92 results on '"G. Werutsky"'
Search Results
2. EP03.01-003 Clinical Features and Molecular Profile of Advanced Non-small Cell Lung Cancer in Latin America: LATINO Lung (LACOG 0116)
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G. Werutsky, O. Arrieta, M. Zukin, C. Mathias, A.C.Z. Gelatti, D.L. Kaen, A.F. Cardona, E. Cronemberg, C. Campos, L.H. Araújo, H. de Andrade, S.L. Reichow, V.C. de Lima, P. Pacheco, J.C. Coelho, G. Borges, A. Silva, E. Mascarenhas, A. Quiroga, L. Fein, F.N.G. de Oliveira, J. Pastorello, C. Dutra, I. Morbeck, F.S.M. Cruz, T.F. Rebelatto, R. Gomes, and C.H. Barrios
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Pulmonary and Respiratory Medicine ,Oncology - Published
- 2022
3. PO-1230 Delay in postoperative radiation in pts with breast cancer in Brazil: a sub-analysis of AMAZONA III
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J. Prestes, D. Rosa, C. Barrios, J. Bines, G. Werutsky, E. Cronemberger, G. Queiroz, S. Simon, T. Rebelatto, R. de Jesus, M. da Silva, and G. Marta
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Oncology ,Radiology, Nuclear Medicine and imaging ,Hematology - Published
- 2022
4. Abstract P5-23-02: Quality of life (QoL) in male breast cancer (BC): Prospective study of the EORTC10085/TBCRC029/BIG2-07/NABCG International male BC program
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E van Leeuwen-Stok, G Werutsky, K Aalders, Sharon H. Giordano, Kathryn J. Ruddy, Nizet H. Dijkstra, C. Poncet, Corneel Coens, Fatima Cardoso, C. P. Schroder, D Morgenstern, Antonio C. Wolff, C. Van Poznak, Barbro Linderholm, Henry L. Gomez, Konstantinos Tryfonidis, and Vesna Bjelic-Radisic
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Cancer Research ,medicine.medical_specialty ,business.industry ,Psychological intervention ,Cancer ,medicine.disease ,humanities ,Breast cancer ,Oncology ,Quality of life ,Internal medicine ,Male breast cancer ,medicine ,Stage (cooking) ,business ,Prospective cohort study ,Sexual function - Abstract
Introduction: Male BC is a rare disease (dx) for which management is extrapolated from trials in female BC. Comprehensive prospective data about QoL in men with BC could inform treatment. The international Male BC Consortium conducted a prospective registry of male BC patients of all stages who newly presented to a participating center between October 2013 and February 2017. A QoL substudy was conducted as part of this registry at most participating sites. Methods: Informed consent for participation in the QoL substudy was requested from new enrollees. Those who consented were asked to complete a survey including the EORTC QLQ-C30 and BR23 (breast cancer specific module), adapted by replacing female-specific items with male-specific sexual activity/function items from the prostate module (PR25). Outcomes were scored according to standard EORTC QLQ procedures on a 0-100 scale (with higher scores on QoL/functioning scales representing better QoL and functioning, and higher scores on symptom scales representing worse symptoms). Forms were analyzed centrally by EORTC. In order to compare to female BC, we used reference data from 2782 mixed age (62% under age 60) women with BC (of whom 1,147 had recurrent or metastatic dx, and 464 had stage 1-2 dx) reported in the EORTC QLQ-C30 Reference Values manual (2008). Results: A total of 557 men were enrolled in EORTC10085, 445 at sites participating in the QoL substudy. Consent forms were received from 422/445 (95%) for the substudy. Baseline survey (required to be completed within 30 days of enrollment) compliance was 85% (359/422). Median age at diagnosis was 67 years. There were 111 men (45%) with node-positive M0/MX dx and 27 men (8%) with M1 dx. Their median global health status score at baseline was 75 (IQR 67-83), higher than that documented historically in female BC (67, with IQR 50-83, in both the 2782 women with mixed stage and the subgroup of 464 with stage 1-2 tumors). The participating men's median social functioning score was 100 (IQR 67-100), also higher than the 83.3 (IQR 67-100) reported in mixed stage female BC patients, though no different than the 100 (IQR 67-100) found in women with stage 1-2 dx. Men's most commonly reported symptoms included fatigue (median score 13.9, IQR 0-33), insomnia (median score 0, IQR 0-33), and pain (median score 0, IQR 0-33), for which women's median scores were 33 (IQR 11-44), 33 (IQR 0-33), and 17 (IQR 0-50) with mixed stage dx, and 22 (IQR 0-33), 33 (IQR 0-33), and 17 (IQR 0-33) with stage 1-2 dx. Men's median sexual activity score was 33.3 (IQR 0-50), with less sexual activity reported by older patients and men with M1 dx. In those who were sexually active, median sexual function score was 83 (IQR 75-92), with no difference by age or stage. Conclusions: QoL and symptom burden in male BC patients appears no worse (and possibly better) than that in female patients. Future analyses of 1- and 5-year surveys from this study will assess the impact of specific treatments on changes in symptoms and QoL over time. These data will be useful in future efforts to tailor treatments and target interventions for male BC. Funding: Breast Cancer Research Foundation, Dutch Pink Ribbon Foundation, Swedish BRO, and EBCC Council. Citation Format: Schroder C, Cardoso F, Dijkstra N, van Leeuwen-Stok E, Linderholm B, Morgenstern D, Van Poznak C, Wolff AC, Poncet C, Gomez HL, Aalders K, Bjelic-Radisic V, Werutsky G, Tryfonidis K, Coens C, Giordano SH, Ruddy KJ. Quality of life (QoL) in male breast cancer (BC): Prospective study of the EORTC10085/TBCRC029/BIG2-07/NABCG International male BC program [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-23-02.
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- 2018
5. Nine-year survival outcome of neoadjuvant lapatinib with trastuzumab for HER2-positive breast cancer (NeoALTTO, BIG 1-06): final analysis of a multicentre, open-label, phase 3 randomised clinical trial
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J. Townend, J Huober, Judith R. Kroep, Martine Piccart-Gebhart, S. Di Cosimo, Anna Manukyants, Cristina Saura, Florentine Hilbers, David Cameron, Judith M Bliss, G. Werutsky, M.A. Colleoni, A.Moreno Aspitia, V Van Dooren, P. Nuciforo, E. de Azumbaja, A. Ferro, R. D. Gelber, and V. Moebus
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Lapatinib ,Survival outcome ,Clinical trial ,Trastuzumab ,Internal medicine ,HER2 Positive Breast Cancer ,Medicine ,Open label ,business ,medicine.drug - Published
- 2020
6. The European Organization for Research and Treatment for Cancer (EORTC) strategy for quality assurance in surgical clinical research: Assessment of the past and moving towards the future
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G. Werutsky, L. Verleye, Laurence Collette, E. Tanis, Carmela Caballero, M. den Dulk, Denis Lacombe, and C. Schuhmacher
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medicine.medical_specialty ,Pathology ,Biomedical Research ,Quality Assurance, Health Care ,Standardization ,media_common.quotation_subject ,Terminology ,03 medical and health sciences ,0302 clinical medicine ,Clinical Protocols ,Neoplasms ,Humans ,Medicine ,Medical physics ,Quality (business) ,030212 general & internal medicine ,media_common ,Protocol (science) ,business.industry ,General Medicine ,Surgical procedures ,humanities ,Europe ,Surgical Oncology ,Clinical research ,Oncology ,Data extraction ,030220 oncology & carcinogenesis ,Surgery ,business ,Quality assurance - Abstract
Aims Quality assurance (QA) in a surgical trial must be planned and implemented from study development to completion. Elements of quality must be consistently described in a protocols, case report forms (CRFs) and reported in publications. The purpose of this review was to evaluate the most common surgical parameters and how consistently they were described in EORTC study documents where surgery was included. This was the preliminary step in mapping out the challenges of developing a surgical QA strategy in EORTC. Methods A systematic review of EORTC surgical protocols from 1980 to 2013 was performed. Two independent reviewers selected and reviewed the protocols. Data extraction was done using a questionnaire developed by EORTC QA committee. The results were compared across the time period. Results The most common quality parameters described in protocols were surgical technique, definition of resectability, surgical margins and methods of assessing adverse events using the Common Terminology Criteria for Adverse Event (CTCAE). However, these were not consistently reported in publications. A general improvement in the method of protocol development was observed since year 2000 after standardization measures by EORTC. A new surgical chapter template has been proposed. Conclusion There is a need to consistently define and report surgical parameters from protocol development to publication as a first step to QA. A standard surgical chapter in the EORTC protocol template can help address this need. A framework to consistently implement QA for future surgical trials is needed and the rationale for this is described in this review.
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- 2016
7. Exploiting HPV-Induced Carcinogenesis for a Rational Drug Development in Cervical Cancer
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Alvaro Henrique Ingles Garces, Carlos Gil Ferreira, G. Werutsky, Andreia Cristina de Melo, and Angélica Nogueira-Rodrigues
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Oncology ,Cancer Research ,medicine.medical_specialty ,020205 medical informatics ,Bevacizumab ,Carcinogenesis ,Uterine Cervical Neoplasms ,Antineoplastic Agents ,02 engineering and technology ,Bioinformatics ,medicine.disease_cause ,Molecular oncology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Drug Discovery ,0202 electrical engineering, electronic engineering, information engineering ,medicine ,Humans ,030212 general & internal medicine ,Papillomaviridae ,Pharmacology ,Cervical cancer ,Cisplatin ,business.industry ,Papillomavirus Infections ,HPV infection ,medicine.disease ,Clinical trial ,Drug development ,Drug Design ,Female ,business ,medicine.drug - Abstract
Cervical carcinomas are almost universally associated with high-risk human papillomavirus (HPV) infections, and are a leading cause of cancer death in women worldwide. Since the late 1990s, when a spate of studies reported the benefit of cisplatin-based chemotherapy, there had been a dearth of clinical trials in cervical cancer (CC). More effective therapies in locally advanced and recurrent or metastatic CC are an urgent clinical need. In the era of molecular oncology one should look beyond conventional chemoradiation and chemotherapy for locally advanced and advanced CC. The fact that the initiating oncogenic insult, infection with a high-risk HPV and viral oncoprotein expression is common to almost all CC offers unique opportunities for disease control. Diverse biologic pathways with an implication in the development and progression of CC are being explored. For the first time, increase in overall survival has recently been obtained for advanced CC patients with a target drug, the antiangiogenic agent bevacizumab, and durable complete responses after HPV-targeted adoptive T cell therapy in metastatic CC patients were achieved. In this review, we will summarize molecular aspects of HPV infection focusing on potential targets to stop the carcinogenic process, present updated drug development data, and discuss challenges and prospects for the future.
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- 2016
8. Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial
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Jan Bogaerts, Jonas Bergh, P. Rouanet, Etienne Brain, David Cameron, Per-Uno Malmström, Tanja Cufer, Saskia Litière, Martine Piccart, Jacek Jassem, Alexandre Bodmer, Gaëtan MacGrogan, Hervé Bonnefoi, C. Moldovan, G. Werutsky, Thierry Petit, Pierre Fumoleau, Mario Campone, Khalil Zaman, Elisabeth Luporsi, and EORTC 10994/BIG 1-00 Study investigators
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Adult ,Oncology ,medicine.medical_specialty ,Anthracycline ,medicine.medical_treatment ,Breast Neoplasms ,Disease-Free Survival ,Breast cancer ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Neoadjuvant therapy ,Proportional Hazards Models ,Taxane ,business.industry ,Proportional hazards model ,Carcinoma, Ductal, Breast ,Hazard ratio ,Original Articles ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Chemotherapy regimen ,Neoadjuvant Therapy ,Treatment Outcome ,Docetaxel ,Chemotherapy, Adjuvant ,Female ,Tumor Suppressor Protein p53 ,business ,medicine.drug - Abstract
BACKGROUND: Pathological complete response (pCR) following chemotherapy is strongly associated with both breast cancer subtype and long-term survival. Within a phase III neoadjuvant chemotherapy trial, we sought to determine whether the prognostic implications of pCR, TP53 status and treatment arm (taxane versus non-taxane) differed between intrinsic subtypes. PATIENTS AND METHODS: Patients were randomized to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel then three cycles of eprirubicin/docetaxel (T-ET). pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in primary tumour and lymph nodes. We used a simplified intrinsic subtypes classification, as suggested by the 2011 St Gallen consensus. Interactions between pCR, TP53 status, treatment arm and intrinsic subtype on event-free survival (EFS), distant metastasis-free survival (DMFS) and overall survival (OS) were studied using a landmark and a two-step approach multivariate analyses. RESULTS: Sufficient data for pCR analyses were available in 1212 (65%) of 1856 patients randomized. pCR occurred in 222 of 1212 (18%) patients: 37 of 496 (7.5%) luminal A, 22 of 147 (15%) luminal B/HER2 negative, 51 of 230 (22%) luminal B/HER2 positive, 43 of 118 (36%) HER2 positive/non-luminal, 69 of 221(31%) triple negative (TN). The prognostic effect of pCR on EFS did not differ between subtypes and was an independent predictor for better EFS [hazard ratio (HR) = 0.40, P < 0.001 in favour of pCR], DMFS (HR = 0.32, P < 0.001) and OS (HR = 0.32, P < 0.001). Chemotherapy arm was an independent predictor only for EFS (HR = 0.73, P = 0.004 in favour of T-ET). The interaction between TP53, intrinsic subtypes and survival outcomes only approached statistical significance for EFS (P = 0.1). CONCLUSIONS: pCR is an independent predictor of favourable clinical outcomes in all molecular subtypes in a two-step multivariate analysis. CLINICALTRIALSGOV: EORTC 10994/BIG 1-00 Trial registration number NCT00017095.
