Antonio C. Buzaid

Beneficência Portuguesa Hospital of São Paulo, Potengy, Rio Grande do Norte, Brazil

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Publications (29)84.75 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Cancer of the exocrine pancreas is a highly lethal malignancy. Surgical resection is the only potentially curative treatment. Unfortunately, because of the late presentation, the majority have either locally advanced cancer at initial diagnosis. Systemic chemotherapy provides benefit to patients with advanced pancreatic cancer, improving disease-related symptoms and survival when compared to best supportive care alone. Based on fase III study, FOLFIRINOX regimen became the standard first-line treatment. But, the optimal management strategy for patients who fail initial FOLFIRINOX is undefined. Despite the lack of clinical trials that report the real benefit of gemcitabine in patients with advanced exocrine pancreatic cancer as second line treatment. We aim at reporting our experience with this regimen. Methods: Patients with advanced exocrine pancreatic cancer who received gemcitabine (1.000 mg/m(2) on days 1, 8 and 15 every 4 weeks) until disease progression, as second-line therapy at our institution were retrospectively evaluated. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Results: A total of 20 patients were reviewed. Median age was 57 years (range, 43-74 years), and 55% were older than 60 years. Most patients were male (80%), had metastatic disease (60%), and ECOG performance status of 0 or 1 (65%). PFS and OS were 2.0 (95% CI, 1.2-2.8) and 5.7 months (95% CI, 3.9-7.4), respectively. There were no deaths due to the treatment. Conclusions: In this study, gemcitabine was a reasonable second-line treatment option for patients with advanced pancreatic adenocarcinoma and good ECOG performance status. Phase III trials are urgently needed comparing gemcitabine versus best supportive of care (BSC) can evaluate the real benefit of this chemotherapy after progression on FOLFIRINOX.
    No preview · Article · Oct 2015 · Journal of gastrointestinal oncology
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    ABSTRACT: Background: A considerable number of patients with mBC progress after exhausting all approved standard therapies but maintain an adequate performance status and could be candidates for further treatment. We aim at reviewing our experience with the use of a NGS platform in refractory mBC and its clinical utility. Methods: We retrospectively reviewed demographics, NGS results, and the suggested therapies received by patients undergoing NGS (Foundation Medicine, Cambridge, MA, USA): exonic sequencing of 315 genes and selective intronic sequencing from 28 genes for refractory mBC. Co-primary endpoints were the percentage of patients with targeted therapy options uncovered by mutational profiling and the percentage of them who received genotype-directed therapy. Results: Samples from 20 patients were tested. Histologic subtype consisted of triple negative (50%), HER 2 +, hormonal receptor [HR] - 15%, HR + and HER 2 - (35%). A targetable genomic alteration was identified in 14 (70%) patients, most frequently in TP53 (11 [55%]), PIK3CA (8 [40%]), FGFR1 (4 [20%]), CCND1 (3 [15%]), PTEN (3[15%]) and BRCA2 (2[10%]). Therapy could be personalized in 9 (45%) of 14 patients. Of the 9 patients who were received targeted therapy, 7 (77%) had an objective response and had stable disease for more than 3 months. Conclusions: Mutational profiling using a targeted NGS panel identified potentially actionable alterations in the majority of advanced breast cancer patients. The assay provided clinical benefit in 35% of the patients.
    No preview · Conference Paper · Oct 2015
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    ABSTRACT: Background: Brain metastasis (BM) are an event relatively frequent in the clinical course of patients with lung adenocarcinoma. Despite all advances in therapeutical approach, it still has a dismal prognosis. I Identifying subgroups with a higher propensity for BM may be useful to follow those patients closer and therefore offer them earlier brain treatment. We aimed at evaluating whether patients harboring EGFR activating mutations are at a higher risk for BM compared to those without such mutations Methods: We retrospectively reviewed data of 306 patients with lung adenocarcinoma at Sao Jose Hospital in Sao Paulo, Brazil, in the past 5 years. Results: Of the 306 patients analyzed, 52 (16,9%) had EGFR mutations and we identified BM in 19 of them (36,5%). Amongst the other 254 patients, we excluded 151 because records were not well-documented for BM or EGFR status, remaining 103 patients certainly EGFR negative and that underwent a brain image. Of those 103, BM were identified in 26 (25,2%). There was a trend towards a higher proportion of BM in EGFR mutated tumors (p = 0.11). Conclusions: This study showed that patients with EGFR activating mutations have a trend towards a higher proportion of BM comparing to those without these mutations.
