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Background: Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in oncology patients. There are no accurate risk assessment tools to predict venous thromboembolism (VTE). Circulating tumor cells (CTCs), circulating tumor microemboli (CTM), and high platelet-lymphocyte ratio (PLR) may predispose to VTE. Objective: To evaluate correlations of CTCs, CTM, and PLR with VTE and progression-free survival (PFS) in gastric cancer patients. Methods: Patients with gastric cancer were recruited (March 2016 to April 2017). CTCs were assayed by ISET at two timepoints: before neoadjuvant treatment (CTC1) and after surgery/before adjuvant therapy (CTC2) for patients with localized disease, and before first-line chemotherapy (CTC1) and after 6 months (CTC2) for patients with metastases. VTE incidence was determined retrospectively. PFS was estimated by Kaplan-Meier analysis. Results: We studied 93 patients. According to Khorana scores, 63 (67.7%) patients were at intermediate and 30 (32.3%) were at high risk for VTE. VTE incidence was 20.4% and CTM were found in 39.8%. VTE developed in 7/37 (18.9%) CTM-positive and in 11/50 (22%) CTM-negative patients (p=0.93). When PLR >288, VTE occurred in 7/14 patients (p=0.005). PLR also associated with poor PFS (p

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.

To investigate the impact of response evaluation after neoadjuvant chemotherapy (NAC) in breast cancer patients, assessed by both magnetic resonance imaging (MRI) and pathology, on disease-free survival (DFS). This single-center, retrospective cohort study included consecutive breast cancer patients who underwent NAC and preoperative breast MRI. Resolution of invasive carcinoma in the breast and axilla was defined as complete pathological response (pCR). Radiological complete response (rCR) was defined as the absence of abnormal enhancement in the tumor site. Kaplan-Meier estimator was used to estimate the disease-free survival on 60 months. Cox regression analysis was used to estimate hazard ratio (HR) values. In total, 317 patients were included with a mean age of 47.3 years and a mean tumor size of 39.8 mm. The most common immunophenotype was luminal (44.9%), followed by triple-negative (26.8%). Overall, 126 patients (39.7%) had an rCR, while 119 (37.5%) had pCR; the radiological and pathological responses agreed in 252 cases (79.5%). During follow-up, patients who had rCR and pCR had a better DFS curve compared to patients with non-rCR and non-pCR, while those who had rCR or pCR presented an intermediate curve (Log-rank p = 0.003). Multivariate analysis showed a higher risk of recurrence in patients with non-rCR and non-pCR (HR: 5,626; p = 0.020) and those who had a complete response on MRI or pathology only (HR: 4,369; p = 0.067), when compared to patients with rCR and pCR. The association of MRI and pathological responses after NAC might better stratify the risk of recurrence and prognosis in breast cancer patients. • Association of response evaluation after neoadjuvant chemotherapy by pathology and MRI allows better stratification of prognosis. • Complete response to neoadjuvant chemotherapy on pathology and MRI was related to better disease-free survival. • Complete response on MRI or pathology only had a greater risk of recurrence.

Background: Although well-established, sentinel node biopsy (SNB) for melanoma is not free from controversies and sometimes it can be questionable if SNB should be considered even for patients who meet the criteria for the procedure. Mathematical tools such as nomograms can be helpful and give more precise answers for both clinicians and patients. We present a nomogram for SNB positivity that has been internally validated. Methods: Retrospective analysis of patients who underwent SNB from 2000 to 2015 in a single institution. Single logistic regressions were used to identify variables that were associated to SNB positivity. All variables with a p value < 0.05 were included in the final model. Overall performance, calibration, and discriminatory power of the final multiple logistic regression model were all assessed. Internal validation of the multiple logistic regression model was performed via bootstrap analysis based on 1000 replications. Results: Site of primary lesion, Breslow thickness, mitotic rate, histologic regression, lymphatic invasion, and Clark level were statistically related to SNB positivity. After internal validation, a good performance was observed as well as an adequate power of discrimination (area under the curve 0.751). Conclusions: We have presented a nomogram that can be helpful and easily used in daily practice for assessing SNB positivity.

