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Jesse Lopes da Silva,1 Giselle de Souza Carvalho,1 Lucas Zanetti de Albuquerque,1 Fabiana Resende Rodrigues,2 Priscila Valverde Fernandes,2 Daniel Kischinhevsky,1 Andreia Cristina de Melo1 1Division of Clinical Research and Technological Development, Brazilian National Cancer Institute, Rio de Janeiro, Brazil; 2Division of Pathology, Brazilian National Cancer Institute, Rio de Janeiro, BrazilCorrespondence: Jesse Lopes da Silva, Brazilian National Cancer Institute (INCA), Clinical Research Division, 37 André Cavalcanti Street, 5th Floor, Annex Building, Rio de Janeiro, 20231-050, Brazil, Tel/Fax +55 21 32076585, Email jesse.silva@inca.gov.brPurpose: This study aimed to compare the clinical behavior, clinicopathological and sociodemographic characteristics of patients with early-stage triple-negative breast cancer (TNBC) who belong to the HER2-low and HER2-zero subgroups.Patients and Methods: This study involved a thorough search in the internal database of a single Brazilian institution to identify women with TNBC who underwent neoadjuvant chemotherapy (NACT) followed by curative surgery within the period from January 2010 to December 2014. HER2 analysis through immunohistochemistry (IHC) and, if required, amplification by in situ hybridization, was conducted using core biopsy samples. The study assesses outcomes of residual cancer burden (RCB), event-free survival (EFS), and overall survival (OS).Results: A total of 170 cases were analyzed, with a mean age of 51.4 years (standard deviation, SD 11.2). The HER2 status was categorized as IHC 0, 1+, or 2+ in 80 (47.1%), 73 (42.9%), and 17 (10%) patients, respectively. No significant differences were observed in the prevalence of clinical pathological characteristics among the subgroups. The absence of significant results for clinicopathological and demographic features hindered the multivariate analysis of HER2 subgroups. Similarly, no significant differences were found in the RCB, EFS, and OS outcomes between HER2 subgroups.Conclusion: The findings of this study suggest that, in early-stage TNBC, the clinical behavior and survival outcomes of the HER2-low subgroup may not differ significantly from those of the HER2-zero subgroup.Keywords: HER2 status, HER2-low, biomarker, triple-negative breast cancer

Jesse Lopes da Silva,1 Fabiana Resende Rodrigues,2 Guilherme Gomes de Mesquita,2 Priscila Valverde Fernandes,2 Luiz Claudio Santos Thuler,1 Andreia Cristina de Melo1 1Division of Clinical Research and Technological Development, Brazilian National Cancer Institute (INCA), Rio de Janeiro, Brazil; 2Pathology Department, Brazilian National Cancer Institute, Rio de Janeiro, BrazilCorrespondence: Jesse Lopes da SilvaDivision of Clinical Research and Technological Development, Brazilian National Cancer Institute (INCA), 37 André Cavalcanti Street - 6th Floor - Annex Building, Downtown, Rio de Janeiro, RJ 20231-050, BrazilTel +55-2132076585Email jesse.silva@inca.gov.brObjective: This study aimed to investigate the influence of immunohistochemical (IHC) biomarkers in the response to neoadjuvant chemotherapy (NACT) and survival outcomes in the subset of locally advanced triple-negative breast cancer (TNBC).Materials and Methods: The epidermal growth factor receptor (EGFR), androgen receptor (AR), cytokeratins (CK5/6, CK14 and CK17), Ki67 and p53 immunohistochemistry were evaluated on 171 cases of TNBC submitted to NACT and subsequently to surgery. Intensity and percentage of the expression of these biomarkers were combined to formulate a specific score, that was correlated with prognostic features and assessed for survival outcomes.Results: Most patients had advanced clinical-stage tumors (stage III: 83.6%; cT3/T4: 85.9%; cN1-3: 71.3%). The predominant histological subtype was high-grade (67.3%) and invasive ductal carcinoma (93.6%). The residual cancer burden (RCB) 0– 1 corresponded to 28.7% of cases and low-risk lymph node ratio (LNR) represented 77.2%. High Ki67 expression only showed a significant correlation with grade 3 tumors (p = 0.0157). CK5/6 was observed in 16% (27/169), CK14 was positive in 10.1% (17/169), CK17 in 91.1% (153/168), p53 in 52.6% (70/133), EGFR in 92.9% (157/169 cases), AR in 13% (22/169) and Ki67 index was scored ≥ 40% in 57.9% (95/165). No IHC biomarker significantly impacted response or survival. Regarding the analysis of the outcomes of event-free survival (EFS) and overall survival (OS), clinical stage (p = 0.014 and p = 0.042, respectively), RCB (p < 0.0001 and p < 0.0001, respectively) and LNR (p < 0.0001 and p < 0.0001, respectively) showed significant association.Conclusion: No IHC biomarker evaluated showed a significant association with a response or survival outcomes in TNBC patients. Clinical stage, LNR and RCB stood out for strongly influencing survival.Keywords: triple-negative breast cancer, neoadjuvant chemotherapy, biomarkers, residual burden cancer, lymph node ratio

