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Abstract Tumor-associated myeloid-derived cells (MDCs) significantly impact cancer prognosis and treatment responses due to their remarkable plasticity and tumorigenic behaviors. Here, we integrate single-cell RNA-sequencing data from different cancer types, identifying 29 MDC subpopulations within the tumor microenvironment. Our analysis reveals abnormally expanded MDC subpopulations across various tumors and distinguishes cell states that have often been grouped together, such as TREM2+ and FOLR2+ subpopulations. Using deconvolution approaches, we identify five subpopulations as independent prognostic markers, including states co-expressing TREM2 and PD-1, and FOLR2 and PDL-2. Additionally, TREM2 alone does not reliably predict cancer prognosis, as other TREM2+ macrophages show varied associations with prognosis depending on local cues. Validation in independent cohorts confirms that FOLR2-expressing macrophages correlate with poor clinical outcomes in ovarian and triple-negative breast cancers. This comprehensive MDC atlas offers valuable insights and a foundation for futher analyses, advancing strategies for treating solid cancers.

By presenting a comprehensive analysis of low-grade serous carcinomas (LGSCs), a subset of epithelial ovarian cancers, this review delves into their distinct molecular characteristics, clinicopathological features and systemic therapy options, emphasizing their differences from high-grade serous carcinomas (HGSCs). Notably, LGSCs exhibit prevalent RAS/RAF/MEK/MAPK pathway activation, KRAS and BRAF mutations, and infrequent p53 mutations. While chemotherapy is commonly employed, LGSCs display lower responsiveness compared to HGSCs. Hormone therapy, particularly endocrine maintenance therapy, is explored due to the higher estrogen receptor expression. Novel therapeutic approaches involving CDK4/6 inhibitors, MEK inhibitors, and antiangiogenic agents like bevacizumab are also investigated. Ongoing clinical trials are striving to enhance LGSC treatment strategies, offering valuable insights for future therapeutic advancements in this challenging ovarian cancer subtype.

Abstract Background Merkel cell carcinoma (MCC) comprises a rare malignant primary skin tumor presenting neuroendocrine differentiation. Recently, agents blocking the programmed cell death protein 1 and programmed cell death protein ligand 1 pathway (PD-1/PD-L1) have demonstrated objective and durable tumor regressions in patients presenting advanced MCC. This study aimed to describe the sociodemographic, clinical, and histopathological characteristics of MCC patients, also assessing the prevalence of PD-L1 expression and Merkel cell Polyomavirus (MCPyV), as well as their prognostic roles. Methods Data from patients diagnosed with MCC between 1996 and 2019 at a reference cancer center in Rio de Janeiro, southeastern Brazil, were evaluated in a retrospective study. Tumor samples were tested for MCPyV and PD-L1 employing immunohistochemistry. Survival analyses were carried out employing the Kaplan–Meier method and curves were compared using the log-rank test. A multiple semiparametric Cox model was used. Values p

Abstract Objective To analyze the outcomes of a cohort of patients with high-risk histologies of endometrial cancer (EC) treated at Instituto Nacional de Câncer (National Cancer Institute, INCA, in Portuguese), in Brazil. Materials and Methods We reviewed the medical records of patients with high-risk histologies of EC in any stage registered at INCA between 2010 and 2016 to perform a clinical and demographic descriptive analysis and to evaluate the outcomes in terms of recurrence and survival. Results From 2010 to 2016, 2,145 EC patients were registered and treated at INCA, and 466 had high-grade histologies that met the inclusion criteria. The mean age of the patients was 65 years, 44.6% were Caucasian, and 90% had a performance status of 0 or 1. The most common histology was high-grade endometrioid (31.1%), followed by serous carcinoma (25.3%), mixed (20.0%), carcinosarcoma (13.5%), and clear cell carcinoma (9.4%). Considering the 2018 Fédération Internationale de Gynécologie et d'Obstétrique (International Federation of Gynecology and Obstetrics, FIGO, in French) staging system, 44.8%, 12.4%, 29.8%, and 12.9% of the patient were in stages I, II, III or IV respectively. Age (> 60 years), more than 50% of myoinvasion, higher stage, poor performance status, serous and carcinosarcoma histologies, and adjuvant treatment were independent factors associated with recurrence-free survival (RFS) and overall survival (OS) in the multivariate analysis. Conclusion The current findings reinforced the international data showing poor outcomes of these tumors, especially for serous and carcinosarcomas and tumors with advanced stages, with shorter survival and high recurrence rates in distant sites, independently of the FIGO stage. Adjuvant therapy was associated with better survival.

