Changes in attachment dimensions during the treatment of acute post-traumatic stress disorder in sexually assaulted Brazilian women.

Introduction: Attachment patterns are established during early childhood; however, extreme experiences throughout life may change this structure, either toward attachment security or insecurity. We analyzed changes in attachment dimensions in women with acute post-traumatic stress disorder (PTSD) following sexual assault, that were randomized to a 14-week treatment with either the medication sertraline or Interpersonal Psychotherapy. Methods: Seventy-four adult women who presented significant reduction in PTSD symptoms across the trial responded to the Revised Adult Attachment Scale at baseline, on week 8 of treatment, and at the end of the trial, on week 14. We fitted a generalized linear model to explain the attachment anxiety and avoidance scores at baseline. A generalized linear mixed model investigated how attachment dimensions changed over time. Socioeconomic data, treatment type, history of childhood trauma, and PTSD severity over the 14-week period were the considered covariates. Results: At baseline, attachment anxiety was associated with a history of early trauma. Attachment anxiety remained stable during the follow-up. Attachment avoidance, on the other hand, significantly increased from baseline to week 14. Higher avoidance was observed in patients with higher total PTSD scores and on the cluster of hyperarousal symptoms. Races other than White (black, mixed-race, or Asian) and younger age were associated with higher attachment avoidance. Discussion: Contrary to our expectations, attachment avoidance increased during follow-up, indicating changes in the interpersonal realm beyond the symptoms of PTSD.

Risk of metastasis in BRCA2 carriers diagnosed with triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is the neoplasia most associated with BRCA1 germline pathogenic variants (PV) and is more likely to develop metastases than the other breast cancer (BC) subtypes, mainly in the lungs and the central nervous system (CNS). Recently, BRCA2 carriers were shown to have a higher risk for developing CNS metastases. However, the patterns of recurrence and metastases of BRCA2 carriers with TNBC are unknown. METHODS: TNBC patient data attending the A.C. Camargo Cancer Center, from 1998 through 2020, were verified either by medical records or by BRCA1/2 genetic testing carried out. Multivariable logistic regression models were fit to the data to assess the independent factors for bone and CNS metastases. Adjustment was done using all independent variables with p < 0.2 in the univariable Cox model to describe the relationship between the independent variables until time of death. RESULTS: A total of 388 TNBC patients were evaluated. We identified PV in BRCA1/2 genes in 21% (82/388), being 17.7% (69/388) in BRCA1 and only 3.3% (13/388) in BRCA2. A total of 120 patients (31%) developed distant metastases. Bone or CNS metastases were observed in 40% and 60% of BRCA2 PV carriers (p = 0.155), respectively. The BRCA2 carriers tended to have a higher likelihood of developing bone metastases (OR, 4.06; 95% CI, 0.82-20.01; p = 0.085), when compared to BRCA1 carriers (OR, 0.6; 95% CI, 0.12-2.87; p = 0.528). BRCA2 carriers had an OR of 1.75 (95% CI, 0.33-9.14; p = 0.503) for CNS metastasis development, while BRCA1 carriers had an OR of 0.72 (95% CI, 0.23-2.23; p = 0.574). CONCLUSIONS: Patients with TNBC and PV in the BRCA2 gene had higher frequencies of secondary bone involvement and CNS in the course of the disease. However, the BRCA2 PV did not represent an independent outcome predictor of metastases and overall survival. Efforts to increase the number of BRCA2 carriers among TNBC patients are crucial for determining their risk of developing bone and CNS metastases compared to BRCA2 noncarriers.

COLORECTAL CANCER: ASSOCIATION BETWEEN SOCIODEMOGRAPHIC VARIABLES AND THE ADHERENCE TO CANCER SCREENING.

BACKGROUND: Colorectal cancer (CRC) is a worldwide health problem whose control depends on public policy establishment and effective prevention and screening programs. In Brazil, there are few studies related to adherence to screening methods. AIMS: The aim of this study was to evaluate the association between demographic and socioeconomic to adherence to CRC screening with fecal immunochemical test (FIT) among average-risk individuals for CRC. METHODS: In this prospective cross-sectional study, conducted between March 2015 and April 2016, 1,254 asymptomatic individuals aged 50-75 years, participating in a hospital screening campaign in Brazil, were invited to participate in the study. RESULTS: The adherence rate to FIT was 55.6% (697/1,254). In the multivariable logistic regression analysis, patients aged 60-75 years (odds ratio (OR)=1.30; 95% confidence interval (CI): 1.02-1.66; p=0.03), religious belief (OR=2.04; 95% CI: 1.34-3.11; p<0.01), previous fecal occult blood test (OR=2.07; 95% CI: 1.55-2.76; p<0.01), and full/part-time working status (OR=0.66; 95% CI: 0.49-0.89; p<0.01) were independently associated with adherence to CRC screening. CONCLUSION: The results of the present study highlight the importance of considering the labor aspects when implementing screening programs, suggesting that campaigns conducted in the workplace and repeated over the years may be more effective.

