Publications by authors named "Angélica Nogueira-Rodrigues"

36 Publications

Characteristics of patients diagnosed with cervical cancer in Brazil: preliminary results of the prospective cohort EVITA study (EVA001/LACOG 0215).

Int J Gynecol Cancer 2021 Dec 29. Epub 2021 Dec 29.

Latin American Cooperative Oncology Group, Porto Alegre, Rio Grande do Sul, Brazil.

Objectives: Cervical cancer is the fourth most common cancer in women worldwide. Epidemiological and quality of life (QoL) data in patients with cervical cancer from low- and middle-income countries are scarce. We aimed to describe sociodemographic and clinicopathological characteristics and quality of life of patients with cervical cancer at diagnosis in Brazil.

Methods: EVITA is a prospective cohort study of newly diagnosed patients with cervical cancer from May 2016 to December 2017, stages I-IVB, from 16 Brazilian sites representing the five Brazilian regions. At baseline, medical evaluation was performed and European Organization for Research and Treatment of Cancer (EORTC) QLQ-CX24/C30 questionnaires were administered.

Results: A total of 631 patients were included. Mean±SD age was 49.3±13.9 years; skin color was non-white in 65.3%, and 68.0% had ≤8 years of formal education. In total, 85.1% of patients had a Pap smear. The main reasons reported by patients for not having a Pap smear were: lack of interest (46.9%), shame or embarrassment (19.7%), lack of knowledge (19.7%), and difficulty with access (9.1%). Most patients were diagnosed with locally advanced or metastatic disease (FIGO clinical stage II-IV in 81.8%- stage II in 35.2%, stage III in 36.1%, and stage IV in 10.5%). Patients with clinical stage III-IV had worse physical functioning and role functioning.

Conclusions: Cervical cancer in Brazil is usually diagnosed at an advanced stage. Most patients have low formal education and are unemployed. Lack of interest was identified as a main reason for not having a screening test, and limited access was reported as a reason by <10% of the patients. Awareness campaigns must be a governmental priority, specially focused on the needy population, along with wide access to treatment.
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http://dx.doi.org/10.1136/ijgc-2021-002972DOI Listing
December 2021

A demographic and clinical panorama of a sixteen-year cohort of soft tissue sarcoma patients in Brazil.

Sci Rep 2021 11 18;11(1):22501. Epub 2021 Nov 18.

Faculty of Medical Sciences of Minas Gerais (FCMMG), Alameda Ezequiel Dias 275, Belo Horizonte, MG, 30130-110, Brazil.

Little is known about soft tissue sarcomas (STS) in Brazil, once the federal statistics regarding estimates on incidence and mortality of the most common cancers that affect the Brazilian population currently do not include STS. This study aims to perform a broad evaluation and description of the epidemiological profile, access to treatment and main clinical outcomes of the Brazilian STS patient. A population-based cohort study of 66,825 patients who underwent procedures related to STS treatment registered in the Brazilian public health system (Sistema Único de Saúde, SUS) databases. Median age was 57 years, 30% of them older than 65 years and 50.7% of the cohort was female. The majority, 50,383 patients (75.4%), was diagnosed between 2008 and 2015. Most prevalent anatomic sites were upper and lower limbs (12.6%) and the registry of sarcomas without a specific location comprehended 29.7% of the cohort. The majority of patients resided in the Northeast (40.2% of the patients). Surgery was the first treatment modality in 77.7% of the cases. For survival analysis, only patients with stage and histological grade information were included. The 1-, 5- and 10-year survival rate of the patients was, respectively, 75.4% (95% CI = 74.1-76.7%), 43.4% (95% CI = 41.5-45.5%) and 18.6% (95% CI = 14.8-23.3%).
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http://dx.doi.org/10.1038/s41598-021-02032-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602280PMC
November 2021

Dealing with cancer screening in the COVID-19 era.

Rev Assoc Med Bras (1992) 2021 13;67Suppl 1(Suppl 1):86-90. Epub 2021 Aug 13.

Universidade Federal de Minas Gerais, School of Medicine - Belo Horizonte (MG), Brasil.

Objective: This article aims to alert health professionals for cancer screening in the face of the possibility of new waves of disease.

Methods: A narrative review was conducted through a search in MEDLINE, Lilacs, Chinese Biomedical Literature Database, and international medical societies publications.

Results: Breast cancer: in high-risk patients (confirmed familial cancer syndrome or with high-risk tools scores), clinicians should act according to usual recommendations; in average-risk individuals, consider screening with mammography with a longer time span (maximum of two years). Cervical cancer: women turning 25 years old who have already been immunized and with no previous Pap test can have the test postponed during the pandemic; if there is no previous dose of Human Papillomavirus vaccination, initiation of screening should be recommended following a more rigid approach for COVID prevention; in women over 30 years of age who have never participated in cervical screening, the first screening exam is also essential. Colorectal cancer: if the individual is at elevated risk for familial cancer, the screening with colonoscopy according to usual recommendations should be supported; if at average risk consider screening with Fecal Occult Blood Test. Prostate cancer: there is a trend to postpone routine prostate cancer screening until the pandemic subsides.

Conclusions: The decision to keep cancer screening must be discussed and individualized, considering the possibility of new waves of COVID-19.
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http://dx.doi.org/10.1590/1806-9282.67.Suppl1.20200889DOI Listing
August 2021

The utility of pretreatment systemic inflammatory response biomarkers on overall survival of cervical cancer patients stratified by clinical staging.

Eur J Obstet Gynecol Reprod Biol 2021 Sep 27;264:281-288. Epub 2021 Jul 27.

Brazilian National Cancer Institute (INCA), Rio de Janeiro, Brazil.