Abstract Merkel cell carcinoma is a rare skin cancer with neuroendocrine differentiation. The risk factors include sun exposure, advanced age, immunosuppression (such as transplant recipients, patients with lymphoproliferative neoplasms, or patients with HIV), and Merkel cell polyomavirus infection. Clinically, Merkel cell carcinoma appears as a cutaneous or subcutaneous plaque or nodule, but this tumor diagnosis is rarely made clinically. Therefore, histopathology and immunohistochemistry are usually necessary. Primary tumors without evidence of metastases are treated with complete surgical excision and appropriate surgical margins. The presence of occult metastasis in a lymph node is frequent and a sentinel lymph node biopsy should be performed. Postoperative adjuvant radiotherapy increases local tumor control. Recently, agents that block the PD-1/PD-L1 pathway have shown objective and durable tumor regression in patients with advanced solid malignancies. The first anti-PD-L1 antibody used in patients with Merkel cell carcinoma was avelumab, but pembrolizumab and nivolumab have also shown efficacy. This article describes the current state of knowledge of the epidemiology, diagnosis, and staging of Merkel cell carcinoma, as well as new strategies for its systemic treatment.

Abstract To investigate similarities in the gene profile of Oral Lichen Planus and Oral Squamous Cell Carcinoma that may justify a carcinogenic potential, we analyzed the gene expression signatures of Oral Lichen Planus and Oral Squamous Cell Carcinoma in early and advanced stages. Based on gene expression data from public databases, we used a bioinformatics approach to compare expression profiles, estimate immune infiltrate composition, identify differentially and co-expressed genes, and propose putative therapeutic targets and associated drugs. Our results revealed gene expression patterns related to processes of keratinization, keratinocyte differentiation, cell proliferation and immune response in common between Oral Lichen Planus and early and advanced Oral Squamous Cell Carcinoma, with the cornified envelope formation and antigen processing cross-presentation pathways in common between Oral Lichen Planus and early Oral Squamous Cell Carcinoma. Together, these results reveal that key tumor suppressors and oncogenes such as PI3, SPRR1B and KRT17, as well as genes associated with different immune processes such as CXCL13, HIF1A and IL1B are dysregulated in OLP.

A 65-years old Peruvian woman was admitted to the Brazilian National Cancer Institute, with a diagnosis of Merkel cell carcinoma in the left shoulder. A PET-CT confirmed the locally advanced disease, with the involvement of lymph nodes in the axillary region. At the time of the proposed surgical procedure, the patient tested positive for COVID-19 without symptoms. She returned for an appointment one month later recovering from COVID-19, reporting a significant decrease in the lesion. One month later, no lesion was clinically found on the left shoulder. Due to the possible remission of the disease, a new PET CT was requested, revealing no metabolic findings suggestive of active neoplastic tissue.

Several formulations of the aromatase inhibitor anastrozole are available in Brazil. We carried out a postmarketing surveillance of the anastrozole (test) formulation in current use at the Brazilian National Cancer Institute (INCA), by comparing anastrozole through plasma concentrations obtained with the test versus the reference formulation. Thirty-three postmenopausal breast cancer patients participated in an open label, bracketed protocol, comprising 3 successive phases of 8-10 days each. The test formulation was used in phases 1 and 3 and the reference formulation in phase 2. Blood samples were collected in the last 2 days of each phase for LC-MS/MS quantification of anastrozole concentration in plasma. Through anastrozole concentrations ranged between 17.4-86.9ng/ml across the three phases, with median (interquartile ranges) values of 43.7 (37.2-52.7), 41.3 (30.9-50.7) and 43.3 (33.9-55.8) ng/ml in phases 1, 2 and 3, respectively. ANOVA detected no statistically significant difference in anastrozole plasma concentrations across the three phases, consistent with switchability between the reference and test formulations. The genetic component (rGC) of through anastrozole plasma concentrations, estimated using the repeated drug administration procedure across the three phases, was 0.94, suggesting an important component of genetic variability in anastrozole pharmacokinetics.