    No preview · Conference Paper · May 2015
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    ABSTRACT: Background: Non-small cell lung cancer (NSCLC) is known to harbor molecular mutations or rearrangements predictive to a variety of targeted therapies, which have been increasing the overall survival (OS) in recent years. There is a lack of studies evaluating the prevalence of those molecular alterations in NSCLC patients in Brazil. Methods: This was a retrospective analysis of patients diagnosed with lung adenocarcinoma who were treated at Antonio Ermirio de Moraes Oncology Center (Brazil) from January 2011 to December 2014. Status of EGFR (epidermal growth factor receptor) mutation, ALK (anaplastic lymphoma kinase) translocation, KRAS (kirsten rat sarcoma) mutation, HER2 (human epidermal receptor-2) ampification, and ROS1 (c-ros oncogene 1) rearrangement status was evaluated. Results: A total of 290 patients with lung adenocarcinoma were included in the analysis. Median age was 65 years (range 30-89), 51.7% were male and 67.9% were smokers or previously smokers. At diagnosis, 57.6% were metastatic and 4.8% were stage IIIB according to AJCC 2010. The analysis of EGFR status was performed in 162 patients (55.9%). The prevalence of EGFR mutation was 32.7%: 23 patients at exon 19, 21 at exon 21; 6 at exon 20; and 1 at exon 18. The prevalence of ALK translocation was 4.0% (3/75 patients). KRAS mutation was detected in 20% (3/15), BRAF mutation in 11.8% (2/17), HER2 amplification in 14.3% (2/14), and ROS1 mutation in 9% (1/11). Conclusions: Despite being a retrospective analysis, a high prevalence of EGFR mutation (32.7%) and ALK translocation (4.0%) was detected in a brazilian population with NSCLC, which offers further clinical benefit.
    No preview · Conference Paper · May 2015
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    ABSTRACT: Background: The long term survival impact of biochemotherapy (BioCT) for patients with metastatic melanoma (MM) is not well established in the literature. We performed a retrospective analysis of MM patients treated with BCT under our care. Methods: This was a retrospective single-team experience of 163 consecutive patients who underwent BioCT from 1998 to 2014. BioCT consisted of cisplatin (20 mg/m2 IV D1-D4), vinblastine (1,6 mg/m² IV D1-D4), dacarbazine (800 mg/m2 IV D1), interleukin-2 (9 MU/m² IV over 24h D1-D4) and interferon-alpha (5 MU/m² SC D1-D5), with G-CSF (300 mcg SC D5- D14) every 3 weeks for a maximum of six cycles. Median progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Results: All 163 patients (58.2% male) were included in the analyses. Median age was 47 (range 19-65). Overall response rate as determined by the local radiologist report was 52% (complete response [CR]: 19%; partial response: 33%). Median PFS was 5.0 months (95% confidence interval [CI] 3.6-6.4 months). Median OS was 19.7 months (95% CI 14.6-24.8 months). Five-year OS was 27.6% (95% CI 19.3-35.8%). Out of the 32 patients who achieved a CR, 8 (25%) were alive and with no evidence of disease at 5 years (5% of the entire cohort). Conclusions: Despite recent advances in the treatment of metastastic melanoma, BioCT remains a solid treatment alternative for MM with curative potential in a small fraction of patients.