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- 2017
9. The EORTC Breast Cancer Group: major achievements of 50 years of research and future directions
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Geertjan van Tienhoven, Helen A. Westenberg, Emiel J. Th. Rutgers, Jan Bogaerts, Fatima Cardoso, Hervé Bonnefoi, David Cameron, Suzette Delaloge, G. Werutsky, Luigi Cataliotti, Jacek Jassem, Tanja Cufer, Sandrine Marreaud, Lissandra Dal Lago, Etienne Brain, Laura J. van't Veer, Cancer Center Amsterdam, and Radiotherapy
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medicine.medical_specialty ,education.field_of_study ,Cancer Research ,business.industry ,Research ,Population ,Translational research ,Disease ,medicine.disease ,Systemic therapy ,Metastatic breast cancer ,Surgery ,Clinical trial ,EORTC ,Clinical research ,Breast cancer ,Oncology ,Family medicine ,medicine ,education ,business - Abstract
The EORTC Breast Cancer Group (BCG), created in 1962, is a multidisciplinary group involving surgeons, medical oncologists, radiation oncologists, pathologists, basic scientists, and clinical research fellows. Currently, more than 80 member's institutions across Europe are participating in the group studies. The main goal of the BCG is to conduct high-quality international clinical trials covering all areas of breast cancer care: from loco-regional to systemic disease control, and from in situ carcinoma to metastatic disease. Over 50 years, the BCG has performed dozens of clinical studies including several thousands of patients. Many practice-changing trials and major achievements were conducted optimizing local control, improving systemic therapy in early and metastatic breast cancer, pioneering work in clinical-translational trials and collaboration within intergroup trials. The strategic plan of the BCG for future research includes three distinct albeit overlapping areas: loco-regional therapy, (neo-) adjuvant systemic therapy, trials in the metastatic setting, and niche population studies. For each of these areas the group has considered the prevailing EORTC strategy of focusing on practice-changing studies and translational research, with an emphasis on niche trials. During five decades, the BCG has successfully performed a series of practice-changing trials enrolling several thousands of patients. These studies have contributed to the clinical knowledge on the treatment of breast cancer and have influenced clinical practice and breast cancer patients' outcome worldwide. (C) 2012 European Organisation for Research and Treatment of Cancer. All rights reserved
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- 2012
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10. The EORTC Gastrointestinal Tract Cancer Group: 50 years of research contributing to improved gastrointestinal cancer management
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Bernard Nordlinger, Eric Van Cutsem, Daniela Aust, Jean-Luc Van Laethem, Gunnar Folprecht, Markus Moehler, Michel Ducreux, Florian Lordick, Murielle Mauer, G. Werutsky, Manfred P. Lutz, Theo J.M. Ruers, and Arnaud Roth
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Oncology ,Gastrointestinal tract ,medicine.medical_specialty ,Chemotherapy ,Gastrointestinal ,Cancer Research ,business.industry ,Colorectal cancer ,medicine.medical_treatment ,Research ,Cancer ,Translational research ,social sciences ,medicine.disease ,Clinical trial ,Radiation therapy ,Cancérologie ,EORTC ,Internal medicine ,medicine ,Gastrointestinal cancer ,business - Abstract
During the last decades, the evolution of treatment - including radiotherapy, chemotherapy and targeted agents - has improved the cure and survival of patients with gastrointestinal (GI) cancer. Within the past 50 years of the EORTC's existence, significant progress has been made in the fight against cancer. During this time several cancer clinical trials were completed, and through these we are able to identify the most notable advances in GI cancer research done by the EORTC Gastrointestinal Tract Cancer Group (GI Group). Several EORTC clinical trials results have changed practice (e.g. standard of care of liver metastases of colorectal cancer has been changed by the EPOC trial) or have helped to support new treatment strategies in either early- or advanced-stage GI cancers. In addition to its clinical activities the group has started an extensive program of translational research. This changed strategy towards a translational, multidisciplinary program regarded as the basis for future developments. This review of the major achievements of the GI Group shows that it has played an important role in the scientific development of the understanding and treatment of GI cancer over the last 50 years. © 2012 European Organisation for Research and Treatment of Cancer., SCOPUS: ar.j, info:eu-repo/semantics/published
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- 2012
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11. Breast conserving therapy versus mastectomy for stage I-II breast cancer: 20 year follow-up of the EORTC 10801 phase 3 randomised trial
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Ian S. Fentiman, Marie-Rose Christiaens, Margreet H.A. Baaijens, Erik Van Limbergen, Emiel J. Th. Rutgers, Harry Bartelink, Saskia Litière, Jan Bogaerts, G. Werutsky, and Radiotherapy
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Adult ,medicine.medical_specialty ,medicine.medical_treatment ,Breast Neoplasms ,Breast cancer ,SDG 3 - Good Health and Well-being ,Clinical endpoint ,Humans ,Medicine ,Cumulative incidence ,Neoplasm Metastasis ,Mastectomy ,Radical mastectomy ,Survival analysis ,Aged ,Neoplasm Staging ,business.industry ,Lumpectomy ,Hazard ratio ,Middle Aged ,medicine.disease ,Survival Analysis ,Surgery ,Oncology ,Female ,Neoplasm Recurrence, Local ,business ,Follow-Up Studies - Abstract
Summary Background The EORTC 10801 trial compared breast-conserving therapy (BCT) with modified radical mastectomy (MRM) in patients with tumours 5 cm or smaller and axillary node negative or positive disease. Compared with BCT, MRM resulted in better local control, but did not affect overall survival or time to distant metastases. We report 20-year follow-up results. Methods The EORTC 10801 trial was open for accrual between 1980 and 1986 in eight centres in the UK, the Netherlands, Belgium, and South Africa. 448 patients were randomised to BCT and 420 to MRM. Randomisation was done centrally, stratifying patients by institute, carcinoma stage (I or II), and menopausal status. BCT comprised of lumpectomy and complete axillary clearance, followed by breast radiotherapy and a tumour-bed boost. The primary endpoint was time to distant metastasis. This analysis was done on all eligible patients, as they were randomised. Findings After a median follow-up of 22·1 years (IQR 18·5–23·8), 175 patients (42%) had distant metastases in the MRM group versus 207 (46%) in the BCT group. Furthermore, 506 patients (58%) died (232 [55%] in the MRM group and 274 [61%] in the BCT group). No significant difference was observed between BCT and MRM for time to distant metastases (hazard ratio 1·13, 95% CI 0·92–1·38; p=0·23) or for time to death (1·11, 0·94–1·33; 0·23). Cumulative incidence of distant metastases at 20 years was 42·6% (95% CI 37·8–47·5) in the MRM group and 46·9% (42·2–51·6) in the BCT group. 20-year overall survival was estimated to be 44·5% (95% CI 39·3–49·5) in the MRM group and 39·1% (34·4–43·9) in the BCT group. There was no difference between the groups in time to distant metastases or overall survival by age (time to distant metastases: vs ≥50 years 1·16 [0·90–1·50]; overall survival vs ≥50 years 1·10 [0·89–1·37]). Interpretation BCT, including radiotherapy, offered as standard care to patients with early breast cancer seems to be justified, since long-term follow-up in this trial showed similar survival to that after mastectomy. Funding European Organisation for Research and Treatment of Cancer (EORTC).
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- 2012
12. The AMAZONA Project: Retrospective Cohort Study Describing Breast Cancer Patients' Characteristics and Survival in Brazil
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Sergio Daniel Simon, G. Santos Borges, J. Soares Nunes, Ruffo Freitas-Junior, Carlos Barrios, B.M. Adam Van Eyll, José Bines, Susanne Crocamo, D. Dornelles Rosa, Facundo Zaffaroni, G. Werutsky, Maira Caleffi, J. Getúlio Martins Segalla, S. Jobim de Azevedo, G. Silva Queiroz, Annelise Costa Machado Gomes, Y. Verônica do Nascimento, Jeovany Martínez-Mesa, G.L. Delgado, F. Chalu Pacheco, D.L. Gimenes, and L. Dal Lago
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Oncology ,Cancer Research ,medicine.medical_specialty ,Breast cancer ,business.industry ,Internal medicine ,medicine ,Patient characteristics ,Cancer ,Retrospective cohort study ,medicine.disease ,business - Abstract
Background: Breast cancer is the most common cancer in women in Brazil and worldwide. There is large variation in survival among patients and molecular subtypes are important prognostic factors. However, most of the data comes from developed countries such as the United States and in Europe. Aim: Our goal was to describe breast cancer patients' demographic and pathologic characteristics, as well as their survival according to estimated molecular subtypes, assessed by common immunohistochemistry stains. Methods: AMAZONA study is a retrospective cohort conducted from June 2008 to January 2009 including women of at least 18 years old, with histologically proven breast cancer diagnosed in the period between 1 January 2001 and 31 December 2001 and between 1 January 2006 and 31 December. Estimated molecular subtypes by local immunohistochemical stains were luminal A, luminal B, HER-2 positive and triple-negative. Data were obtained from medical records and public databases. Kaplan-Meier method was used for data description and log-rank test for comparison between the subgroups. Results: 2296 patients were included in this analysis. Mean age was 54 years. Most subjects included came from hospitals located in the southeast region of the country, treated in the public health system and had stage II invasive ductal carcinoma of breast. Regarding subtype, 71.3% had hormonal receptor positive disease, 15.7% were HER-2 positive and 21.1% had triple-negative breast cancer. Overall survival (OS) was significantly different among molecular subtypes and was independent of pathologic stage for stages II and III patients. For stage III patients 5-years OS for luminal A subtype was 75.8% and for triple-negative was 56.1% ( P .0002). Conclusion: Classification of breast cancer patients in predicted molecular subtypes using immunohistochemistry is currently available in most underdeveloped countries and is a useful prognostic tool that goes beyond clinical or pathologic stage.
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- 2018
13. A phase I pharmacokinetics study of lapatinib and tamoxifen in metastatic breast cancer (EORTC 10053 Lapatam study)
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Jan Bogaerts, Etienne Brain, Larry Hayward, Fatima Cardoso, Ahmad Awada, G. Werutsky, Kevin M. Koch, Pierre Fumoleau, Sandrine Marreaud, Keyvan Rezai, and François Lokiec
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Adult ,Oncology ,medicine.medical_specialty ,Phases of clinical research ,Phase 1 clinical trials ,Antineoplastic Agents ,Breast Neoplasms ,Lapatinib ,Drug Administration Schedule ,Breast cancer ,Pharmacokinetics ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,Humans ,Medicine ,Neoplasm Metastasis ,Adverse effect ,skin and connective tissue diseases ,Chirurgie ,Aged ,Aged, 80 and over ,Dose-Response Relationship, Drug ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Metastatic breast cancer ,Tamoxifen ,Treatment Outcome ,Receptors, Estrogen ,Tolerability ,Quinazolines ,Female ,Surgery ,Receptors, Progesterone ,business ,medicine.drug - Abstract
Objective: This phase I study assessed the pharmacokinetic (PK), tolerability, safety and preliminary clinical activity of tamoxifen (T) and lapatinib (L) in patients with metastatic breast cancer (MBC). Methods: Patients (pts) with hormone receptor positive MBC, irrespective of HER-2 status, were randomly assigned to T→T+L group, tamoxifen in cycle 1 for 28 days then adding lapatinib on day 1 of cycle 2; or L→T+L group, lapatinib in cycle 1 for 14 days, then adding tamoxifen on day 1 of cycle 2 to evaluate the potential drug-drug PK interaction at steady-state. The dose of tamoxifen was 20mg/day and lapatinib 1500mg/day. Results: Twenty-five pts were enrolled of which 23 started treatment, five (22%) of them were HER-2 positive. Median age was 59 years and 96% had PS ≤1. Eleven (91.7%) pts in the T→T+L group and 10 (76.9%) in L→T+L group received at least 2 cycles of treatment. The most frequently reported drug-related adverse events (>25% of patients) were diarrhoea (62%), anaemia (56%), rash (52%), fatigue (52%), dermatology other (34%) and leukopenia (28%). Grade 3-4 drug-related toxicities were infrequent (, SCOPUS: ar.j, info:eu-repo/semantics/published
- Published
- 2014
14. Comparison of the sentinel node procedure between patients with multifocal and unifocal breast cancer in the EORTC 10981-22023 AMAROS Trial: Identification rate and nodal outcome
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Huub van der Mijle, Grard A. P. Nieuwenhuijzen, Willem H. Bouma, Cornelis J.H. van de Velde, Emiel J. Th. Rutgers, Lorenzo Orzalesi, A. Helen Westenberg, Saskia Litière, Nicole Duez, Marieke E. Straver, M. Donker, Robert E. Mansel, Geertjan van Tienhoven, Sanne C. Veltkamp, and G. Werutsky
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Adult ,Oncology ,Cancer Research ,medicine.medical_specialty ,Breast Neoplasms ,law.invention ,Metastasis ,Breast cancer ,Randomized controlled trial ,law ,Internal medicine ,Biopsy ,Humans ,Medicine ,Prospective Studies ,Prospective cohort study ,Multifocal ,Aged ,medicine.diagnostic_test ,Sentinel Lymph Node Biopsy ,business.industry ,Middle Aged ,Sentinel node ,medicine.disease ,Axilla ,EORTC ,Treatment Outcome ,medicine.anatomical_structure ,Lymphatic Metastasis ,Lymph Node Excision ,Female ,Lymph Nodes ,business ,NODAL - Abstract
Introduction Multifocal breast cancer is associated with a higher risk of nodal involvement compared to unifocal breast cancer and the drainage pattern from multifocal localisations may be different. For this reason, the value of the sentinel node biopsy (SNB) procedure for this indication is debated. The aim of the current analysis was to evaluate the sentinel node identification rate and nodal involvement in patients with a multifocal tumour in the EORTC 10981-22023 AMAROS trial. Patients and Methods From the first 4000 registered patients, 342 were identified with a multifocal tumour on histological examination and compared to a randomly selected control group of 684 patients with a unifocal tumour. The outcome of the SNB was assessed. Results The sentinel node was identified in 96% of the patients with a multifocal tumour and in 98% of those with unifocal disease. In the multifocal group, 51% had a metastasis in the sentinel node compared to 28% in the unifocal group; and further nodal involvement after a positive sentinel node was found in 40% (38/95) and 39% (39/101) respectively. Conclusion In this prospective international multicentre study, the 96% detection rate indicates that the SNB procedure can be highly effective in patients with a multifocal tumour. Though the tumour-positive rate of the sentinel node was twice as high in the multifocal group compared to the unifocal group, further nodal involvement after a positive sentinel node was similar in both groups. This suggests that the SNB procedure is safe in patients with multifocal breast cancer.
