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.

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.

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.

Sentinel Node Status is the Most Important Prognostic Information for Clinical Stage IIB and IIC Melanoma Patients.

BACKGROUND: Sentinel node biopsy (SNB) for melanoma patients has been questioned. We aimed to study high-risk stage II melanoma patients who underwent SNB to determine what the prognostic factors regarding recurrence and mortality were, and evaluate how relevant SNB status is in this scenario. METHODS: This was a retrospective analysis of clinical stage IIB/IIC melanoma patients who underwent SNB from 2000 to 2015 in a single institution. Prognostic factors related to distant recurrence-free survival (DRFS) and melanoma-specific survival (MSS) were assessed from multiple Cox regression. Relevant variables were used to create risk predictor nomograms for DRFS and MSS. RESULTS: From 1213 SNB, 259 were performed for clinical stage IIB/IIC melanoma patients. SNB status was the most important variable for both endpoints. Patients with positive SNB presented median DRFS of 35.73 months (95% CI 21.38-50.08, SE 7.32) and median MSS of 66.4 months (95% CI 29.76-103.03, SE 18.69), meanwhile both median DRFS and MSS were not achieved for those with negative SNB (logrank < 0.0001). Both nomograms have been internally validated and presented adequate calibration (C-index was 0.734 for DRFS and 0.718 for MSS). CONCLUSIONS: SNB status was the most important risk factor in our cohort of clinical stage IIB and IIC patients and, in conjunction with well-established primary tumor characteristics, should not be abandoned. Their use in prognosis for these patients remains extremely useful for daily practice.

Small renal masses in Latin-American population: characteristics and prognostic factors for survival, recurrence and metastasis - a multi-institutional study from LARCG database.

BACKGROUND: To evaluate demographic, clinical and pathological characteristics of small renal masses (SRM) (≤ 4 cm) in a Latin-American population provided by LARCG (Latin-American Renal Cancer Group) and analyze predictors of survival, recurrence and metastasis. METHODS: A multi-institutional retrospective cohort study of 1523 patients submitted to surgical treatment for non-metastatic SRM from 1979 to 2016. Comparisons between radical (RN) or partial nephrectomy (PN) and young or elderly patients were performed. Kaplan-Meier curves and log-rank tests estimated 10-year overall survival. Predictors of local recurrence or metastasis were analyzed by a multivariable logistic regression model. RESULTS: PN and RN were performed in 897 (66%) and 461 (34%) patients. A proportional increase of PN cases from 48.5% (1979-2009) to 75% (after 2009) was evidenced. Stratifying by age, elderly patients (≥ 65 years) had better 10-year OS rates when submitted to PN (83.5%), than RN (54.5%), p = 0.044. This disparity was not evidenced in younger patients. On multivariable model, bilaterality, extracapsular extension and ASA (American Society of Anesthesiologists) classification ≥3 were predictors of local recurrence. We did not identify significant predictors for distant metastasis in our series. CONCLUSIONS: PN is performed in Latin-America in a similar proportion to developed areas and it has been increasing in the last years. Even in elderly individuals, if good functional status, sufficiently fit to surgery, and favorable tumor characteristics, they should be encouraged to perform PN. Intending to an earlier diagnosis of recurrence or distant metastasis, SRM cases with unfavorable characteristics should have a more rigorous follow-up routine.

Validation of a Nomogram for Non-sentinel Node Positivity in Melanoma Patients, and Its Clinical Implications: A Brazilian-Dutch Study.

BACKGROUND: Non-sentinel node (NSN) positivity impacts the prognosis of melanoma patients; however, the benefits of completion lymph node dissection in patients with positive sentinel nodes (SNs) are limited. OBJECTIVE: We aimed to present a predictive nomogram for NSN positivity in melanoma patients with a positive SN biopsy. METHODS: This retrospective analysis from patients who underwent SN biopsy in a Brazilian institution from 2000 to 2015 was used for the construction and internal validation of the nomogram. This nomogram was then externally validated in a cohort of Dutch patients. RESULTS: The Brazilian cohort comprised 1213 patients, with a mean follow-up of 5.11 years. Breslow thickness (odds ratio [OR] 1.170, 95% confidence interval [CI] 1.043-1.314]; p = 0.008), number of positive SNs (OR 1.092, 95% CI 1.034-1.153; p = 0.001), and largest diameter of the metastatic deposit (OR 3.217, 95% CI 1.551-6.674; p = 0.002) were statistically significant for NSN positivity. Internal validation was performed using a bootstrapping technique. A good performance was observed (Brier score 0.097) and an excellent power of discrimination was achieved (area under the curve [AUC] 0.822). The nomogram was then applied to the Dutch cohort, and its overall performance (Brier score 0.085), calibration (Hosmer-Lemeshow goodness-of-fit test; p = 0.198), and discriminatory power (AUC 0.752, 95% CI 0.615-0.890) were all adequate. CONCLUSIONS: We presented a nomogram for assessing NSN probability that should not only be used for surgical considerations but also for risk stratification and clinical decisions. Internal validation has shown that this is an adequate model, while external validation increases the model's reliability and suggests that it can be globally incorporated.

Predicting overall and major postoperative morbidity in gastric cancer patients.

