Molecular characterization of metastatic penile squamous cell carcinoma in developing countries and its impact on clinical outcomes: LACOG 2018 translational study.

BACKGROUND: Penile squamous cell carcinoma (PSCC) is a rare malignancy. However, in developing countries the incidence rate is higher. The understanding of molecular alterations is essential for evaluating possible targets for more effective systemic therapies. METHODS: We retrospectively collected clinical data of metastatic PSCC (mPSCC) patients who had received at least one prior systemic treatment from 3 Brazilian hospitals. Tumor samples were evaluated using the next-generation sequencing (NGS) Foundation One DX and immunohistochemistry (IHC). The objective was to identify and describe somatic genomic alterations known to be functional or pathogenic and their association with survival outcomes. RESULTS: Twenty-three patients were identified, 22 and 18 patients had tumor samples analyzed by IHC and NGS, respectively. PD-L1 expression (CPS ≥ 1%) was positive in 14 patients (63.6%). Regarding the genomic alterations, 16 patients (88.9%) had some clinically relevant genomic alterations. TP53, TERT, CDKN2A, PIK3CA, NOTCH1, and CDKN2B loss were identified in 66.7%, 50%, 50%, 33.3%, 27.8%, and 22.2% of the patients, respectively. No MSI or TMB high (≥10 mutations/MB) cases were identified. NOTCH1 mutation was identified only in HPV-negative patients and it was associated with worse OS (yes: 5.5 vs no: 12.8 months, P = .049) and progression-free survival (yes: 5.5 vs no: 11.7 months, P = .032). CONCLUSION: This study demonstrated that molecular alterations in mPSCC from developing countries are similar to those from developed countries. Predictive biomarkers for immunotherapy response such as TMB high or MSI were not identified. Specific gene mutations may identify patients with worse prognoses and open new avenues for therapeutic development.

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.

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.

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 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.

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.