Melanoma represents an increasing public health burden with extensive unmet needs in Latin America (LA). A mutation in the BRAF gene is present in approximately 50% of all melanomas in White populations and is a target of precision medicine, with the potential to dramatically improve patient outcomes. Thus, increased access to BRAF testing and therapy is LA must be explored. At a multi-day conference, a panel of Latin American experts in oncology and dermatology were provided with questions to address the barriers limiting access to testing for BRAF mutation in patients with melanoma in LA, who may be eligible for targeted therapy to improve their prognosis. During the conference, responses were discussed and edited until a consensus on addressing the barriers was achieved. Identified challenges included ignorance of BRAF-status implications, limited human and infrastructural resources, affordability and reimbursement, fragmented care delivery, pitfalls in the sample journey, and lack of local data. Despite the clear benefits of targeted therapies for BRAF-mutated melanoma in other regions, there is no clear path to prepare LA for a sustainable personalized medicine approach to this disease. Due to melanoma’s time-sensitive nature, LA must aim to provide early access to BRAF testing and consider mutational status within treatment decision making. To this end, recommendations are provided and include establishing multidisciplinary teams and melanoma referral centers and improving access to diagnosis and treatment.

Abstract Objective To examine the prevalence and prognostic role of tumor microenvironment (TME) markers in uterine carcinosarcoma (UCS) through immunohistochemical characterization. Methods The internal database of our institution was queried out for women with UCS who underwent surgery and thereafter postoperative chemotherapy with carboplatin and paclitaxel between January 2012 and December 2017. Tissue microarrays containing surgical samples of UCS from 57 women were assessed by immunohistochemistry for CD3, CD4, CD8, FOXP3, PD-1, PD-L1, and PD-L2. Results The mean age was 65.3 years (range, 49 to 79 years). For the epithelial component (E), CD3_E and CD4_E were highly expressed in 38 (66.7%) and in 40 (70.1%) patients, respectively, and were significantly associated with more advanced stages (p = 0.038 and p = 0.025, respectively). CD8_E was highly expressed in 42 (73.7%) patients, FOXP3_E 16 (28.1%), PD-1_E 35 (61.4%), PD-L1_E 27 (47.4%) and PD-L2_E 39 (68.4%). For the sarcomatous component (S), the prevalence of high expression was: CD3_S 6 (10.5%), CD4_S 20 (35.1%), CD8_S 44 (77.2%), FOXP3_S 8 (14%), PD-1_S 14 (24.6%), PD-L1_S 14 (24.6%) and PD-L2_S 8 (14%). By multivariate analysis, the CD8/FOXP3_S ratio (p = 0.026), CD4_E (p = 0.010), PD-L1_E (p = 0.013) and PD-L1_S (p = 0.008) markers significantly influenced progression-free survival. CD4/FOXP3_S ratio (p = 0.043), PD-1_E (p = 0.011), PD-L1_E (p = 0.036) and PD-L1_S (p = 0.028) had a significant association with overall survival. Conclusion Some differences in UCS clinical outcomes may be due to the subtype of TILs and PD-1/PD-L1 axis immune checkpoint signaling.

BackgroundUterine Carcinosarcomas (UCS) are a rare type of cancer composed of an admixture of high-grade carcinomatous and sarcomatous elements. Clinicopathological prognostic factors in UCS are well established, but studies that approach the impact of biomarkers in this unusual disease are scarce. The study objective was to evaluate the prevalence and prognostic impact of a panel of prominent biomarkers in uterine carcinosarcoma (UCS) using an immunohistochemical characterization with four biomarkers.Methods and findingsThe internal database of a single Brazilian institution was carefully explored to select women diagnosed with UCS who were submitted to surgery and postoperative chemotherapy with carboplatin and paclitaxel between January 2012 and December 2017. Tissue microarrays containing UCS samples were evaluated by immunohistochemistry for L1CAM, CDX2, p53 and microsatellite instability markers. A total of 57 cases were included. The mean age was 65.3 years (standard deviation, SD 7.0). L1CAM was negative (score 0, no staining) in 27 (47.4%) patients. Of L1CAM-positive, 10 (17.5%) showed weak (score 1, ConclusionThe strong influence of CDX2 on prognosis requires further investigation. Biological or molecular variability may have impaired the assessment of the impact of the other markers on survival.