BACKGROUND: Postoperative complications after gastric cancer resection vary in different series and they might have a significant impact in long-term outcomes. Our aim was to build a prediction rule on gastric cancer patients' overall and major morbidity risks. METHODS: This retrospective study included 1223 patients from a single center who were resected between 1992 and 2016. Overall and major morbidity predictors were identified through multiple logistic regression. Models' performances were assessed through discrimination, calibration, and cross-validation, and nomograms were constructed. RESULTS: The mean age was 61.3-year old and the male gender was more frequent (60%). The most common comorbidities were hypertension (HTN), diabetes, and chronic obstructive pulmonary disease (COPD). A D2-distal gastrectomy was the most frequent procedure and 87% of all lesions were located in the middle or distal third. Age, COPD, coronary heart disease, chronic liver disease, pancreatic resection, and operative time were independent predictors of overall and major morbidity. The extent of resection and splenectomy was associated with overall events and HTN with major ones. Both models were very effective in predicting events among patients at higher risk. CONCLUSIONS: The overall and major morbidity models and nomograms included clinical- and surgical-related data that were very effective in predicting events, especially for high-risk patients.

A nomogram to identify high-risk melanoma patients with a negative sentinel lymph node biopsy.

BACKGROUND: Melanoma patients with negative nodes after sentinel lymph node biopsy are a heterogeneous group. Current guidelines fail to adequately stratify surveillance and treatment for this group. Also, there is scarce data on adjuvant treatments for these patients. OBJECTIVE: To create a nomogram including clinical and pathologic characteristics capable of evaluating the risk for recurrence of primary melanoma patients with negative sentinel lymph node biopsies (SLNBs). METHODS: We used a retrospective cohort of patients who underwent SLNB during 2000-2015 at a single institution. RESULTS: Our cohort comprised 1213 patients. Among these patients, 967 (79.7%) had a negative SLNB, and mean follow-up was 59.67 months. There were 133 recurrences (13.8%); 45 (33.8%) presented with nodal recurrence, and 35 (26.3%) recurred where a SLNB was performed. Breslow thickness, ulceration, and microsatellitosis were found to be predictive of risk for recurrence at 1, 2, 5, and 10 years. LIMITATION: Single center analysis. CONCLUSION: We created a predictive nomogram for melanoma patients with negative SLNBs. This nomogram is easy to use and identifies high-risk patients who should have more strict surveillance and be considered for adjuvant treatment.

Decrease in uterine perforations with ultrasound image-guided applicator insertion in intracavitary brachytherapy for cervical cancer: A systematic review and meta-analysis.

PURPOSE: To estimate uterine perforations rates during intracavitary brachytherapy for cervical cancer with and without ultrasound (US) image guidance. MATERIALS AND METHODS: A systematic search of databases (PubMed and EMBASE) was performed. The pooled summary uterine perforation rate (detected by postinsertion CT or MRI) for the un-guided insertion group and the guided insertion group was calculated by using the random-effects model weighted by the inverse variance. RESULTS: A total of 690 articles were initially found, resulting in 12 studies that met the inclusion criteria. A total of 1757 insertions and 766 patients were included in the meta-analysis. The overall uterine perforation rate per insertion was 4.56% (95%CI: 2.35-8.67) and per patient was 7.39% (95%CI: 3.92-13.50). The pooled perforation rate per insertion without image guidance was 10.54% (95%CI: 6.12-17.57) versus 1.06% (95%CI: 0.41-2.67) with image guidance (p < 0.01). The pooled perforation rate per patient without guidance was 16.67% (95%CI: 10.01-26.45) versus 2.54% (95%CI: 1.21-5.24) with image guidance (p < 0.01). The ratio of perforations in the un-guided/guided groups was 9.94 and 6.56, per insertion and per patient, respectively. The most common sites of perforation were the posterior wall (>47 events) and the uterine fundus (24 events). None of the studies reported significant acute clinical consequences. Prophylactic antibiotic after perforation was used in 3 of the 4 studies that described the management. CONCLUSION: Using postinsertion CT or MRI to detect the perforation, the rate of uterine perforation per insertion in patients who received US-guided intracavitary brachytherapy insertion is 90% lower than with un-guided insertion.

Does para-aortic irradiation reduce the risk of distant metastasis in advanced cervical cancer? A systematic review and meta-analysis of randomized clinical trials.

PURPOSE: To evaluate the impact of the extension of the radiotherapy field cranially toward para-aortic lymph nodes (EF-RT) in advanced cervical cancer. MATERIALS AND METHODS: A systematic search of databases (PubMed, CENTRAL, Clinical Trials) was performed and included studies that were published between 1960 and November 2015 without language restrictions. All randomized clinical trials (RCTs) were analyzed further. All patients must have undergone pelvic radiotherapy and the same systemic therapy in both arms. The primary endpoints were locoregional failure, incidence of distant metastasis, para-aortic failure, and cancer related death. The Mantel-Haenszel method was used in the meta-analysis. The risk of bias analysis was determined using the 7-domain method per the Cochrane Handbook for Systematic Reviews of Interventions V5.1.0. A review of the treatment technique and toxicity was also performed. RESULTS: A total of 1309 studies were evaluated, 4 RCTs of which met the inclusion criteria; 506 patients were allocated to standard pelvic irradiation, and 494 underwent EF-RT. The risk of bias was considered to be low in nearly 80% of the domains. EF-RT significantly reduced the rate of para-aortic failure (HR 0.35, 95% CI 0.19-0.64; p<0.01) and the incidence of other distant metastases (HR 0.69, 95% CI 0.50-0.96; p=0.03). Locoregional failure and cancer-related death were not significantly altered (OR 1.06 [0.80-1.42]; p=0.67, and 0.68 [0.45-1.01]; p=0.06, respectively). The radiotherapy technique was conventional in 3 studies and conformational in 1 study. In total, 10 treatment-related deaths occurred-4 in pelvic radiation and 6 in EF-RT (OR 2.12 [0.71-6.27]; p=0.18). CONCLUSIONS: EF-RT that targets the para-aortic lymphatic chain reduces distant metastatic events, but its impact on survival is unknown. Future studies should examine the value of EF-RT using modern radiation techniques.

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.

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.

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.

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.

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.