Sex with animals among men attended in referral centers for sexually transmitted infections in northeast Brazil: prevalence, associated factors and behavioral aspects

ABSTRACT Purpose Our objective was to investigate the prevalence of SWA, associated factors, relationship with STIs, and behavioral aspects in men attended at Referral Centers for STIs and acquired immunodeficiency syndrome (AIDS)/CR-STI/AIDS in northeast Brazil. Materials and Methods In this cross-sectional study, a questionnaire with sociodemographic, clinical, sexual and SWA practices information was applied to 400 men attended at two CR-STI/AIDS in Northeast Brazil on the years of 2018 and 2019. Clinical and laboratory diagnoses of STIs were confirmed in medical records. Logistic regression models were performed to identify the independent predictors for SWA. Results The prevalence of SWA over total samples was 15.00%. Of the participants, 239 (59.75%) of the participants were diagnosed with STIs, and of these 37 (15.48%) reported SWA. Most men practiced SWA in adolescence, being the last episode more than 20 years ago, usually with asinine and mules, in vaginal route and without a condom. SWA practitioners have higher percentages of occurrence of some viral STIs. SWA was associated with increasing age, history of residence in a rural area with remained over 12 years, married or widowed/separated, heterosexuals, with less than 7 years of study, Catholics, with hepatitis B, former user of alcoholic beverages and smokers, with a history of STI and intercourse with sex workers. Conclusion SWA practices increase STIs vulnerability. The association between hepatitis B and SWA highlights the importance of educational campaigns and conclusive studies on the topic.

Sex with animals among men attended in referral centers for sexually transmitted infections in northeast Brazil: prevalence, associated factors and behavioral aspects.

PURPOSE: Our objective was to investigate the prevalence of SWA, associated factors, relationship with STIs, and behavioral aspects in men attended at Referral Centers for STIs and acquired immunodeficiency syndrome (AIDS)/CR-STI/AIDS in northeast Brazil. MATERIALS AND METHODS: In this cross-sectional study, a questionnaire with sociodemographic, clinical, sexual and SWA practices information was applied to 400 men attended at two CR-STI/AIDS in Northeast Brazil on the years of 2018 and 2019. Clinical and laboratory diagnoses of STIs were confirmed in medical records. Logistic regression models were performed to identify the independent predictors for SWA. RESULTS: The prevalence of SWA over total samples was 15.00%. Of the participants, 239 (59.75%) of the participants were diagnosed with STIs, and of these 37 (15.48%) reported SWA. Most men practiced SWA in adolescence, being the last episode more than 20 years ago, usually with asinine and mules, in vaginal route and without a condom. SWA practitioners have higher percentages of occurrence of some viral STIs. SWA was associated with increasing age, history of residence in a rural area with remained over 12 years, married or widowed/separated, heterosexuals, with less than 7 years of study, Catholics, with hepatitis B, former user of alcoholic beverages and smokers, with a history of STI and intercourse with sex workers. CONCLUSION: SWA practices increase STIs vulnerability. The association between hepatitis B and SWA highlights the importance of educational campaigns and conclusive studies on the topic.

Intraoperative radiotherapy for brain metastases: first-stage results of a single-arm, open-label, phase 2 trial.

OBJECTIVE: Focal stereotactic radiosurgery to the surgical cavity lowers local recurrence after resection of brain metastases (BM). To evaluate local control (LC) and brain disease control (BDC) after intraoperative radiotherapy (IORT) for resected BM. METHODS: Adult patients with completely resected single supratentorial BM were recruited and underwent IORT to the cavity with a prescribed dose of 18 Gy to 1 mm-depth. Primary endpoints were actuarial LC and BDC. Local failure (LF) and distant brain failure (DBF), with death as a competing risk, were estimated. Secondary endpoints were overall survival (OS) and incidence of radiation necrosis (RN). Simon's two-stage design was used and estimated an accrual of 10 patients for the first-stage analysis and a LC higher than 63% to proceed to second stage. We report the final analysis of the first stage. RESULTS: Between June 2019 to November 2020, 10 patients were accrued. Median clinical and imaging FU was 11.2 and 9.7 months, respectively. Median LC was not reached and median BDC was 5 months. The 6-month and 12-month LC was 87.5%. The 6-month and 12-month BDC was 39% and 13%, respectively. Incidence of LF at 6 and 12 months was 10% and of DBF at 6 and 12 months was 50% and 70%, respectively. Median OS was not reached. The 6-month and 12-month OS was 80%. One patient had asymptomatic RN. CONCLUSION: IORT for completely resected BM is associated with a potential high local control and low risk of RN, reaching the pre-specified criteria to proceed to second stage and warranting further studies.