Background: The mitotic index is no longer used to classify T1 melanoma patients into T1a and T1b, so it should not be used to indicate sentinel node biopsy in these patients. Objectives: To evaluate patients with T1 melanoma who underwent sentinel lymph node biopsy and to compare those who were classified as T1a with those classified T1b, according to the 7th and 8th Edition of the melanoma staging system, regarding a positive biopsy result. The authors also aimed to assess whether there is any difference in the results in both staging systems. Material and methods: This was a retrospective analysis of 1213 patients who underwent sentinel lymph node biopsy for melanoma, from 2000 to 2015, in a single institution. Results: Of 399 patients with thin melanomas, 27 (6.7%) presented positive sentinel lymph nodes; there was no difference in positivity for sentinel node biopsy when comparing T1a vs. T1b in both staging systems. Furthermore, the clinical results were also similar between the two groups. However, in the complete cohort analysis, the mitotic index was associated with positivity for sentinel lymph node biopsy (p < 0.0001), positivity for non-sentinel lymph node (p < 0.0001), recurrence-free survival (p < 0.0001), and specific melanoma survival (p = 0.023). Study limitation: Unicentric study. Conclusion: The mitotic index was shown to be a very important prognostic factor in the present study, but it was not observed in patients classified as T1. The mitotic index should no longer be used as the only reason to refer sentinel lymph node biopsy in patients with thin melanoma.

Purpose To estimate the overall rate, symptomatic proportion, and most common sites of pelvic insufficiency fracture (PIF) after external beam radiation therapy for gynecologic cancers based on posttreatment computed tomography, magnetic resonance imaging, positron emission tomography, or bone scintigraphy. Methods and Materials A systematic search of databases (PubMed and EMBASE) was performed (CRD42019125679). The pooled summary of overall PIF and the proportion of symptomatic cases were calculated using the random-effects model weighted by the inverse variance. A multivariate meta-regression was performed to evaluate potential sources of heterogeneity regarding PIF fractures. Results Twenty-one studies met the inclusion criteria (total 3929 patients). Five hundred four patients developed PIF, translating to an overall rate of 14% (95% confidence interval, 10%-18%, based on 21 studies). Among these cases with PIF, the proportion of symptomatic patients was 61% (95% confidence interval, 52%-69%, based on 14 studies). The total number of PIFs was 704 (mean, 1.72 PIFs per each patient to develop PIF, based on 14 studies). More recent series (P = .0074) and the use of intensity modulated radiation therapy (P = .0299) were associated with lower fracture rates. The most common fracture sites were sacroiliac joint (39.7%), body of the sacrum (33.9%), pubis (13%), lumbar vertebra (7%), iliac bone (2.8%), acetabulum (2.1%), and femoral head/neck (1.5%). The median time to fracture was 7.1 to 19 months after radiation therapy. Conclusions The incidence of PIF after radiation therapy for gynecologic cancers is high (14%), with the majority affecting the sacral bone or joint (73.6%), although this risk appears to be lower with intensity modulated radiation therapy. Posttreatment bone surveillance is warranted in this population because nearly 40% of patients were asymptomatic at the time of PIF diagnosis.