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- 2013
15. Breast-Conserving Treatment With or Without Radiotherapy in Ductal Carcinoma In Situ: 15-Year Recurrence Rates and Outcome After a Recurrence, From the EORTC 10853 Randomized Phase III Trial
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P. Rouanet, G. Werutsky, Nina Bijker, Roberto Agresti, Harry Bartelink, Emiel J. Th. Rutgers, Saskia Litière, Nicole Duez, Ian S. Fentiman, Christine Tunon de Lara, Mila Donker, Jean-Pierre Julien, CCA -Cancer Center Amsterdam, and Radiotherapy
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Adult ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Breast surgery ,Urology ,Breast Neoplasms ,Kaplan-Meier Estimate ,Mastectomy, Segmental ,medicine ,Carcinoma ,Humans ,Proportional Hazards Models ,Gynecology ,Proportional hazards model ,business.industry ,Hazard ratio ,Lumpectomy ,Carcinoma, Ductal, Breast ,Ductal carcinoma ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Radiation therapy ,Treatment Outcome ,Oncology ,Female ,Radiotherapy, Adjuvant ,Neoplasm Recurrence, Local ,business ,Mastectomy ,Carcinoma in Situ - Abstract
Purpose Adjuvant radiotherapy (RT) after a local excision (LE) for ductal carcinoma in situ (DCIS) aims at reduction of the incidence of a local recurrence (LR). We analyzed the long-term risk on developing LR and its impact on survival after local treatment for DCIS. Patients and Methods Between 1986 and 1996, 1,010 women with complete LE of DCIS less than 5 cm were randomly assigned to no further treatment (LE group, n = 503) or RT (LE+RT group, n = 507). The median follow-up time was 15.8 years. Results Radiotherapy reduced the risk of any LR by 48% (hazard ratio [HR], 0.52; 95% CI, 0.40 to 0.68; P < .001). The 15-year LR-free rate was 69% in the LE group, which was increased to 82% in the LE+RT group. The 15-year invasive LR-free rate was 84% in the LE group and 90% in the LE+RT group (HR, 0.61; 95% CI, 0.42 to 0.87). The differences in LR in both arms did not lead to differences in breast cancer–specific survival (BCSS; HR, 1.07; 95% CI, 0.60 to 1.91) or overall survival (OS; HR, 1.02; 95% CI, 0.71 to 1.44). Patients with invasive LR had a significantly worse BCSS (HR, 17.66; 95% CI, 8.86 to 35.18) and OS (HR, 5.17; 95% CI, 3.09 to 8.66) compared with those who did not experience recurrence. A lower overall salvage mastectomy rate after LR was observed in the LE+RT group than in the LE group (13% v 19%, respectively). Conclusion At 15 years, almost one in three nonirradiated women developed an LR after LE for DCIS. RT reduced this risk by a factor of 2. Although women who developed an invasive recurrence had worse survival, the long-term prognosis was good and independent of the given treatment.
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- 2013
16. The EORTC 10041/BIG 03-04 MINDACT trial is feasible: results of the pilot phase
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Fatima Cardoso, Jean-Yves Pierga, G. Werutsky, Jan Bogaerts, Ulrike Nitz, A. Vindevoghel, Emiel J. Th. Rutgers, Alastair M. Thompson, Martine Piccart-Gebhart, Giuseppe Viale, Suzette Delaloge, Isabel T. Rubio, Laura Van t.L. Veer, Peter M. Ravdin, and Rodolfo Passalacqua
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Oncology ,Adult ,Cancer Research ,medicine.medical_specialty ,Breast Neoplasms ,Pilot Projects ,law.invention ,Capecitabine ,Breast cancer ,MammaPrint ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Adjuvant therapy ,Humans ,Aged ,medicine.diagnostic_test ,business.industry ,Letrozole ,Middle Aged ,medicine.disease ,Confidence interval ,Docetaxel ,Chemotherapy, Adjuvant ,Patient Compliance ,Female ,business ,medicine.drug - Abstract
Background The MINDACT (Microarray In Node-negative and 1–3 node positive Disease may Avoid ChemoTherapy) trial investigates the clinical utility of the 70-gene profile (MammaPrint) for the selection of breast cancer patients for adjuvant chemotherapy (CT) together with standard clinicopathological criteria. We present the results of the pilot phase consisting of first 800 patients included. Methods MINDACT has enrolled 6600 patients, classified into high or low risk by MammaPrint and clinicopathological risk through Adjuvant! Online. Patients with both clinical (C) and genomic (G) high risks are offered adjuvant CT; those with both C and G low risks do not receive CT; patients with discordant risk are randomised for the decision of adjuvant CT based on C or G risk. CT randomisation of anthracycline-based versus docetaxel/capecitabine and endocrine therapy randomisation between letrozole and tamoxifen → letrozole are offered. Results During the pilot phase 46% of screened patients were enrolled. Main reasons for non-enrolment were node positivity before trial amendment, sample quality problems and failure to meet logistic settings. Among the 800 patients, 386 (48%) were C-low/G-low, 198 (24.8%) as C-high/G-high, 75 (9.4%) as C-low/G-high and 141 (17.6%) as C-high/G-low. In total 216 (27%) cases were discordant. The difference between patients with C-high (42%) and G-high risk (34%) is 8.25% (95% confidence interval (CI), 4.7–11.8%; P 92%). Conclusions The logistically complex MINDACT trial is feasible in a multinational setting. The proportion of discordant patients, the potential reduction in CT by using the genomic signature and compliance to treatment assignment are in accordance with the trial hypotheses.
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- 2011
17. OC-0134 LOCAL EXCISION WITH OR WITHOUT RADIOTHERAPY IN DUCTAL CARCINOMA IN SITU: TREATMENT AND PROGNOSIS AFTER A RECURRENCE
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P. Rouanet, R. Agresti, E.J.T. Rutgers, Saskia Litière, Jean-Pierre Julien, Nina Bijker, C. Tunon de Lara, I.S. Fentiman, G. Werutsky, and M. Donker
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Oncology ,In situ ,medicine.medical_specialty ,Local excision ,business.industry ,medicine.medical_treatment ,Hematology ,Ductal carcinoma ,Radiation therapy ,Internal medicine ,Medicine ,Radiology, Nuclear Medicine and imaging ,Radiology ,business - Published
- 2012
18. 211 Phase III Trial (EORTC 10801) Comparing Breast-conserving Therapy with Radical Mastectomy – Twenty Year Follow-up Results
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I.S. Fentiman, Saskia Litière, G. Werutsky, E. Van Limbergen, Jan Bogaerts, H. Bartelink, E.J.T. Rutgers, Margreet H.A. Baaijens, and M-R Christiaens
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Cancer Research ,medicine.medical_specialty ,Oncology ,business.industry ,medicine.medical_treatment ,medicine ,Follow up results ,business ,Radical mastectomy ,Surgery - Published
- 2012
19. 93. Local excision with or without radiotherapy in ductal carcinoma in situ – Treatment and prognosis after a recurrence
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N. Bijker, R. Agresti, E.J.T. Rutgers, J.P. Julien, I.S. Fentiman, Saskia Litière, G. Werutsky, P. Rouanet, M. Donker, and C. Tunon de Lara
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In situ ,Oncology ,medicine.medical_specialty ,Local excision ,business.industry ,medicine.medical_treatment ,General Medicine ,Ductal carcinoma ,Radiation therapy ,Internal medicine ,medicine ,Surgery ,Radiology ,business - Published
- 2012
20. 217 Adjuvant Radiotherapy After Breast-conserving Surgery for Ductal Carcinoma in Situ – Fifteen-year Results of the EORTC Randomized Phase III Trial 10853
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M. Donker, E.J.T. Rutgers, P. Rouanet, Jean-Pierre Julien, C. Tunon de Lara, G. Werutsky, I.S. Fentiman, R. Agresti, Saskia Litière, and N. Bijker
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Oncology ,Cancer Research ,Adjuvant radiotherapy ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine.medical_treatment ,medicine ,Breast-conserving surgery ,Ductal carcinoma ,business - Published
- 2012
21. 412 The EORTC 10041/BIG 03-04 MINDACT Trial Quality Assurance Program – Results of the Questionnaire for Pathologists
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Jan Bogaerts, E.J.T. Rutgers, Fatima Cardoso, L.J. van 't Veer, M.J. Piccart, Camilo Moulin, G. Werutsky, L. Dal Lago, and G. Viale
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Cancer Research ,medicine.medical_specialty ,Oncology ,Nursing ,business.industry ,Medicine ,Medical physics ,business ,Quality assurance - Published
- 2012
22. The EORTC 10041/BIG 03–04 MINDACT (Microarray in Node Negative and 1 to 3 Positive Lymph Node Disease May Avoid ChemoTherapy) Trial: Patients' Baseline Characteristics and Logistics Aspects After a Successful Accrual
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J-Y Pierga, Kristel Engelen, Jan Bogaerts, L van 't Veer, G. Viale, S. Delaloge, Ulrike Nitz, G. Werutsky, E.J.T. Rutgers, Isabel T. Rubio, Fatima Cardoso, M.J. Piccart, A. Thompson, Rodolfo Passalacqua, Camilo Moulin, and Peter Vuylsteke
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Oncology ,Cancer Research ,medicine.medical_specialty ,Chemotherapy ,Microarray ,Accrual ,business.industry ,medicine.medical_treatment ,Disease ,Node negative ,Surgery ,Internal medicine ,Baseline characteristics ,medicine ,Positive lymph node ,business - Published
- 2011
23. The Impact of Fibroblast Growth Factor Receptor Alterations in Clinical Outcomes of Patients With Advanced Urothelial Carcinoma: Real-World Data From a Latin American Population.
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Souza VC, Monteiro FSM, Maluf FC, Werutsky G, Fabrício VC, Gidekel R, Gandur-Quiroga MN, Freitas MRP, Luz M, Campos-Gomez S, Junior JAR, Bastos DA, Sade JP, da Trindade KM, Mota ACA, Fernandes RC, Ruíz AOB, Pereira E Silva BD, de Oliveira FNG, Cutuli HJ, Nogueira L, Aceituno LFG, Fernandez M, Inman E, Caitano M, Herchenhorn D, Ardila-Salcedo J, Pacheco P, de Jesus RG, Gössling G, Soares A, and Fay AP
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- Humans, Male, Female, Retrospective Studies, Aged, Middle Aged, Latin America epidemiology, Prognosis, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Urinary Bladder Neoplasms genetics, Urinary Bladder Neoplasms pathology, Urinary Bladder Neoplasms metabolism, Receptors, Fibroblast Growth Factor genetics, Receptors, Fibroblast Growth Factor metabolism, Urologic Neoplasms genetics, Urologic Neoplasms pathology, Aged, 80 and over, Kaplan-Meier Estimate, Mutation, Carcinoma, Transitional Cell genetics, Carcinoma, Transitional Cell pathology, Carcinoma, Transitional Cell drug therapy
- Abstract
Introduction: Fibroblast growth factor receptor (FGFR) mutations and fusions are relevant biomarkers in metastatic urothelial carcinoma (mUC). However, the prevalence of genomic alterations and their impact on clinical outcomes in a Latin American population remains unknown. This study aimed to explore the prevalence of FGFR mutations and/or fusions in patients with mUC in Latin America (LATAM) and its association with clinicopathological characteristics, Bellmunt's prognostic model, and survival outcomes., Patients and Methods: A multicenter retrospective cohort study from 2016 to 2019 of patients with mUC from several LACOG LATAM institutions. FGFR alterations were analyzed by real-time PCR and/or next-generation sequencing in tumor samples and clinicopathologic characteristics and survival outcomes data were collected. The prevalence of FGFR, patient characteristics, and treatment in real-world settings were summarized. Kaplan-Meier survival estimates and Cox regression analyses were used to evaluate the associations of FGFR mutation and/or fusion status with median overall survival (mOS), median time to treatment failure (mTTF), and clinicopathological characteristics., Results: In total, 222 patients were screened. Of these, 196 patients were considered eligible and were included in the analysis. FGFR mutations and/or fusions were found in 35 (17.9%) patients. There was no statistical difference in mOS and mTTF in FGFR-altered and non-altered patients (13.1 vs. 16.8 months, P = .20 and 3.9 vs. 4.1 months, P = .96, respectively). Bellmunt's prognostic model correctly predicted overall survival (P = .049)., Conclusions: This is the largest study evaluating the prevalence of FGFR alterations in patients with mUC in the LATAM population. FGFR alterations in mUC were found in 17.9% of the patients, and the presence of this biomarker was not associated with OS. We validated Bellmunt's prognostic model in this cohort., Competing Interests: Disclosure Dr. Gustavo Werutsky reports personal fees from AstraZeneca, Bayer, Beigene, Daiichi Sankyo, Genentech/Roche, GSK, Lilly, MSD, Novartis, Pfizer, Sanofi, and Seattle Genetics outside the submitted work. All remaining authors have declared no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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24. Exploring locoregional treatment reporting in neoadjuvant systemic breast cancer treatment studies: A systematic review.