Objective: Inflammation plays a crucial role in the initiation and progression of many cancers. This study aimed to investigate the utility of pretreatmentneutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), derived neutrophil-lymphocyte ratio (dNLR), and a combination of PLR and NLR in predicting the risk of death according to clinical staging in cervical cancer (CC) patients.

Methods: A cohort study of women with CC, diagnosed and treated at a single cancer referral center in Brazil, from 2006 to 2009. A multivariate Cox regression analysis and ROC curve analysis accessed the predictive value of inflammatory response biomarkers in overall survival (OS). The median values of the biomarkers were used as cut-off points.

Results: A total of 1,266 patients were included in the study, 76.0% with locally advanced disease. After adjusting for clinical variables, NLR > 2.57, PLR ≥ 146.70, dNLR ≥ 1.778 and PLR + NLR in combination had equivalent performance in predicting worse OS, but only among patients with locally advanced disease (adjusted Hazard Ratio [aHR] = 1.453, 95% Confidence Interval [CI] = 1.227-1.722; p < 0.001; aHR = 1.429; 95% CI = 1.209-1.688; p < 0.001; aHR = 1.486, 95% CI = 1.257-1.756, p < 0.001, aHR = 1.731; 95% CI = 1.411-2.123; p < 0.001, respectively).

Conclusion: In conclusion, PLR, NLR, dNLR and PLR + NLR in combination presented equivalent performance in predicting OS in locally advanced CC patients. They are simple and readily available from routine blood tests, not entailing additional costs. PLR, NLR, dNLR and PLR + NLR in combination are strong prognostic biomarkers candidates in locally advanced CC and should be further explored in prospective trials.
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http://dx.doi.org/10.1016/j.ejogrb.2021.07.034DOI Listing
September 2021

Impact of the COVID-19 Pandemic on Oncology Clinical Research in Latin America (LACOG 0420).

JCO Glob Oncol 2021 04;7:649-658

Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil.

Purpose: COVID-19 has affected cancer care worldwide. Clinical trials are an important alternative for the treatment of oncologic patients, especially in Latin America, where trials can be the only opportunity for some of them to access novel and, sometimes, standard treatments.

Methods: This was a cross-sectional study, in which a 22-question survey regarding the impact of the COVID-19 pandemic on oncology clinical trials was sent to 350 representatives of research programs in selected Latin American institutions, members of the Latin American Cooperative Oncology Group.

Results: There were 90 research centers participating in the survey, with 70 of them from Brazil. The majority were partly private or fully private (n = 77; 85.6%) and had confirmed COVID-19 cases at the institution (n = 57; 63.3%). Accruals were suspended at least for some studies in 80% (n = 72) of the responses, mostly because of sponsors' decision. Clinical trials' routine was affected by medical visits cancelation, reduction of patients' attendance, reduction of other specialties' availability, and/or alterations on follow-up processes. Formal COVID-19 mitigation policies were adopted in 96.7% of the centers, including remote monitoring and remote site initiation visits, telemedicine visits, reduction of research team workdays or home office, special consent procedures, shipment of oral drugs directly to patients' home, and increase in outpatient diagnostic studies. Importantly, some of these changes were suggested to be part of future oncology clinical trials' routine, particularly the ones regarding remote methods, such as telemedicine.

Conclusion: To our knowledge, this was the first survey to evaluate the impact of COVID-19 on Latin American oncology clinical trials. The results are consistent with surveys from other world regions. These findings may endorse improvements in clinical trials' processes and management in the postpandemic period.
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http://dx.doi.org/10.1200/GO.20.00663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162498PMC
April 2021

Panorama of Gynecologic Cancer in Brazil.

JCO Glob Oncol 2020 10;6:1617-1630

Brazilian Gynecologic Oncology Group, Grupo EVA, Brazil.

Purpose: Little is known, or has been published previously, regarding consolidated data on the epidemiology of gynecologic cancers (GC) in Brazil. This article describes the incidence, morbidity, and mortality of women in Brazil affected with GC between the years of 2000 and 2017.

Methods: Incidence, morbidity, and mortality data from patients with a diagnosis of one out of the five most common GC, cervical (CC), uterine (UC), ovarian (OC), vulvar (VvC), and vaginal (VgC), were obtained from three governmental sources of data.

Results: From 2000 to 2015 CC, OC, and VgC incidence rates (IRs) decreased, whereas the IRs for UC and VvC remained relatively stable. Data from 382,932 women with GC were analyzed. Most patients presented with locally advanced or advanced disease at diagnosis: 60.1% of patients with CC, 31.2% of patients with UC, 67.2% of patients with OC, 45.2% of patients with VvC, and 67.0% of patients with VgC. Time from diagnosis to first treatment was ≥ 60 days in 58.0% of patients with CC, 58.5% of patients with UC, 27.0% of patients with OC, 55.3% of patients with VvC, and 52.7% of patients with VgC. Regarding mortality rates (MRs), with the exception of CC, UC, and VvC, which showed a slight decrease, MRs remained stable between 2000 and 2017.

Conclusion: A comparison with international data indicates that Brazilian patients are diagnosed with more advanced disease and face a longer delay between diagnosis and first treatment. Despite advances in screening and treatment, GC mortality has not decreased satisfactorily in this country.
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http://dx.doi.org/10.1200/GO.20.00099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605369PMC
October 2020

Delivering Cancer Care During the COVID-19 Pandemic: Recommendations and Lessons Learned From ASCO Global Webinars.

JCO Glob Oncol 2020 Sep;6:1461-1471

Department of Surgical Oncology, Gifu University, Graduate School of Medicine, Gifu, Japan.