Randomized clinical trial of tissue equivalent bolus prescription in postmastectomy radiotherapy stratified by skin involvement status.

Purpose: To assess the impact and optimize the prescription of tissue-equivalent bolus in postmastectomy radiotherapy (PMRT), we compared the use of different bolus regimens tailored by skin involvement status. Methods: Patients with breast cancer who required PMRT were recruited (NCT01925651) and classified into two groups: standard-risk (SR, without skin involvement) and high-risk (HR, with skin involvement). SR was randomized between no bolus or 5 mm-bolus on alternate days and HR between 5 mm-bolus on alternate days or daily. Conventional fractionation (50.4 Gy; 1.8 Gy/daily) was used. Acute skin toxicity was evaluated blindly and the radiodermatitis-specific toxicity index [rads-TI] calculated. Subsequently, patients were followed up to assess oncologic outcomes, focusing on chest wall (CW) local control. Results: Fifty-eight patients were enrolled (34 SR and 24 HR). Baseline characteristics were similar between arms within the same risk group. Overall, maximal radiodermatitis rates were 29.4 % (G2) and 15.7 % (G3). In the SR group, no difference existed in G2 radiodermatitis incidence between the subgroups (p = 0.70) and no G3 events occurred. In the HR group, incidences of G2 (100 % vs 44.5 %, p = 0.01) and G3 radiodermatitis (70 % vs 11.1 %, p = 0.02) were higher with daily bolus. After adjusting for confounders, the daily bolus had a higher incidence of G2 (p = 0.03), G3 radiodermatitis (p = 0.04), and worse rads-TI (p < 0.01). After a median follow-up of 6.2 years, the 5-year local control was 95.8 % (95 %CI: 88.2 %-100 %) in the SR and 91.7 % (95 %CI: 77.3 %-100 %) in the HR groups. Per risk group, there was no difference in local control between the SR (p = 0.90) or the HR bolus regimens (p = 0.70). Conclusion: Daily 5 mm bolus prescription significantly increased the overall toxicity burden. In this preliminary study, within the same risk group, no detriment in CW local control was detected with less intense bolus regimens (SR: no bolus; HR: alternate-days bolus). Additionally, the rads-TI was able to distinguish overall radiodermatitis burden.

Câncer colorretal: associação entre variáveis sociodemográficas e a adesão a programas de rastreamento / Colorectal cancer: association between sociodemographic variables and the adherence to cancer screening

ABSTRACT BACKGROUND Colorectal cancer (CRC) is a worldwide health problem whose control depends on public policy establishment and effective prevention and screening programs. In Brazil, there are few studies related to adherence to screening methods. AIMS: The aim of this study was to evaluate the association between demographic and socioeconomic to adherence to CRC screening with fecal immunochemical test (FIT) among average-risk individuals for CRC. METHODS: In this prospective cross-sectional study, conducted between March 2015 and April 2016, 1,254 asymptomatic individuals aged 50-75 years, participating in a hospital screening campaign in Brazil, were invited to participate in the study. RESULTS: The adherence rate to FIT was 55.6% (697/1,254). In the multivariable logistic regression analysis, patients aged 60-75 years (odds ratio (OR)=1.30; 95% confidence interval (CI): 1.02-1.66; p=0.03), religious belief (OR=2.04; 95% CI: 1.34-3.11; p<0.01), previous fecal occult blood test (OR=2.07; 95% CI: 1.55-2.76; p<0.01), and full/part-time working status (OR=0.66; 95% CI: 0.49-0.89; p<0.01) were independently associated with adherence to CRC screening. CONCLUSION: The results of the present study highlight the importance of considering the labor aspects when implementing screening programs, suggesting that campaigns conducted in the workplace and repeated over the years may be more effective.

RESUMO RACIONAL: O câncer colorretal (CCR) é um problema de saúde mundial cujo controle depende do estabelecimento de políticas públicas e programas de prevenção e rastreamento eficazes. No Brasil existem poucos estudos relacionados à adesão métodos de rastreamento. OBJETIVO: Avaliar a associação de características sócio-demográficas à realização de testes de sangue oculto nas fezes do tipo imunoquimicomecanizado (FIM) em população de médio risco para o desenvolvimento de câncer colorretal. MÉTODOS: Estudo observacional transversal, com coleta prospectiva de dados. Entre março de 2015 e abril de 2016, 1.254 indivíduos assintomáticos, com idade entre 50 e 75 anos, foram consecutivamente selecionados a partir de uma campanha hospitalar de rastreamento para neoplasias. RESULTADOS: As taxas de adesão ao teste FIM foi 55.6% (697/1254). Na análise de regressão logística múltipla os fatores independentes associados à adesão ao rastreamento do CCR foram: Idade entre 60-75 anos (oddsratio (OR)=1.30; intervalo de confiança de 95% (IC): 1.02-1.66; p=0.03), crença religiosa (OR=2.04; 95%IC: 1.34-3.11; p<0.01), realização prévia de exame de sangue oculto nas fezes (OR=2.07; 95%IC: 1.55-2.76; p<0.01) e vínculo empregatício em período integral ou parcial (OR=0.66; 95%IC: 0.49-0.89; p<0.01). CONCLUSÃO: Este estudo enfatiza a importância de considerar aspectos laborais ao implementar programas de rastreamento do câncer colorretal e sugere que campanhas de rastreamento implantadas no ambiente de trabalho e de maneira repetida ao longo dos anos podem ser mais efetivas.