Purpose: This scoping review aims to evaluate the evidence for stereotactic body radiotherapy (SBRT) boost as a potential alternative for brachytherapy (BCT) in treating cervical cancer., Material and Methods: A comprehensive literature search was conducted across multiple databases. Studies investigating SBRT boost in cervical cancer patients who were either contraindicated for or refused BCT were included. The review examined SBRT efficacy and safety., Results: Sixteen studies were included, encompassing prospective (n = 4) and retrospective cohort studies (n = 8), as well as phase I and II trials (n = 4). The most common SBRT boost dose was 25 Gray(Gy)/5 fractions (ranging from 18 to 40 Gy/3-5 fractions). Local control rates at 1-year, 3-year, and 5-year ranged from 86 % to 100 %, 78-92 %, and 81-92 %, respectively. Overall survival (OS) rates at 1-year, 3-year, and 5-year rates ranged from 49 % to 95 %, 50-77 %, and 50-69 %, respectively. Two studies reported a pathological complete response rate of 93 % and 94 % three months after the SBRT boost. Most studies reported low rates of late grade 3 or higher genitourinary (0-14 %) and gastrointestinal (0-26 %) toxicities. The overall incidence of rectovaginal fistulas ranged from 0 % to 13 %., Conclusion: This scoping review suggests SBRT boost as a promising alternative to selected cervical cancer patients who cannot receive BCT. The results indicate a high local control with acceptable toxicity profiles. However, further research is needed to define optimal SBRT boost parameters, identify patient selection criteria, and address knowledge gaps regarding long-term outcomes and cost-effectiveness., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Uveal melanoma is a rare malignancy originating from extracutaneous melanocytes on the uveal layer of the eyes. The incidence varies depending on the ethnic and racial global distribution, as uveal melanoma is more frequently diagnosed in non-Hispanic White subjects when compared with Hispanic, Asian, or Black individuals. Despite all the local effective management of uveal melanoma, roughly 50% of the cases will develop distant metastases. For these cases, the historical median overall survival is around 12 months. Recently, tebentafusp became the first therapy to receive Food and Drug Administration approval following a phase 3 trial demonstrating a continued long-term benefit for overall survival among adult HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma. Since 2021, high-resolution sequence-based HLA typing has been considered the gold standard for determining HLA alleles and haplotypes for the Brazilian Bone Marrow Donor Registry (REDOME) donors. To depict the HLA-A*02:01-positivity in Brazilian individuals, the REDOME database was queried out for the donors included from 2021 to 2023 and tested for HLA in high-resolution platforms. A total of 203, 44 donors were included and the frequency of the HLA-A*02:01 was 21.01%, much lower compared to the frequency in North Americans and Europeans (around 45%). Despite tebentafusp has demonstrated promising results in the treatment of uveal melanoma, the number of patients to benefit from this new approach can strongly vary by ethnic and racial issues. New strategies for the systemic treatment of advanced uveal melanoma have to be developed and tested as this disease still represents an unmet medical need., (© The Author(s) 2024. Published by Oxford University Press.)

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., (© 2024. The Author(s).)