Purpose: In response to the COVID-19 pandemic, the ASCO launched a Global Webinar Series to address various aspects of cancer care during the pandemic. Here we present the lessons learned and recommendations that have emerged from these webinars.

Methods: Fifteen international health care experts from different global regions and oncology disciplines participated in one of the six 1-hour webinars to discuss the latest data, share their experiences, and provide recommendations to manage cancer care during the COVID-19 pandemic. These sessions include didactic presentations followed by a moderated discussion and questions from the audience. All recommendations have been transcribed, categorized, and reviewed by the experts, who have also approved the consensus recommendations.

Results: The summary recommendations are divided into different categories, including risk minimization; care prioritization of patients; health care team management; virtual care; management of patients with cancer undergoing surgical, radiation, and systemic therapy; clinical research; and recovery plans. The recommendations emphasize the protection of patients and health care teams from infections, delivery of timely and appropriate care, reduction of harm from the interruption of care, and preparation to handle a surge of new COVID-19 cases, complications, or comorbidities thereof.

Conclusion: The recommendations from the ASCO Global Webinar Series may guide practicing oncologists to manage their patients during the ongoing pandemic and help organizations recover from the crisis. Implementation of these recommendations may improve understanding of how COVID-19 has affected cancer care and increase readiness to manage the current and any future outbreaks effectively.
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http://dx.doi.org/10.1200/GO.20.00423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529523PMC
September 2020

Primary results from CECILIA, a global single-arm phase II study evaluating bevacizumab, carboplatin and paclitaxel for advanced cervical cancer.

Gynecol Oncol 2020 10 4;159(1):142-149. Epub 2020 Aug 4.

Clínica Universidad de Navarra, Madrid, Spain.

Objective: Adding bevacizumab to cisplatin-paclitaxel for advanced cervical cancer significantly improves overall and progression-free survival. We evaluated bevacizumab with a widely used carboplatin-paclitaxel backbone.

Methods: Patients with metastatic/recurrent/persistent cervical cancer not amenable to curative surgery and/or radiotherapy received 3-weekly bevacizumab 15 mg/kg, paclitaxel 175 mg/m, and carboplatin AUC 5 until progression or unacceptable toxicity. Maintenance bevacizumab was allowed. Patients with ongoing bladder/rectal involvement, prior cobalt radiotherapy, a history of fistula/gastrointestinal perforation, or recent bowel resection/chemoradiation were excluded. The primary objective was to determine incidences of gastrointestinal perforation/fistula, gastrointestinal-vaginal fistula, and genitourinary fistula.

Results: Among 150 treated patients, disease at study entry was persistent in 21%, recurrent in 56%, and newly diagnosed metastatic in 23%. After 27.8 months' median follow-up, median bevacizumab duration was 6.7 months; 57% received maintenance bevacizumab. Seventeen patients (11.3%; 95% CI: 6.7-17.5%) experienced ≥1 perforation/fistula event: gastrointestinal perforation/fistula in 4.7% (1.9-9.4%), gastrointestinal-vaginal fistula in 4.0% (1.5-8.5%), and genitourinary fistula in 4.7% (1.9-9.4%). Of these, 16 were previously irradiated, several with ongoing radiation effects. The most common grade 3/4 adverse events were neutropenia (25%), anemia (19%), and hypertension (14%). Five patients (3%) had fatal adverse events. Objective response rate was 61% (95% CI: 52-69%), median progression-free survival was 10.9 (10.1-13.7) months, and median overall survival was 25.0 (20.9-30.4) months.

Conclusions: Bevacizumab can be combined with carboplatin-paclitaxel in the CECILIA study population. The fistula/gastrointestinal perforation incidence is in line with GOG-0240; efficacy results are encouraging.

Trial Registration Number: NCT02467907 (ClinicalTrials.gov).
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http://dx.doi.org/10.1016/j.ygyno.2020.07.026DOI Listing
October 2020

COVID-19 threatens to cause collateral delay in cancer diagnosis.

Sao Paulo Med J 2020 Jul-Aug;138(4):347-348

PhD. Physician, Núcleo de Oncologia da Bahia - Oncoclínicas Group, Salvador (BA), Brazil.

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http://dx.doi.org/10.1590/1516-3180.2020.033730062020DOI Listing
October 2020

Recommendations for Advancing the Diagnosis and Management of Hereditary Breast and Ovarian Cancer in Brazil.

JCO Glob Oncol 2020 03;6:439-452

Departmento de Genética, Universidade Federal do Rio Grande do Sul.

Purpose: The objective of this review was to address the barriers limiting access to genetic cancer risk assessment and genetic testing for individuals with suspected hereditary breast and ovarian cancer (HBOC) through a review of the diagnosis and management steps of HBOC.

Methods: A selected panel of Brazilian experts in fields related to HBOC was provided with a series of relevant questions to address before the multiday conference. During this conference, each narrative was discussed and edited by the entire group, through numerous drafts and rounds of discussion, until a consensus was achieved.

Results: The authors propose specific and realistic recommendations for improving access to early diagnosis, risk management, and cancer care of HBOC specific to Brazil. Moreover, in creating these recommendations, the authors strived to address all the barriers and impediments mentioned in this article.

Conclusion: There is a great need to expand hereditary cancer testing and counseling in Brazil, and changing current policies is essential to accomplishing this goal. Increased knowledge and awareness, together with regulatory actions to increase access to this technology, have the potential to improve patient care and prevention and treatment efforts for patients with cancer across the country.
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http://dx.doi.org/10.1200/JGO.19.00170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113069PMC
March 2020

Efficacy of Dexrazoxane in Preventing Anthracycline Cardiotoxicity in Breast Cancer.

JACC CardioOncol 2019 Sep 24;1(1):68-79. Epub 2019 Sep 24.

