Challenges and opportunities for sarcoma care and research in Latin America: a position paper from the LACOG sarcoma group.

As a developing region, Latin America faces unique cancer control and prevention challenges, which are intensified when considering rare cancers, including sarcomas. Sarcomas are a group of malignancies that arise in the connective tissues of the body-such as muscle, fat, nerves, blood vessels, and bones-accounting for a diverse range of tumours that, although rare, require specialized attention. Sarcoma care and research in Latin America require a comprehensive approach that includes deeper epidemiologic knowledge, diagnostic capacity building, access to innovative treatments, increased patient advocacy, and strengthening of clinical research capacity. This article will review current challenges and opportunities for treating patients with sarcoma in Latin America and outline a pathway toward improvement for regional collaborative groups.

Addressing the unmet needs of patients with BRAF-mutated melanoma in Latin America: Expert perspective.

Melanoma represents an increasing public health burden with extensive unmet needs in Latin America (LA). A mutation in the BRAF gene is present in approximately 50% of all melanomas in White populations and is a target of precision medicine, with the potential to dramatically improve patient outcomes. Thus, increased access to BRAF testing and therapy is LA must be explored. At a multi-day conference, a panel of Latin American experts in oncology and dermatology were provided with questions to address the barriers limiting access to testing for BRAF mutation in patients with melanoma in LA, who may be eligible for targeted therapy to improve their prognosis. During the conference, responses were discussed and edited until a consensus on addressing the barriers was achieved. Identified challenges included ignorance of BRAF-status implications, limited human and infrastructural resources, affordability and reimbursement, fragmented care delivery, pitfalls in the sample journey, and lack of local data. Despite the clear benefits of targeted therapies for BRAF-mutated melanoma in other regions, there is no clear path to prepare LA for a sustainable personalized medicine approach to this disease. Due to melanoma's time-sensitive nature, LA must aim to provide early access to BRAF testing and consider mutational status within treatment decision making. To this end, recommendations are provided and include establishing multidisciplinary teams and melanoma referral centers and improving access to diagnosis and treatment.

Merkel cell carcinoma in Latin America: a contribution from an expanded access program for avelumab to address issues from experts' recommendations.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive malignancy, associated with poor outcomes in patients with metastatic disease (mMCC). Management has been dramatically altered as a result of incorporating immune checkpoint blockade agents. MCC data from Latin America (LATAM) come from case-series or individual records. Regional registries are lacking. A need for better registries to improve current knowledge about MCC is highlighted. Our objectives were to describe a real-world experience with avelumab as a second-line (or first-line in unfit patients) treatment in a subset of LATAM participants enrolled in a global Expanded Access Program (EAP) for patients with mMCC, and to evaluate its contribution to the resolution of the concerns described in a recent regional experts review. MATERIALS AND METHODS: We reviewed data of LATAM participants in an avelumab EAP for mMCC treatment (NCT03089658). EAP patient had unresectable or mMCC with progressive disease after one line of chemotherapy, and were ineligible for clinical trials or unfit for chemotherapy. RESULTS: 46 patients (median age: 71.6 years; 60.9% males; median treatment duration: 7.9 months) were included in the LATAM EAP. Physician-assessed objective responses were available for 19 patients. Complete response rate was 15.8% and partial response rate reached 42.1%, summarizing an objective response rate of 57.9%. Stable disease rate was 10.5%, with a disease control response of 68.4%. CONCLUSION: Avelumab showed robust efficacy and a safety profile consistent with global EAP data. Results are aimed to improve current knowledge about mMCC treatment and access to immunooncologic strategies for treating LATAM patients.

Demographic, Clinical, and Pathologic Features of Patients With Cutaneous Melanoma: Final Analysis of the Brazilian Melanoma Group Database.