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Jiang M, Avery K, Ahmed R, de Boniface J, Chatterjee S, Dodwell D, Dubsky P, Finestone S, Iwata H, Lee HB, MacKenzie M, Meyn A, Poulakaki F, Richardson AL, Sepulveda K, Spillane A, Thompson AM, Werutsky G, Wright JL, Zdenkowski N, Cowan K, McIntosh SA, and Potter S
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- Humans, Female, Breast Neoplasms therapy, Breast Neoplasms pathology, Neoadjuvant Therapy
- Abstract
Accurate information about locoregional treatments in breast cancer neoadjuvant systemic therapy (NST) trials is vital to support surgical decision-making and allow meaningful interpretation of long-term oncological outcomes. This systematic review (PROSPERO registration CRD42023470891) aimed to describe the current practice of outcome reporting in NST studies. A systematic search identified primary research studies published 01/01/2018-08/09/2023 reporting outcomes in patients receiving NST for breast cancer followed by locoregional treatment. Included were randomised controlled trials (RCTs) and non-randomised studies (NRS) with >250 participants reporting at least one locoregional treatment outcome. Outcomes were extracted verbatim and categorised using content analysis. Descriptive statistics were used to summarise results. Of the 3111 abstracts screened, 137 studies (22 RCTs and 115 NRS) reporting at least one locoregional outcome in 575,531 patients were included. The 137 studies reported a total of 510 surgical outcomes with a median of 3 (range 1-12) per study. No single outcome was reported in all studies. Type of breast (n = 129, 94.2 %) and axillary (n = 86, 62.8 %) surgery were reported most frequently. Only 34 % (n = 47) studies reported how treatment response was assessed and if/how this informed surgical decision-making. Only a fifth (n = 28) reported outcomes relating to surgical de-escalation. Only 72 studies (52.6 %) reported any radiation therapy (RT)-related outcome, most frequently whether RT had been received (n = 63/72, 87.5 %). Current reporting of locoregional treatment outcomes in NST studies is poor, inconsistent and urgently needs to be improved. A core outcome set and reporting guidelines may improve the quality and value of future research., Competing Interests: Declaration of competing interest SMcI reports speaker honoraria from MSD, Roche, BD and Astra Zeneca; advisory boards for Lilly, Novartis, MSD, Roche and Astra Zeneca; conference travel and support from Roche, Lilly and MSD, and institutional research funding from Novartis. HI reports consulting fees from Daiichi Sankyo, Chugai, Astra Zeneca, Lilly, MSD, Pfizer and Gilead; honoraria from Daiichi Sankyo, Chugai, Astra Zeneca, Lilly, MSD, Pfizer, Taiho and Kyowa Kirin, and institutional research funding from Chugai, Daiichi Sankyo and Astra Zeneca. H-BL reports being a co-founder and member of the DCGen Co., Ltd board of directors; research funding from Devicor Medical Product, Inc.; consulting fees and honoraria from Alvogen, Boryung, Hologic, Lilly, Need, Novartis, Roche, Takeda, Celltrion, and Shin Poong. PD reports institutional research funding from Cepheid and Roche; consulting fees from Roche, and honoraria from Astra Zeneca and Oncoviews, and conference and travel support from Roche. NZ reports consulting fees from Lilly, Eisai, Astra Zeneca, MSD, Novartis and Gilead; honorarium from Roche, Pfizer, Eisai, Gilead, Novartis, Lilly and Astra Zeneca; and conference travel support from Novartis, Roche, Pfizer and Lilly. The remaining authors have no conflicts or competing of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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25. Long-Term Safety and Effectiveness of Rituximab Biosimilar RTXM83: A Retrospective Extension Study in Brazilian Patients with Diffuse Large B-Cell Lymphoma.
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Delamain MT, Cardoso ACF, Pericole FV, da Silva Araújo SS, Fogliatto L, Higashi M, Pereira J, da Silva RL, Werutsky G, de Paulo Giacon Radtke P, Salvino MA, and Castilho V
- Abstract
Introduction: RTXM83, a biosimilar of rituximab, was approved after physicochemical, functional, non-clinical, and clinical studies demonstrated their similarity; these studies included RTXM83-AC-01-11, a multicentric double-blind international prospective pivotal study. Long-term data on biosimilars can potentially elucidate their clinical robustness and facilitate their broader adoption., Methods: In this retrospective observational study, we analyzed a dataset from a Brazilian cohort previously randomized in the RTXM83-AC-01-11 study followed by the assessment of long-term outcomes in an observational extension phase from randomization in the RTXM83-AC-01-11 study to the last recorded evaluation. Patients with diffuse large B cell lymphoma (DLBCL) received either reference rituximab (R) or RTXM83 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as adjuvant treatment., Results: The median follow-up period was 77.0 months. Patients with initial DLBCL stages III and IV comprised 50% of the R-CHOP group and 40% of the biosimilar group. Five (18.5%) patients, including two RTXM83-CHOP-treated and three R-CHOP-treated individuals, experienced late adverse events (AEs) of interest. No new safety signs were established. At the final assessment, the progression-free survival (PFS) rates were 93.3% and 50.0% in the RTXM83-CHOP and R-CHOP groups, respectively. Median PFS was not achieved in the RTXM83-CHOP group, which was 40.5 months in the R-CHOP group. The overall survival (OS) rates were 100% and 66.7% in the RTXM83-CHOP and R-CHOP groups, respectively. The median OS was not reached in any group., Conclusion: This study demonstrated the long-term safety and effectiveness of RTXM83 in treating DLBCL; outcomes comparable to those of the reference product and potentially improved access to treatment have been indicated. However, further research with more diverse patient groups can validate these findings and advocate the broader adoption of biosimilars in cancer care., Trial Registration: ClinicalTrials.gov Identifier: NCT04928573. June 16, 2021, "retrospectively registered"., (© 2024. The Author(s).)
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- 2024
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26. The impact of a breast cancer diagnosis on marital outcomes and factors associated with divorce and separation.
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Werutsky G, Lopes M, de Jesus RG, Gazola AA, Pellegrini RA, Rebelatto TF, Freitas LVW, Heck AP, da Silva AF, Rodrigues MF, Gössling G, Giacomazzi J, Rocha MS, Rosa DD, Barrios CH, Cronemberger EH, Queiroz GS, Bines J, Simon SD, and Fay AP
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- Humans, Female, Retrospective Studies, Middle Aged, Adult, Brazil epidemiology, Marital Status, Socioeconomic Factors, Aged, Risk Factors, Cancer Survivors statistics & numerical data, Divorce statistics & numerical data, Breast Neoplasms diagnosis, Breast Neoplasms surgery
- Abstract
Objective: To analyze marital outcomes, divorce or separation, and its association with demographic, socioeconomic, and clinicopathological factors among breast cancer (BC) survivors after 2-years of diagnosis., Methods: We performed a retrospective analysis of marital status at baseline and at years 1 and 2 of follow-up of women aged ≥ 18 years diagnosed with invasive BC participating in the AMAZONA III (GBECAM0115) study. The BC diagnosis occurred between January 2016 and March 2018 at 23 institutions in Brazil., Results: Of the 2974 women enrolled in AMAZONA III, 599 were married or living under common law at baseline. Divorce or separation occurred in 35 (5.8%) patients at 2 years of follow-up. In the multivariate analysis, public health insurance coverage was associated with a higher risk of marital status change (8.25% vs. 2.79%, RR 3.09, 95% CI 1.39 - 7.03, p = 0.007). Women who underwent mastectomy, adenomastectomy or skin-sparing mastectomy were associated with a higher risk of divorce or separation (8.1% vs. 4.49%, RR 1.97, 95 CI 1.04 - 3.72, p = 0.0366) than those who underwent breast-conserving surgery., Conclusion: Women covered by the public health system and those who underwent mastectomy, adenomastectomy or skin-sparing mastectomy were associated with a higher risk of divorce or separation. This evidence further supports the idea that long-term marital stability is associated with a complex interplay between socioeconomic conditions and stressors, such as BC diagnosis and treatment. ClinicalTrials Registration: NCT02663973., Competing Interests: Conflicts to interest: none to declare
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- 2024
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27. Equitable inclusion of diverse populations in oncology clinical trials: deterrents and drivers.
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Vidal L, Dlamini Z, Qian S, Rishi P, Karmo M, Joglekar N, Abedin S, Previs RA, Orbegoso C, Joshi C, Azim HA, Karkaria H, Harris M, Mehrotra R, Berraondo M, Werutsky G, Gupta S, Niikura N, Chico I, and Saini KS
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- Humans, Patient Selection ethics, Clinical Trials as Topic, Neoplasms therapy, Neoplasms ethnology, Medical Oncology
- Abstract
The burden of cancer exerts a disproportionate impact across different regions and population subsets. Disease-specific attributes, coupled with genetic and socioeconomic factors, significantly influence cancer treatment outcomes. Precision oncology promises the development of safe and effective options for specific ethnic phenotypes and clinicodemographic profiles. Currently, clinical trials are concentrated in resource-rich geographies with younger, healthier, white, educated, and empowered populations. Vulnerable and marginalized people are often deprived of opportunities to participate in clinical trials. Despite consistent endeavors by regulators, industry, and other stakeholders, factors including diversity in trial regulations and patient and provider-related cultural, logistic, and operational barriers limit the inclusiveness of clinical trials. Understanding and addressing these constraints by collaborative actions involving regulatory initiatives, industry, patient advocacy groups, community engagement in a culturally sensitive manner, and designing and promoting decentralized clinical trials are vital to establishing a clinical research ecosystem that promotes equity in the representation of population subgroups., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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28. Protocol for the development of a core outcome set and reporting guidelines for locoregional treatment in neoadjuvant systemic breast cancer treatment trials: the PRECEDENT project.
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Potter S, Avery K, Ahmed R, de Boniface J, Chatterjee S, Dodwell D, Dubsky P, Iwata H, Jiang M, Lee HB, MacKenzie M, Poulakaki F, Richardson AL, Sepulveda K, Spillane A, Thompson AM, Werutsky G, Wright JL, Zdenkowski N, Cowan K, and McIntosh S
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- Humans, Female, Delphi Technique, Consensus, Outcome Assessment, Health Care, Breast Neoplasms therapy, Neoadjuvant Therapy, Research Design
- Abstract
Introduction: Neoadjuvant systemic anticancer therapy (neoSACT) is increasingly used in the treatment of early breast cancer. Response to therapy is prognostic and allows locoregional and adjuvant systemic treatments to be tailored to minimise morbidity and optimise oncological outcomes and quality of life. Accurate information about locoregional treatments following neoSACT is vital to allow the translation of downstaging benefits into practice and facilitate meaningful interpretation of oncological outcomes, particularly locoregional recurrence. Reporting of locoregional treatments in neoSACT studies, however, is currently poor. The development of a core outcome set (COS) and reporting guidelines is one strategy by which this may be improved., Methods and Analysis: A COS for reporting locoregional treatment (surgery and radiotherapy) in neoSACT trials will be developed in accordance with Core Outcome Measures in Effectiveness Trials (COMET) and Core Outcome Set-Standards for Development guidelines. Reporting guidance will be developed concurrently.The project will have three phases: (1) generation of a long list of relevant outcome domains and reporting items from a systematic review of published neoSACT studies and interviews with key stakeholders. Identified items and domains will be categorised and formatted into Delphi consensus questionnaire items. (2) At least two rounds of an international online Delphi survey in which at least 250 key stakeholders (surgeons/oncologists/radiologists/pathologists/trialists/methodologists) will score the importance of reporting each outcome. (3) A consensus meeting with key stakeholders to discuss and agree the final COS and reporting guidance., Ethics and Dissemination: Ethical approval for the consensus process will be obtained from the Queen's University Belfast Faculty Ethics Committee. The COS/reporting guidelines will be presented at international meetings and published in peer-reviewed journals. Dissemination materials will be produced in collaboration with our steering group and patient advocates so the results can be shared widely., Registration: The study has been prospectively registered on the COMET website (https://www.comet-initiative.org/Studies/Details/2854)., Competing Interests: Competing interests: SM reports speaker honoraria from MSD, Roche, BD and Astra Zeneca; advisory boards for Lilly, Novartis, MSD, Roche and Astra Zeneca; conference travel and support from Roche, Lilly and MSD; and institutional research funding from Novartis. HI reports consulting fees from Daiichi Sankyo, Chugai, Astra Zeneca, Lilly, MSD, Pfizer and Gilead; honoraria from Daiichi Sankyo, Chugai, Astra Zeneca, Lilly, MSD, Pfizer, Taiho and Kyowa Kirin; and institutional research funding from Chugai, Daiichi Sankyo and Astra Zeneca. PD reports institutional research funding from Cepheid and Roche; consulting fees from Roche, and honoraria from Astra Zeneca and Oncoviews; and conference and travel support from Roche. H-BL reports research funding from Devicor Medical Product Inc. and is a co-founder and director of DCGen Co. Ltd. ALR reports consulting fees from Astra Zeneca and royalties from Myriad Genetics. GW reports consulting fees from Astra Zeneca, MSD, Novartis, Daiichi Sankyo and Roche; honoraria from Astra Zeneca, MSD, Novartis, Roche, Pfizer and Daiichi-Sankyo; and institutional research funding from Astra Zeneca/Medimmune, Roche/Genentech, GlaxoSmithKline, Novartis, Pfizer, Roche, MSD, Merck, Bayer, Janssen, Astellas Pharma, Libbs and Takeda. NZ reports consulting fees from Lilly, Eisai, Astra Zeneca, MSD, Novartis and Gilead; honoraria from Roche, Pfizer, Eisai, Amgen, Gilead, Novartis, Lilly and Astra Zeneca; and conference travel and support from Novartis, Astra Zeneca and Lilly. The remaining authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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29. Improving access to cancer clinical research in Brazil: recent advances and new opportunities. Expert opinions from the 4th CURA meeting, São Paulo, 2023.