Department of Cardiology of Hospital das Clínicas, Federal University of Minas Gerais and Department of Internal Medicine, School of Medicine of Federal University of Minas Gerais, Belo Horizonte, Brazil.

Objectives: The authors performed a systematic review and meta-analysis of randomized and nonrandomized trials on the efficacy of dexrazoxane in patients with breast cancer who were treated with anthracyclines with or without trastuzumab.

Background: Breast cancer treatment with anthracyclines and trastuzumab is associated with an increased risk of cardiotoxicity. Among the various strategies to reduce the risk of cardiotoxicity, dexrazoxane is an option for primary prevention, but it is seldom used in clinical practice.

Methods: Online databases were searched from January 1990 up to March 1, 2019, for clinical trials on the use of dexrazoxane for the prevention of cardiotoxicity in patients with breast cancer receiving anthracyclines with or without trastuzumab. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model meta-analysis.

Results: Seven randomized trials and 2 retrospective trials with a total of 2,177 patients were included. Dexrazoxane reduced the risk of clinical heart failure (RR: 0.19; 95% CI: 0.09 to 0.40; p < 0.001) and cardiac events (RR: 0.36; 95% CI: 0.27 to 0.49; p < 0.001) irrespective of previous exposure to anthracyclines. The rate of a partial or complete oncological response, overall survival, and progression-free survival were not affected by dexrazoxane.

Conclusions: Dexrazoxane reduced the risk of clinical heart failure and cardiac events in patients with breast cancer undergoing anthracycline chemotherapy with or without trastuzumab and did not significantly impact cancer outcomes. However, the quality of available evidence is low, and further randomized trials are warranted before the systematic implementation of this therapy in clinical practice.
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http://dx.doi.org/10.1016/j.jaccao.2019.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352186PMC
September 2019

Interest In and Practices Related to Gynecologic Oncology among Members of the Brazilian Federation of Associations of Gynecology and Obstetrics.

Rev Bras Ginecol Obstet 2019 Jun 27;41(6):394-399. Epub 2019 Jun 27.

Department of Obstetrics and Gynecology, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista "Júlio de Mesquita Filho," Botucatu, SP, Brazil.

Objective:  The present study aims to obtain basic demographic information, the level of interest and of training in gynecology oncology among Brazilian obstetricians and gynecologists (OB-GYNs) to create a professional profile.

Methods:  An online questionnaire was sent to 16,008 gynecologists affiliated to the Brazilian Federation of Associations of Gynecology and Obstetrics (FEBRASGO, in the Portuguese acronym). We considered gynecologists dedicated to gynecologic oncology (OB-GYNs ONCO) those who self-reported that > 50% of their daily practice consists in working with women's cancer care.

Results:  A total of 1,608 (10%) of 16,008 FEBRASGO members responded. The OB-GYNs are concentrated in the southern and southeastern states of Brazil. Gynecologic oncology was considered the 8 greatest area of interest in gynecology among the OB-GYNs. A total of 95 (5.9%) of the OB-GYNs were considered OB-GYNs ONCO. Obstetricians and gynecologists are actively engaged in cancer care: > 60% of them dedicate up to 25% of their daily practice to oncology. The role of the physicians in screening and prevention, diagnosis, in the treatment of precancerous lesions, and in low complexity surgical procedures is notably high. Gynecologists dedicated to gynecologic oncology in Brazil have a heterogeneous, nonstandardized and short training period in gynecologic oncology. These professionals had a more significantly role in performing medium- and high-complexity operations compared with OB-GYNs (65.2% versus 34%, and 47.3% versus 8.4%, respectively).

Conclusion:  The role of OB-GYNs and of OB-GYNs ONCO appears to be complementary. Obstetricians and gynecologists act more often in screening and prevention and in low-complexity surgical procedures, whereas OB-GYNs ONCO are more involved in highly complex cases. Strategies to raise standards in cancer training and to encourage the recognition of gynecologic oncology as a subspecialty should be adopted in Brazil.
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http://dx.doi.org/10.1055/s-0039-1692467DOI Listing
June 2019

HPV Vaccination in Latin America: Global Challenges and Feasible Solutions.

Am Soc Clin Oncol Educ Book 2019 Jan 17;39:e45-e52. Epub 2019 May 17.

1 Federal University of Minas Gerais, Belo Horizonte, Brazil.

HPV vaccine programs in Latin America run the risk of repeating the problems associated with Papanicolaou (Pap) test programs, an efficient, life-saving tool that is unfortunately underutilized for cancer prevention, in low- and middle-income countries. There is a great need for vigilance in the ongoing implementation of the HPV vaccine in Latin America.
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http://dx.doi.org/10.1200/EDBK_249695DOI Listing
January 2019

Challenges in the diagnosis and treatment of gestational trophoblastic neoplasia worldwide.

World J Clin Oncol 2019 Feb;10(2):28-37

Department of Medical Oncology, Charing Cross Gestational Trophoblastic Disease Centre, Charing Cross Hospital, Imperial College London, London W6 8RF, United Kingdom.