PURPOSE: National epidemiologic data on melanoma are scarce in Brazil. The current work presents final demographic, clinical, and pathologic results from the Brazilian Melanoma Group database to detail how patients with melanoma present at diagnosis. METHODS: The online database includes patients diagnosed between 1982 and 2015 and evaluated at their centers of origin between 2001 and 2016. The primary objective was to describe the demographic, clinical, and pathologic characteristics of the patients, and secondary objectives were to investigate the association between clinical and pathologic variables of interest. RESULTS: A total of 1,596 patients were included. Median age was 52 years, 57% were women, and the majority were identified as white. Invasive melanoma was diagnosed in 1,297 patients, mostly localized, whereas 299 (19%) had in situ disease (TisN0M0). Only 165 patients had initial lymph node involvement. Fitzpatrick skin types I or II were slightly more frequent with in situ melanoma (73%) than with invasive disease (67%; P = .054). The median Breslow thickness was 0.95 mm, Clark levels 2 and 3 comprised nearly 70% of cases, and ulceration was present in 18% of patients. The mitotic rate was significantly associated with the presence of ulceration and both vascular and perineural invasion but not with margin positivity, whereas histologic regression was associated with both intratumoral and peritumoral inflammatory infiltrates. CONCLUSION: Despite the limitations of an observational, registry-based study, the current results provide a general profile of patients with cutaneous melanoma in Brazil at the time of diagnosis.

Brazilian consensus on the diagnosis and treatment of extremities soft tissue sarcomas.

INTRODUCTION: Soft tissue sarcomas (STSs) are rare tumors and constitute only 1% of all tumors in adults. Indeed, due to their rarity, most cases in Brazil are not treated according to primary international guidelines. METHODS: This consensus addresses the treatment of STSs in the extremities. It was made by workgroups from Brazilian Societies of Surgical Oncology, Orthopaedics, Clinical Oncology, Pathology, Radiology and Diagnostic Imaging, and Radiation Oncology. The workgroups based their arguments on the best level of evidence in the literature and recommendations were made according to diagnosis, staging, and treatment of STSs. A meeting was held with all the invited experts and the topics were presented individually with the definition of the degree of recommendation, based on the levels of evidence in the literature. RESULTS: Risk factors and epidemiology were described as well as the pathological aspects and imaging. All recommendations are described with the degree of recommendation and levels of evidence. CONCLUSION: Recommendations based on the best literature regional aspects were made to guide professionals who treat STS. Separate consensus on specific treatments for retroperitoneal, visceral, trunk, head and neck sarcomas, and gastrointestinal stromal tumor, are not contemplated into this consensus.

Immune manifestations with checkpoint inhibitors in a single Brazilian center: experience and literature review.

OBJECTIVES: The presence of autoimmune events were recorded in patients receiving immune checkpoint inhibitors. MATERIALS & METHODS: Retrospective study in patients receiving immune checkpoint inhibitors (ICIs) during the period of 2012-2019. RESULTS: A total of 554 patients received ICIs of which 123 developed an immune related adverse event. Twenty one (17%) with toxicity were identified as having a pre-existing autoimmune disease and 88 required treatment with corticosteroids or hormone replacement. Thirty two (26%) out of 123 had to temporarily discontinue ICIs due to autoimmune manifestations. Endocrine and skin manifestations were the most prevalent immune disorders in our cohort. In melanoma better efficacy was seen in patients with immune toxicity. CONCLUSION: Autoimmune diseases appear in patients receiving ICIs in this real world experience. Our results differ from other series on the frequency of autoimmunity. Complete discontinuation of ICIs due to autoimmunity was rare.

Analysis of the Abscopal Effect With Anti-PD1 Therapy in Patients With Metastatic Solid Tumors.

Abscopal effect is a rare phenomenon characterized by tumor regression of untreated metastatic lesions after a local therapy (eg, radiotherapy). We studied the probability of abscopal effect with radiotherapy associated with anti-programmed death cell 1 (PD1) therapy after progression on anti-PD1. This study is a retrospective analysis of patients treated with nivolumab or pembrolizumab for melanoma, non-small cell lung cancer (NSCLC) and renal cancer at Antônio Ermírio de Moraes Oncology Center, Brazil. To be eligible for this analysis, patients must have had unequivocal evidence of disease progression on anti-PD1 therapy and subsequent radiotherapy for any tumor site while still receiving anti-PD1. The abscopal effect was characterized as a response outside the irradiated field after radiotherapy plus anti-PD1. Sixteen patients were evaluated, including 12 metastatic melanoma, 2 metastatic NSCLC, and 2 metastatic renal cell carcinoma. The median time to disease progression on anti-PD1 was 3 months. The radiotherapy field included lung, lymph nodes, and bones, with a median total dose of 24 Gy (1-40 Gy), usually in 3 fractions (1-10 fractions). Three patients with melanoma developed an abscopal effect at a rate of 18.7% (25% among melanoma patients). Of note, one of them achieved a remarkable complete response lasting >6 months. Three patients with melanoma obtained a significant local response after radiotherapy, despite no response in distant metastases. Eleven patients presented disease progression after radiotherapy. No increased toxicity was observed. In conclusion, no patients with NSCLC or renal cancer showed abscopal effect, but 25% of patients with melanoma showed regression of nonirradiated lesions when anti-PD1 was continued after radiation to a tumor site that had progressed on anti-PD1 monotherapy.