Introduction: Neoadjuvant chemotherapy in addition to increasing the rate of breast conservation, offers a invaluable opportunity to monitor individual tumor response which may be related to survival outcomes. In view of this, neoadjuvant treatment has been increasingly used.However, several distinct strategies and protocols are employed in this scenario, depending on the histological subtype and local preferences, and there is no clear definition of which one is the best. Most of the published series are from developed countries. Here we describe results of neoadjuvant therapy for non metastaic breast cancer treated in a single Brazilian cancer center.Objective: To evaluate the clinical and pathological characteristics and survival outcomes of breast cancer patients treated with neoadjuvant chemotherapy diagnosed in a single specialized Brazilian institution. Method: This is an observational, retrospective cohort, which included patients diagnosed with invasive breast cancer (stage I to III) submitted to neoadjuvant chemotherapy between January 2007 and December 2018.Results: We evaluated 685 patients with a median age of 46 years, 23.9% were younger than 40 years of age, 64.2% were premenopausal, 24% had a mutation in the BRCA1/2 gene and 70% were treated in the private.Regarding staging, 2.2% had stage I disease, 33.9% stage II, and 63.9% stage III. Approximately 95% of patients received anthracycline-containing regimens. Among patients with ERBB2+ tumors, 97.1% received an anthracycline regimen and 30.3% received double anti-HER2 blockade. Eleven percent of patients with triple-negative triple tumors received carboplatin, and only 0.5% of the hormone receptor positive patients received neoadjuvant hormone therapy. Forty percent of the patients demonstrated complete clinical response and only 30% of thenderwent conservative surgery. Thirty-seven percent had complete pathological response (RCB-0), 13.1% had minimal residual disease (RCB-1,) 40% had moderate to extensive residual disease (RCB-2 and RCB-3), and 0, 8% presented disease progression. The RCB-0 rate was 45.7% for AC dense dose and 31.9% AC for conventional dose (p=0.001). Regardless of hormonal status, in the subgroup with ERBB2 + tumors, the rate of RCB-0 was 61% for those who received HER2 double-blockade versus 55.1% for those who received anti-HER2 monotherapy (p=0.049). Nineteen percent of the patients progressed during the follow-up, with 17% having locoregional progression. In the last follow-up, 70% of the patients were alive without disease, with a median cancer-specific survival (CSS) of 133 months. The median CSS was 129 months among luminal tumors, 116 months for triple-positive, 117 months for triple-negative, and 91 months for HER2 super-expressors (p=0.008). The median SCC of the patients that achieved RCB-0 was 116 months, 89 months for those who had RCB-III, and 27 months for those who presented disease progression (p=0.004). CSS was the same for patients who received or not anthracycline and for those who were treated or not with dense dose schedules. Twenty percent of patients with triple-negative tumors received carboplatin, 52% had RCB-0 versus 34% for those who did not receive carboplatin (p=0.002), however, we did not observe any difference in CSS between these groups (p=0.109). Patients with triple-negative tumors were the only ones in which we observed a direct association between achieving RCB-0 and better CSS and progression-free survival (PFS) (p=0.001 for both). Conclusion: The administration of dose-dense anthracycline, of carboplatin and of anti-HER2 double-blockade increased the rate of RCB-0, nevertheless, this did not translate into improved CSS. Achiving complete pathological response in the triple-negative subtype was was associated with improved CSS and PFS. Citation Format: Monique Celeste Tavares, Marcelle G Cesca, Fernanda A Oliveira, Poliana Andrade, Camilla A Fogassa, Rafaela Pirolli, Bruna R Mattos, Mariana P Xerfan, Sinara Figueiredo, Fernando AB Campos, Vinicius F Calsavara, Solange M Sanches, Fabiana B Makdissi, Cynthia A Bueno, Marina Sonagli, Marina Canal, Vladmir CC Lima. Neoadjuvant therapy outcomes in non metastatic invasive breast carcinomas - Results from a large Brazilian cohort [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-30.