Objective: Endometrial cancer (EC) treatment changed substantially with the introduction of molecular classification. Low-middle income (LMIC) countries will face barriers to including molecular classification to guide treatment. This study aims to analyse the value of p53 immunohistochemistry to delineate adjuvant treatment in FIGO stages I and II., Methods: Patients with EC treated between 2010 and 2016 were retrospectively evaluated. Patients included in this analysis must have reviewed FIGO stage I/II high-grade histologies (endometrioid grade 3, serous, clear cell, carcinosarcoma, mixed and undifferentiated). Samples were subjected to p53 immunohistochemistry. Recurrence-free and overall survival were analysed using the Kaplan-Meier method and log-rank test. Cox proportional hazards regression was performed for multivariable analysis., Results: From 2010 to 2016, 265 patients met the inclusion criteria. Patients with aberrant p53 (71.4 %) were associated with older age (59.7 % vs 77.8 % with more than 60 years), relapse (12.5 vs 29.6 %) and death (22.2 vs 46.7 %). The pattern of relapse was not different, with most being at extrapelvic sites (55.5 % vs 62.3 % for p53 wild type and aberrant, respectively). The median overall survival was not reached versus 92.2 months for p53 wild type and aberrant, respectively (p = 0.003). In multivariate analysis, chemotherapy decreased death (p = 0.014) in p53 aberrant tumours, a benefit not seen in the wild-type cohort (p = 0.22)., Conclusion: This retrospective analysis corroborates the finding of worse outcomes for p53 aberrant tumours in stage I/II EC and the benefit of more aggressive adjuvant treatment (systemic therapy and radiotherapy). Although not ideal as a sole molecular marker, p53 immunohistochemistry could complement the classical anatomopathological features and be part of the decision-making process with patients in LMIC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To investigate breast cancer (BC) incidence and mortality rates among specific racial groups in Brazil., Methods: BC incidence was evaluated from 2010 to 2015, using Brazilian Population-Based Cancer Registries, incorporating crude ratios and annual average percentage change (AAPC). Clinical and sociodemographic data from 2000 to 2019 were obtained from Hospital-Based Cancer Registries. Mortality data from 2000 to 2020 were sourced from the National Mortality Information System, comparing White women and Black women., Results: Across 13 Brazilian registries, 70,896 new BC cases were reported from 2010 to 2015. The median BC incidence rate was notably higher for White women (101.3 per 100,000) compared to Black women (59.7 per 100,000). In the general population, non-significant decrease in annual BC incidence was observed (AAPC = - 1.2; p = 0.474). Black women were more likely to live in underdeveloped areas, have lower education levels, live without a partner, and have higher alcohol consumption as compared to White women. A higher proportion of Black women received advanced-stage diagnoses (60.1% versus 50.6%, p < 0.001). BC-related mortality analysis showed 271,002 recorded deaths, with significant increase in BC-specific mortality rates in both racial groups. Black women displayed an AAPC of 2.3% (p < 0.001), while White women demonstrated a moderately elevated AAPC of 0.6% (p < 0.001)., Conclusion: This study underscores the need for targeted policies to address disparities in access to early detection and proper treatment, particularly for Black women in underprivileged regions, aiming to improve the survival rates of Brazilian women grappling with BC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: GG, JS, GO, AS, LB, and AM were employed by company Oncoclínicas&Co – Medica Scientia Innovation Research (MEDSIR). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Giannecchini, da Silva, de Oliveira Bretas, dos Santos, Baltar and de Melo.)

Aims: The objective of the study was to evaluate two translucent resin composite systems for customizing light-polymerized fiber posts with light-emitting diode (LED) curing units regarding adhesion using conventional cement at 24 h and 6 months., Settings and Design: This was an experimental in vitro study., Methods: Forty roots were prepared and divided into four groups ( n = 10): ZV-Z350 resin and LED Valo; ZR-Z350 resin and LED Radii-Cal; OV-Opallis resin and LED Valo; and OR-Opallis resin and LED Radii-Cal. The fiber post was customized and cemented with conventional resin cement and was photoactivated by two different sources., Statistical Analysis Used: The data were subjected to two-way ANOVA and Tukey's post hoc tests ( P = 0.05). The data regarding the pattern of adhesive failures were described in terms of the frequency of occurrence in each third of the postspace., Results: Both at 24 h and 6 months, bond strength among groups was similar, regardless of the analyzed postspace 3 rd ( P > 0.05). Adhesive failure Type 4 was the most frequent in all thirds., Conclusions: Customizing the fiber post with Z350 and Opallis has the same effect on bond strength and adhesive failure pattern, regardless of the LED curing units used for photopolymerization., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Conservative Dentistry and Endodontics.)

