Quality of Life in Male Breast Cancer: Prospective Study of the International Male Breast Cancer Program (EORTC10085/TBCRC029/BIG2-07/NABCG).

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.

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).

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.

Results of a survey study on health professionals' perceptions of tumor boards in Brazil.

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.

Moderately hypofractionated post-operative radiation therapy for breast cancer: preferences amongst radiation oncologists from countries in Latin America and the Caribbean.

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.

Influence of physician's lifestyle on the prescription of healthy habits to breast cancer patients (LACOG 1218).

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.

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

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.

Perspectives on emerging technologies, personalised medicine, and clinical research for cancer control in Latin America and the Caribbean.

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.

Cancer control in Latin America and the Caribbean: recent advances and opportunities to move forward.

The increasing burden of cancer represents a substantial problem for Latin America and the Caribbean. Two Lancet Oncology Commissions in 2013 and 2015 highlighted potential interventions that could advance cancer care in the region by overcoming existing challenges. Areas requiring improvement included insufficient investment in cancer control, non-universal health coverage, fragmented health systems, inequitable concentration of cancer services, inadequate registries, delays in diagnosis or treatment initiation, and insufficient palliative services. Progress has been made in key areas but remains uneven across the region. An unforeseen challenge, the COVID-19 pandemic, strained all resources, and its negative effect on cancer control is expected to continue for years. In this Series paper, we summarise progress in several aspects of cancer control since 2015, and identify persistent barriers requiring commitment of additional resources to reduce the cancer burden in Latin America and the Caribbean.

The impact of sociodemographic factors and health insurance coverage in the diagnosis and clinicopathological characteristics of breast cancer in Brazil: AMAZONA III study (GBECAM 0115).

PURPOSE: In Brazil, the available cancer registries are deficient in number and quality and, hence, little information is known regarding sociodemographic, clinicopathological characteristics, treatment patterns, and outcomes of breast cancer (BC) patients. We performed the AMAZONA III/ GBECAM 0115 study and in this analysis, we describe patients' characteristics at diagnosis and their association with health insurance type. METHODS: This is a prospective cohort study developed in 23 sites in Brazil including women with newly diagnosed invasive BC from January 2016 to March 2018. In order to compare healthcare insurance type, we considered patients who were treated under the Brazilian public health system as publicly insured, and women who had private insurance or paid for their treatment as privately insured. RESULTS: A total of 2950 patients were included in the study. Median age at diagnosis was 53.9 years; 63.1% were publicly insured. The majority of patients (68.6%) had stage II-III breast cancer and ductal carcinoma histology (80.9%). The most common breast cancer subtype was luminal A-like (48.0%) followed by luminal B-HER2 positive-like (17.0%) and triple-negative (15.6%). Luminal A was more frequent in private (53.7% vs. 44.2%, p < .0001) than public, whereas Luminal B HER2-positive (19.2% vs. 14.2%, p = 0.0012) and HER2-positive (8.8% vs. 5.1%, p = 0.0009) were more common in patients with public health system coverage. Only 34% of patients were diagnosed by screening exams. Privately insured patients were more frequently diagnosed with stage I disease when compared to publicly insured patients; publicly insured patients had more stage III (33.5% vs. 14.7%; p-value < 0.0001) disease than privately insured ones. Breast cancer was detected by symptoms more frequently in publicly than in privately insured patients (74.2% vs 25.8%, respectively; p-value < 0.0001). CONCLUSIONS: Patients with public health coverage were diagnosed with symptomatic disease, later stages and more aggressive subtypes when compared to privately insured patients.

The LACOG-0415 phase II trial: abiraterone acetate and ADT versus apalutamide versus abiraterone acetate and apalutamide in patients with advanced prostate cancer with non-castration testosterone levels.