The semiparametric Cox regression model is often fitted in the modeling of survival data. One of its main advantages is the ease of interpretation, as long as the hazards rates for two individuals do not vary over time. In practice the proportionality assumption of the hazards may not be true in some situations. In addition, in several survival data is common a proportion of units not susceptible to the event of interest, even if, accompanied by a sufficiently large time, which is so-called immune, “cured,” or not susceptible to the event of interest. In this context, several cure rate models are available to deal with in the long term. Here, we consider the generalized time-dependent logistic (GTDL) model with a power variance function (PVF) frailty term introduced in the hazard function to control for unobservable heterogeneity in patient populations. It allows for non-proportional hazards, as well as survival data with long-term survivors. Parameter estimation was performed using the maximum likelihood method, and Monte Carlo simulation was conducted to evaluate the performance of the models. Its practice relevance is illustrated in a real medical dataset from a population-based study of incident cases of melanoma diagnosed in the state of São Paulo, Brazil.

Background Gastric adenocarcinoma (GAC) is the third deadliest malignant neoplasm worldwide, mostly because of late disease diagnosis, low chemotherapy response rates, and an overall lack of tumor biology understanding. Therefore, tools for prognosis and prediction of treatment response are needed. Quantification of circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) and their expression of biomarkers has potential clinical relevance. Our aim was to evaluate CTCs and CTM and their expression of HER2 and plakoglobin in patients with nonmetastatic GAC, correlating the findings to clinicopathological data. Materials and Methods CTC enrichment was performed with isolation by size of epithelial tumor cells, and the analysis was performed with immunocytochemistry and microscopy. Two collections were made: one at diagnosis (55 samples before neoadjuvant treatment) and one after surgery and before adjuvant therapy (33 samples). Results A high detection rate of CTCs (90%) was observed at baseline. We evaluated HER2 expression in 45/55 biopsy samples and in 42/55 CTC samples, with an overlap of 36 subjects. Besides the good agreement observed for HER2 expression in primary tumors and paired CTCs for 36 cases (69.4%; κ = 0.272), the analysis of HER2 in CTCs showed higher positivity (43%) compared with primary tumors (11%); 3/5 patients with disease progression had HER2-negative primary tumors but HER2-positive CTCs. A significant CTC count drop in follow-up was seen for CTC-HER2-positive cases (4.45 to 1.0 CTCs per mL) compared with CTC-HER2-negative cases (2.6 to 1.0 CTCs per mL). The same was observed for CTC-plakoglobin-positive cases (2.9 to 1.25 CTCs per mL). Conclusion CTC analysis, including their levels, plakoglobin, and HER2 expression, appears to be a promising tool in the understanding the biology and prognosis of GAC. Implications for Practice The analysis of circulating tumor cell levels from the blood of patients with gastric adenocarcinoma, before and after neoadjuvant treatment, is useful to better understand the behavior of the disease as well as the patients more likely to respond to treatment.

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.

Survival models with a frailty term are presented as an extension of Cox’s proportional hazard model, in which a random effect is introduced in the hazard function in a multiplicative form with the aim of modeling the unobserved heterogeneity in the population. Candidates for the frailty distribution are assumed to be continuous and non-negative. However, this assumption may not be true in some situations. In this paper, we consider a discretely distributed frailty model that allows units with zero frailty, that is, it can be interpreted as having long-term survivors. We propose a new discrete frailty-induced survival model with a zero-modified power series family, which can be zero-inflated or zero-deflated depending on the parameter value. Parameter estimation was obtained using the maximum likelihood method, and the performance of the proposed models was performed by Monte Carlo simulation studies. Finally, the applicability of the proposed models was illustrated with a real melanoma cancer data set.