Gestational trophoblastic neoplasia (GTN) is a rare tumor that originates from pregnancy that includes invasive mole, choriocarcinoma (CCA), placental site trophoblastic tumor and epithelioid trophoblastic tumor (PSTT/ETT). GTN presents different degrees of proliferation, invasion and dissemination, but, if treated in reference centers, has high cure rates, even in multi-metastatic cases. The diagnosis of GTN following a hydatidiform molar pregnancy is made according to the International Federation of Gynecology and Obstetrics (FIGO) 2000 criteria: four or more plateaued human chorionic gonadotropin (hCG) concentrations over three weeks; rise in hCG for three consecutive weekly measurements over at least a period of 2 weeks or more; and an elevated but falling hCG concentrations six or more months after molar evacuation. However, the latter reason for treatment is no longer used by many centers. In addition, GTN is diagnosed with a pathological diagnosis of CCA or PSTT/ETT. For staging after a molar pregnancy, FIGO recommends pelvic-transvaginal Doppler ultrasound and chest X-ray. In cases of pulmonary metastases with more than 1 cm, the screening should be complemented with chest computed tomography and brain magnetic resonance image. Single agent chemotherapy, usually Methotrexate (MTX) or Actinomycin-D (Act-D), can cure about 70% of patients with FIGO/World Health Organization (WHO) prognosis risk score ≤ 6 (low risk), reserving multiple agent chemotherapy, such as EMA/CO (Etoposide, MTX, Act-D, Cyclophosphamide and Oncovin) for cases with FIGO/WHO prognosis risk score ≥ 7 (high risk) that is often metastatic. Best overall cure rates for low and high risk disease is close to 100% and > 95%, respectively. The management of PSTT/ETT differs and cure rates tend to be a bit lower. The early diagnosis of this disease and the appropriate treatment avoid maternal death, allow the healing and maintenance of the reproductive potential of these women.
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http://dx.doi.org/10.5306/wjco.v10.i2.28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390119PMC
February 2019

Mutation screening of TP53, CHEK2 and BRCA genes in patients at high risk for hereditary breast and ovarian cancer (HBOC) in Brazil.

Breast Cancer 2019 May 11;26(3):397-405. Epub 2018 Dec 11.

Universidade Federal de São João del Rei (UFSJ), 400 Sebastião Gonçalves Coelho Ave., Chanadour, Divinópolis, MG, 35501-296, Brazil.

Background: Few studies related to hereditary breast and ovarian cancer syndrome (HBOC) have been conducted in Brazil, and they are restricted to only small areas of the country. Here, we report the mutation profile of BRCA1/2, CHEK2 and TP53 genes in a cohort from Minas Gerais state.

Methods: These genes from 44 patients at high risk for HBOC were screened through high-resolution melting and/or sequencing. The pathogenicity of the alterations was checked using ClinVar database and bioinformatics programs.

Results: In BRCA genes we identified 46 variants, 38 without clinical significance and 8 pathogenic mutations including a new pathogenic mutation in BRCA1 gene (c.4688_4694delACCTGGAinsG). The most prevalent pathogenic mutation was c.4829_4830delTG, in the BRCA2 gene. This mutation was not described in the Brazilian population up to now and in this study, it was described with a prevalence of 6.8%. The p.R337H mutation in TP53 gene was found in one patient clinically diagnosed as HBOC and without clinical criteria for Li-Fraumeni syndrome. In CHEK2 gene, the undescribed variant c.485A > G was found and it presents as probably pathogenic through in silico analyses. Pathogenic mutations were found in 29.5% of the patients, 11.3% in BRCA1, 15.9% in BRCA2 and 2.3% in TP53 gene.

Conclusions: Brazilian population is one of the most heterogeneous in the world and the mutational profile knowledge of genes related to HBOC from different regions can contribute to the definition of more cost-effective strategies for the prevention, identification and treatment of cancer.
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http://dx.doi.org/10.1007/s12282-018-00938-zDOI Listing
May 2019

Endometrial Cancer in Brazil: Preparing for the Rising Incidence.

Rev Bras Ginecol Obstet 2018 Oct 23;40(10):577-579. Epub 2018 Oct 23.

Global Cancer Institute, Boston, Masachussets, United States.

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http://dx.doi.org/10.1055/s-0038-1673644DOI Listing
October 2018

Disparities in Breast, Lung, and Cervical Cancer Trials Worldwide.

J Glob Oncol 2018 09;4:1-11

Ramya Ramaswami, Imperial College London, Hammersmith Hospital, London, United Kingdom; Eduardo Paulino, Adriana Barrichello, Angelica Nogueira-Rodrigues, Alexandra Bukowski, Jessica St. Louis, and Paul E. Goss, The Global Cancer Institute; and Massachusetts General Hospital, Boston, MA.

Purpose: As cancer burden has risen worldwide, physicians, patients, and their advocates have become aware that the clinical cancer trial research paradigm is not ubiquitous. Furthermore, the number and characteristics of trials that are registered in low- and middle-income countries (LMICs) compared with that in high-income countries (HICs) are unknown.

Methods: We collected retrospective data on trials for breast, lung, and cervical cancer registered in ClinicalTrials.gov or with the WHO International Clinical Trial Registry Platform between 2010 and 2017. The data were then classified as trials within LMICs or HICs using definitions from the World Bank.

Results: Included in these analyses were 6,710 trials, of which 3,164 (47%) were breast cancer trials, 3,283 (49%) were lung cancer trials, and 263 (4%) were cervical cancer trials. There were 1,951 (29%) trials from LMICs and 4,759 (71%) trials from HICs ( P < .001). Although the proportion of phase III trials in HICs versus LMICs was similar (18% v 17%; P = .66), the number of phase I trials in LMICs was significantly lower than that of HICs (20% v 2%; P < .001). For several LMICs with the highest mortality-to-incidence ratios for breast, lung, or cervical cancer, there were no cancer trials registered in the registration data bases searched for this work.

Conclusion: There are differences in access to cancer clinical trials in LMICs compared with HICs. Several factors, such as excessive cost and a lack of infrastructure and expertise, may explain these differences.
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http://dx.doi.org/10.1200/JGO.17.00226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223472PMC
September 2018

Lack of Impact of Race Alone on Cervical Cancer Survival in Brazil

Asian Pac J Cancer Prev 2018 May 26;19(5):1209-1214. Epub 2018 May 26.