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Resende H, Arai RJ, Barrios CH, Schwyter F, Teich NLS, Gomes A, Dallari AB, Bonilha LAS, Souza CMA, Francisco FR, Munhoz RR, Werutsky G, Madi M, Fernandes P, Figueiredo JM, Fedozzi F, Arruda L, Aguiar VQ, and Melo AC
- Abstract
Clinical research is the cornerstone of improvements in cancer care. However, it has been conducted predominantly in high-income countries with few clinical trials available in Brazil and other low-and-middle-income countries (LMIC). Of note, less than one-third of registered clinical trials addressing some of the most commonly diagnosed cancers (breast, lung and cervical) recruited patients from LMIC in the last years. The Institute Project CURA promoted the fourth CURA meeting, discussing barriers to cancer clinical research and proposing potential solutions. A meeting was held in São Paulo, Brazil, in June 2023 with representatives from different sectors: Brazilian Health Regulatory Agency (Anvisa), National Commission of Ethics in Research (CONEP), non-governmental organisations, such as the Latin American Cooperative Oncology Group, the Brazilian Society of Clinical Oncology (SBOC), Contract Research Organisations, pharmaceutical companies and investigators. A total of 16 experts pointed out achievements as shortening the time of regulatory processes involving Anvisa and CONEP, development of staff training programs, maintenance of the National Program of Oncological Attention (PRONON), and the foundation of qualified centres in North and Northeast Brazilian regions. Participants also highlighted the need to be more competitive in the field, which requires optimising ongoing policies and implementing new strategies as decentralisation of clinical research centres, public awareness campaigns, community-centered approaches, collaborations and partnerships, expansion of physicians-directed policies, exploring the role of the steering committee. Active and consistent reporting of the initiatives might help to propagate ongoing advances, increasing Brazilian participation in clinical cancer research. Engagement of all players is crucial to maintain continuous progress with further improvements in critical points including regulatory timelines and increments in qualified human resources which aligned with new educational initiatives focused on physicians and the general population will expand access to cancer clinical trials in Brazil., Competing Interests: Heloisa Resende has received research funding from Novartis and Roche, all outside the scope of this manuscript. Gustavo Werutsky has received research funding from AstraZeneca/MedImmune, Bristol-Myers Squibb Brazil, Pfizer, Roche and Roche/Genentech, all outside the scope of this manuscript. Has consulting or advisory role at Merck. Carlos H Barrios has received research funding from AB Science, Abbvie, Abraxis BioScience, Amgen, Asana Biosciences, Astellas Pharma, AstraZeneca, Biomarin, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Clinica Atlantis, Covance, Daiichi Sankyo, Exelixis, GlaxoSmith-Kline, Halozyme, ImClone Systems, INC Research, inVentiv Health, Janssen, LEO Pharma, Lilly, Medivation, Merck, Merck KGaA, Merrimack, Millennium, Mylan, Novartis, Pfizer, PharmaMar, Polyphor, Roche/Genentech, Sanofi, Shanghai Henlius Biotech and Taiho Pharmaceutical, all outside the scope of this manuscript. Has consulting or advisory role at AstraZeneca, Boehringer Ingelheim, Eisai, GlaxoSmithKline, Libbs, Lilly, MSD Oncology, Novartis, Pfizer, Roche/Genentech and United Medical. Has stock and other ownership interests in MedSIR and Tummi. All other authors have no conflicts of interest to disclose., (© the authors; licensee ecancermedicalscience.)
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- 2024
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30. Real-World Evidence of Ribociclib Plus Aromatase Inhibitors as First-Line Treatment in Advanced Breast Cancer: The BrasiLEEira Study.
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Suzuki DA, Morelle AM, de Brito ML, Paes FR, Mattar A, Leal JHS, Simon SD, Lima EMA, Werutsky G, Piotto GHM, Bines J, Damiani LP, Macedo A, Campos L, and Buehler AM
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- Female, Humans, Aminopyridines adverse effects, Middle Aged, Aromatase Inhibitors adverse effects, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Purines
- Abstract
Purpose: Cyclin inhibitors plus endocrine therapy represent the reference standard for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) locally advanced or metastatic breast cancer (ABC). Efficacy results on hard end points such as overall survival come from well-designed randomized clinical trials (RCTs). However, a limitation of RCTs is the low external results validity, and their extrapolation to a broader population may not be appropriate. Real-world studies can overcome these limitations, also increasing the reliability of RCTs., Materials and Methods: The BrasiLEEira was an observational, longitudinal, retrospective, multicenter study to evaluate the effectiveness and safety of ribociclib plus nonsteroidal aromatase inhibitors in Brazilian women age 18 years or older with HR+/HER2- ABC. The study was approved by the institutional review boards of all 11 hospitals. Data were collected anonymously from medical records using an electronic case report form designed by an independent academic research organization, which conducted the study considering all recommendations of international guidelines. The primary end point was 1-year progression-free survival (PFS) rate. Secondary end points included mortality, dose reduction, and safety., Results: The mean age of 76 patients was 57 years, and 28.9% were Black/Brown. The most prevalent comorbidity was arterial hypertension (34.7%). About 26.0% had endocrine-resistant disease, and 54.1% had more than three metastatic sites. The PFS rate was 77.6%. Three patients died (3.9%). Dose reductions occurred in 37.7% of patients. The most common adverse event was neutropenia (68.4%)., Conclusion: The high-quality evidence from the BrasiLEEira study corroborates the RCTs' findings, expanding its validity to a broader spectrum and underrepresented population who may benefit from ribociclib treatment.
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- 2024
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31. Health Services Access Inequalities in Brazil Result in Poorer Outcomes for Stage III NSCLC-RELANCE/LACOG 0118.
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Cordeiro de Lima VC, Gelatti A, Moura JFP, Fares AF, de Castro G Jr, Mathias C, Terra RM, Werutsky G, Corassa M, Araújo LHL, Cronenberger E, Fujiki FK, Reichow S, da Silva AVT, Reis TV, Padoan MLA, Pacheco P, Yamamura R, Kawamura C, Mascarenhas E, de Jesus RG, Gössling G, and Baldotto C
- Abstract
Introduction: Stage III NSCLC is a heterogeneous disease, representing approximately one-third of newly diagnosed lung cancers. Brazil lacks detailed information regarding stage distribution, treatment patterns, survival, and prognostic variables in locally advanced NSCLC., Methods: RELANCE/LACOG 0118 is an observational, retrospective cohort study assessing sociodemographic and clinical data of patients diagnosed with having stage III NSCLC from January 2015 to June 2019, regardless of treatment received. The study was conducted across 13 cancer centers in Brazil. Disease status and survival data were collected up to June 2021. Descriptive statistics, survival analyses, and a multivariable Cox regression model were performed. p values less than 0.05 were considered significant., Results: We recruited 403 patients with stage III NSCLC. Most were male (64.0%), White (31.5%), and smokers or former smokers (86.1%). Most patients had public health insurance (67.5%), had stage IIIA disease (63.2%), and were treated with concurrent chemoradiation (53.1%). The median follow-up time was 33.83 months (95% confidence interval [CI]: 30.43-37.50). Median overall survival (OS) was 27.97 months (95% CI: 21.57-31.73), and median progression-free survival was 11.23 months (95% CI: 10.70-12.77). The type of treatment was independently associated with OS and progression-free survival, whereas the types of health insurance and histology were independent predictors of OS only., Conclusions: Brazilian patients with stage III NSCLC with public health insurance are diagnosed later and have poorer OS. Nevertheless, patients with access to adequate treatment have outcomes similar to those reported in the pivotal trials. Health policy should be improved to make lung cancer diagnosis faster and guarantee prompt access to adequate treatment in Brazil., Competing Interests: Dr. Cordeiro de Lima reports receiving research grant from 10.13039/100002491Bristol-Myers Squibb (for the institution); payment or honoraria from AstraZeneca, Roche, Bristol-Myers Squibb, Merck Sharp & Dohme, Merck Serono, and Novartis; support for attending meetings from 10.13039/100004325AstraZeneca and 10.13039/100004337Roche; and having participation on data safety monitoring board or advisory board in AstraZeneca, Daiichi Sankyo, Amgen, Pfizer, Eli Lilly, Merck Sharp & Dohme, Bristol-Myers Squibb, Merck Serono, and Janssen. Dr. De Castro Jr., reports having consulting or advisory roles from Boehringer Ingelheim, Pfizer, Bayer, Roche, Merck Sharp & Dohme, Bristol-Myers Squibb, AstraZeneca, Yuhan, Merck Serono, Janssen, Libbs, Sanofi, Novartis, Eli Lilly, Amgen, and Takeda; receiving payment or honoraria from AstraZeneca, Pfizer, Merck Sharp & Dohme, Bristol-Myers Squibb, Novartis, Roche, Amgen, Janssen, Merck Serono, Bayer, and Takeda; receiving support for attending meetings from Boehringer Ingelheim, 10.13039/100004319Pfizer, 10.13039/100004326Bayer, Roche, 10.13039/100009947Merck Sharp & Dohme, Bristol-Myers Squibb, AstraZeneca, Merck Serono, 10.13039/100004336Novartis, Eli Lilly, and 10.13039/100002429Amgen; and having participation on data safety monitoring board or advisory board in Boehringer Ingelheim, Pfizer, Bayer, Roche, Merck Sharp & Dohme, Bristol-Myers Squibb, AstraZeneca, Yuhan, Merck Serono, Janssen, Libbs, Sanofi, Novartis, Eli Lilly, Amgen, and Takeda. Dr. Werutsky reports receiving grants or contracts from Novartis, Roche/10.13039/100004328Genentech, AstraZeneca/10.13039/501100004628MedImmune, Eli Lilly, 10.13039/100004330GlaxoSmithKline, Novartis, Pfizer, Bristol-Myers Squibb Brazil, Merck Sharp & Dohme, Merck, Bayer, 10.13039/100005565Janssen, Bristol-Myers Squibb, Astellas, Libbs, Takeda, 10.13039/100006436Celgene, and GlaxoSmithKline; consulting fees from Merck; and payment or honoraria for lectures from Pfizer, AstraZeneca/MedImmune, Libbs, and Merck. The remaining authors declare no conflict of interest., (© 2024 The Authors.)
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- 2024
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32. Current scenario and future perspectives of clinical research in Brazil: a national survey.
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Resende H, Rebelatto TF, Werutsky G, Gossling G, Aguiar VQ, Lopes GMC, de Assis BR, Arruda L, and Barrios CH
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Background: Epidemiological and clinical cancer research is essential to understanding tumour behaviour and developing new therapies in oncology. However, several countries including Brazil as well as many other regions of the world have limited participation in cancer research. Despite 625,000 new cancer cases recorded in Brazil in 2022, only 2.2% of ongoing cancer clinical trials are available in the country. We conducted an online survey to describe physician engagement with research and to identify the main barriers precluding participation in and conduct of clinical cancer research in the country., Methods: An anonymous online survey of 23 objective questions was sent by e-mail to Brazilian members of the Latin American Cooperative Oncology Group and the Brazilian Society of Clinical Oncology. The first 13 questions addressed demographic information, medical training and previous research participation. In the second part, the main barriers to engagement and participation in clinical trials in Brazil were addressed. Continuous variables were measured by median and range. Analyses were performed using SAS statistical software (version 9.4; SAS Institute, Inc. Cary, NC)., Results: 109 physicians answered the survey. Most participants were oncologists ( N = 98, 89.9%), living in capital cities ( N = 84, 77.1%), were from the Southeast region of Brazil ( N = 63, 57.8%) and worked at institutions providing exclusively private healthcare ( N = 59, 54.1%). Of the 109 respondents, 83 (76.1%) reported working in research centres (as investigators or sub-investigators). Surprisingly, 31.2% of physicians recognised they invite less than 1% of their patients to participate in clinical trials, even though 98 (89.9%) considered the participation of patients in clinical trials extremely relevant. The main barriers compromising the conduct of research in the country were the low number of available trials (48.2%) and the lack of qualified human resources to staff research sites (22.9%). Other reported barriers were the lengthy regulatory approval process (42.2%), followed by a lack of awareness of clinical research by patients resulting in low recruitment rates (24.1%). Of the 26 (23.8%) respondents not working with research, 25 (96.1%) reported interest in being involved, 31.8% have tried participating in research and 62.4% reported limited knowledge of trial procedures., Conclusion: These results suggest a clear need to further engage physicians in clinical research activities in Brazil. Patient education strategies should improve the low recruitment rates and secondarily increase the number of proposed trials in the country., Competing Interests: Heloisa Resende has received research funding from Novartis and Roche, all outside the scope of this manuscript. Taiane Francieli Rebelatto has no relationships to disclose. Gustavo Werutsky has received research funding from AstraZeneca/MedImmune, Bristol-Myers Squibb Brazil, GlaxoSmithKline, Lilly, Novartis, Pfizer, Roche and Roche/Genentech, all outside the scope of this manuscript. Has consulting or advisory role at Merck. Gustavo Gössling has received research funding from AstraZeneca/Merck and Janssen Oncology, all outside the scope of this manuscript. Vinícius Aguiar has no relationships to disclose. Guilherme Lopes has no relationships to disclose. Biazi Assis has no relationships to disclose. Lilian Arruda has no relationships to disclose. Carlos H Barrios has received research funding from AB Science, Abbvie, Abraxis BioScience, Amgen, Asana Biosciences, Astellas Pharma, AstraZeneca, Biomarin, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Clinica Atlantis, Covance, Daiichi Sankyo, Exelixis, GlaxoSmithKline, Halozyme, ImClone Systems, INC Research, inVentiv Health, Janssen, LEO Pharma, Lilly, Medivation, Merck, Merck KGaA, Merrimack, Millennium, Mylan, Novartis, Pfizer, PharmaMar, Polyphor, Roche/Genentech, Sanofi, Shanghai Henlius Biotech and Taiho Pharmaceutical, all outside the scope of this manuscript. Has consulting or advisory role at AstraZeneca, Boehringer Ingelheim, Eisai, GlaxoSmithKline, Libbs, Lilly, MSD Oncology, Novartis, Pfizer, Roche/Genentech and United Medical. Has stock and other ownership interests in MedSIR and Tummi., (© the authors; licensee ecancermedicalscience.)
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- 2023
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33. Real-world data on triple-negative breast cancer in Latin America and the Caribbean.
