia posterior. Cuarenta y cinco realizaron tratamiento concurrente con PLA y 15 con platinos/gemcitabine (PLA/GEM). En el grupo que recibió PLA, uno requirió reducción de dosis de quimioterapia (QT), dos suspendieron algún ciclo por toxicidad y tres realizaron split de RT. El 100% completó el tratamiento de quimioradioterapia (QRT) concurrente. En el grupo que recibió PLA/GEM: 9 requirieron reducción de dosis de QT, 11 suspendieron algún ciclo y 4 no completaron el esquema por toxicidad; 4 hicieron split de RT, y 87% completó el tratamiento de RT. En este estudio, el esquema concurrente con quimioterapia combinada muestra mayor toxicidad que impacta en el cumplimiento del tratamiento, 15% no lo completó por toxicidades graves. No obstante, un correcto manejo institucional de toxicidades, permite utilizar la combinación de tratamiento para obtener potenciales beneficios (AU)
This is a retrospective analysis of profile toxicity and treatment impact of gemcitabine plus platinum radiotherapy in patients with locally advanced cervix cancer, treated at our Centre. Descriptive, retrospective and observational study of patients with locally advanced cervix cancer (Ila/IVa stages), since March 2011 until February 2016. The analysis included the pathological characteristics, chemo radiotherapy doses, as well as severs toxicity (GIII/V) and it impact in treatment observed as reduction or suspension of doses and/or radiotherapy (RT) split. There were evaluated 60 patients of 47 median age (17-75), 93-5 PS0-1. Histology: 89% of squamous cell carcinoma and 8% of adenocarcinoma. 40% of IIb 24 and 27% of IIIB 16 stages. RT doses used 5040cGy; 35 pts (58%) did boost and 47 pts (78%) followed with brachytherapy. 45pts took PLA concurrent treatment, 15pts gemcitabine plus platinum (PLA/GEM). Regarding PLA group, one required a doses reduction of chemotherapy (QT), 2pts suspended a cycle due to toxicity and 3pts did RT split. 100% pts completed chemo radiotherapy (QRT) concurrent treatment. Regarding PLA/GEM group: 9pts required QT doses reduction, 11pts suspended a cycle due to toxicity and 4 didn´t complete the cycle due to toxicity; 4 did RT split and 87% completed RT. The study shown that the scheme of concurrent combined chemotherapy presents higher toxicity that impacts in the fulfillment of treatment, 66 ONCOLOGÍA CLÍNICA - Vol. 21 Nº 3 - Diciembre 2016 15% couldn´t complete due to sever toxicity. However, a correct institutional manage of toxicities allows to use treatment combination to obtain potential benefits (AU)