Faculdade de Medicina da UFMG. Belo Horizonte, Minas Gerais, Brazil. Email:

Objective: To analyze differences in survival between black and non-black women diagnosed with cervical cancer and treated at the National Cancer Institute in Brazil. Methods: This retrospective cohort study was conducted using medical records of patients who were treated for cervical cancer between 2006 and 2009 at the Brazilian National Cancer Institute - Rio de Janeiro - Brazil. The clinical and epidemiological characteristics of black and non-black patients were compared using the chi-square test. Survival functions over five years were calculated using the Kaplan-Meier estimator and compared using the log-rank test. Associations between race and mortality risk were analyzed using the Cox proportional hazards model. P-values <0.05 were considered statistically significant. Results: The study included 1,482 women, of whom 188 (12.7%) were black, 1,209 (81.6%) were non-black and 85 (5.7%) were of unspecified race. The age at diagnosis of the patients ranged from 19 to 84 years (mean 50.1 years; SD±13.2). Hemoglobin <12 g/dL at the time of diagnosis (p=0.008) and absence of surgery as primary treatment (p = 0.005) were more frequent among black women. Cox analysis adjusted for these two factors showed no statistically significant difference in the mortality risk associated with cervical cancer among black and non-black women (HR=1.1 95% CI 0.9-1.5; p=0.27). Conclusion: After adjusting for hemoglobin levels and surgery, race alone was not shown to be a prognostic factor for patients with cervical cancer.
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http://dx.doi.org/10.22034/APJCP.2018.19.5.1209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031817PMC
May 2018

The Challenge of Evaluating Adnexal Masses in Patients With Breast Cancer.

Clin Breast Cancer 2018 08 12;18(4):e587-e594. Epub 2018 Mar 12.

Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil. Electronic address:

This narrative literature review addresses the problem of an adnexal mass discovered during the course of breast cancer (BC) care, which may represent a benign condition, a metastatic process, or a primary ovarian cancer (OC), clinical scenarios associated with distinct physiopathology and prognosis. Furthermore, the coexistence of BC and OC in the same patient may be owing to a hereditary disorder, deserving specific management strategies and counseling. The initial detection and evaluation of an adnexal mass in a patient with BC requires a high index of suspicion, and the initial workup should include a thorough medical history and physical examination, measurement of tumor markers, complete blood count, and imaging tests. Transvaginal ultrasonography remains the standard tool, and findings suggestive of malignancy include bilateral tumors, thick septations, predominance of a solid component, Doppler flow to the solid component, and ascites. From the pathology point of view, features that are suggestive of metastatic disease include bilaterality, mild ovarian enlargement, vascular emboli, no omental deposits, and the absence of transition from benign to malignant epithelium. Although there is a considerable overlap in OC and BC immunohistochemical profiles, BC usually stain positive for GCDFP-15 and negative for vimentine, PAX8, and WT1, and OC often stain positive for CK7, PAX8, WT1, and to mesothelin. Genetic counselling should always be indicated in this clinical scenario. In conclusion, diagnostic spectrum of an ovarian mass in a patient with BC is broad, and a systematic multi-professional strategy is necessary to conduct these challenging cases.
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http://dx.doi.org/10.1016/j.clbc.2018.03.006DOI Listing
August 2018

Gynecologic cancer in Brazil and the law of sixty days.

J Gynecol Oncol 2018 05 1;29(3):e44. Epub 2018 Mar 1.

Instituto Nacional do Câncer (INCA), Hospital do Câncer II, Santo Cristo, Rio de Janeiro, Brazil.

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http://dx.doi.org/10.3802/jgo.2018.29.e44DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920227PMC
May 2018

Immunohistochemical WWOX Expression and Association with Angiogenesis, p53 Expression, Cell Proliferation and Clinicopathological Parameters in Cervical Cancer.

Rev Bras Ginecol Obstet 2018 Feb 8;40(2):79-85. Epub 2018 Jan 8.

Universidade Federal Minas Gerais, Belo Horizonte, MG, Brazil.

Objective:  The current study evaluated the expression of WW domain-containing oxidoreductase (WWOX), its association with clinicopathological features and with p53, Ki-67 (cell proliferation) and CD31 (angiogenesis) expression in patients with invasive cervical squamous cell carcinoma (ICSCC). To the best of our knowledge, no other study has evaluated this association.

Methods:  Women with IB stage-ICSCC ( = 20) and women with uterine leiomyoma ( = 20) were prospectively evaluated. Patients with ICSCC were submitted to type B-C1 radical hysterectomy and pelvic lymphadenectomy. Patients in the control group underwent vaginal hysterectomy. Tissue samples were stained with hematoxylin and eosin for histological evaluation and protein expression was detected by immunohistochemistry studies.

Results:  The WWOX expression was significantly lower in the tumor compared with the expression in the benign cervix ( = 0.019). The WWOX expression was inversely associated with the CD31 expression in the tumor samples ( = 0.018). There was no association between the WWOX expression with the p53 expression ( = 0.464) or the Ki-67 expression ( = 0.360) in the samples of invasive carcinoma of the cervix. There was no association between the WWOX expression and tumor size ( = 0.156), grade of differentiation ( = 0.914), presence of lymphatic vascular invasion ( = 0.155), parametrium involvement ( = 0.421) or pelvic lymph node metastasis ( = 0.310) in ICSCC tissue samples.

Conclusion:  The results suggested that WWOX may be involved in ICSCC carcinogenesis, and this marker was associated with tumor angiogenesis.
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http://dx.doi.org/10.1055/s-0037-1618597DOI Listing
February 2018

Patient Navigation to Improve Access to Breast Cancer Care in Brazil.