A cross-sectional study of clinical, dermoscopic, histopathological, and molecular patterns of scalp melanoma in patients with or without androgenetic alopecia.

Scalp melanoma (SM) has a worse prognosis than melanoma in other locations likely because of late diagnosis due to hair coverage, difficulties in interpreting dermoscopy findings, and its unique molecular profile. We aimed to describe the clinical, histopathological, molecular, and dermoscopic patterns of SM and its relation to androgenetic alopecia/elastosis at the tumor site. Through a retrospective cross-sectional study, we identified all SM diagnosed at the A.C.Camargo Cancer Center between 2008 and 2018. In all, 48 SM were analyzed: 45.8% of which exhibited moderate/severe androgenetic alopecia and 54.1% exhibited elastosis. Androgenetic alopecia/elastosis at the site of the SM was associated with older age (p < 0.001), chronic sun damage (p < 0.001), lentigo maligna subtype (p = 0.029), and photodamaged dermoscopic pattern (p < 0.001). Additionally, 41 cases were evaluated with a 14-gene panel: 53.7% displayed mutations and 46.3% were wild-type. BRAF mutations were most common (77%), with BRAF V600K being more frequent (50%) than BRAF V600E (31.2%). The NF1 gene was evaluated in 40 samples, of which 20% exhibited mutations. SM presents differently in areas covered by hair compared to in areas with androgenetic alopecia. Patients without alopecia may have higher Breslow thickness due to late diagnosis because of hair concealment. The high frequency of detrimental mutations can also explain the poor prognosis of SM.

Heterogeneity of HER2 Expression in Circulating Tumor Cells of Patients with Breast Cancer Brain Metastases and Impact on Brain Disease Control.

HER2 expression switching in circulating tumor cells (CTC) in breast cancer is dynamic and may have prognostic and predictive clinical implications. In this study, we evaluated the association between the expression of HER2 in the CTC of patients with breast cancer brain metastases (BCBM) and brain disease control. An exploratory analysis of a prospective assessment of CTC before (CTC1) and after (CTC2) stereotactic radiotherapy/radiosurgery (SRT) for BCBM in 39 women was performed. Distant brain failure-free survival (DBFFS), the primary endpoint, and overall survival (OS) were estimated. After a median follow-up of 16.6 months, there were 15 patients with distant brain failure and 16 deaths. The median DBFFS and OS were 15.3 and 19.5 months, respectively. The median DBFFS was 10 months in patients without HER2 expressed in CTC and was not reached in patients with HER2 in CTC (p = 0.012). The median OS was 17 months in patients without HER2 in CTC and was not reached in patients with HER2 in CTC (p = 0.104). On the multivariate analysis, DBFFS was superior in patients who were primary immunophenotype (PIP) HER2-positive (HR 0.128, 95% CI 0.025-0.534; p = 0.013). The expression of HER2 in CTC was associated with a longer DBFFS, and the switching of HER2 expression between the PIP and CTC may have an impact on prognosis and treatment selection for BCBM.

Comparison of hormonal receptor expression and HER2 status between circulating tumor cells and breast cancer metastases.

OBJECTIVES: Breast cancer (BC) is the most common neoplasm in women. Biopsy of metastatic lesions is recommended to confirm estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status as there are discrepancies in these patterns between primary tumors and metastases in up to 40% of the cases. Circulating tumor cells (CTCs) are related to BC outcomes and could potentially be an alternative to the invasive procedures of metastasis rebiopsy. ISET® technology is not currently employed to detect CTCs in patients with BC. Emerging data support that the characterization of CTC protein expression can refine its prognostic value. Transforming growth factor (TGF)-ß plays a role in BC progression and invasiveness. Thus, in this study, we aimed to compare ER, PR, and HER2 expression in primary tumors, CTCs, and metastases and evaluate TGF-ß type 1 receptor (TGF-ß RI) expression in CTCs as prognostic factor for progression free survival (PFS) and overall survival (OS). METHODS: This prospective study was conducted at the A.C. Camargo Cancer Center, Brazil. Blood samples were processed in ISET® (Isolation by SizE of Tumors, Rarecells, France) before computed tomography-guided biopsy of suspected metastatic lesions. Protein expression levels in CTCs were compared to those in primary tumors/metastases (medical records). RESULTS: Of the 39 patients initially included, 27 underwent both biopsies of metastases and blood collection and were considered for analysis. The concordance rates for ER, PR, and HER2 expression between primary tumors and metastases were high. No loss of HER2 expression at any metastasis site and retention of the same pattern of protein expression in all triple-negative (TN) tumors (92.5%, 81.5% and 96.2% respectively) (p<0.0001) was observed. When metastases/CTCs were classified as TN/non-TN, CTCs showed high specificity (93%), accuracy (84.2%), and negative predictive value (88%). The median OS of patients without TGF-ß RI expression in CTCs was 42.6 versus 20.8 months for TGF-ß RI expression-positive ones (p>0.05). CONCLUSION: The role of CTCs detected by ISET has not yet been established in BC. Here, we suggest that this methodology may be useful to evaluate metastasis in non-TN cases as well as TGF-ß RI expression in CTCs, which may impact patient survival. Due to sample limitations, future studies must focus on specific BC subtypes and an expansion of the cohort.