    No preview · Conference Paper · May 2015
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    ABSTRACT: Background: Several patients with advanced cancer maintain good performance status even after disease progression following all standard therapies. Next-generation sequencing (NGS) is a powerful tool to identify tumor-specific genetic changes. We aim at exploring the role of a NGS assay in identifying therapeutic targets for refractory cancers. Methods: Patients diagnosed with metastatic cancer with available paraffin-embedded tissue evaluated by the method of NGS (Foundation Medicine, USA) were included. Hybridization capture of 3,769 exons from 236 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer was applied to ≥ 50 ng of DNA extracted from 121 specimens and sequenced to high, uniform coverage. Genomic alterations (GA) were reported for each patient sample. Actionable GA were defined as those identifying anti-cancer targeted therapies available on the market or in registered clinical trials. Co-primary endpoints were the percentage of patients with targeted therapy options uncovered by mutational profiling and the percentage of them who received genotype-directed therapy. Results: Samples from 121 patients were tested (median age 56 years; range 24-83; 51% female). The most frequent primary tumor sites were gastrointestinal (28%), lung (25%), and breast (15%). All patients had stage IV malignancy and were heavily pretreated. Most patients (52%) were found to harbor potentially actionable GA involving mitogen-activated protein kinase (63,4%), phosphatidylinositol 3-kinase-AKT (36,5%) and cell-cycle regulation (47,6%) pathways. 25,6% of the patients received genotype directed treatments which were suggested by the NGS report, leading to significant benefit in several cases. Conclusions: Mutational profiling using a targeted NGS panel identified potentially actionable alterations and novel mutations, which may serve as genetic biomarkers for personalized therapeutics. We are just at the dawn of exploring this strategy and NGS can effectively contribute to increasing the understanding of the disease.
    No preview · Conference Paper · May 2015

  • No preview · Article · May 2015 · Cancer Research

  • No preview · Conference Paper · Jan 2015
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    ABSTRACT: Background: There is only limited data regarding efficacy and safety of FOLFIRINOX in elderly patients with advanced pancreatic adenocarcinoma. We aim to evaluate our experience with dose-reduced FOLFIRINOX in patients > 65 years-old. Methods: All patients > 65 years-old with biopsy-proven advanced pancreatic adenocarcinoma who received at least one cycle of modified dose-attenuatedFOLFIRINOX (no bolus FU and reduced dose of oxaliplatin and/or irinotecan) at our institution were identified. Results: Twenty-one consecutive patients (62% males) were reviewed. Median age was 67 (range 65-79). Grade 3/4 toxicities were reported in 7 (33%) patients ; the most common toxicities were anemia (62%), and nausea/vomiting (45%). Elevations in AST and/or ALT above the upper limit of normality were identified in 38%. No deaths due to toxicities were reported. Prophylactic granulocyte colony stimulator factor (G-CSF) was given in 16 (70 %) patients. Dose reductions were substantial with median reductions of 27,8 % (range 15 - 50%) for 5-FU, 27,1% (range 6-50%) for oxaliplatin and 25% (range 12-75%) for irinotecan. Median overall survival (OS) was 11,8 months (95% CI 10,2 - 13,3). Median progression free survival (PFS) was 6,9 months (95% CI 5,3 - 8,5). Conclusions: Modified dose-attenuated FOLFIRINOX is a reasonable option for elderly patients with advanced pancreatic adenocarcinoma. Adverse events were manageable and no deaths due to toxicity were reported. Median OS and PFS were similar to the pivotal phase III trial, demonstrating that dose-attenuated FOLFIRINOX may be beneficial to elderly patients.