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Tiscoski KA, Giacomazzi J, Rocha MS, Gössling G, and Werutsky G
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Breast cancer (BC) is the most prevalent cancer in women in Latin America and the Caribbean. We compiled real-world data (RWD) on the epidemiology, diagnosis, treatment, and patient outcomes of triple-negative breast cancer (TNBC), addressing the main barriers to optimal care in Latin America. The prevalence of TNBC varies between 11% and 38.5% of all BC cases diagnosed in the region, and TNBC primarily affects young patients. Delays in BC diagnosis, with consequent advanced disease stages and barriers to access efficient therapies, particularly due to high costs, negatively impact patient outcomes. Cancer clinical trials are an opportunity to access standard and novel therapies for patients with this aggressive BC subtype and thus must be prioritised. Finally, generating RWD and cost-effectiveness studies in a region with limited resources is critical for decision-makers to define the incorporation of new technologies for the treatment of BC., Competing Interests: JG reports grants from Roche. GW reports grants or contracts from Novartis, Roche/Genentech, AstraZeneca/MedImmune, Lilly, GlaxoSmithKline, Novartis, Pfizer, Bristol-Myers Squibb Brazil, MSD, Merck, Bayer, Janssen, BMS, Astellas, Libbs, Takeda, Celgene, GSK; consulting fees from Merck; payment or honoraria for lectures from Pfizer, AstraZeneca/MedImmune, Libbs, and Merck. The other authors declare no conflict of interest., (© the authors; licensee ecancermedicalscience.)
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- 2023
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34. Quality of Life in Male Breast Cancer: Prospective Study of the International Male Breast Cancer Program (EORTC10085/TBCRC029/BIG2-07/NABCG).
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Schröder CP, van Leeuwen-Stok E, Cardoso F, Linderholm B, Poncet C, Wolff AC, Bjelic-Radisic V, Werutsky G, Abreu MH, Bozovic-Spasojevic I, den Hoed I, Honkoop AH, Los M, Leone JP, Russell NS, Smilde TJ, van der Velden AWG, Van Poznak C, Vleugel MM, Yung RL, Coens C, Giordano SH, and Ruddy KJ
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- Female, Humans, Male, Aged, Child, Preschool, Quality of Life, Prospective Studies, Health Status, Surveys and Questionnaires, Breast Neoplasms, Male therapy, Breast Neoplasms therapy
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Introduction: Prospective data about quality of life (QoL) in men with breast cancer (BC) are lacking. A prospective registry (EORTC10085) of men with all BC stages, including a QoL correlative study, was performed as part of the International Male Breast Cancer Program., Methods: Questionnaires at BC diagnosis included the EORTC QLQ-C30 and BR23 (BC specific module), adapted for men. High functioning and global health/QoL scores indicate high functioning levels/high QoL; high symptom-focused measures scores indicate high symptoms/problems levels. EORTC reference data for healthy men and women with BC were used for comparisons., Results: Of 422 men consenting to participate, 363 were evaluable. Median age was 67 years, and median time between diagnosis and survey was 1.1 months. A total of 114 men (45%) had node-positive early disease, and 28 (8%) had advanced disease. Baseline mean global health status score was 73 (SD: 21), better than in female BC reference data (62, SD: 25). Common symptoms in male BC were fatigue (22, SD: 24), insomnia (21, SD: 28), and pain (16, SD: 23), for which women's mean scores indicated more burdensome symptoms at 33 (SD: 26), 30 (SD: 32), and 29 (SD: 29). Men's mean sexual activity score was 31 (SD: 26), with less sexual activity in older patients or advanced disease., Conclusions: QoL and symptom burden in male BC patients appears no worse (and possibly better) than that in female patients. Future analyses on impact of treatment on symptoms and QoL over time, may support tailoring of male BC management., (© The Author(s) 2023. Published by Oxford University Press.)
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- 2023
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35. Core Needle Biopsy Accuracy for Androgen Receptor Expression in Invasive Breast Cancer.
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Santos MMD, Frasson AL, Silva VDD, Maciel ACA, Watte G, Werutsky G, Reinert T, and Fay AP
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- Humans, Middle Aged, Female, Biopsy, Large-Core Needle, Receptors, Androgen metabolism, Androgens, Biomarkers, Tumor, Breast Neoplasms pathology
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Objective: Breast cancer (BC) biomarkers, such as hormone receptors expression, are crucial to guide therapy in BC patients. Antiandrogens have been studied in BC; however, limited data are available on androgen receptor (AR) expression test methodology. We aim to report the core needle biopsy (CNB) accuracy for AR expression in BC., Methods: Patients diagnosed with stage I-III invasive BC from a single institution were included. Androgen receptor expression was evaluated by immunohistochemistry (IHC) using 1 and 10% cutoff and the AR expression in surgical specimens (SS) was the gold standard. Kappa coefficients were used to evaluate the intraprocedural agreement., Results: A total of 72 patients were included, with a mean age of 61 years old and 84% were Luminal A or B tumors. The prevalence of AR expression in all BC samples was 87.5% using a cutoff ≥ 10% in SS. With a cutoff value ≥ 1%, CNB had an accuracy of 95.8% (Kappa value = 0.645; 95% confidence interval [CI]: 0.272-1.000; p < 0.001) and 86.1% (Kappa value = 0.365; 95% CI: 0.052-0.679; p < 0.001) when ≥ 10% cutoff was used for AR positivity. Androgen receptor expression in CNB (cutoff ≥ 1%) had a sensitivity of 98.5%, specificity of 60%, positive predictive value of 97.0%, and a negative predictive value of 76.9% in the detection of AR expression in SS., Conclusion: Core needle biopsy has good accuracy in evaluating AR expression in BC. The accuracy of CNB decreases with higher cutoff values for AR positivity., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)
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- 2023
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36. Global Cancer Drug Development-A Report From the 2022 Accelerating Anticancer Agent Development and Validation Meeting.
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Wilson BE, Sullivan R, Peto R, Abubakar B, Booth C, Werutsky G, Adams C, Saint-Raymond A, Fleming TR, Lyerly K, and Gralow JR
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- Humans, Developing Countries, Income, Drug Development, Neoplasms drug therapy, Neoplasms radiotherapy, Antineoplastic Agents therapeutic use
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Rapidly expanding systemic treatment options, combined with improved screening, diagnostic, surgical, and radiotherapy techniques, have led to improved survival outcomes for many cancers over time. However, these overall survival gains have disproportionately benefited patients in high-income countries, whereas patients in low- and middle-income countries (LMICs) continue to experience challenges in accessing timely and guideline concordant care. In September 2022, the Accelerating Anticancer Agent Development and Validation workshop was held, focusing on global cancer drug development. Panelists discussed key barriers such as the lack of diagnostic services and human resources, drug accessibility and affordability, lack of research infrastructure, and regulatory and authorization challenges, with a particular focus on Africa and Latin America. Potential opportunities to improve access and affordability were reviewed, such as the importance of prioritizing investments in diagnostics, investing health infrastructure and work force planning, coordinated drug procurement efforts and streamlined regulatory processing, incentivized pricing through regulatory change, and the importance of developing and promoting clinical trials that can answer relevant clinical questions for patients in LMICs. As a cancer community, we must continue to advocate for and work toward equitable access to high-quality interventions for patients, regardless of their geographical location.
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- 2023
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37. An international comparative analysis and roadmap to sustainable biosimilar markets.
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Alnaqbi KA, Bellanger A, Brill A, Castañeda-Hernández G, Clopés Estela A, Delgado Sánchez O, García-Alfonso P, Gyger P, Heinrich D, Hezard G, Kakehasi A, Koehn C, Mariotte O, Mennini F, Mayra Pérez-Tapia S, Pistollato M, Saada R, Sasaki T, Tambassis G, Thill M, Werutsky G, Wilsdon T, and Simoens S
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Background: Although biosimilar uptake has increased (at a variable pace) in many countries, there have been recent concerns about the long-term sustainability of biosimilar markets. The aim of this manuscript is to assess the sustainability of policies across the biosimilar life cycle in selected countries with a view to propose recommendations for supporting biosimilar sustainability. Methods: The study conducted a comparative analysis across 17 countries from North America, South America, Asia-Pacific, Europe and the Gulf Cooperation Council. Biosimilar policies were identified and their sustainability was assessed based on country-specific reviews of the scientific and grey literature, validation by industry experts and 23 international and local non-industry experts, and two advisory board meetings with these non-industry experts. Results: Given that European countries tend to have more experience with biosimilars and more developed policy frameworks, they generally have higher sustainability scores than the other selected countries. Existing approaches to biosimilar manufacturing and R&D, policies guaranteeing safe and high-quality biosimilars, exemption from the requirement to apply health technology assessment to biosimilars, and initiatives counteracting biosimilar misconceptions are considered sustainable. However, biosimilar contracting approaches, biosimilar education and understanding can be ameliorated in all selected countries. Also, similar policies are sometimes perceived to be sustainable in some markets, but not in others. More generally, the sustainability of the biosimilar landscape depends on the nature of the healthcare system and existing pharmaceutical market access policies, the experience with biosimilar use and policies. This suggests that a general biosimilar policy toolkit that ensures sustainability does not exist, but varies from country to country. Conclusion: This study proposes a set of elements that should underpin sustainable biosimilar policy development over time in a country. At first, biosimilar policies should guarantee the safety and quality of biosimilars, healthy levels of supply and a level of cost savings. As a country gains experience with biosimilars, policies need to optimise uptake and combat any misconceptions about biosimilars. Finally, a country should implement biosimilar policies that foster competition, expand treatment options and ensure a sustainable market environment., Competing Interests: GC-H has received consultancy and speaker fees from AbbVie, Amgen, Janssen-Cilag, Libbs, Novartis, Pfizer, Roche, Sanofi, Takeda, and UCB. OM and GH work at Nile, secretary general of the French think tank “Biosimilaires” and have links of interest with Accord Healthcare, Amgen, Biogen, and Sandoz. MT has received personal honoraria for lectures and participation in advisory boards from Amgen, Medscape, Jörg Eickeler, Onkowissen, Organon, Pfizer, Viatris, Vifor. He received manuscript support by Amgen, Roche, Servier and travel expenses by Amgen, Hexal, I-Med-Institute, Pfizer, Roche. Congress support was given by Amgen, Hexal, Pfizer, Roche. TW, MP, and RS were commissioned to support the project that informed this analysis and they assume editorial responsibility as contributors to the study. Charles River Associates is an economic consultancy company. SS is one of the founding members of the KU Leuven Fund on Market Analysis of Biologics and Biosimilars following Loss of Exclusivity (MABEL Fund). SS was involved in a stakeholder roundtable on biologics and biosimilars sponsored by Amgen, Pfizer and MSD, and he has participated in advisory board meetings for Amgen, Pfizer, Organon and Sandoz. He has contributed to studies on biologics and biosimilars for Hospira, Celltrion, Mundipharma and Pfizer; and he has had speaking engagements for Amgen, Celltrion, Organon and Sandoz. Author AB was employed by Matrix Global Advisors. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed., (Copyright © 2023 Alnaqbi, Bellanger, Brill, Castañeda-Hernández, Clopés Estela, Delgado Sánchez, García-Alfonso, Gyger, Heinrich, Hezard, Kakehasi, Koehn, Mariotte, Mennini, Mayra Pérez-Tapia, Pistollato, Saada, Sasaki, Tambassis, Thill, Werutsky, Wilsdon and Simoens.)
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- 2023
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38. Clinical validation and diagnostic accuracy of 99m Tc-EDDA/HYNIC-TOC compared to 111 In-DTPA-octreotide in patients with neuroendocrine tumours: the LACOG 0214 study.
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Moriguchi-Jeckel CM, Madke RR, Radaelli G, Viana A, Nabinger P, Fernandes B, Gössling G, Berdichevski EH, Vilas E, Giacomazzi J, Rocha MS, Borges JA, Hoffmann E, Greggio S, Venturin GT, Barrios CH, Zaffaroni F, Werutsky G, and da Costa JC
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99m Tc-EDDA/HYNIC-TOC is an easily available and cheaper radionuclide that could be used for somatostatin-receptor-based imaging of neuroendocrine tumours (NETs). We aimed to evaluate the diagnostic performance of99m Tc-EDDA/HYNIC-TOC compared to111 In-DTPA-octreotide in patients (pts) with NETs. We performed a prospective diagnostic study including pts with biopsy-confirmed NET and at least one visible lesion at conventional imaging. Two independent nuclear medicine physicians evaluated pts who underwent99m Tc and111 In scans and images. The primary outcome was comparative diagnostic accuracy of99m Tc and111 In. Secondary outcomes include safety. Nine pts were included and performed 14 paired scans. Overall, 126 lesions were identified.99m Tc demonstrated superior sensitivity both when all images were analysed (93.7, 95% CI 88.1% - 96.8% versus 74.8%, 95% CI 66.6 - 81.6%, p < 0.001) and when liver-specific images were analysed (97.8%, 95% CI 92.7% - 99.5% versus 85.1%, 95% CI 76.6% - 91.0%, p < 0.001).99m Tc was also associated with a lower negative likelihood ratio (LR) (0.002, 95% CI 0.009 - 0.1 versus 0.19, 95% CI 0.12 - 0.42, p = 0.009) when evaluating hepatic lesions. Adverse events happened in 3 pts after111 In and in 2 pts after99m Tc, all grade 1. The99m Tc demonstrated a higher sensitivity overall and a better negative LR in liver-specific images compared to111 In in pts with NETs. Our findings suggest that99m Tc is an alternative to111 In and is especially useful in ruling out liver metastases. NCT02691078., Competing Interests: Dr Moriguchi-Jeckel and Dr Werutsky report grants from Financiadora de Estudos e Projetos (FINEP) for the conduct of the study. Drs R. Madke, Viana, Nabinger, and Fernandes report employment relationships with the RPH Group. Dr. Werutsky reports personal fees from AstraZeneca, Bayer, Beigene, Daiichi Sankyo, Genentech/Roche, GSK, Lilly, MSD, Novartis, Pfizer, Sanofi, and Seattle Genetics outside the submitted work. The other authors declare that they have no conflict of interest., (© the authors; licensee ecancermedicalscience.)- Published
- 2023
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39. Moderately hypofractionated post-operative radiation therapy for breast cancer: preferences amongst radiation oncologists from countries in Latin America and the Caribbean.