Molecular and Dynamic Evaluation of Proteins Related to Resistance to Neoadjuvant Treatment with Chemoradiotherapy in Circulating Tumor Cells of Patients with Locally Advanced Rectal Cancer.

The heterogeneity of response to neoadjuvant chemoradiotherapy (NCRT) is still a challenge in locally advanced rectal cancer (LARC). The evaluation of thymidylate synthase (TYMS) and RAD23 homolog B (RAD23B) expression in circulating tumor cells (CTCs) provides complementary clinical information. CTCs were prospectively evaluated in 166 blood samples (63 patients) with LARC undergoing NCRT. The primary objective was to verify if the absence of RAD23B/TYMS in CTCs would correlate with pathological complete response (pCR). Secondary objectives were to correlate CTC kinetics before (C1)/after NCRT (C2), in addition to the expression of transforming growth factor-ß receptor I (TGF-ßRI) with survival rates. CTCs were isolated by ISET and evaluated by immunocytochemistry (protein expression). At C1, RAD23B was detected in 54.1% of patients with no pCR and its absence in 91.7% of patients with pCR (p = 0.014); TYMS- was observed in 90% of patients with pCR and TYMS+ in 51.7% without pCR (p = 0.057). Patients with CTC2 > CTC1 had worse disease-free survival (DFS) (p = 0.00025) and overall survival (OS) (p = 0.0036) compared with those with CTC2 ≤ CTC1. TGF-ßRI expression in any time correlated with worse DFS (p = 0.059). To conclude, RAD23B/TYMS and CTC kinetics may facilitate the personalized treatment of LARC.

Spinal block and delirium in oncologic patients after laparoscopic surgery in the Trendelenburg position: A randomized controlled trial.

Delirium is the most common postsurgical neurological complication and has a variable incidence rate. Laparoscopic surgery, when associated with the Trendelenburg position, can cause innumerable physiological changes and increase the risk of neurocognitive changes. The association of general anesthesia with a spinal block allows the use of lower doses of anesthetic agents for anesthesia maintenance and facilitates better control over postoperative pain. Our primary outcome was to assess whether a spinal block influences the incidence of delirium in oncologic patients following laparoscopic surgery in the Trendelenburg position. Our secondary outcome was to analyze whether there were other associated factors. A total of 150 oncologic patients who underwent elective laparoscopic surgeries in the Trendelenburg position were included in this randomized controlled trial. The patients were randomized into 2 groups: the general anesthesia group and the general anesthesia plus spinal block group. Patients were immediately evaluated during the postoperative period and monitored until they were discharged, to rule out the presence of delirium. Delirium occurred in 29 patients in total (22.3%) (general anesthesia group: 30.8%; general anesthesia plus spinal block: 13.8% p = 0.035). Patients who received general anesthesia had a higher risk of delirium than patients who received general anesthesia associated with a spinal block (odds ratio = 3.4; 95% confidence interval: 1.2-9.6; p = 0.020). Spinal block was associated with reduced delirium incidence in oncologic patients who underwent elective laparoscopic surgeries in the Trendelenburg position.

Baseline and Kinetic Circulating Tumor Cell Counts Are Prognostic Factors in a Prospective Study of Metastatic Colorectal Cancer.

The discovery of predictive biomarkers in metastatic colorectal cancer (mCRC) is essential to improve clinical outcomes. Recent data suggest a potential role of circulating tumor cells (CTCs) as prognostic indicators. We conducted a follow-on analysis from a prospective study of consecutive patients with mCRC. CTC analysis was conducted at two timepoints: baseline (CTC1; before starting chemotherapy), and two months after starting treatment (CTC2). CTC isolation/quantification were completed by ISET® (Rarecells, France). CTC expressions of drug resistance-associated proteins were evaluated. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Seventy-five patients were enrolled from May 2012 to May 2014. A CTC1 cut-off of >1.5 CTCs/mL was associated with an inferior median OS compared to lower values. A difference of CTC2-CTC1 > 5.5 CTCs/mL was associated with a reduced median PFS. By multivariate analysis, CTC1 > 1.5 CTCs/mL was an independent prognostic factor for worse OS. Multi-drug resistance protein-1 (MRP-1) expression was associated with poor median OS. CTC baseline counts, kinetics, and MRP-1 expression were predictive of clinical outcomes. Larger studies are warranted to explore the potential clinical benefit of treating mCRC patients with targeted therapeutic regimens guided by CTC findings.