    No preview · Conference Paper · Jan 2015
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    ABSTRACT: Background: Despite a large number of randomized trials, there is no consensus as to the best regimen for advanced gastroesophageal cancer. Combination therapy with docetaxel, cisplatin, and 5-FU has shown increased response rates, progression-free survival (PFS) and overall survival (OS), but at the cost of significant toxicity. Based on a small phase II study, FLOT has been adopted by some groups given its better toxicity profile. We aim at reporting our experience with this regimen Methods: Patients with unresectable advanced gastroesophageal adenocarcinoma who received FLOT (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, and fluorouracil 2600 mg/m2 as a 24h infusion in combination with docetaxel 50 mg/m2 on day 1 every 2 weeks) as first-line therapy at our institution were retrospectively evaluated. PFS and OS were estimated by the Kaplan-Meier method. Results: A total of 23 patients were reviewed, most of them with metastatic disease (60%). Median age was 56 years (range 26–76) and 74% were male. Median PFS and OS were 5,2 (95% CI 4,0-6,3) and 8,5 months (95% CI 4,4-12,6), respectively. Only 13%of the patients experienced prolonged PFS (>12 months). There were no deaths due to the treatment. Conclusions: Before FLOT could be adopted as a first-line regimen for metastatic gastroesophageal cancer, phase III trials are urgently needed comparing FLOT with more traditional regimens.
    No preview · Conference Paper · Jan 2015
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    ABSTRACT: Background: Inoperable sarcoma may be associated with limiting local symptoms . To date, there are no data regarding the efficacy of palliative intra-arterial cisplatin for unresectable sarcoma. Methods: We retrospectively reviewed all patients with unresectable symptomatic sarcoma who underwent at least one course of palliative superselective intra-arterial chemotherapy with high-dose cisplatin (150 mg/m2/week) treated by the authors from 2004 to 2014. Sodium thiosulfate was administered intravenously to minimize cisplatin side effects. Progression-free survival (PFS) was calculated by the Kaplan Meier method. Objetive responses were reported according to the attending physician´s evaluation. Results: A total of 10 patients (6 males) were included in the analysis. Median age was 53 (range: 23-74). Histologic subtypes included chondrosarcomas (2), 1 chordoma (1), angiosarcoma (1), liposarcoma (1), 1 alveolar rhabdomyosarcoma (1), osteosarcoma (1), epithelioid sarcoma (1), 1 spindle cell sarcoma (1) and pleomorphic sarcoma (1). Treated anatomic sites included nasal clivus (1), gluteal muscle (2), sacrum (2), mastigatory space (1), supraclavicular fossa (1), mediastinum (1), thigh (1) and face (1). Number of cycles ranged from 1 to 5. Three patients received concomitant radiation therapy while 3 had received it previously. Five patients had significant objective tumor responses, as documented by imaging studies. Median PFS was 1.9 months. Four patients had tumor control for more then 3 months. Only 3 patients experienced adverse events (1 reversible acute renal failure, 1 grade 2 nausea and 1 hearing loss). Conclusions: Intra-arterial high-dose cisplatin with thiosulfate rescue was well-tolerated and produced significant palliation in approximately half of the patients treated. This strategy should be further evaluated in prospective trials.
    No preview · Conference Paper · Jan 2015
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    ABSTRACT: Background: FOLFIRINOX was found to have higher response rates and overall survival (OS) compared to gemcitabine-based regimens in the metastatic setting. However, the contribution of chemoradiotherapy to outcomes after FOLFIRINOX in LAPC remains uncertain. We aim at evaluating our experience with FOLFIRINOX followed by chemoradiation (IMRT) with capecitabine for patients with LAPC. Methods: Patients with unresectable LAPC who received induction FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan and oxaliplatin) followed by chemoradiation with capecitabine at our institution were screened and accrued at the time of radiotherapy and are being followed prospectively. Radiation technique consisted of IMRT with simultaneous integrated boost (SIB) - dose of 45 Gy (1.8Gy/day) to high-risk lymph nodes and 55 Gy (2.2Gy/day) to the primary tumor. Progression-free survival (PFS) and OS were estimated by the Kaplan-Meier method. Results: Fourteen patients (58% female) were included in the analyses. Median age at diagnosis of LAPC was 61 years (range 38-78). Median number of FOLFIRINOX cycles was 11 (range 4-13). With a median follow up fo 11.7 months, 43% of the patients have died. Median PFS and OS were 15.9 (95% CI 6.8 – 25.1) and 16.7 months (95% CI 10.9 – 22.4), respectively. There were no treatment-related deaths. Conclusions: Our data suggest that sequential treatment with FOLFIRINOX followed by chemoradiation with capecitabine is feasible and may offer promising PFS and OS among selected patients with LAPC. Randomized trials are urgently needed to assess the role of sequential treatment in this population.