Objectives The prognostic impact of circulating tumor cells (CTCs) or circulating tumor microemboli (CTM) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is yet to be determined, with conflicting results in previous trials. The role of induction chemotherapy (ICT) in the management of LA-HNSCC is controversial with no predictive biomarkers to guide treatment strategy in this scenario. The aim of this trial is to determine the prognostic impact of CTCs and CTM, their biomarkers expression by immunocytochemistry (ICC), and its potential role as predictors of ICT benefit in LA-HNSCC. Materials and Methods Prospective study, with newly diagnosed stage III/IV non-metastatic LA-HNSCC patients treated with curative intent. Blood samples analyzed for CTCs and CTM before treatment using the ISET method. Results A total of 83 patients were included. CTCs counts were an independent prognostic factor for overall survival (OS; HR: 1.17; 95 %CI: 1.05–1.31; p = 0.005) and progression free survival (PFS; HR:1.14; 95 %CI: 1.03–1.26; p = 0.007). Using the Lausen and Schumacher technique, 2.8 CTCs/mL for OS and 3.8 CTCs/mL for PFS were defined as the best cut-offs. CTM were detected in 27.7% of patients, correlating with worse PFS (HR = 2.70; IC95%: 1.30–5.58; p = 0.007). MRP-7 expression in CTM correlated with worse OS (HR = 3.49; 95 %CI: 1.01–12.04; p = 0.047) and PFS (HR = 3.62; 95 %CI: 1.08–12.13; p = 0.037). CTCs counts were predictive of complete response to treatment (OR = 0.74; 95 %CI: 0.58–0.95; p = 0.022) and high counts (cut-off 3.8/mL) and CTM were potential predictors of ICT benefit. Conclusion CTCs/CTM had significant prognostic impact and potential role as predictors of ICT benefit in LA-HNSCC.

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 &gt, 1.5 CTCs/mL was associated with an inferior median OS compared to lower values. A difference of CTC2−CTC1 &gt, 5.5 CTCs/mL was associated with a reduced median PFS. By multivariate analysis, CTC1 &gt, 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.

Background Tumour budding (TB) refers to loss of tumour cohesiveness and is defined as isolated cells or a cell cluster of up to four tumour cells at the microscopic analysis. The International Tumour Budding Consensus Conference (ITBCC) in 2016 proposed a scoring system to standardise the pathology evaluation of TB in colorectal cancer (CRC) as high (H), intermediate (I) and low (L) TB. Objective To evaluate the recurrence-free survival (RFS) of stage II CRC patients as per the ITBCC 2016 classification and associations between TB and clinical pathological features. Methods Cases of stage II CRC undergoing surgery with available tumour tissue underwent central pathology review for TB. Prognostic factors, retrospectively retrieved from electronic medical charts, were evaluated in univariate and multivariate Cox regression analyses for RFS (primary end point). Results Among 137 patients included, L-TB was observed in 107 (78.1%), I-TB in 21 (15.3%) and H-TB in 9 (6.6%). In a median follow-up of 69 months, the median RFS was 134 months, with 14 patients (10.2%) presenting with tumour recurrence: 10 (9.3%) with L-TB, 2 (9.5%) with I-TB and 2 (22.2%) with H-TB. Perineural invasion was more commonly seen in the H-TB group. In multivariate analysis, TB (H and I versus L; HR = 2.6; p = 0.059) and not receiving adjuvant chemotherapy (HR 3.7; p = 0.020) were independently associated with RFS. Adjuvant chemotherapy was associated longer RFS (HR = 3.7; p = 0.022). Conclusion In this series of Western patients, TB grade was associated with perineural invasion and increased risk of disease relapse.

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 OSCC patients 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 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. 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. 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