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Marta GN, Moraes FY, de Oliveira Franco RC, de Andrade Carvalho H, Gouveia AG, de Lima Gössling GC, de Jesus RG, Ferraris G, Schuffenegger PM, Bardales GS, Chacón MAP, Murillo R, Sánchez LEM, Gamarra-Cabezas E, Rosa AA, da Silva MF, de Mattos MD, Morais DCR, de Castro DG, Dal Pra A, Amêndola BE, Barros JM, Lara TM, Isa N, de la Mata Moya D, Hidalgo I, Velilla DG, Loayza LEA, Montenegro FG, Sanchez Chacin NO, Werutsky G, and Viani GA
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Background: The safety and effectiveness of moderately hypofractionated post-operative radiation therapy for breast cancer were demonstrated by several trials. This study aimed to evaluate the current patterns of practice and prescription preference about moderately hypofractionated post-operative radiation therapy to assess possible aspects that affect the decision-making process regarding the use of fractionation in breast cancer patients in Latin America and the Caribbean (LAC). We also aimed to identify factors that can restrain the utilization of moderately hypofractionated post-operative radiation therapy for breast cancer., Materials an Methods: Radiation oncologists from LAC were invited to contribute to this study. A 38-question survey was used to evaluate their opinions., Results: A total of 173 radiation oncologists from 13 countries answered the questionnaire. The majority of respondents (84.9%) preferred moderately hypofractionated post-operative radiation therapy as their first choice in cases of whole breast irradiation. Whole breast plus regional nodal irradiation, post-mastectomy (chest wall and regional nodal irradiation) without reconstruction, and post-mastectomy (chest wall and regional node irradiation) with reconstruction hypofractionated post-operative radiation therapy was preferred by 72.2% 71.1%, and 53.7% of respondents, respectively. Breast cancer stage, and flap-based breast reconstruction were the factors associated with absolute contraindications for the use of hypofractionated schedules., Conclusion: Even though moderately hypofractionated post-operative radiation therapy for breast cancer is considered a new standard to the vast majority of the patients, its unrestricted application in clinical practice across LAC still faces reluctance., Competing Interests: Conflict of interest None declared., (© 2023 Greater Poland Cancer Centre.)
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- 2023
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40. Results of a survey study on health professionals' perceptions of tumor boards in Brazil.
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Menezes TU, Serra MM, Barrios CH, Oliveira LJ, Godo VS, Cascelli F, Clara RO, Gössling G, Werutsky G, and Mano MS
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- Humans, Brazil, Emotions, Health Facilities, Health Personnel, Physicians
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Background: Tumor boards (TB) are synonymous with quality of care but have been occasionally misunderstood and underutilized. This survey aimed to evaluate health professionals' perceptions of TBs in Brazil. Materials & methods: The survey was sent electronically. Results: Of 206 respondents, 67.8% attended TBs at least once and 82.4% dedicated at least 1 h weekly to them; 64.2% preferred a more &educational' model over case discussions only; 63.1% had institutional leadership capable of promoting multidisciplinarity; 21.1 and 32.7% of the physicians and nonphysicians, respectively, felt intimidated to express their opinions; 91.6% believed that TBs improve cancer outcomes. Postpandemic, 52.7% preferred a hybrid (virtual/face-to-face) model. Conclusion: This study provides a glimpse of the reality of TBs in Brazil, with potential implications for clinical practice.
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- 2023
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41. Ten-year survival of neoadjuvant dual HER2 blockade in patients with HER2-positive breast cancer.
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Nuciforo P, Townend J, Piccart MJ, Fielding S, Gkolfi P, El-Abed S, de Azambuja E, Werutsky G, Bliss J, Moebus V, Colleoni M, Aspitia AM, Gomez H, Gombos A, Coccia-Portugal MA, Tseng LM, Kunz G, Lerzo G, Sohn J, Semiglazov V, Saura C, Kroep J, Ferro A, Cameron D, Gelber R, Huober J, and Di Cosimo S
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- Humans, Female, Lapatinib therapeutic use, Neoadjuvant Therapy, Receptor, ErbB-2, Trastuzumab adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Treatment Outcome, Breast Neoplasms pathology
- Abstract
Background: Dual anti-HER2-targeted therapy in breast cancer (BC) significantly increased the rate of pathological complete response (pCR) compared to single blockade when added to chemotherapy. However, limited data exist on the long-term impact on survival of the additional increase in pCR., Methods: Neoadjuvant lapatinib and/or trastuzumab treatment optimisation (NCT00553358) is an international, randomised, open-label, phase III study investigating the addition of lapatinib to chemotherapy plus trastuzumab in HER2-positive early BC. Ten-year event-free survival (EFS), overall survival (OS) and safety were assessed on intention-to-treat population. The association between pCR and EFS or OS was investigated in landmark population., Results: A total of 455 patients were randomised to receive lapatinib (154), trastuzumab (149) or the combination (152). Ten-year EFS estimates were 63% (95% confidence interval [CI], 54%-71%) in the lapatinib group, 64% (95% CI, 55%-72%) in the trastuzumab group and 67% (95% CI, 58%-74%) in the combination group. Ten-year OS rates were 76% (95% CI, 67%-83%), 75% (95% CI, 66%-82%) and 80% (95% CI, 73%-86%) in the lapatinib, trastuzumab and combination groups, respectively. Women who achieved a pCR had improved EFS (hazard ratio 0.48, 95% CI, 0.31-0.73) and OS (hazard ratio 0.37, 95% CI, 0.20-0.63) compared with those who did not. The numerical difference in survival according to pCR status was greater in women treated with the combination and those with hormone-receptor-negative tumours. There were no new or long-term safety concerns., Conclusions: Patients with HER2-positive BC showed a durable survival benefit of neoadjuvant anti-HER2, irrespective of treatment arm. Patients who achieve pCR have significantly better outcomes than patients without pCR., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2023
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42. Time interval between diagnosis to treatment of breast cancer and the impact of health insurance coverage: a sub analysis of the AMAZONA III Study (GBECAM 0115).
- Author
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Maschmann RM, De Jesus RG, Werutsky G, Rebelatto TF, Queiroz G, Simon SD, Bines J, Barrios CHE, and Rosa DD
- Subjects
- Humans, Female, Animals, Prospective Studies, Disease-Free Survival, Insurance Coverage, Neoplasm Staging, Breast Neoplasms diagnosis, Breast Neoplasms epidemiology, Breast Neoplasms therapy, Amazona
- Abstract
Purpose: Breast cancer (BC) is the most common type of cancer among women in Brazil. Evidence shows that delayed treatment onset is associated with increased mortality. This study aimed to evaluate median days between diagnosis and treatment and factors associated with delayed start of treatment (> 60 days after diagnosis): stage, treatment received, subtype, epidemiological characteristics, and type of healthcare coverage., Methods: This analysis included 1709 stage I-III BC patients from AMAZONA III, a prospective, observational study, diagnosed from January 2016 to March 2018 in 22 centers in Brazil., Results: The median number of days from diagnosis to beginning of first oncologic treatment was 46 days (IQR 28-75) overall, 43 days (IQR 25-75) for stage I disease, 49 days (IQR 28-81) for stage II, and 44 days (IQR 30-68) for stage III, (p = 0.1180). According to first treatment received, diagnosis-to-treatment interval was 43 days (IQR 29-65) for neoadjuvant chemotherapy and 48 days (IQR 26-81) for surgery. Diagnosis-to-treatment interval was higher in women treated in the public system versus the private system (56 vs. 34 days, p < 0.0001). Patients in the public system had an increased odds of delayed treatment initiation (OR 4.74 95% CI 3.09-7.26, p < .0001). The longer interval from diagnosis to treatment in the public system was independent of clinical stage, type of treatment (systemic vs surgery first), subtype and region of the country., Conclusion: By characterizing the delays in care delivery, our study will aid stakeholders to better design interventions and allocate resource to improve timely treatment for breast cancer in Brazil., Clinicaltrials: gov Identifier: NCT02663973, registered on January, 26th, 2016., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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43. Current Scenario of Clinical Cancer Research in Latin America and the Caribbean.
- Author
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Gössling G, Rebelatto TF, Villarreal-Garza C, Ferrigno AS, Bretel D, Sala R, Giacomazzi J, William WN Jr, and Werutsky G
- Subjects
- Humans, Latin America epidemiology, Caribbean Region epidemiology, Research, Medical Oncology, Neoplasms therapy
- Abstract
In Latin America and the Caribbean (LAC), progress has been made in some national and regional cancer control initiatives, which have proved useful in reducing diagnostic and treatment initiation delays. However, there are still significant gaps, including a lack of oncology clinical trials. In this article, we will introduce the current status of the region's clinical research in cancer, with a special focus on academic cancer research groups and investigator-initiated research (IIR) initiatives. Investigators in LAC have strived to improve cancer research despite drawbacks and difficulties in funding, regulatory timelines, and a skilled workforce. Progress has been observed in the representation of this region in clinical trial development and conduct, as well as in scientific productivity. However, most oncology trials in the region have been sponsored by pharmaceutical companies, highlighting the need for increased funding from governments and private foundations. Improvements in obtaining and/or strengthening the LAC cancer research group's financing will provide opportunities to address cancer therapies and management shortcomings specific to the region. Furthermore, by including this large, ethnic, and genetically diverse population in the world's research agenda, one may bridge the gap in knowledge regarding the applicability of results of clinical trials now mainly conducted in populations from the Northern Hemisphere.
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- 2023
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44. Socioeconomic Impact of Cancer in Latin America and The Caribbean.
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Werutsky G, Gössling G, Pellegrini RA, Ampuero GAS, and Rebelatto T
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- Female, Humans, Latin America epidemiology, Income, Incidence, Caribbean Region epidemiology, Neoplasms epidemiology, Neoplasms therapy
- Abstract
The incidence of cancer in Latin America and the Caribbean (LAC) is increasing yearly and is expected to reach 2.4 million new cases by 2040, with a more pronounced effect in Central America and South America. In addition, cancer is already the most frequent cause of premature death for most countries in LAC, and the second cause of death independent of country socioeconomic status, clearly demonstrating that the cancer burden in LAC should be addressed now rather than considered as an issue to be dealt with in the future. LAC countries performed in a mid-range zone in terms of income and mortality-to-incidence ratio compared to other countries globally. The LAC continent has, in general, a median income per capita and a median availability of radiotherapy (RDT) machines per capita. Patients that have private health coverage are more likely to receive preventive care such as pap smears and mammography in many countries of the LAC. The human development index was negatively related to mortality from oral cancer in the LAC countries with medium and low Human Development Index (HDI). Cancer treatment adverse events can negatively affect survivors' workability compromising their return to work after diagnosis. In conclusion, the cancer burden can be a major public health issue with a considerable socioeconomic impact in LAC countries. It is demonstrated in several studies that unequal access to optimal care is frequent in LAC and that health insurance type may impact patients' diagnosis and outcome., Competing Interests: Conflict of Interest All authors have no conflict of interest to declare., (Copyright © 2022 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.)
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- 2022
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45. Assessing Oncologists' Attitudes Concerning Comprehensive Genomic Profiling in Stage IV Lung Adenocarcinoma in Brazil.
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Fares AF, Martinez PH, Farina PH, Bicalho de Souza I, Araújo DV, Paiva NS, Orlando LF, Colombo TE, Mascarenhas E, Gelatti ACZ, Baldotto C, Zukin M, Araujo LH, Mathias C, Werutsky G, de Castro G Jr, and Cordeiro de Lima VC
- Abstract
Introduction: Advances in comprehensive genomic profiling (CGP) of lung adenocarcinomas (LUADs) led to personalized treatment for patients. This study evaluated medical oncologists' attitudes toward CGP in a scenario where sponsored funding for CGP was available., Methods: We designed an online survey assessing CGP use and treating physicians' confidence, composed of three self-confidence domains, which are as follows: confidence in interpreting CGP results, confidence in treating oncogenic-driven LUAD, and confidence in managing tyrosine kinase inhibitor adverse events. The survey was distributed to medical oncologists who treat lung cancer in Brazil. Comparisons between groups were performed using the chi-square or Fisher's exact test. Univariable and multivariable (adjusted OR) analyses were performed., Results: Among 104 respondents who treat patients with lung cancer, 55% were from the Southeast region, 28% had high lung cancer clinical load, and 33% had in-house molecular testing. More than half (51%) of the participants request CGP systematically to stage IV LUAD. As for provider confidence, 67% stated being confident in all three domains: 76% confident in interpreting CGP, 84% confident in treating oncogenic-driven LUAD, and 81% in managing tyrosine kinase inhibitor adverse events. Providers' confidence was associated with systematically requesting CGP to stage IV LUAD ( p = 0.013). After controlling for the variables of interest, systematic requesting CGP for stage IV LUAD revealed a significant association with the provider's confidence (adjusted OR = 0.35, p = 0.028, 95% CI: 0.14-0.84). The major challenge for properly requesting CGP was the long turnaround time and the fear of treatment delays., Conclusions: Even though CGP for stage IV LUAD in Brazil is fully sponsored, only half of the oncologists in our survey systematically request it.. Requesting CGP was associated with providers' confidence. Improving access and promoting providers' awareness of CGP utility is necessary to increase CGP use and better inform treatment decisions., (© 2022 The Authors.)
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- 2022
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46. Influence of physician's lifestyle on the prescription of healthy habits to breast cancer patients (LACOG 1218).