    No preview · Conference Paper · Jan 2015
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    ABSTRACT: Background: Cancer of the exocrine pancreas is a highly lethal malignancy. Based on a phase III study, FOLFIRINOX regimen became the standard first-line treatment for patients with good performance status. However, the optimal management strategy for patients who fail initial FOLFIRINOX remains undefined. We aim at reporting our experience with single-agent gemcitabine as a second-line treatment for advanced pancreatic cancer patients who progressed on FOLFIRINOX. Methods: Patients with advanced exocrine pancreatic adenocarcinoma who received gemcitabine (1.000 mg/m² on days 1, 8 and 15 every 4 weeks) until disease progression, as second-line therapy after FOLFIRINOX failure at our institution were retrospectively evaluated. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Results: A total of 20 patients were reviewed. Most of them (60%) had metastatic disease while 40% had locally advanced tumors. Median age was 60 years (range 43–74) and 80% were male. Eastern Cooperative Oncology Group (ECOG) performance status was 0 or 1 in 65% and 2 or 3 in 35% of the patients. Median time on prior FOLFIRINOX therapy was 5 months. Median PFS and OS with gemcitabine were 2,0 (95% CI 1,2-2,8) and 5,7 months (95% CI 3,9-7,4), respectively. There were no deaths due to the treatment. Conclusions: In this study, gemcitabine was a reasonable second-line treatment option for patients with advanced pancreatic adenocarcinoma. Phase III trials are urgently needed exploring the role of gemcitabine in the second-line setting.
    No preview · Conference Paper · Jan 2015
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    ABSTRACT: Background: Metastatic PA is a lethal malignancy with poor prognosis and limited therapeutic options. We hypothesized that a comprehensive next-generation sequencing (NGS) assay could identify novel therapy targets not routinely explored in PA patients. Methods: We included patients with advanced pancreatic adenocarcinoma (PA) with accessible lesion for biopsy. Paraffin-embedded tumor tissues were evaluated by the method of NGS (Foundation Medicine, Cambridge, MA, USA). Hybridization capture of 3,769 exons from 236 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer was applied to ≥ 50 ng of DNA extracted from 10 PA specimens and sequenced to high, uniform coverage. Genomic alterations (GAs), were characterized and reported for each patient sample. Actionable GAs were defined as those identifying anti-cancer targeted therapies either available on the market or in registered clinical trials. Results: A total of 10 PA patients were included. Median age was 56 years (range 31-79). All cases harbored at least one GA with a mean of 2.7 actionable GAs per tumor. The most common actionable GAs were KRAS (90%), PTCH1 (20%), STK11 (10%) and GNAS (10%). KRAS mutations potentially treatable with MEK-inhibitor were identified in 9 patients. However, none of them received a MEK-inhibitor. Activating STK11 point mutations not detectable by IHC/FISH, potentially targetable with m-Tor inhibitor therapies were identified in 1 patient, who received everolimus and had a long-lasting (> 6 months) partial response. Conclusions: NGS of PA was able to reveal genomic alterations that may be potentially responsive to available targeted therapy. We are just at the dawn of exploring this strategy and NGS can effectively contribute for increasing the understanding of the disease.