Prospective Assessment of the Association Between Circulating Tumor Cells and Control of Brain Disease After Focal Radiation Therapy of Breast Cancer Brain Metastases.

PURPOSE: Predicting the risk of early distant brain failure (DBF) is in demand for management decisions in patients who are candidates for local treatment of brain metastases. This study aimed to analyze the association between circulating tumor cells (CTCs) and brain disease control after stereotactic radiation therapy/radiosurgery (SRT) for breast cancer brain metastasis (BCBM). METHODS AND MATERIALS: We prospectively assessed CTCs before (CTC1) and 4 to 5 weeks after (CTC2) SRT and their relationship with the number of new lesions (NL) suggestive of BCBM before SRT. CTC were quantified and analyzed by immunocytochemistry to evaluate the expression of the proteins COX2, EGFR, ST6GALNAC5, NOTCH1, and HER2. Distant brain failure-free survival (DBFFS), the primary endpoint, diffuse DBFFS (D-DBFFS), and overall survival were estimated. Analysis for DBF within 6 months, with death as competing risk, was performed. RESULTS: Patients were included between 2016 and 2018. CTCs were detected in all 39 patients before and in 34 of 35 patients after SRT. After median follow-up of 16.6 months, median DBFFS, D-DBFFS, and overall survival were 15.3, 14.1, and 19.5 months, respectively. DBF at 6 months was 40% with CTC1 ≤0.5 and 8.82% with CTC1 >0.5 CTC/mL (P = .007), and D-DBF at 6 months was 40% with CTC1 ≤0.5 and 0 with CTC1 >0.5 CTC/mL (P = .005) and 25% with NL/CTC1 >6.8 and 2.65% with NL/CTC1 ≤6.8 (P = .063). On multivariate analysis, DBFFS was inferior with CTC1 ≤0.5 (hazard ratio, 8.27; 95% confidence interval, 2.12-32.3; P = .002), and D-DBFFS was inferior with CTC1 ≤0.5 (hazard ratio, 10.22; 95% confidence interval, 1.99-52.41; P = .005). Protein expression was not associated with outcomes. CONCLUSIONS: These data suggest that CTC1 and NL/CTC1 may have a role as a biomarker of early diffuse DBF and as a subsequent guide between focal or whole-brain radiation therapy in patients with BCBM.

Efficacy and Incontinence Rates After Urethroplasty for Radiation-induced Urethral Stenosis: A Systematic Review and Meta-analysis.

OBJECTIVE: To estimate the efficacy of urethroplasty and rates of de novo stress urinary incontinence (SUI) in the specific setting of radiation-induced urethral stenosis. METHODS: A systematic search of databases (PubMed and EMBASE) was performed between 1980-2019 (CRD42020144845). Inclusion criteria were: (1) prior pelvic radiotherapy; (2) surgical urethroplasty; (3) rates of successful treatment and/or SUI development and (4) total case number provided. The pooled summary of stenosis resolution rate and SUI were calculated using the random-effects model weighted by the inverse variance. Accessory analyses were performed by reconstructive technique and type of RT. RESULTS: Ninety-six studies were identified, of which 8 retrospective studies met inclusion criteria, comprising 256 patients. The proportion of cases treated with external beam RT (EBRT), brachytherapy (BT), or combination (EBRT+BT) were 52%, 33%, and 15%, respectively, of studies that specified modality. Most strictures involved the bulbomembranous region (n = 212; 83%). Sixty-one percent of cases (n = 157) entailed primary anastomosis, while the remainder underwent augmentation reconstruction (graft or flap). The mean follow-up time after urethroplasty varied from 10 to 50.5 months. The pooled stenosis resolution rate was 80% (95% CI: 74%-86%). There were no significant associations between stenosis resolution rate and reconstructive technique (rho=0.20, P = .74) or RT modality (rho=-0.31, P = .53). Fifty-three cases developed subsequent SUI, with a pooled complication rate of 19% (95% CI: 10%-31%). CONCLUSIONS: Urethroplasty after radiation-induced urethral stenosis is effective for 80% of cases, independent of prior RT modality or urethroplasty technique; however, 1 out of every 5 patients develops SUI post-procedure.