Consensus of the Brazilian Society of Infectious Diseases and Brazilian Society of Clinical Oncology on the management and treatment of Kaposi's sarcoma

Kaposi's sarcoma is a multifocal vascular lesion of low-grade potential that is most often present in mucocutaneous sites and usually also affects lymph nodes and visceral organs. The condition may manifest through purplish lesions, flat or raised with an irregular shape, gastrointestinal bleeding due to lesions located in the digestive system, and dyspnea and hemoptysis associated with pulmonary lesions. In the early 1980s, the appearance of several cases of Kaposi's sarcoma in homosexual men was the first alarm about a newly identified epidemic, acquired immunodeficiency syndrome. In 1994, it was finally demonstrated that the presence of a herpes virus associated with Kaposi's sarcoma called HHV-8 or Kaposi's sarcoma herpes virus and its genetic sequence was rapidly deciphered. The prevalence of this virus is very high (about 50%) in some African populations, but stands between 2% and 8% for the entire world population. Kaposi's sarcoma only develops when the immune system is depressed, as in acquired immunodeficiency syndrome, which appears to be associated with a specific variant of the Kaposi's sarcoma herpes virus. There are no treatment guidelines for Kaposi's sarcoma established in Brazil, and thus the Brazilian Society of Clinical Oncology and the Brazilian Society of Infectious Diseases developed the treatment consensus presented here.

Consensus of the Brazilian Society of Infectious Diseases and Brazilian Society of Clinical Oncology on the management and treatment of Kaposi's sarcoma.

Kaposi's sarcoma is a multifocal vascular lesion of low-grade potential that is most often present in mucocutaneous sites and usually also affects lymph nodes and visceral organs. The condition may manifest through purplish lesions, flat or raised with an irregular shape, gastrointestinal bleeding due to lesions located in the digestive system, and dyspnea and hemoptysis associated with pulmonary lesions. In the early 1980s, the appearance of several cases of Kaposi's sarcoma in homosexual men was the first alarm about a newly identified epidemic, acquired immunodeficiency syndrome. In 1994, it was finally demonstrated that the presence of a herpes virus associated with Kaposi's sarcoma called HHV-8 or Kaposi's sarcoma herpes virus and its genetic sequence was rapidly deciphered. The prevalence of this virus is very high (about 50%) in some African populations, but stands between 2% and 8% for the entire world population. Kaposi's sarcoma only develops when the immune system is depressed, as in acquired immunodeficiency syndrome, which appears to be associated with a specific variant of the Kaposi's sarcoma herpes virus. There are no treatment guidelines for Kaposi's sarcoma established in Brazil, and thus the Brazilian Society of Clinical Oncology and the Brazilian Society of Infectious Diseases developed the treatment consensus presented here.

Multiple metastases of malignant melanoma in the head and neck: a case report and literature review.

Malignant melanoma (MM) with multiple metastases (including the oral mucosa) is an extremely rare condition that is difficult to manage due to its complexity. This article presents the case of a 27-year-old man who first developed MM on the scalp, which subsequently metastasized to the mandible, parotid gland, infratemporal fossa, and the cervical regions of the larynx, kidneys, liver, and lungs. The findings of the present case report are compared with 31 other cases published in the English literature. Multiple metastases of MMs in the head and neck region are rare and generally are associated with a poor prognosis. In such cases, dentists play a role in the diagnosis, prevention, and treatment of sequelae stemming from oncologic treatment, with the aim of improving the patient's quality of life.

Toxicity of checkpoint inhibitors.