While the positive impact of early palliative care on the quality of life of cancer patients is well established, there is a noticeable research gap in developing countries. This study sought to determine the impact of an outpatient palliative care (OPC) program on the location of death among patients in Brazil. This was a retrospective study including patients with cancer who died between January 2022 and December 2022 in 32 private cancer centers in Brazil. Data were collected from medical records, encompassing demographics, cancer characteristics, and participation in the OPC program. The study involved 1980 patients, of which 32.3% were in the OPC program. OPC patients were predominantly younger (average age at death of 66.8 vs. 68.0 years old, p = 0.039) and composed of women (59.4% vs. 51.3%, p = 0.019) compared to the no-OPC patients. OPC patients had more home/hospice deaths (19.6% vs. 10.4%, p < 0.001), and participation in the outpatient palliative care program strongly predicted home death (OR: 2.02, 95% CI: 1.54-2.64). Our findings suggest a significant impact of the OPC program on increasing home and hospice deaths among patients with cancer in our sample. These findings emphasize the potential of specialized OPC programs to enhance end-of-life care, particularly in low-resource countries facing challenges related to social and cultural dimensions of care and healthcare access.

Objective: This study aimed to explore trends in cervical cancer (CC) incidence and mortality rates according to race/skin color in Brazil focusing on the seriousness of the racial disparity., Methods: Data from Brazilian Population-Based Cancer Registries (PBCRs) were analyzed for trends in incidence between 2010 and 2015. For mortality, data from the National Mortality Information System were retrieved between 2000 and 2020. A self-declaration on race/skin color was collected following the classification proposed by the Brazilian Institute of Geography and Statistics - white, black, brown/mixed race, yellow, or indigenous. For the analysis, black and brown/mixed race were grouped as black., Results: Between 2010 and 2015, 10,844 new cases of CC were registered in the participating PBCRs, distributed among white women (49.6%), black (48.0%), and other race/skin color (2.3%). Compared with white counterparts, black women had a 44% higher risk of incident CC. As for mortality, between 2000 and 2020, 108,590 deaths from CC occurred nationwide. The mean age-adjusted mortality rates according to race/skin color were 3.7/100,000 for white, 4.2/100,000 for black, 2.8 for yellow, and 6.7 for indigenous women. Taking the mortality rates in white women as a reference, there was a 27% increase in death risk in black women (RR = 1.27) and 82% in indigenous women (RR = 1.82)., Conclusion: These findings suggest that the higher rates of incidence and mortality from CC in vulnerable populations of black and more impactfully indigenous women in Brazil remain alarming. More efficient HPV vaccination strategies synchronized with well-conducted Pap smear-based screening should be prioritized in these more vulnerable populations., (© 2023. W. Montague Cobb-NMA Health Institute.)

Bauhinia ungulata is an antioxidant medicinal plant that has been manipuled in Brazil to lower glycemic index as well is for alternative treatment for diabetes. Therefore, the present hearch has aimed to investigates the antioxidant effects of the essential oil of Bauhinia ungulata L. (EOBU) collected in Amazon region better specified in Boa Vista, Roraima, Brazil, located in the Amazon region. Gas chromatography had been used to characterize the components, and antioxidant assays such as DPPH, TAC, reducing power, Fe 2+ chelation, and total phenols had also been performed. The major constituents had molecularly anchored with the human catalase (CAT) enzyme, and maltol has showed as a positive control. Among the 25 revealed components, the main ones have been α-bisabolol (27.2 %), β-Caryophyllene (12.5 %) and Epi-γ-eudesmol (13.6 %). The EOBU has comproved a TAC value of 618.79 mg of ascorbic acid equivalent, free radical scavenging capacity (DPPH) around 53.7 % and 65.27 %, Fe 2+ chelation capacity of 161±6 and 126.7±39.6, for 0.1 mg.mL -1 and 0.5 mg.mL -1 , respectively. The power around the EOBU has appeared percentages equals to 28.66 %, 44.6 %, and 77.03 % in the concentrations tested. As well as, 96.5 % of total phenols. The compounds α-bisabolol (-5.7±0.4 Kcal.mol -1 ) and β-caryophyllene (-6.1±0.5 Kcal.mol -1 ) have showed good interaction with CAT compared to Maltol (-4.4±0.4 Kcal.mol -1 ). The present work has demonstrated that EOBU functions as a potent antioxidant, capable of scavenging free radicals and reducing oxidative stress damage., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Purpose: Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease., Methods: This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control., Results: Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents., Conclusion: Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer.