    No preview · Conference Paper · Jan 2015
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    ABSTRACT: Triple-negative breast cancer is the most aggressive subtype of breast tumors. After a better molecular understanding of breast cancer, the treatment of triple-negative tumors is challenging because there is no known potential therapeutic target. Recently, interesting data about the use of platinum has been published and has generated excitement, especially in patients harboring mutations in BRCA gene. In this paper, the use of platinum agents will be reviewed as a new therapeutic option for mutated BRCA and triple-negative breast cancer. (J CANCEROL. 2015;2:15-20) Corresponding author: Raphael Brandão Moreira, raphamoreira@gmail.com
    Full-text · Article · Jan 2015
  • Fabio A. Schutz · Antonio C. Buzaid · Oliver Sartor
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    ABSTRACT: Androgen deprivation is the therapy of choice in the majority of patients with metastatic prostate cancer. However, a state of castration resistance ultimately occurs after hormone therapy, thus defining metastatic castration-resistant prostate cancer (mCRPC). mCRPC has historically been considered a relatively chemoresistant tumor. However, due to its ability to improve survival and the quality of life in comparison with mitoxantrone, docetaxel has been established as the standard chemotherapeutic agent for first-line therapy since 2004. Moreover, recent results have shown that the novel taxane cabazitaxel is able to prolong the overall survival of patients with mCRPC previously treated with docetaxel. Even though these taxanes display a favorable toxicity profile, their routine use in clinical practice requires knowledge about the most frequent and distinct adverse events that may result from their administration.
    No preview · Article · Sep 2014 · Critical reviews in oncology/hematology
  • Raphael Brandão Moreira · Rafael Aron Schmerling · Antônio Carlos Buzaid
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    ABSTRACT: Nos últimos anos vários medicamentos foram aprovados para o tratamento do melanoma metastático. Inicialmente o ipilimumabe, um anticorpo monoclonal cuja ação incrementa a resposta imune, dava início a uma série de avanços na imunoterapia do melanoma metastático e ofereceu uma perspectiva de ganho de sobrevida. Após o ipilimumabe tivemos o vemurafenibe, uma droga inibidora de BRAF, que também demonstrou ganho de sobrevida para os pacientes com melanoma que tivessem a mutação desse gene. Mais do que duas novas drogas, naquele momento se estabeleciam duas frentes de ação para a melhoria do tratamento do melanoma. O vemurafenibe, representando a terapia-alvo, ofereceu reduções rápidas da massa tumoral em pacientes com tumores com mutação do BRAF. Mais recentemente, outro inibidor de BRAF, dabrafenibe, e um inibidor de MEK, trametinibe, mostrou excelente atividade anti-tumoral quando combinados. A principal característica dessa terapia alvo combinada é a sua alta taxa de resposta (40-70%), resultando em melhora imediata. Neste artigo, vamos discutir a melhor forma de integrar as opções de tratamento disponíveis atualmente, incluindo IL-2 em altas doses, bioquimioterapia, quimioterapia sistêmica, ipilimumabe e terapia-alvo em diversos cenários clínicos.
    No preview · Article · Sep 2014
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    Full-text · Article · Mar 2014
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    ABSTRACT: Radiation-induced necrosis is a complication of brain irradiation. Treatment options are limited. The response to treatment with low-dose bevacizumab in 2 patients with radiation-induced necrosis was reported. Both patients with metastatic melanoma, aged 48 and 51 years, had significant symptomatic and radiological improvement with low-dose bevacizumab treatment. Doses as low as 5 mg/kg every 6 weeks and 7.5 mg/kg i.v. every 4 weeks were used and were highly effective. Low-dose bevacizumab is a solid option in the management of edema associated with radiation necrosis.
    Full-text · Article · Sep 2013 · Case Reports in Oncology
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    ABSTRACT: 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. 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. 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. 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.
    No preview · Article · Nov 2011 · Revista Panamericana de Salud Pública

Publication Stats

109 Citations
84.75 Total Impact Points

Institutions

  • 2014
    • Beneficência Portuguesa Hospital of São Paulo
      Potengy, Rio Grande do Norte, Brazil
  • 2011-2013
    • Hospital São José
      Cresciúma, Santa Catarina, Brazil
  • 2007-2009
    • Hospital Sirio Libanes
      Potengy, Rio Grande do Norte, Brazil