Due to immunosuppressive cancer therapies, cancer patients diagnosed with COVID-19 have a higher chance of developing severe symptoms and present a higher mortality rate in comparison to the general population. Here we show a comparative analysis of the microbiome from naso-oropharyngeal samples of breast cancer patients with respect to SARS-CoV-2 status and identified bacteria associated with symptom severity. Total DNA of naso-oropharyngeal swabs from 74 women with or without breast cancer, positive or negative for SARS-CoV-2 were PCR-amplified for 16S-rDNA V3 and V4 regions and submitted to massive parallel sequencing. Sequencing data were analyzed with QIIME2 and taxonomic identification was performed using the q2-feature-classifier QIIME2 plugin, the Greengenes Database, and amplicon sequence variants (ASV) analysis. A total of 486 different bacteria were identified. No difference was found in taxa diversity between sample groups. Cluster analysis did not group the samples concerning SARS-CoV-2 status, breast cancer diagnosis, or symptom severity. Three taxa (Pseudomonas, Moraxella, and Klebsiella,) showed to be overrepresented in women with breast cancer and positive for SARS-CoV-2 when compared to the other women groups, and five bacterial groups were associated with COVID-19 severity among breast cancer patients: Staphylococcus, Staphylococcus epidermidis, Scardovia, Parasegitibacter luogiensis, and Thermomonas. The presence of Staphylococcus in COVID-19 breast cancer patients may possibly be a consequence of nosocomial infection.

IntroductionDue to scant literature and the absence of high-level evidence, the treatment of vulvar cancer is even more challenging in countries facing limited resources, where direct application of international guidelines is difficult. Recommendations from a panel of experts convened to address some of these challenges were developed.MethodsThe panel met in Rio de Janeiro in September 2019 during the International Gynecological Cancer Society congress and was composed of specialists from countries in Africa, Asia, Eastern Europe, Latin America, and the Middle East. The panel addressed 62 questions and provided recommendations for the management of early, locally advanced, recurrent, and/or metastatic vulvar cancer. Consensus was defined as at least 75% of the voting members selecting a particular recommendation, whereas a majority vote was considered when one option garnered between 50.0% and 74.9% of votes. Resource limitation was defined as any issues limiting access to qualified surgeons, contemporary imaging or radiation-oncology techniques, antineoplastic drugs, or funding for the provision of contemporary medical care.ResultsConsensus was reached for nine of 62 (14.5%) questions presented to the panel, whereas a majority vote was reached for 29 (46.7%) additional questions. For the remaining questions, there was considerable heterogeneity in the recommendations.ConclusionThe development of guidelines focusing on areas of the world facing more severe resource limitations may improve medical practice and patient care.

IntroductionNearly 85% of cervical cancer new cases are diagnosed in limited resources countries. Although several strategies have been proposed to reduce the disease burden, challenges remain to provide the best possible care. We report recommendations from an expert consensus meeting convened to address from prevention to management of cervical cancer in limited resources countries.MethodsThe expert panel, composed by invited specialists from 38 developing countries in Africa, Asia, Eastern Europe, Latin America, and the Middle East, convened in Rio de Janeiro in September 2019, during the Global Meeting of the International Gynecological Cancer Society (IGCS). Panel members considered the published scientific evidence and their practical experience on the topics, as well as the perceived cost-effectiveness of, and access to, the available interventions. The focus of the recommendations was on geographic regions rather than entire countries because medical practice varies considerably in the countries represented. Resource limitation was qualified as limited access to qualified surgeons, contemporary imaging or radiation-oncology techniques, antineoplastic drugs, or overall funding for provision of state-of-the-art care. Consensus was defined as at least 75% of the voting members selecting a particular answer of the multiple-choice questionnaire, whereas the majority vote was considered as 50% to 74.9%.ResultsConsensus was reached for 25 of the 121 (20.7%) questions, whereas for 54 (44.6%) questions there was one option garnering between 50% to 74.9% of votes (majority votes). For the remaining questions, considerable heterogeneity in responses was observed.DiscussionThe implementation of international guidelines is challenging in countries with resource limitations or unique health-care landscapes. The development of guidelines by the health care providers in those regions is more reflective of the reality on the ground and may improve medical practice and patient care. However, challenges remain toward achieving that goal at political, economic, social, and medical levels.