Immunologic checkpoint inhibitor is a new class of antineoplastic drugs which mechanism of action depends on the interaction with the immune system. The first in class was ipilimumab, anti-CTLA4, and soon the anti-PD1 (Programmed Death 1) and anti-PDL1 are expected to be available. Although the profile of adverse events is unique, they are predictable and, by complying with the guidelines available, the management of these drugs is safe in the great majority of patients. Here, it is provided a review of adverse events and their management.

Workflow in clinical trial sites & its association with near miss events for data quality: ethnographic, workflow & systems simulation.

BACKGROUND: With the exponential expansion of clinical trials conducted in (Brazil, Russia, India, and China) and VISTA (Vietnam, Indonesia, South Africa, Turkey, and Argentina) countries, corresponding gains in cost and enrolment efficiency quickly outpace the consonant metrics in traditional countries in North America and European Union. However, questions still remain regarding the quality of data being collected in these countries. We used ethnographic, mapping and computer simulation studies to identify/address areas of threat to near miss events for data quality in two cancer trial sites in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: Two sites in Sao Paolo and Rio Janeiro were evaluated using ethnographic observations of workflow during subject enrolment and data collection. Emerging themes related to threats to near miss events for data quality were derived from observations. They were then transformed into workflows using UML-AD and modeled using System Dynamics. 139 tasks were observed and mapped through the ethnographic study. The UML-AD detected four major activities in the workflow evaluation of potential research subjects prior to signature of informed consent, visit to obtain subject́s informed consent, regular data collection sessions following study protocol and closure of study protocol for a given project. Field observations pointed to three major emerging themes: (a) lack of standardized process for data registration at source document, (b) multiplicity of data repositories and (c) scarcity of decision support systems at the point of research intervention. Simulation with policy model demonstrates a reduction of the rework problem. CONCLUSIONS/SIGNIFICANCE: Patterns of threats to data quality at the two sites were similar to the threats reported in the literature for American sites. The clinical trial site managers need to reorganize staff workflow by using information technology more efficiently, establish new standard procedures and manage professionals to reduce near miss events and save time/cost. Clinical trial sponsors should improve relevant support systems.

Cutaneous melanoma in Latin America: the need for more data / El melanoma cutâneo en América Latina: la necesidad de mßs datos

OBJECTIVE: To identify the scientific literature on cutaneous melanoma in Latin America and compile all available epidemiologic data to demonstrate the need for reliable regional and country-specific data on incidence and mortality estimates. METHODS: Literature searches were conducted in PubMed, Embase, LILACS, and Google Scholar databases for epidemiologic studies from 1 January 2000 to 31 October 2010 related to melanoma in Argentina, Brazil, Colombia, Mexico, Puerto Rico, and Venezuela. A final search on melanoma cases was carried out using country-specific population-based cancer registries. No statistical analyses were conducted. RESULTS: For all six countries, most epidemiological research on cutaneous melanoma consists of hospital-based or case-control studies. Very few studies report incidence and mortality rates. Attempts to estimate disease rates have relied on national incidence and mortality data and information extracted from cancer registries. While predominance of European ancestry is a known risk factor for developing melanoma, the association of melanoma and ethnicity is not well-documented in some of the populations reviewed. Latin Americans are frequently exposed to ultraviolet (UV) radiation due to the tropical weather, high altitude, and thinning ozone layer in some regions. Tanned skin is viewed as healthy and beautiful. While melanoma public health campaigns have been under way in Latin America for decades, increasing melanoma awareness remains imperative. CONCLUSIONS: There is an urgent need to collect accurate epidemiologic melanoma data in Latin America. Future research in the region should include more comprehensive, countryspecific, population-based studies to allow for comparative evaluation of incidence and mortality rates.

