BackgroundGlioblastoma (GBM) confers a dismal prognosis despite advances in current therapy. Cancer-testis antigens (CTA) comprise families of tumor-associated antigens that are immunogenic in different cancers. The aim of this study was to determine the expression profile of a large number of CTA genes in GBM.MethodsWe selected, from 153 CTA genes, those genes potentially expressed in GBM. The expression pattern of 30 CTA was then evaluated by RT-PCR in a series of 48 GBM and 5 normal brain samples. The presence of CTCFL protein was also evaluated by immunohistochemical staining.ResultsAmong the genes with no expression in normal brain, ACTL8 (57%), OIP5 (54%), XAGE3 (44%) and CTCFL (15%) were frequently expressed in GBM, while over 85% of the tumors expressed at least 1 of these four CTA. Coexpression of two or more CTA occurred in 49% of cases. CTCFL protein expression was detected in 13% of the GBM and was negative in normal brain samples. GBM expressing 3-4 CTA was associated with significantly better overall survival (OS) rates (P = 0.017). By multivariate analysis, mRNA positivity for 3-4 CTA (P = 0.044), radiotherapy (P = 0.010) and chemotherapy (P = 0.001) were independent prognostic factors for OS.ConclusionsGBM frequently express ACTL8, OIP5, XAGE3 and CTCFL. A relatively high percentage of tumors expressed at least one of these four CTA, opening the perspective for their utility in antigen-specific immunotherapy. Furthermore, mRNA positivity for 3-4 CTA is an independent predictor of better OS for GBM patients.
PURPOSE To generate and present survey results on important issues relevant to treatment and follow-up of localized and locally advanced, high-risk prostate cancer (PCa) focusing on developing countries. METHODS A panel of 99 PCa experts developed more than 300 survey questions of which 67 questions concern the main areas of interest of this article: treatment and follow-up of localized and locally advanced, high-risk PCa in developing countries. A larger panel of 99 international multidisciplinary cancer experts voted on these questions to create the recommendations for treatment and follow-up of localized and locally advanced, high-risk PCa in areas of limited resources discussed in this article. RESULTS The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion and not on a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations considered cost-effectiveness as well as the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. Results were tabulated in real time. CONCLUSION The voting results and recommendations presented in this article can guide physicians managing localized and locally advanced, high-risk PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for treatment of localized and locally advanced, high-risk PCa in developing countries have not been defined, this article will serve as a point of reference when confronted with this disease.
Standard prognostic criteria showed no correlation with Oncotype DX.
PURPOSE A group of international urology and medical oncology experts developed and completed a survey on prostate cancer (PCa) in developing countries. The results are reviewed and summarized, and recommendations on consensus statements for very low-, low-, and intermediate-risk PCa focused on developing countries were developed. METHODS A panel of experts developed more than 300 survey questions of which 66 questions concern the principal areas of interest of this paper: very low, low, and intermediate risk of PCa in developing countries. A larger panel of 99 international multidisciplinary cancer experts voted on these questions to create the recommendations for treatment and follow-up for very low-, low-, and intermediate-risk PCa in areas of limited resources discussed in this manuscript. RESULTS The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion not a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations consider cost-effectiveness and the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. The results were tabulated in real time. CONCLUSION The voting results and recommendations presented in this document can be used by physicians to support management for very low, low, and intermediate risk of PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for treatment for very low, low, and intermediate risk of PCa in developing countries have not been developed, this document will serve as a point of reference when confronted with this disease.
e16549 Background: Treatment of Urothelial Cancer (UC) is rapidly evolving with innovative biomarker-based approaches. Alterations in the gene encoding fibroblast growth factor receptor (FGFR) are frequent in UC and are an emerging focus for targeted therapy. However, real-world data on FGFR prevalence, as well as clinicopathological characteristics and outcomes of patients (pts) with advanced UC in Latin America is lacking. Methods: LACOG 1518 is a multicenter multinational study that retrospectively included pts diagnosed with metastatic or relapsed UC between Jan-2016 and Dec-2019. Clinicopathological characteristics, outcomes and treatment patterns were retrieved from medical records. Archival tumor samples were analyzed for FGFR alterations by NGS. Results: Two hundred thirteen pts were included across 24 centers in 4 Latin American countries. Median age was 68 years (range, 31-90), most pts (75%) had PS 0-1, and 83 (39%) pts had clinical stage IV at diagnosis. Bladder was the primary site of disease in 190 (89%) pts, 92 (43.2%) pts had histological variants of UC - 46 (21.6%) pts with adenocarcinoma differentiation and 16 (7.5%) with squamous-cell differentiation. Patients with relapsed locoregional disease not candidates for curative therapy comprised 10.3% of the sample. Among pts with metastatic disease, visceral metastases were present in 99 (51%) pts. FGFR alterations eligible for treatment with FGFR inhibitors (FGFRi) were identified in 29 (14.8%) out of 196 pts tested and included 29 mutations (14 S249C, 7 Y373C, 5 R248C and 3 G370C) and 13 fusions (8 FGFR3-TACC3, 2 FGFR3-BAIAP2L1, 2 FGFR2-BICC1 and 1 FGFR2-CASP7). Other FGFR alterations were also present in 6 (3.1%) pts. Median overall survival since initial diagnosis and advanced disease were 31.6 months (95% CI, 25.5 – 37.6) and 15.2 months (95% CI, 12.4 – 17.9), respectively. Median time to treatment failure to the first treatment line was 3.9 months (95% CI, 3.0 – 4.4). Regarding treatment patterns, 175 (82.1%) pts received first line treatment: 127 (72.6%) combined chemotherapy, 29 (16.6%) immunotherapy alone, 15 (8.6%) single agent chemotherapy, and 4 (2.3%) chemo-immunotherapy. Gemcitabine-platinum combinations were the backbone of choice in 93.7% of pts receiving combined chemotherapy. Pembrolizumab and atezolizumab were the chosen first-line agents for 10.3% and 4% of the treated pts, respectively. Considering all treatment lines, 75 (35.2%) and 3 (1.4%) pts were exposed to immunotherapy and FGFRi in the course of their disease, respectively. Conclusions: The prevalence of FGFR alterations in advanced UC in Latin America is similar to those described in other regions. Our data suggest limited access to FGFR inhibitors for the treatment of advanced UC in Latin America.
TPS497 Background: There is lack of high-quality and comprehensive data on advanced urothelial cancer in Latin America. Pathological and clinical outcomes information of this cancer can help the scientific community to understand the current standard of treatment and identify possible gaps for optimal care. Very few translational studies were performed in advanced urothelial cancer in developing countries describing the prevalence of key biomarkers for targeted agents and immunotherapy. Methods: LACOG 1518 is a large multi-institutional retrospective study that will collect information about sociodemographic data, treatment and outcome of patients diagnosed with recurrent/ metastatic urothelial cancer in Latin America between January 2016 and December 2019. Socio-demographic characteristics, clinical-pathological features, treatment patterns and outcomes will be extracted from medical charts. Tumor tissue will be collected for fibroblast growth factor receptor (FGFR) gene mutation or fusion test in a central laboratory. A biorepository will be built for future translational research including PD-L1 test and next generation sequencing. Primary endpoint consists on characterize demographic, socioeconomic factors, medical and oncological history of patients diagnosed with recurrent/metastatic urothelial cancer. This study aim to describe treatment sequence, duration, best response and progression time in each line of therapy as well as survival at 1 and 2 years. Translational research endpoints are biomarkers prevalence and association with treatment responses and outcomes.
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