Opinião de médicos brasileiros sobre o tratamento da COVID-19 / Opinion of Brazilian physicians on the treatment of COVID-19 / Opinión de médicos brasileños sobre el tratamiento de la COVID-19

Objetivo: Investigar a opinião de médicos brasileiros sobre o tratamento precoce da COVID-19 com hidroxicloroquina/ cloroquina e azitromicina em pacientes com suspeita clínica e sobre o tratamento com corticoterapia na fase inflamatória da doença. Métodos: Trata-se de uma pesquisa de opinião, com amostragem por conveniência, com médicos atuantes no Brasil. A coleta dos dados ocorreu no período de 26 de maio a 8 de junho de 2020 (13 dias), por meio de um formulário Google, disponibilizado publicamente nas redes sociais e aplicativos de comunicação. Realizou-se uma análise descritiva dos dados, teste de independência, teste T Student e modelo de regressão logística com análise multivariada. Resultados: A pesquisa contou com 1.020 médicos participantes, com média de 21,9 anos de formado. 72,4% dos participantes apresentaram-se a favor do tratamento precoce com hidroxicloroquina/cloroquina e azitromicina e 89,7% dos médicos apresentaram-se favoráveis ao uso da corticoterapia para o tratamento da fase inflamatória da COVID-19. Constatou-se também que participantes com maior idade, com residência médica, atuantes nas regiões Nordeste e Norte possuíam mais chances de serem favoráveis aos tratamentos. Por outro lado, profissionais especialistas em medicina intensiva, infectologia e pneumologia, além de atuantes nas unidades de terapia intensiva, mostraram-se mais desfavoráveis. Conclusão: A maioria dos médicos investigados nesta pesquisa de opinião mostrou-se a favor do tratamento precoce apresentado e do uso da corticoterapia no tratamento da COVID-19. Já os especialistas em medicina intensiva, infectologia e pneumologia e profissionais atuantes nas Unidades de Terapia Intensiva mostraram-se mais desfavoráveis.

Objective: To investigate the opinion of Brazilian physicians on the early treatment of COVID-19 with hydroxychloroquine/ chloroquine and azithromycin in patients with clinical suspicion and on the treatment with corticosteroid therapy in the inflammatory stage of the disease. Methods: This is an opinion survey conducted with a convenient sample of physicians working in Brazil. Data were collected from May 26 to June 8, 2020 (13 days) through Google forms made publicly available on social media and chat applications. Data underwent descriptive analysis, independence test, Student t-test, and a logistic regression model using multivariate analysis. Results: The survey included 1020 physicians with a mean of 21.9 years since graduation. 72.4% of the participants were in favor of early treatment with hydroxychloroquine/chloroquine and azithromycin and 89.7% of the physicians were in favor of using corticosteroid therapy to treat the inflammatory stage of COVID-19. We also observed that older participants, those who completed medical residency, and those working in the Northeast and North regions were more likely to be in favor of the treatments. On the other hand, professionals specialized in intensive care medicine, infectious diseases and pneumology and working in intensive care units were more opposed. Conclusion: Most physicians in this opinion survey were in favor of the early treatment presented and the use of corticosteroid therapy in the treatment of COVID-19. But specialists in intensive care medicine, infectious diseases and pulmonology, and professionals working in Intensive Care Units were more opposed to them.

Objetivo: Investigar la opinión de médicos brasileños sobre el tratamiento precoz de la COVID-19 con la hidroxicloroquina/ cloroquina y la azitromicina en pacientes con sospecha clínica y bajo el tratamiento de corticoterapia en la fase inflamatoria de la enfermedad. Métodos: Se trata de una investigación de opinión con la muestra de conveniencia realizada con médicos de Brasil. La recogida de datos se dio en el periodo entre 26 de mayo y 8 de junio de 2020 (13 días) a través de un formulario Google que ha estado disponible públicamente en las redes sociales y los aplicativos de comunicación. Se realizó un análisis descriptivo de los datos, la prueba de independencia, la prueba T Student y el modelo de regresión logística con el análisis multivariado. Resultados: La investigación tuvo 1.020 médicos participantes, con la media de 21,9 años de término del grado. El 72,4% de los participantes se presentaron a favor del tratamiento precoz con la hidroxicloroquina/cloroquina y la azitromicina y el 89,7% de los médicos se presentaron favorables a la utilización de la corticoterapia para el tratamiento de la fase inflamatoria de la COVID-19. Se constató también que los participantes de más edad, con el curso de residencia medica y que eran de las regiones Noreste y Norte del país eran más favorables a los tratamientos. Los profesionales especialistas de la medicina intensiva, la infectologia y la neumología, además de actuaren en las unidades de cuidados intensivos parecieron más desfavorables. Conclusión: La mayoría de los médicos investigados de esa investigación de opinión se mostró favorable al tratamiento precoz presentado y a la utilización de la corticoterapia para el tratamiento de la COVID-19. Los especialistas de la medicina intensiva, la infectología y la neumología y los profesionales de las Unidades de Cuidados Intensivos se presentaron más desfavorables a los tratamientos.