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 < 0.05 were considered significant., Results: A total of 65 patients were included in the study, with a mean age at diagnosis of 72 (standard deviation 13.9). A total of 56.9% (37/65) of the patients were male, 86.2% (56/65) were white, and 56.9% (37/64) were illiterate or with incomplete elementary school. MCPyV immunohistochemistry was positive in 29 cases (44.6%) and PD-L1 positivity was ≥ 1% in 42 cases (64.6%). Significant associations between MCPyV and PD-L1 expression ≥ 1% (p = 0.003) and PD-L1 expression ≥ 5% (p = 0.005) were noted. Concerning the multivariate analysis, only education level and advanced MCC stage indicated statistically significant worse progression-free survival. Regarding overall survival (OS), being male, education level and advanced stage comprised risk factors. The estimated OS at 60 months for stages I to III was of 48.9% and for stage IV, 8.9%., Conclusions: This is the first large Brazilian cohort to assess the prevalence of MCPyV in MCC tumors, as well as PD-L1 expression and their associations. No correlations were noted between MCPyV infection or PD-L1 expression and survival rates., (© 2023. The Author(s).)

The Bauhinia ungulata, also known by its common name "pata de vaca", is one of the species used in Brazil for medicinal purposes, and is commonly used for the treatment of diabetes. In this study, the authors studied the interaction between the chemical constituents which are present in the essential oil of Bauhinia ungulata (EOBU), collected in Boa Vista-RR, Legal Amazon, and their effects on the enzyme acetylcholinesterase (AChE) in the essential oil. The analysis that we perform includes proton magnetic resonance ( 1 H NMR), enzymatic inhibition, molecular docking, in silico toxicity prediction, enrichment analysis, and target prediction for biological interactions. According to the tests performed on the essential oil, it obtained 100% inhibition of the enzyme AChE. During 1 H NMR experiments, it was found that α- Bisabolol, one of the main components, had a significant alteration in its chemical shift. A molecular docking analysis confirmed that this compound binds to the AChE enzyme, which confirms the 1 H NMR analysis. The results of this work showed that the major component of EOBU acted as a possible inhibitor of AChE enzyme in vitro and in silico assays. These results show that EOBU could be potentially applied in Alzheimer's disease treatment.

Despite enormous recent advances in stage IV melanoma treatment, it continues to have a significant mortality. Five-years survival is below 50% even when granted full access to effective therapeutic regimens. Considering the real world, mostly with low or medium-income countries like Brazil, where 75% of population depends on public health system receiving ineffective Dacarbazine chemotherapy, more than 95% of stage IV patients are dead before 5 years. Knowing the survival process of melanoma end-of-life time is imperative to help physicians to establish better symptoms control and improve the quality of death of these patients., Methods: Relative caregiver of melanoma end of life patients were invited to participate in a specific interview answering questions for the purpose of gathering information regarding symptoms and patients' complaints at the last 30 days, 7 days and at the day of death., Results: Although melanoma has a highest propensity for brain dissemination, seizure and focal neurological deficits were not a major complaint. Most of dying melanoma symptoms are shared among other solid terminality tumor process and get worse from 30 days to 7 days, but the majority of symptoms kept unchanged from 7 days till time to death. Wound bleeding and bad odor were the only complaints that got worse during the whole terminality process and could be improved with better commitment of assistant team., Conclusions: although a strong effort is made to control brain metastasis, local and regional open wound metastasis represents a major remediable complaint that should receive more attention at end-of-life melanoma patients., Competing Interests: CONFLICT OF INTEREST All the authors declare that they have no conflict of interest.