Abstract Background The landscape of cutaneous melanoma (CM) diagnosis, staging, prognosis, and treatment has undergone fundamental changes in the past decade. While the benefits of new health resources are recognized, there is a distinct lack of accurate cost-of-illness information to aid healthcare decision makers. Methods The cost-of-illness study for CM was conducted from the perspective of two health systems in Brazil: the public health system (Unified Health System, SUS) and the private health system (Health Management Organization, HMO). The study considered the direct medical cost in a bottom-up analysis, using melanoma incidence, knowledge of the disease’s progression, and the overall survival rates. The executional costs for the complete healthcare delivery cycle were investigated considering different disease stages and possible clinical course variations. The structural cost was assessed qualitatively considering the health value chain in Brazil. Results CM represents a critical financial burden in Brazil, and the cost of illness varied according to the health system and by stage at diagnosis. HMO patient costs are approximately 10-fold and 90-fold more than a SUS patient in the early-stage and advanced disease, respectively. Overall, spending on advanced disease patients can be up to 34-fold (SUS) or 270-fold (HMO) higher than that required for the early-stage disease. Given the massive amount of resources spent by the SUS and HMO, significant efforts must be made to improve the health value chain to deliver the right mix of medical care goods and services using available resources. Conclusion The cost-of-illness study for CM has the potential to inform policymakers and decision-makers regarding the economic burden that melanoma impose on a society in terms of the use of health care services, assisting them in making projections of future health care costs and resource allocation decisions. We believe that cost-of-illness analysis from a strategic perspective could be of help in assessing executional costs and be used to support the change in structural costs required for long-term strategies related to the health value chain.

ABSTRACT The standard treatment for locally advanced cervical cancer (CC) is chemoradiotherapy. Once the bladder receives part of the radiation, a typical inflammatory condition that configures radiation-induced cystitis may develop. Chronic radiation-induced cystitis is commonly characterized by the bladder new submucosal vascularization, which is typically fragile and favors hematuria. The current study aims to investigate if Hypoxia-Induced Factor (HIF-1α) and its transcriptional target Vascular Endothelial Growth Factor A (VEGF-A) could be a primary pathway leading to increased submucosal vascularization. HIF-1α and VEGF-A mRNA levels in bladder core biopsies from CC patients treated with radiotherapy versus untreated (non-irradiated) patients were analyzed using a droplet digital polymerase chain reaction technology. Gene expression results showed that HIF-1α and VEGF-A had no significant differences between bladder samples from patients previously irradiated and untreated patient samples. However, a direct relationship between the degree of late morbidity and the expression of HIF-1α and VEGF-A has been demonstrated. Despite the lack of statistical significance precludes a definitive conclusion, the data presented herein suggests that further studies investigating the role of HIF-1α in bladder neovascularization in radiation-induced cystitis are highly recommended.

Abstract Purpose To report the prevalence of uveal melanoma in a Hospital database in Brazil over the period of 16 years (2000 to 2016). Design Descriptive epidemiological study evaluating the Brazilian Hospital Based Cancer Registries. Participants/methods Uveal melanomas were identified based on ICD-O-3 codes C69.3 [choroid], C69.4 [ciliary body and iris], and C69.2 [retina]) derived from the Integrator Registry database. Kolmogorov–Smirnov Test was used for evaluation of normality of data, t-test and Chi square were used for categorical and continuous variables respectively using SPSS Software. Main outcome measures Age, sex, education, regional distribution, clinical staging at the diagnosis, time from diagnosis to treatment (≤ 60 days versus > 60 days) and first-course therapy (surgery, chemotherapy, radiotherapy or a combination of such). Results There were 2166 cases of uveal melanoma representing 5.4% of all cases of melanoma. Histological confirmation of uveal melanoma was available in all cases. Higher prevalence of 1139 cases (52.6%) in women than 1027 cases (47.4%) in men was observed. Age distribution revealed 1411 cases (65.1%) in the group between 41 and 69 years old. A total of 429 (19.8%) patients were classified as initial disease and 334 (15.4%) as advanced (regional or distant metastases). Staging as initial disease was more frequent (113–24.8%) in patients with > 8 school years than in patients with

PURPOSELittle is known, or has been published previously, regarding consolidated data on the epidemiology of gynecologic cancers (GC) in Brazil. This article describes the incidence, morbidity, and mortality of women in Brazil affected with GC between the years of 2000 and 2017.METHODSIncidence, morbidity, and mortality data from patients with a diagnosis of one out of the five most common GC, cervical (CC), uterine (UC), ovarian (OC), vulvar (VvC), and vaginal (VgC), were obtained from three governmental sources of data.RESULTSFrom 2000 to 2015 CC, OC, and VgC incidence rates (IRs) decreased, whereas the IRs for UC and VvC remained relatively stable. Data from 382,932 women with GC were analyzed. Most patients presented with locally advanced or advanced disease at diagnosis: 60.1% of patients with CC, 31.2% of patients with UC, 67.2% of patients with OC, 45.2% of patients with VvC, and 67.0% of patients with VgC. Time from diagnosis to first treatment was ≥ 60 days in 58.0% of patients with CC, 58.5% of patients with UC, 27.0% of patients with OC, 55.3% of patients with VvC, and 52.7% of patients with VgC. Regarding mortality rates (MRs), with the exception of CC, UC, and VvC, which showed a slight decrease, MRs remained stable between 2000 and 2017.CONCLUSIONA comparison with international data indicates that Brazilian patients are diagnosed with more advanced disease and face a longer delay between diagnosis and first treatment. Despite advances in screening and treatment, GC mortality has not decreased satisfactorily in this country.