Mutational Signatures Driven by Epigenetic Determinants Enable the Stratification of Patients with Gastric Cancer for Therapeutic Intervention.

DNA mismatch repair deficiency (dMMR) is associated with the microsatellite instability (MSI) phenotype and leads to increased mutation load, which in turn may impact anti-tumor immune responses and treatment effectiveness. Various mutational signatures directly linked to dMMR have been described for primary cancers. To investigate which mutational signatures are associated with prognosis in gastric cancer, we performed a de novo extraction of mutational signatures in a cohort of 787 patients. We detected three dMMR-related signatures, one of which clearly discriminates tumors with MLH1 gene silencing caused by promoter hypermethylation (area under the curve = 98%). We then demonstrated that samples with the highest exposure of this signature share features related to better prognosis, encompassing clinical and molecular aspects and altered immune infiltrate composition. Overall, the assessment of the prognostic value and of the impact of modifications in MMR-related genes on shaping specific dMMR mutational signatures provides evidence that classification based on mutational signature exposure enables prognosis stratification.

PD-L1 expression patterns in oral cancer as an integrated approach for further prognostic classification.

BACKGROUND: Despite the well-known role of programmed cell death ligand 1 (PD-L1) in promoting immune resistance in oral squamous cell carcinoma (OSCC), its potential utility as a prognostic biomarker is undetermined. We evaluated PD-L1 expression as predictor of survival in patients with OSCC and explored PD-L1 expression patterns. METHODS: We conducted a retrospective cohort study that assessed PD-L1 expression through immunohistochemistry in 123 surgical specimens of OSCC. A first approach evaluated tumor proportion scores (TPS) and combined proportion scores (CPS). Next, expression patterns were examined by evaluating PD-L1 localization in tumor nests, as well as the interfaces of tumor cells (TC) and immune cells (IC) in the tumor microenvironment. RESULTS: High-level PD-L1 expression determined by TPS and CPS using variable cutoffs was not associated with survival. Immunohistochemistry revealed that TC expressed PD-L1 in either patchy or diffuse patterns. The patchy pattern was an independent risk factor for overall survival. Furthermore, expression patterns in the tumor immune microenvironment showed that most cases expressed PD-L1 on both TC and IC, while PD-L1 non-expressors had the lowest overall survival. CONCLUSION: PD-L1 expression patterns in the context of localization in tumor nests and TC-IC interactions represent antitumor immune responses better than either TPS or CPS. Our suggested classification system may have important implications for the characterization of OSCC and for the use of PD-L1 as a prognostic biomarker.

Comparison of hormonal receptor expression and HER2 status between circulating tumor cells and breast cancer metastases

OBJECTIVES: Breast cancer (BC) is the most common neoplasm in women. Biopsy of metastatic lesions is recommended to confirm estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status as there are discrepancies in these patterns between primary tumors and metastases in up to 40% of the cases. Circulating tumor cells (CTCs) are related to BC outcomes and could potentially be an alternative to the invasive procedures of metastasis rebiopsy. ISET® technology is not currently employed to detect CTCs in patients with BC. Emerging data support that the characterization of CTC protein expression can refine its prognostic value. Transforming growth factor (TGF)-β plays a role in BC progression and invasiveness. Thus, in this study, we aimed to compare ER, PR, and HER2 expression in primary tumors, CTCs, and metastases and evaluate TGF-β type 1 receptor (TGF-β RI) expression in CTCs as prognostic factor for progression free survival (PFS) and overall survival (OS). METHODS: This prospective study was conducted at the A.C. Camargo Cancer Center, Brazil. Blood samples were processed in ISET® (Isolation by SizE of Tumors, Rarecells, France) before computed tomography-guided biopsy of suspected metastatic lesions. Protein expression levels in CTCs were compared to those in primary tumors/metastases (medical records). RESULTS: Of the 39 patients initially included, 27 underwent both biopsies of metastases and blood collection and were considered for analysis. The concordance rates for ER, PR, and HER2 expression between primary tumors and metastases were high. No loss of HER2 expression at any metastasis site and retention of the same pattern of protein expression in all triple-negative (TN) tumors (92.5%, 81.5% and 96.2% respectively) (p<0.0001) was observed. When metastases/CTCs were classified as TN/non-TN, CTCs showed high specificity (93%), accuracy (84.2%), and negative predictive value (88%). The median OS of patients without TGF-β RI expression in CTCs was 42.6 versus 20.8 months for TGF-β RI expression-positive ones (p>0.05). CONCLUSION: The role of CTCs detected by ISET has not yet been established in BC. Here, we suggest that this methodology may be useful to evaluate metastasis in non-TN cases as well as TGF-β RI expression in CTCs, which may impact patient survival. Due to sample limitations, future studies must focus on specific BC subtypes and an expansion of the cohort.