BACKGROUND: Hospital-based studies recently have shown increases in colorectal cancer survival, and better survival for women, young people, and patients diagnosed at an early disease stage. OBJECTIVE: To describe the overall survival and analyze the prognostic factors of patients treated for colorectal cancer at an oncology center. METHODS: The analysis included patients diagnosed with colon and rectal adenocarcinoma between 2000 and 2013 and identified in the Hospital Cancer Registry at A.C.Camargo Cancer Center. Overall 5-year survival was estimated using the Kaplan-Meier method, and prognostic factors were evaluated in a Cox regression model. Hazard ratios (HR) are reported with 95% confidence intervals (CI). RESULTS: Of 2,279 colorectal cancer cases analyzed, 58.4% were in the colon. The 5-year overall survival rate for colorectal cancer patients was 63.5% (65.6% and 60.6% for colonic and rectal malignancies, respectively). The risk of death was elevated for patients in the 50-74-year (HR=1.24, 95%CI =1.02-1.51) and ≥75-year (HR=3.02, 95%CI =2.42-3.78) age groups, for patients with rectal cancer (HR=1.37, 95%CI =1.11-1.69) and for those whose treatment was started >60 days after diagnosis (HR=1.22, 95%CI =1.04-1.43). The risk decreased for patients diagnosed in recent time periods (2005-2009 HR=0.76, 95%CI =0.63-0.91; 2010-2013 HR=0.69, 95%CI =0.57-0.83). CONCLUSION: Better survival of patients with colorectal cancer improves with early stage and started treatment within 60 days of diagnosis. Age over 70 years old was an independent factor predictive of a poor prognosis. The overall survival increased to all patients treated in the period 2000-2004 to 2010-2013. RESUMO CONTEXTO: Estudos hospitalares recentes têm demonstrado aumento da sobrevida do câncer colorretal e melhor sobrevida para mulheres, jovens e pacientes diagnosticados em estágio precoce da doença. OBJETIVO: Descrever a sobrevida global e analisar os fatores prognósticos de pacientes tratados para câncer colorretal em um centro de oncologia. MÉTODOS: Foram incluídos pacientes com diagnóstico de adenocarcinoma de cólon e reto entre 2000 e 2013, identificados no Registro Hospitalar de Câncer do A.C.Camargo Cancer Center. A sobrevida global aos 5 anos foi estimada pelo método de Kaplan-Meier e os fatores prognósticos foram avaliados pelo modelo de Cox. As razões de risco (HR) são relatadas com intervalos de confiança (IC) de 95%. RESULTADOS: Dos 2.279 casos de câncer colorretal analisados, 58,4% eram de cólon. A taxa de sobrevida global aos 5 anos para pacientes com câncer colorretal foi de 63,5% (65,6% e 60,6% para câncer de cólon e retal, respectivamente). O risco de óbito foi elevado para pacientes na faixa etária de 50-74 anos (HR=1,24; IC95% =1,02-1,51) e ≥75 anos (HR=3,02; IC95% =2,42-3,78), para pacientes com câncer retal (HR=1,37; IC95% =1,11-1,69) e para aqueles cujo tratamento foi iniciado >60 dias após o diagnóstico (HR=1,22; IC95% =1,04-1,43). O risco diminuiu para pacientes diagnosticados em períodos recentes (2005-2009 HR=0,76; IC95% =0,63-0,91; 2010-2013 HR=0,69; IC95% =0,57-0,83). CONCLUSÃO: A sobrevida dos pacientes com câncer colorretal é maior naqueles em estágio inicial e com início do tratamento antes dos 60 dias.. Idade acima de 70 anos foi fator independente preditivo de mau prognóstico. A sobrevida global aumentou para todos os pacientes tratados no período de 2000-2004 a 2010-2013.

DNA mismatch repair deficiency (dMMR) leads to increased mutation load, which in turn may impact anti-tumor immune responses and treatment effectiveness. Currently, there are different mutational signatures described in primary cancers that are associated with dMMR. Whether the somatic and epigenetic changes in MMR genes precede one or more dMMR signatures, and if so by which mechanism remains unknown. To investigate the relationship between these changes and dMMR signatures, we performed a de novo extraction of mutational signatures in a large cohort of 787 gastric cancer patients. We detected three dMMR-related signatures, one of which clearly discriminates tumors with MLH1 gene silencing caused by hyper-methylation within its promoter (AUC = 98%). We then demonstrate that samples with the highest exposures to signature share features related to better prognosis, encompassing clinical and molecular aspects, as well as altered immune infiltrate composition, predictive of a better response to immune checkpoint inhibitors. Overall, our analysis explored the impact of modifications in MMR-related genes on shaping specific mutational signatures and we provide evidence that patient classification based on mutational signature exposure can identify a group of patients with a good prognosis and who are potentially good candidates for immunotherapy.