PURPOSE National epidemiologic data on melanoma are scarce in Brazil. The current work presents final demographic, clinical, and pathologic results from the Brazilian Melanoma Group database to detail how patients with melanoma present at diagnosis. METHODS The online database includes patients diagnosed between 1982 and 2015 and evaluated at their centers of origin between 2001 and 2016. The primary objective was to describe the demographic, clinical, and pathologic characteristics of the patients, and secondary objectives were to investigate the association between clinical and pathologic variables of interest. RESULTS A total of 1,596 patients were included. Median age was 52 years, 57% were women, and the majority were identified as white. Invasive melanoma was diagnosed in 1,297 patients, mostly localized, whereas 299 (19%) had in situ disease (TisN0M0). Only 165 patients had initial lymph node involvement. Fitzpatrick skin types I or II were slightly more frequent with in situ melanoma (73%) than with invasive disease (67%; P = .054). The median Breslow thickness was 0.95 mm, Clark levels 2 and 3 comprised nearly 70% of cases, and ulceration was present in 18% of patients. The mitotic rate was significantly associated with the presence of ulceration and both vascular and perineural invasion but not with margin positivity, whereas histologic regression was associated with both intratumoral and peritumoral inflammatory infiltrates. CONCLUSION Despite the limitations of an observational, registry-based study, the current results provide a general profile of patients with cutaneous melanoma in Brazil at the time of diagnosis.

PURPOSESarcomas are a heterogeneous group of cancers classified as rare cancers and are often poorly characterized. In Brazil, little is known about the adult sarcoma burden and patients' clinical pathways.MATERIALS AND METHODSWe analyzed data from the Brazilian Hospital–Based Cancer Registries System, which encompasses the entire country. The histologic criteria included sarcomas according to the International Classification of Diseases for Oncology, 3rd edition. All cases were histology-based. No central pathology review was performed. Patients < 18 years old were excluded. The variables were analyzed according to the center type, hospital patient volume (> 70 patients/year for 3 consecutive years), and geographical region. The results were based on valid data, and the missing values were reported.RESULTSFrom 2000 to 2017, a total of 312 units and 49,878 cases were identified. Missing data proportion was stable. Soft tissue sarcomas were predominant, followed by bone sarcomas and gastrointestinal stromal tumors. The Southeast concentrated on the largest number of patients (51%), of high-complexity centers (CACONs; 52%), and of patients treated at CACONs (56.9%). In all regions, the majority of patients had localized disease at diagnosis. The proportion of patients starting their treatment within 60 days from diagnosis at CACON was 59.3% and 62.3% at others. Ten hospitals achieved the established threshold for high-volume center, of which seven were CACON.CONCLUSIONThis article highlights the need for further research on the profile of patients with sarcoma in Brazil and the importance of providing them a more effective diagnostic and therapeutic approach. This initiative is critical not just for planning treatment strategies but also to allocate medical resources and to improve quality of care and sarcoma patients outcomes.

ObjectiveThis study aimed to examine the prevalence and prognostic role of tumor microenvironment (TME) in triple-negative breast cancer (TNBC) after neoadjuvant chemotherapy (NACT) through immunohistochemical characterization.MethodsThe internal database of the Brazilian National Cancer Institute for women diagnosed with TNBC who underwent NACT and thereafter curative surgery between January 2010 and December 2014 was queried out. Core biopsy specimens and tissue microarrays containing surgical samples of TNBC from 171 and 134 women, respectively, were assessed by immunohistochemistry for CD3, CD4, CD8, CD14, CD56, CD68, CD117, FOXP3, PD-1, PD-L1, and PD-L2. Immune cell profiles were analyzed and correlated with response and survival.ResultsMean age was 50.5 years, and most cases were clinical stage III [143 cases (83.6%)]. According to the multivariate analysis, only Ki67 and clinical stage significantly influenced the pattern of response to systemic treatment (p = 0.019 and p = 0.033, respectively). None of the pre-NACT IHC markers showed a significant association with event-free survival (EFS) or overall survival (OS). As for post-NACT markers, patients with high CD14 had significantly shorter EFS (p = 0.015), while patients with high CD3 (p = 0.025), CD4 (p = 0.025), CD8 (p = 0.030), CD14 (p = 0.015), FOXP3 (p = 0.005), high CD4/FOXP3 (p = 0.034), and CD8/FOXP3 (p = 0.008) showed longer EFS. Only high post-NACT CD4 showed significantly influenced OS (p = 0.038).ConclusionThe present study demonstrated that the post-NACT TIL subtype can be a determining factor in the prognosis of patients with TNBC.