BACKGROUND: Testosterone suppression is the standard treatment for advanced prostate cancer, and it is associated with side-effects that impair patients' quality of life, like sexual dysfunction, osteoporosis, weight gain, and increased cardiovascular risk. We hypothesized that abiraterone acetate with prednisone (AAP) and apalutamide, alone or in combination, can be an effective hormonal therapy also possibly decreasing castration-associated side effects. METHODS: Phase II, open-label, randomized, efficacy trial of abiraterone acetate plus prednisone (AAP) and Androgen Deprivation Therapy (ADT) versus apalutamide versus the combination of AAP (without ADT) and apalutamide. Key eligibility criteria are confirmed prostate adenocarcinoma; biochemical relapse after definitive treatment (PSA ≥ 4 ng/ml and doubling time less than 10 months, or PSA ≥ 20 ng/ml); newly diagnosed locally advanced or metastatic prostate cancer; asymptomatic to moderately symptomatic regarding bone symptoms. Patients with other histology besides adenocarcinoma or previous use of hormonal therapy or chemotherapy were excluded. DISCUSSION: There is an urgent need to study and validate regimens such as new hormonal agents that may add benefit to castration with an acceptable safety profile. We aim to evaluate if apalutamide in monotherapy or in combination with AAP is an effective and safety hormonal treatment that can spare patients of androgen deprivation therapy. TRIAL REGISTRATION: This trial was registered in ClinicalTrials.gov on October 16, 2017, under Identifier: NCT02867020.

PET-CT has low specificity for mediastinal staging of non-small-cell lung cancer in an endemic area for tuberculosis: a diagnostic test study (LACOG 0114).

BACKGROUND: The present study aims to assess the performance of 18F-FDG PET-CT on mediastinal staging of non-small cell lung cancer (NSCLC) in a location with endemic granulomatous infectious disease. METHODS: Diagnostic test study including patients aged 18 years or older with operable stage I-III NSCLC and indication for a mediastinal lymph node biopsy. All patients underwent a 18F-FDG PET-scan before invasive mediastinal staging, either through mediastinoscopy or thoracotomy, which was considered the gold-standard. Surgeons and pathologists were blinded for scan results. Primary endpoint was to evaluate sensitivity, specificity and positive and negative predictive values of PET-CT with images acquired in the 1st hour of the exam protocol, using predefined cutoffs of maximal SUV, on per-patient basis. RESULTS: Overall, 85 patients with operable NSCLC underwent PET-CT scan followed by invasive mediastinal staging. Mean age was 65 years, 49 patients were male and 68 were white. One patient presented with active tuberculosis and none had HIV infection. Using any SUV_max > 0 as qualitative criteria for positivity, sensitivity and specificity were 0.87 and 0.45, respectively. Nevertheless, even when the highest SUV cut-off was used (SUV_max ≥5), specificity remained low (0.79), with an estimated positive predictive value of 54%. CONCLUSIONS: Our findings are in line with the most recent publications and guidelines, which recommend that PET-CT must not be solely used as a tool to mediastinal staging, even in a region with high burden of tuberculosis. TRIAL REGISTRATION: The LACOG 0114 study was registered at ClinicalTrials.gov , before study initiation, under identifier NCT02664792.

Planning cancer control in Latin America and the Caribbean.

Non-communicable diseases, including cancer, are overtaking infectious disease as the leading health-care threat in middle-income and low-income countries. Latin American and Caribbean countries are struggling to respond to increasing morbidity and death from advanced disease. Health ministries and health-care systems in these countries face many challenges caring for patients with advanced cancer: inadequate funding; inequitable distribution of resources and services; inadequate numbers, training, and distribution of health-care personnel and equipment; lack of adequate care for many populations based on socioeconomic, geographic, ethnic, and other factors; and current systems geared toward the needs of wealthy, urban minorities at a cost to the entire population. This burgeoning cancer problem threatens to cause widespread suffering and economic peril to the countries of Latin America. Prompt and deliberate actions must be taken to avoid this scenario. Increasing efforts towards prevention of cancer and avoidance of advanced, stage IV disease will reduce suffering and mortality and will make overall cancer care more affordable. We hope the findings of our Commission and our recommendations will inspire Latin American stakeholders to redouble their efforts to address this increasing cancer burden and to prevent it from worsening and threatening their societies.

Long-Term Safety and Effectiveness of Rituximab Biosimilar RTXM83: A Retrospective Extension Study in Brazilian Patients with Diffuse Large B-Cell Lymphoma.

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".

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.

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).

Real-World Evidence of Ribociclib Plus Aromatase Inhibitors as First-Line Treatment in Advanced Breast Cancer: The BrasiLEEira Study.

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.

Health Services Access Inequalities in Brazil Result in Poorer Outcomes for Stage III NSCLC-RELANCE/LACOG 0118.

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.

Improving access to cancer clinical research in Brazil: recent advances and new opportunities. Expert opinions from the 4th CURA meeting, São Paulo, 2023.

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.

The impact of a breast cancer diagnosis on marital outcomes and factors associated with divorce and separation.

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.

Exploring locoregional treatment reporting in neoadjuvant systemic breast cancer treatment studies: A systematic review.

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.

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.

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.