J Glob Oncol 2017 Oct 30;3(5):433-437. Epub 2016 Nov 30.

, , and , Avon International Breast Cancer Research Program, Massachusetts General Hospital; , , , , , , , and , The Global Cancer Institute, Boston, MA; and , Instituto Nacional de Câncer José Alencar Gomes da Silva; Rio de Janeiro; , Federal University of Minas Gerais, Belo Horizonte, Brazil; and and , Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

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http://dx.doi.org/10.1200/JGO.2016.006726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5646893PMC
October 2017

Barriers to Primary Debulking Surgery for Advanced Ovarian Cancer in Latin America.

Int J Gynecol Cancer 2017 10;27(8):1645-1649

*Brazilian National Cancer Institute; †Grupo COI, Rio de Janiero, Brazil; ‡Global Cancer Institute, Boston, MA; §Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; ∥Wilheminen Hospital, Vienna Austria; ¶MGH-Avon Global Cancer Program; and #Harvard Medical School, Boston, MA.

Ovarian cancer is gynecologic tumor with particularly high mortality because it is usually diagnosed in advanced stages. In Latin America and the Caribbean, it is the eighth most common malignancy in women, with an estimated 18,000 new cases and 11,500 deaths annually. Standard of care for women diagnosed with advanced ovarian cancer (AOC) is primary cytoreductive surgery followed by systemic chemotherapy using a combination of paclitaxel plus carboplatin. To pursue upfront surgery, highly specialized and well-trained gynecologic oncologists are required, in addition with well-equipped hospitals. Neoadjuvant chemotherapy (NACT) has been gaining greater acceptance in the past decade for patients with AOC. Two phase III randomized clinical trials have demonstrated that NACT is noninferior to primary cytoreductive surgery for women with stages III and IV epithelial ovarian cancer, and since publication of these results, NACT is more commonly used. Apart from medical reasons of inoperability and unresectability, there may be nonmedical barriers to upfront debulking surgery in clinical practice. These barriers include inadequate expertise of the surgeon, inadequate resources, and/or barriers to access. The aim of this article was to discuss patterns of care and barriers to upfront ovarian debulking surgery, as well as a possible shift toward overuse of NACT as the primary approach for patients with AOC (stages III and IV) in Latin America.
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http://dx.doi.org/10.1097/IGC.0000000000001098DOI Listing
October 2017

A Rare Presentation of Primary Breast Carcinoma in the Vulva: A Case Report and Literature Review.

Clin Breast Cancer 2018 06 23;18(3):e291-e294. Epub 2017 Jun 23.

The Global Cancer Institute, Boston, MA; MGH-Avon Global Breast Cancer Program, Boston, MA; Harvard Medical School, Boston, MA. Electronic address:

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http://dx.doi.org/10.1016/j.clbc.2017.06.004DOI Listing
June 2018

Systematic Review and Network Meta-Analysis of Bevacizumab Plus First-Line Topotecan-Paclitaxel or Cisplatin-Paclitaxel Versus Non-Bevacizumab-Containing Therapies in Persistent, Recurrent, or Metastatic Cervical Cancer.

Int J Gynecol Cancer 2017 07;27(6):1237-1246

*Optum, Eden Prairie, MN; †Mapi Group, Uxbridge; and ‡University College London Hospitals, London, UK; §Federal University, Belo Horizonte; and ∥State University of Campinas, Campinas, Brazil; and ¶F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Objective: Despite advances in cervical cancer prevention and diagnosis, outcomes for patients given a diagnosis of advanced and recurrent disease are poor. In the GOG240 trial, the addition of bevacizumab to paclitaxel-topotecan or paclitaxel-cisplatin has been shown to prolong survival compared with paclitaxel-topotecan or paclitaxel-cisplatin in patients with persistent, recurrent, or metastatic disease. However, standards of care vary between regions and countries. The purpose of this systematic review and network meta-analysis was to enable a comparison between bevacizumab + chemotherapy with multiple monotherapy or combination chemotherapy regimens in the treatment for women with advanced, recurrent, or persistent cervical cancer.

Methods/materials: A systematic literature review was conducted to identify randomized or nonrandomized controlled trials of patients with recurrent, persistent, or metastatic cervical cancer published in English from 1999 to 2015. A feasibility study was performed to assess the heterogeneity of the trials, and a network meta-analysis was conducted. Fixed- and random-effects models were fitted to calculate the hazard ratio for overall survival (OS) for all pairwise comparisons and ranking of all interventions.

Results: Twenty-three studies (19 trials) met inclusion criteria and were included in the review. Sample sizes ranged from 69 to 452, and median patient age ranged from 45 to 53 years. There was a trend toward prolonged OS with cisplatin-paclitaxel-bevacizumab and topotecan-paclitaxel-bevacizumab compared with all non-bevacizumab-containing therapies. Cisplatin-paclitaxel-bevacizumab had the highest probability of being the most efficacious compared with all regimens (68.1%), and cisplatin monotherapy had the lowest (0%).

Conclusions: The results of this network meta-analysis show that bevacizumab in combination with paclitaxel-topotecan or paclitaxel-cisplatin is likely to prolong OS over other non-bevacizumab-containing chemotherapies (eg, paclitaxel-carboplatin), which were not included in the GOG240 trial. In patients with advanced, persistent, and recurrent cervical cancer, cisplatin-paclitaxel-bevacizumab and topotecan-paclitaxel-bevacizumab showed the highest efficacy in all regimens investigated in this analysis.
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http://dx.doi.org/10.1097/IGC.0000000000001000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499964PMC
July 2017

Patterns of Care and Outcome of Elderly Women Diagnosed With Cervical Cancer in the Developing World.