OBJETIVO: Identificar la literatura científica sobre el melanoma cutßneo en América Latina y recopilar todos los datos epidemiológicos disponibles, con objeto de demostrar la necesidad de información fiable a escala regional y de país sobre los datos de incidencia y mortalidad. MÉTODOS: Se realizaron búsquedas bibliogrßficas en las bases de datos PubMed, Embase, LILACS y Google Scholar para encontrar estudios epidemiológicos relacionados con el melanoma llevados a cabo del 1 de enero del 2000 al 31 de octubre del 2010 en Argentina, Brasil, Colombia, México, Puerto Rico y Venezuela. Se efectuó una búsqueda final de casos de melanoma mediante la consulta de los registros poblacionales de cßncer de cada país. No se realizó ningún anßlisis estadístico. RESULTADOS: En los seis países, la mayor parte de la investigación epidemiológica sobre el melanoma cutßneo consiste en estudios hospitalarios o estudios de casos y testigos. Muy pocos estudios informan sobre las tasas de incidencia y mortalidad. Los intentos de calcular las tasas de la enfermedad se han basado en los datos nacionales de incidencia y mortalidad, y en la información extraída de los registros de cßncer. Aunque el predominio de la ascendencia europea constituye un conocido factor de riesgo de melanoma, la asociación entre el melanoma y el grupo étnico no puede demostrarse adecuadamente en algunas de las poblaciones estudiadas. Los latinoamericanos estßn frecuentemente expuestos a la radiación ultravioleta como consecuencia del clima tropical, la elevada altitud y la disminución de la capa de ozono en algunas regiones. La piel bronceada se considera como saludable y bella. Aunque hace decenios que se llevan a cabo campa±as de salud pública dedicadas al melanoma en América Latina, es indispensable incrementar la conciencia de esta enfermedad. Conclusiones: Existe la urgente necesidad de recopilar datos epidemiológicos precisos sobre el melanoma en América Latina. Las futuras actividades...

High-dose interleukin-2 in patients with metastatic melanoma whose disease progressed after biochemotherapy.

The objective of this study was to report our experience with 38 consecutive patients with metastatic melanoma treated with high-dose (HD) bolus interleukin (IL)-2 after disease progression on or after biochemotherapy as the only earlier treatment for metastatic disease. We conducted a retrospective review of all patients with metastatic melanoma treated with HD IL-2 at the Oncology Center of Hospital Sirio-Libanes between October 2000 and December 2009. The treatment consisted of IL-2, of 600,000 U/kg every 8 h for up to 14 doses, followed by 1-week rest and readmission for the second cycle. Responders received up to four additional cycles. Median follow-up was 9 months. The overall response rate was 23.6%, and we found no correlation between earlier response to biochemotherapy and response to HD IL-2. The median survival was 9.5 months for all patients and 36.1 months for the responders. The most frequent grade 3 or 4 adverse events were hypotension, diarrhea, and respiratory distress, and one patient died from septic shock. We concluded that HD IL-2 has clinically meaningful antitumor activity in patients with metastatic melanoma whose disease has progressed after biochemotherapy. This is a treatment alternative in patients with no central nervous system involvement and who are fit enough to tolerate it, regardless of the initial response to biochemotherapy.

Cutaneous melanoma in Latin America: the need for more data.

OBJECTIVE: To identify the scientific literature on cutaneous melanoma in Latin America and compile all available epidemiologic data to demonstrate the need for reliable regional and country-specific data on incidence and mortality estimates. METHODS: Literature searches were conducted in PubMed, Embase, LILACS, and Google Scholar databases for epidemiologic studies from 1 January 2000 to 31 October 2010 related to melanoma in Argentina, Brazil, Colombia, Mexico, Puerto Rico, and Venezuela. A final search on melanoma cases was carried out using country-specific population-based cancer registries. No statistical analyses were conducted. RESULTS: For all six countries, most epidemiological research on cutaneous melanoma consists of hospital-based or case-control studies. Very few studies report incidence and mortality rates. Attempts to estimate disease rates have relied on national incidence and mortality data and information extracted from cancer registries. While predominance of European ancestry is a known risk factor for developing melanoma, the association of melanoma and ethnicity is not well-documented in some of the populations reviewed. Latin Americans are frequently exposed to ultraviolet (UV) radiation due to the tropical weather, high altitude, and thinning ozone layer in some regions. Tanned skin is viewed as healthy and beautiful. While melanoma public health campaigns have been under way in Latin America for decades, increasing melanoma awareness remains imperative. CONCLUSIONS: There is an urgent need to collect accurate epidemiologic melanoma data in Latin America. Future research in the region should include more comprehensive, country-specific, population-based studies to allow for comparative evaluation of incidence and mortality rates.