Objective: To investigate the benefit of radiotherapy alone in patients diagnosed with locally advanced cervical cancer when the addition of chemotherapy was contraindicated. Methods: A single-center cohort study of patients diagnosed with locally advanced cervical cancer as defined by the FIGO 2009 (stage IB2 to IVA) and contraindication for concomitant chemotherapy was retrospectively evaluated. Patients included were treated with radiotherapy in a curative intent and those patients who completed the external beam radiotherapy were considered for brachytherapy. Patient’s demographics, reasons for not receiving concomitant chemotherapy and treatment responses were analyzed. Disease-free survival (DFS) and overall survival (OS) were calculated. Results: With a median follow-up of 13.9 months (range 0.10-81.8), the median DFS was 11.6 months (95% CI: 10.2-13.1), and the median OS was 15.9 months (95% CI: 11.5-20.3). Conclusion: This real-world study provides descriptive information confirming that radiotherapy with curative intent should be offered to patients with locally advanced cervical cancer even when chemotherapy is not an option due to clinical or laboratory contraindications.

PURPOSE: New scientific evidence has led to modifications in the clinical practice of handling melanoma. In health care systems, there is currently a wide variety of clinical procedures to treat cancer, and the various routes have different effects on the survival of patients with cancer. Thus, this article aimed to evaluate the journey of patients with melanoma in the public and private health care systems in Brazil from the viewpoint of different medical professionals involved in the diagnosis and treatment of the disease. The study also considers the resources used for the complete delivery cycle of health care at different stages of the evolution of melanoma. METHODS: We conducted a behavioral study by applying a questionnaire to a group of medical professionals. A nonprobabilistic sampling method for convenience was used, justified by the heterogeneous national incidence and the limited availability of medical professionals who diagnose and treat melanoma. RESULTS: The questionnaire was answered by 138 doctors, including doctors from the Brazilian states with the highest concentration of medical specialists and regions with a higher melanoma incidence. The results of this study have the potential to enrich our understanding of the reality of Brazilian health care systems and, at the same time, allow us to discuss the multiple ways in which professionals from diverse specialist fields understand and explain decision making in health care. CONCLUSION: Health care decision making is complex and, among other factors, depends on the diversity of available health resources and the knowledge of which treatments provide the greatest benefit to patients and greatest value to the system as a whole. This work can inform debates and reflection that are applicable not only in Brazil, but also in various other countries with similar realities.

Thermal burns of the oral cavity usually arise from ingestion of hot foods or beverages. A 38-year-old female patient presented with two painful ulcerative erythematous patches of the palate. The patient was consulted on the same day lesions appeared. Medical history was unremarkable. Clinically significant self-inflicted injuries may result in wide ulcers in the mouth and usually do not take less than 2 weeks to heal, whereas our patient, treated with low-level laser therapy, had a complete response in day 4, after 2 days of treatment. The fact that multiple lesions were present signaled against the World Health Organization exclusion diagnosis of erythroplakia for red patches. A traumatic ulcer, regardless of its cause of origin, usually heals within 2 weeks, after the source of injury is resolved. A thermal burn in the oral cavity usually takes longer than that to heal, but whenever this time frame is not respected, the suspicion of a potentially malignant disorder should always arise, and a biopsy should be performed. The present case showed two painful thermal burns with great results in terms of speeding up the relieve of symptoms and healing time with soft laser as opposed to the traditional treatment with oral topical corticosteroid.