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Cangussú R, Mascarenhas E, Rebelatto TF, Zaffaroni F, de Jesus RG, Filho PRN, and Werutsky G
- Subjects
- Habits, Humans, Life Style, Male, Middle Aged, Prescriptions, Breast Neoplasms therapy, Physicians
- Abstract
Background: Healthy lifestyle is capable of positively modifying the survival of breast cancer (BC) patients. We aimed to evaluate how physician's lifestyle influences on the prescription of healthy habits to BC patients., Methods: An online questionnaire to evaluate physician lifestyle and prescription of healthy habits to BC patients was developed and circulated by e-mail to physicians dedicated to treat BC patients. A multivariate Poisson regression analysis assessed which factors of physician lifestyle could influence on prescription of healthy habits., Results: A total of 267 physicians answered the questionnaire from October to November 2018. In terms of physician lifestyle, 228 (85.4%) had healthy eating habits and 236 (88.4%) practiced physical activity. Overall, 84.3% of the physicians advised their BC patients on the importance of lifestyle modification. Physicians who did not exercise regularly have a higher probability of not advising for health lifestyle (RR 2.48; p = 0.0265) as opposite to physicians ≥ 50 years-old (RR 0.37; p = 0.0118). Obesity treatment and management was performed by 45.3% of physicians. Being a breast surgeon (RR 1.29; p = 0.0025) or radiation oncologists (RR 1.82; p = 0.0025) were associated with not performing obesity treatment and management. About 53.4% of physicians referred overweight or obese patients to a dietitian and/or endocrinologist. Male gender (RR 1.35; p = 0.0296), breast surgeons (RR 1.99; p = 0.0001), and clinical practice in public health system (RR 1.53; p = 0.0012) were associated with not referring as opposed to physicians ≥ 50 years-old (RR 0.46; p = 0.0005)., Conclusion: Our survey showed some influence of physician's lifestyle on the prescription of healthy habits to BC patients. Physicians who practice physical activity regularly had a higher probability of advising lifestyle modification and about half of physicians did some type of overweight and obese management., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2022
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47. Non-Small-Cell Lung Cancer With CNS Metastasis: Disparities From a Real-World Analysis (GBOT-LACOG 0417).
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Coelho JC, de Souza Carvalho G, Chaves F, de Marchi P, de Castro G Jr, Baldotto C, Mascarenhas E, Pacheco P, Gomes R, Werutsky G, and Araujo LH
- Subjects
- Cranial Irradiation, Humans, Retrospective Studies, Brain Neoplasms secondary, Brain Neoplasms surgery, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung therapy, Central Nervous System Neoplasms therapy, Lung Neoplasms pathology, Lung Neoplasms therapy, Neoplasms, Second Primary
- Abstract
Purpose: Despite the advances in the approach to non-small-cell lung cancer (NSCLC) with CNS metastasis, access to timely diagnosis and treatment may not be optimal in many instances. Our main objective was to describe a cohort of patients with NSCLC with brain metastases from public and private cancer centers, and the differences between patients' presentation, treatment, and outcomes., Methods: GBOT-LACOG 0417 is a multi-institutional retrospective cohort study of patients diagnosed with NSCLC and CNS metastasis in Brazil. All patients had confirmed diagnosis of NSCLC between January 2010 and December 2015. CNS metastases were identified by imaging., Results: A total of 273 patients were included. Patients treated at public institutions were more often Black or Brown (38.8% v 15.4%), current or former smoker (88.6% v 60.0%), of squamous cell histology (25.0% v 9.1%), EGFR- and ALK -negative (95.9% v 74.9%), and were less frequently assessed by using brain magnetic resonance imaging (38.8% v 83.6%). At public institutions, patients were more often symptomatic (78.1% v 44.6%) and had worse performance status (Eastern Cooperative Oncology Group 2 or higher 61.5% v 10.3%). CNS metastases were larger (median size 25 v 15 mm) and more often surrounded by edema (67.7% v 55.2%) at public institutions. Patients at public institutions were more frequently treated with whole-brain radiation therapy (72.9% v 45.4%) and less frequently with radiosurgery (6.3% v 24.1%). Among patients from private care, median overall survival was 24.2 months (95% CI, 20.0 to 30.6), significantly higher than in public care (median 12.1 months; 95% CI, 6.7 to 13.6; P < .001)., Conclusion: Our results demonstrate the discrepancy between public and private health care system in the critical setting of patients with CNS metastasis from NSCLC., Competing Interests: Fabio ChavesConsulting or Advisory Role: AstraZeneca/BrazilSpeakers' Bureau: AstraZeneca/Brazil, Servier Pedro de MarchiHonoraria: SanofiConsulting or Advisory Role: Merck Sharp & Dohme, AstraZeneca, Bristol Myers Squibb, Roche, BayerSpeakers' Bureau: Merck Sharp & Dohme, Bristol Myers Squibb, Roche, AstraZeneca, Novartis, Merck, Boehringer Ingelheim, Janssen, TakedaResearch Funding: AstraZeneca, Amgen, Merck Sharp & Dohme, RocheTravel, Accommodations, Expenses: Merck Sharp & Dohme, AstraZeneca, Roche, Bristol Myers Squibb Gilberto de Castro JrHonoraria: AstraZeneca, Pfizer, Merck Sharp & Dohme, Bristol Myers Squibb, Novartis, Roche, Amgen, JanssenConsulting or Advisory Role: Boehringer Ingelheim, Pfizer, Bayer, Roche, Merck Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, Yuhan, Merck Serono, Janssen, Libbs, Sanofi, NovartisSpeakers' Bureau: AstraZeneca, Bayer, Novartis, Roche, Merck Serono, Bristol Myers Squibb, Merck Sharp & Dohme, Boehringer Ingelheim, Pfizer, Janssen, AmgenTravel, Accommodations, Expenses: Merck Sharp & Dohme, Novartis, Pfizer, Roche, AstraZeneca, Boehringer Ingelheim, Bayer, Bristol Myers Squibb, Merck Serono Clarissa BaldottoHonoraria:AstraZeneca, MSD Oncology Brazil, Roche Oncology Brazil, Takeda Oncology Brazil, BMS Brazil, Janssen Oncology Brazil, Pfizer Oncology Brazil, MD HealthConsulting or Advisory Role: MSD, AstraZeneca, Janssen Oncology Brazil, Novartis, Novartis, Takeda Brazil, Roche Oncology BrazilSpeakers' Bureau: Roche Oncology Brazil, BMS Brazil, Janssen Oncology Brazil, MSD, MSD, Instituto D'Or de Pesquisa e EnsinoResearch Funding: AstraZeneca, Roche/Genentech, Janssen OncologyTravel, Accommodations, Expenses: Janssen Oncology Eldsamira MascarenhasConsulting or Advisory Role: AstraZeneca, Janssen, Pfizer Gustavo WerutskyHonoraria: Pfizer, AstraZeneca/MedImmune, Libbs, MerckConsulting or Advisory Role: OrganonResearch Funding: Novartis, Lilly (Inst), AstraZeneca/MedImmune (Inst), Roche/Genentech, GlaxoSmithKline (Inst), Novartis (Inst), Pfizer (Inst), Bristol Myers Squibb Brazil (Inst), Roche (Inst) Luiz H. AraujoConsulting or Advisory Role: Merck Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, Pfizer, Boehringer Ingelheim, Merck, RocheSpeakers' Bureau: AstraZeneca, Pfizer, Merck, Roche, Merck Sharp & Dohme, Bristol Myers Squibb, Boehringer IngelheimResearch Funding: Merck Sharp & Dohme (Inst), Bristol Myers Squibb (Inst), AstraZeneca (Inst), Pfizer (Inst), Merck (Inst), Roche (Inst), Boehringer Ingelheim (Inst)No other potential conflicts of interest were reported.
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- 2022
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48. Characteristics of patients diagnosed with cervical cancer in Brazil: preliminary results of the prospective cohort EVITA study (EVA001/LACOG 0215).
- Author
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Rodrigues AN, de Melo AC, Calabrich AFC, Cronenberger E, Torres KL, Damian F, Cossetti R, de Azevedo CRAS, da Fonseca AJ, Nerón Y, Nunes J, Lopes A, Thomé F, Leal R, Borges G, da Silva AF, Rodrigues MF, Nunes Filho PRS, Zaffaroni F, Freitas RDS, Werutsky G, and Maluf F
- Subjects
- Adult, Brazil epidemiology, Carcinoma, Squamous Cell psychology, Female, Health Services Accessibility statistics & numerical data, Humans, Middle Aged, Papanicolaou Test statistics & numerical data, Prospective Studies, Quality of Life, Socioeconomic Factors, Surveys and Questionnaires, Uterine Cervical Neoplasms psychology, Carcinoma, Squamous Cell epidemiology, Health Knowledge, Attitudes, Practice, Mass Screening statistics & numerical data, Uterine Cervical Neoplasms epidemiology
- Abstract
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., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2022
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49. Real-world Data on First-line Systemic Therapy for Hormone Receptor-positive HER2-negative Metastatic Breast Cancer: A Trend Shift in the Era of CDK 4/6 Inhibitors.
- Author
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Werutsky G, Reinert T, Rosa ML, and Barrios CH
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms pathology, Female, Humans, Neoplasm Staging, Receptors, Progesterone metabolism, Risk Factors, Antineoplastic Agents, Hormonal therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Databases, Factual, Receptor, ErbB-2 metabolism
- Abstract
Hormone receptor-positive (HR
+ ) human epidermal growth factor receptor-2 negative (HER2- ) tumors represent the most common subtype of metastatic breast cancer (MBC). International guidelines clearly state that endocrine therapy (ET) should be considered the preferred first-line therapy for these patients in the absence of very symptomatic visceral disease or evidence of endocrine resistance. Nonetheless compliance with guidelines significantly vary worldwide for many different reasons. Historically, a substantial proportion of patients with HR+ HER2- MBC have been treated with chemotherapy (CT) in first-line setting, jeopardizing patients' quality of life without a significant benefit in outcome. In 17 observational studies, including more than 63,000 patients, ET was most frequently used in first-line treatment of HR+ /HER2- MBC (range, 42%-87%), nonetheless a high proportion of patients received CT (13%-66%) as initial therapy. More recently, results of clinical trials with CDK 4/6 inhibitors improved response, progression-free and overall survival in this population and are currently the standard of care. There was a trend toward increased use of ET in recent years. This review article aims to evaluate real-world data on patterns of first-line treatment of HR+ HER2- MBC with a special focus on the use of CT in this setting and the potential implications and perceived preliminary changes after the introduction of CDK 4/6 inhibitors., (Copyright © 2021. Published by Elsevier Inc.)- Published
- 2021
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50. Perspectives on emerging technologies, personalised medicine, and clinical research for cancer control in Latin America and the Caribbean.
- Author
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Werutsky G, Barrios CH, Cardona AF, Albergaria A, Valencia A, Ferreira CG, Rolfo C, de Azambuja E, Rabinovich GA, Sposetti G, Arrieta O, Dienstmann R, Rebelatto TF, Denninghoff V, Aran V, and Cazap E
- Subjects
- Artificial Intelligence, Big Data, Biomedical Research statistics & numerical data, Caribbean Region epidemiology, Digital Technology, Electronic Health Records, Humans, Latin America epidemiology, Neoplasms epidemiology, Precision Medicine statistics & numerical data, Biomedical Research trends, Neoplasms prevention & control, Precision Medicine trends
- Abstract
Challenges of health systems in Latin America and the Caribbean include accessibility, inequity, segmentation, and poverty. These challenges are similar in different countries of the region and transcend national borders. The increasing digital transformation of health care holds promise of more precise interventions, improved health outcomes, increased efficiency, and ultimately reduced health-care costs. In Latin America and the Caribbean, the adoption of digital health tools is in early stages and the quality of cancer registries, electronic health records, and structured databases are problematic. Cancer research and innovation in the region are limited due to inadequate academic resources and translational research is almost fully dependent on public funding. Regulatory complexity and extended timelines jeopardise the potential improvement in participation in international studies. Emerging technologies, artificial intelligence, big data, and cancer research represent an opportunity to address the health-care challenges in Latin America and the Caribbean collectively, by optimising national capacities, sharing and comparing best practices, and transferring scientific and technical capabilities., Competing Interests: Declaration of Interests CHB reports institutional research grant from Pfizer, Pharma Mar, Polyphor, Henlius Biotech, Merck KGaA, Millennium, LEO Pharma, ImClone Systems, Exelixis, Medivation, Asana Biosciences, AB Science, Abraxis Biosciences, Daiichi Sankyo, Bristol Myers Squibb, BioMarin, Astellas Pharma, AbbVie, Merck Sharp & Dohme, Merrimack, Mylan, Taiho Pharmaceutical, Sanofi, GlaxoSmithKline, Roche/Genentech, Lilly, Boehringer Ingelheim, Novartis, AstraZeneca, and Amgen; advisory board consulting from Boehringer Ingelheim, Sanofi, Lilly, Zodiac, AstraZeneca, Merck Sharp & Dohme, Bayer, Eisai, Roche/Genentech, Pfizer, Novartis, and GlaxoSmithKline; and stocks from MedSIR, Biomarker, and Tummi, outside the submitted work; he declares no relevant conflicts of interests related to this Series paper. AFC declares financial research support from Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol Myers Squibb, and The Foundation for Clinical and Applied Cancer Research (FICMAC); he received honoraria as advisor, participated in speakers’ bureau, and gave expert testimony to Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol Myers Squibb, Pfizer, Novartis, Celldex Therapeutics, Foundation Medicine, Eli Lilly, and FICMAC. CR reports grants or contracts from Pfizer–Lung Cancer Research Foundation (for the EMPOWER ME trial); consulting fees (for advisory board) from ArcherDX, Bristol Myers Squibb, Novartis, and Boston Pharmaceuticals; payment or honoraria for educational events from AstraZeneca, Roche, and Merck Sharp & Dohme; participation on a safety monitoring board from MD Serono; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from the International Society of Liquid Biopsy (Vice President), the International Association for the Study of Lung Cancer (Deputy Chair of the Educational Committee), European School of Oncology (Scientific Board Member), the European Society for Medical Oncology (Faculty of Advanced Lung Cancer), and research support (unpaid) from Guardant Health. EdA reports research support and grants from Roche; and grants from Libbs, Pierre Fabre, Zodiacs, Seattle Genetics, Novartis, Roche, Servier, AstraZeneca, and GlaxoSmithKline, outside the submitted work. OA reports personal fees from Pfizer, Lilly, Merck, and Bristol Myers Squibb; and grants and personal fees from AstraZeneca, Boehringer Ingelheim, and Roche, outside the submitted work. RD declares advisory role for Roche and Boehringer Ingelheim; speaker's fees from Roche, Ipsen, Amgen, Servier, Sanofi, Libbs, and Merck Sharp & Dohme; and research grants from Merck and Pierre Fabre, outside the submitted work. EC reports honoraria for lectures and consulting or advisory role from Merck outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
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- 2021
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