Background: There are no randomized data to guide treatment decisions for patients with advanced pancreatic adenocarcinoma following first-line FOLFIRINOX. We performed a systematic review and meta-analysis of studies using gemcitabine-based chemotherapy after FOLFIRINOX to assess treatment efficacy and toxicity. Methods: We included studies published between 2011 and 2018 that evaluated the efficacy and toxicity of gemcitabine-based chemotherapy after FOLFIRINOX in patients with advanced pancreatic adenocarcinoma. We searched PubMed, Embase, Scopus, and Web of Science. Primary outcomes were objective response rate (ORR), disease control rate (DCR), any grade 3/4 toxicity rate, and progression-free survival (PFS). We used the random-effects model to generate pooled estimates for proportions. Results: Sixteen studies met the eligibility criteria. Overall, ORR was 10.8%, DCR was 41.1%, and any grade 3/4 toxicity rate was 28.6%. In subgroup analyses, gemcitabine plus nab-paclitaxel was associated with superior ORR (14.4 versus 8.4%; p = 0.038) and DCR (53.5 versus 30.5%; p Conclusions: Our study suggests gemcitabine-based chemotherapy likely outperforms best supportive care after FOLFIRINOX in advanced pancreatic cancer. Also, gemcitabine plus nab-paclitaxel seems to be more active than single-agent gemcitabine (CRD42018100421).

To estimate uterine perforations rates during intracavitary brachytherapy for cervical cancer with and without ultrasound (US) image guidance.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.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.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.

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. We aimed to present a predictive nomogram for NSN positivity in melanoma patients with a positive SN biopsy. 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. 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. 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.

Background Circulating tumor microemboli (CTM) are clusters of circulating tumor cells (CTCs), involved in metastasis, as also transforming growth factor-β (TGF-β). The purpose of this study was to verify their role in progression-free survival (PFS). Methods Blood from patients with locally advanced head and neck squamous cell carcinoma (HNSCC; n = 53) was analyzed in 2 moments. TGF-β receptor I (TGF-βRI) expression was evaluated by immunocytochemistry. Results Comparing CTM1 (baseline) with CTM2 (first follow-up), patients with CTM1-positive disease who became CTM2-negative were classified as favorable (PFS 20 months). Patients with unfavorable evolution (CTM1-negative/CTM2-positive), had PFS of 17.5 months. Patients always CTM-negative showed PFS of 22.4 months, those always positive, 4.7 months (P