Introdução: O tromboembolismo venoso é uma condição potencialmente fatal e frequente no paciente oncológico. Muitas vezes, a anticoagulação é inviável, e a colocação do filtro de veia cava (FVC) torna-se uma opção. A indicação clínica, entretanto, é controversa e gera alto custo. Objetivo: Descrever as características demográficas, clínicas e epidemiológicas dos pacientes com colocação de FVC e seu impacto na sobrevida global. Método: Estudo de coorte retrospectiva com pacientes em tratamento oncológico no INCA, que tiveram FVC implantado de janeiro/2015 até abril/2017. Na análise de sobrevida global em cinco anos, foram considerados o tempo entre o diagnóstico de câncer e o óbito por qualquer causa. Realizaram-se análise descritiva, estimativas de sobrevida (Kaplan-Meier) e regressão de Cox. Resultados: Foram incluídos 74 pacientes com média de idade 54 (+-15) anos. Em sua maioria, apresentavam tumores ginecológicos (52,7%) e digestivos (20,3%). O tempo mediano entre o diagnóstico de câncer e a colocação do FVC foi de 3,48 meses (0-203). No seguimento, foram observados 40 óbitos (54,1%) com mediana de tempo de 25 meses (IC 95%; 1,76-47,32). Na análise ajustada, verificou-se risco 5,63 vezes maior de morrer nos pacientes com colocação do FVC em até seis meses após o diagnóstico de câncer (HR=4,99; IC 95%; 2,20-11,33; p

Em 12 de dezembro de 2019, um conjunto de casos de pneumonia causada por um coronavírus recém-identificado foi anunciado em Wuhan, China. Esse coronavírus foi inicialmente nomeado como novo coronavírus de 2019 (2019-nCoV) em 12 de janeiro de 2020 pela Organização Mundial da Saúde (OMS).

Introduction Cutaneous melanoma is an aggressive type of skin cancer. Anaesthetic agents may have an impact on the immune response, postoperative neurohumoral response and tumour progression. This systematic review aims to evaluate the impact of general anaesthesia on overall and disease-free survival compared with other types anaesthesia in patients undergoing surgery for cutaneous melanoma.Methods and analysis The review will analyse data from controlled and observational studies of patients undergoing surgery for melanoma under general anaesthesia compared with other types of anaesthesia. The primary outcomes are overall survival and disease-free survival. The secondary outcomes are health-related quality of life, time to tumour progression, distant disease-free survival, time to treatment failure, cancer-specific survival, biochemical recurrence, return of intended oncological therapy, days alive and out of the hospital at 90 days, cost analysis and adverse events. A comprehensive literature search will be performed using the MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, LILACS and IBECS databases. Grey literature will also be searched. Risk of methodological bias will be assessed using The Cochrane Collaboration’s revised tool for assessing risk of bias in randomised trials (RoB 2.0) and the Newcastle–Ottawa scale. Two reviewers will independently assess the eligibility of studies and risk of bias; a third author will solve discrepancies. One author will perform data extraction and the other will check the process and data. Qualitative analysis will be carried out using all included studies. A meta-analysis using a random-effects model for pooled risk estimates will be carried out for the two main outcomes and for selected secondary outcomes if they conform to previously stated criteria. The GRADE approach will be used to summarise the quality of evidence.Ethics and dissemination Ethics approval is not required as we analyse data from previously reported studies.PROSPERO registration number CRD42018114918.

Geopropolis is produced by some stingless bee species, such as Melipona fasciculata Smith, a native species from Brazil. This study aims to investigate the antioxidant and anti-inflammatory activities and cytotoxicity effects of geopropolis hydroethanolic extracts against lung (H460 and A549) and ovarian (A2780 and ES2) cancer cell lines and non-tumor (HUVEC) cell lines using chemical identification by LC/MS/MS analysis and in silico assays to determine which compounds are associated with bioactivity. The antioxidant activity of extracts and inhibitory activity against COX enzymes were assessed by in vitro assays; cytotoxicity effect was evaluated by the MTT assay; cell cycle was assessed by flow cytometry and apoptosis by Western blotting. The geopropolis extracts showed great radical scavenging potential, preferential inhibition of COX-2, decreased cancer cell viability, non-cytotoxic effects against the non-tumoral cell line, besides modulating the cell cycle and inducing cancer cell apoptosis through the activation of caspase-3 and PARP protein cleavage. The in silico study suggests that corilagin, typhaneoside, taraxerone and marsformosanone, identified by LC/MS/MS, can be associated with anti-inflammatory activity and cytotoxic effects. Thus, the current study suggests the potential of geopropolis concerning the research field of new pharmacological alternatives regarding cancer therapy.