Int J Gynecol Cancer 2016 09;26(7):1246-51

*National Cancer Institute, Rio de Janeiro; †EVA, Brazilian Group of Gynecologic Oncology; and ‡University of Itauna, Minas Gerais, Brazil.

Scarce data exist about the impact of age in cervical cancer (CC) patients in the developing world. The objective of the current study was to examine the patterns of care and outcome of elderly patients treated in a developing country. Medical records of patients treated from 2006-2009 at the Brazilian National Cancer Institute were reviewed. Patients were divided between women 70 years or older and women younger than 70 years. The χ tests were used and odds ratios were calculated. Survival was examined using the Kaplan-Meier method. Single and multivariate Cox proportional hazards modeling were used. A total of 1482 patients were analyzed: 1339 patients younger than 70 years and 143 patients 70 years or older. A marked difference in treatment was noted, even after stratifying by disease stage. Only 21% of the older patients underwent surgical treatment compared with 27.6% of the younger. After adjusting for confounding variables, the hazard ratio for death from CC in the elderly was 1.05 (95% confidence interval, 0.81-1.36; P = 0.11). These results corroborate previous data from developed countries: elderly patients have more advanced disease at diagnosis, and age is an important factor in the allocation of treatment for patients with CC. Worse outcome seemed to be mainly the result of more advanced stage and treatment allocation rather than age itself.
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http://dx.doi.org/10.1097/IGC.0000000000000756DOI Listing
September 2016

Cervical cancer control in Latin America: A call to action.

Cancer 2016 Feb 15;122(4):502-14. Epub 2015 Dec 15.

Harvard Medical School, Boston, Massachusetts.

Cervical cancer (CC) is second most common cause of cancer in Latin America and is a leading cause of cancer mortality among women. In 2015, an estimated 74,488 women will be diagnosed with CC in Latin America and 31,303 will die of the disease. CC mortality is projected to increase by 45% by 2030 despite human papillomavirus (HPV) vaccination and screening efforts. In this setting, the goal was of the current study was to examine CC control efforts in Latin America and identify deficiencies in these efforts that could be addressed to reduce CC incidence and mortality. The authors found that HPV vaccination has been introduced in the majority of Latin American countries, and there is now a need to monitor the success (or shortcomings) of these programs and to ensure that these programs are sustainable. This topic was also reviewed in light of emerging data demonstrating that visual inspection with acetic acid and HPV DNA testing without Papanicolaou tests have efficacy from a screening perspective and are good alternatives to cytology-based screening programs. Overall, there is a need to build capacity for CC control in Latin America and the best strategy will depend on the country/region and must be tailored to meet the needs of the population as well as available resources.
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http://dx.doi.org/10.1002/cncr.29813DOI Listing
February 2016

Screening of the BRCA1 gene in Brazilian patients with breast and/or ovarian cancer via high-resolution melting reaction analysis.

Fam Cancer 2016 Apr;15(2):173-81

Universidade Federal de São João del Rei (UFSJ), 400 Sebastião Gonçalves Coelho Ave., Chanadour, Divinópolis, MG, 35501-296, Brazil.

The aim of this study was to evaluate the profile of BRCA1 mutations among cancer-affected Brazilian women from the Midwest region of Minas Gerais state with clearly defined risk factors for hereditary breast and ovarian cancer (HBOC) syndrome. In this Brazilian region, the first Center for Hereditary Cancer Control began operation in 2011, and 90% of patients receive assistance from the public health service. Eighteen patients at high risk for HBOC were subjected to molecular analysis. Primers were designed for 22 coding exons of the gene; DNA was extracted; and real-time PCR followed by high-resolution melting reaction was performed. The amplicons were sequenced to confirm the identified profiles. Only exon 11 was directly sequenced due its length. Multiplex ligation-dependent probe amplification (MLPA) was performed for those patients in whom no pathogenic mutations were found. Among the 14 alterations identified in this study, the c.5263_5264insC pathogenic mutation was present in two patients (11.1%). Four alterations showed no clinical relevance; one exhibited inconclusive clinical relevance according to the examined databases; and eight alterations presented a divergent classification between the databases. No deletions or duplications were found using the MLPA technique. The HRM methodology was highly sensitive in identifying variants in the BRCA1 gene and can dramatically reduce the amount of sequencing required to identify germline mutations in BRCA genes, enabling cheaper tests and increasing their availability to Brazilian women assisted by the public health service.
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http://dx.doi.org/10.1007/s10689-015-9858-0DOI Listing
April 2016

Progress and remaining challenges for cancer control in Latin America and the Caribbean.

Lancet Oncol 2015 Oct;16(14):1405-38

The Global Cancer Institute, Boston, MA, USA; Avon International Breast Cancer Research Program, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address:

Cancer is one of the leading causes of mortality worldwide, and an increasing threat in low-income and middle-income countries. Our findings in the 2013 Commission in The Lancet Oncology showed several discrepancies between the cancer landscape in Latin America and more developed countries. We reported that funding for health care was a small percentage of national gross domestic product and the percentage of health-care funds diverted to cancer care was even lower. Funds, insurance coverage, doctors, health-care workers, resources, and equipment were also very inequitably distributed between and within countries. We reported that a scarcity of cancer registries hampered the design of credible cancer plans, including initiatives for primary prevention. When we were commissioned by The Lancet Oncology to write an update to our report, we were sceptical that we would uncover much change. To our surprise and gratification much progress has been made in this short time. We are pleased to highlight structural reforms in health-care systems, new programmes for disenfranchised populations, expansion of cancer registries and cancer plans, and implementation of policies to improve primary cancer prevention.
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http://dx.doi.org/10.1016/S1470-2045(15)00218-1DOI Listing
October 2015
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