Background: Recent studies suggest that the percentage of TILs is a predictive factor for response to NAC and a prognostic factor associated with long-term disease control in hormone receptor-negative breast cancer. The TILs working group's current recommendation is to evaluate stromal TILs as the principal parameter in future studies. The term lymphocyte-predominant breast cancer (LPBC) can be used as a descriptive term for tumors that contain more lymphocytes than carcinoma cells. Typically, the threshold of stromal lymphocytes for LPBC is around 50% of the stromal surface area. It is unclear if this cutoff will be used in the future as such an intense TIL infiltration in tumors has been reported to be infrequent (∼10%). Studies with TNBC have demonstrated increasingly better overall survival (OS) and disease-free survival (DFS) associated with continuous scores of TIL in patients treated with adjuvant chemotherapy. In patients treated with NAC, TILs predicted pathological complete response (pCR). Our goal was to evaluate the impact of TIL on OS in TNBC patients treated with NAC. Methods: Data from patients with histologically confirmed TNBC treated with NAC from a single institution (A. C. Camargo Cancer Center - ACCCC), between July 2002 and November 2013, were retrospectively collected using electronic medical records. Patients with metastatic disease or in situ carcinoma at diagnosis were excluded. The density of TILs was evaluated in full-face hematoxylin and eosin-stained (HE) slides. Three blinded pathologists made the assessment of each slide, and a consensus on the TIL percentage was achieved. A cut-off of 10% for TIL percentage was employed for OS and DFS calculations, based on technical statistical maximizing log-rank test. We use this cut-off to test the association with pathological pCR rate as well. For pCR rate, we also used a cut-off of 50% (LPBC). We used Chi-square test to evaluate the association with pCR. A p-value Results: We identified 78 patients that fulfilled all inclusion and exclusion criteria. The median age was 42 years (range 17-70), and the clinical stage distribution was IIA (14%), IIB (22%), IIIA (19%), IIIB (33%) and IIIC (11%). 58 patients had archival FFPE blocks available and suitable for pathological analysis. Median follow-up was 4,1 years. Overall survival in 5 years in this subgroup was 62% (median not reached). 23 (39.7%) tumors had TIL> 10%, however only 10 had TIL > 50%. TIL >10% was associated with improved OS (HR 0.33, 95% CI, 1.0 to 0.11; p = 0.04). The same cut-off was associated with better DFS, although not statistically significant (HR 0.46, 95% CI, 1.1 to 0.18; p = 0.1). The overall pCR rate was 39.6% (48% for patients with TIL > 10% and 34% for patients with TIL Conclusion: We observed improved OS associated with TIL>10% in TNBC patients treated with NAC. pCR was also associated with better OS. Citation Format: Sampaio CdDAT, de Lima VCC, de Andrade VP, Neotti T, Tavares MC, Sessa VA, Calsavara VF, Zenun GR, Giongo AA, da Costa AABA. Tumor-infiltrating lymphocytes (TILs) is associated with improved overall survival in triple-negative breast cancer (TNBC) patients treated with neoadjuvant chemotherapy (NAC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-44.

To evaluate the impact of the extension of the radiotherapy field cranially toward para-aortic lymph nodes (EF-RT) in advanced cervical cancer.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.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; p0.01) 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).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.

Gastric cancer (GC) is the fifth most common type of cancer worldwide with high incidences in Asia, Central, and South American countries. This patchy distribution means that GC studies are neglected by large research centers from developed countries. The need for further understanding of this complex disease, including the local importance of epidemiological factors and the rich ancestral admixture found in Brazil, stimulated the implementation of the GE4GAC project. GE4GAC aims to embrace epidemiological, clinical, molecular and microbiological data from Brazilian controls and patients with malignant and pre-malignant gastric disease. In this letter, we summarize the main goals of the project, including subject and sample accrual and current findings.

Introduction We evaluated overall survival (OS) benefit of complete metastasectomy (CM) in metastatic renal cell carcinoma (mRCC) using a propensity score-matched (PSM) analysis to balance groups by age, gender and by the International Metastatic RCC Database Consortium prognostic model (IMDC). Methods We included patients (pts) treated at the AC Camargo Cancer Center between 2007 and 2016. Pairs were matched by age, gender and IMDC. Kaplan–Meier survival estimates and Cox proportional hazard models were used to evaluate OS on CM and no-CM group. Results We found 116 pts with clear cell mRCC. After PSM, the number was reduced to 74 (37 CM, 37 no-CM). The median OS for CM and no-CM was 98.3 months and 40.5 months, respectively (hazard ratio 0.24 95%CI 0.11–0.53 p < 0.001). The OS benefit of CM was confirmed on favourable and intermediate IMDC but was absent on poor IMDC. The CM group received less systemic therapy than the no-CM group. Ten pts in the CM group still have no evidence of disease (NED). Conclusion After matching for age, gender and IMDC, we found CM impacts on OS and also diminishes the need for systemic treatment. Survival benefit was confirmed for favourable/intermediate IMDC but not for the poor IMDC prognostic model. Further studies correlating IMDC and metastasectomy are needed to guide clinical decision-making.