Purpose: This study aimed to describe the demographic and clinical characteristics of cancer patients with COVID-19, exploring factors associated with adverse outcomes., Patients and Methods: This retrospective cohort study methodically extracted and curated data from electronic medical records (EMRs) of numerous healthcare institutions on cancer patients diagnosed with a confirmed SARS-CoV-2 infection between May 2020 and August 2021, to identify risk factors linked to extended hospitalization and mortality. The retrieved information encompassed the patients' demographic and clinical characteristics, including the incidence of prolonged hospitalization, acute complications, and COVID-19-related mortality., Results: A total of 1446 cancer patients with COVID-19 were identified (mean [Standard deviation] age, 59.2 [14.3] years). Most patients were female (913 [63.1%]), non-white (646 [44.7%]), with non-metastatic (818 [56.6%]) solid tumors (1318 [91.1%]), and undergoing chemotherapy (647 [44.7%]). The rate of extended hospitalization due to COVID-19 was 46% (n = 665), which was significantly impacted by age (p = 0.012), sex (p = 0.003), race and ethnicity (p = 0.049), the presence of two or more comorbidities (p = 0.006), hematologic malignancies (p = 0.013), metastatic disease (p = 0.002), and a performance status ≥ 2 (p = 0.001). The COVID-19-related mortality rate was 18.9% (n = 273), and metastatic disease (<0.001), performance status ≥2 (<0.001), extended hospitalization (p = 0.028), renal failure (p = 0.029), respiratory failure (p < 0.001), sepsis (p = 0.004), and shock (p = 0.040) significantly and negatively influenced survival., Conclusion: The rate of extended hospitalization and COVID-19-specific death in cancer patients was notably high and could be influenced by comorbidities, cancer treatment status, and clinical fragility. These observations may aid in developing risk counseling strategies regarding COVID-19 in individuals diagnosed with cancer., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 da Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Melanoma is the most lethal skin cancer, and its incidence has increased worldwide. About 10% of cases are classified as hereditary melanoma (HM). CDKN2A and CDK4 are the major high-risk genes. Families are also more prone to develop pancreatic cancer, and different forms of oncological surveillance are recommended., Objectives: Describe the prevalence of CDKN2A/CDK4 germline mutations in melanoma-prone patients and their phenotypic and histopathological features., Methods: A total of 69 patients meeting the clinical criteria for HM were included in this cross-sectional descriptive study. Amplification by PCR and genomic sequencing were used. The variants were classified according to American College of Medical Genetics (ACMG) criteria., Results: The mean age at first diagnosis of melanoma was 44.8 years (SD ± 17.83). Most patients had phototype II (44.9%), more than 50 melanocytic nevi (76.8%), atypical nevus syndrome (72.5%), history of sunburn (76.8%), and multiple primary melanomas without a family history of this tumor (74.3%). Two hundred melanomas were observed. Most tumors had a Breslow index ≤1.0 mm (84.5%), location in the trunk (60.5%), and superficial spreading histological subtype (22.5%). Four variants were found in CDKN2A exons in seven patients (c.305C>A, c.26T>A, c.361G>A e c.442G>A), two variants in the 5'UTR region in five patients (c.-25C>T and c.-33G>C), and two variants in the 3'UTR region in 21 patients (c.*29C>G and c.*69C>T). One likely pathogenic variant (c.305C>A) was identified in one patient (1.4%). No variant was found in CDK4., Conclusion: The prevalence of CDKN2A mutations was 1.4% in Brazilian patients meeting clinical criteria for HM., (© 2023 the International Society of Dermatology.)

Introduction: Acute lymphoblastic leukemia (ALL) presents a poor prognosis in adults. The adoption of pediatric protocols has been changing this scenario, especially for adolescents and young adults (AYA)., Objective and Method: We aimed to evaluate a consecutive series of patients treated at the State Institute of Hematology of Rio de Janeiro between 2012 and 2020, focusing on the AYA subgroup., Result: The B-ALL was the most frequent subtype (81.6%) and AYA, the predominant age group (57.7%). The median overall survival (OS) was 9.4 months. High early mortality was observed and sepsis was the main cause of death. Better OS results were noted in AYA, in comparison to over 39y (13.3 × 6.2 months, respectively), the Berlin-Frankfurt-Münster (BFM) being the protocol of choice in this group., Conclusion: The use of the pediatric protocol seems to improve the OS of AYA, however, high rates of deaths from infection were observed, demonstrating the need for advances in the Brazilian public system clinical support., Competing Interests: Conflicts of interest None., (Copyright © 2022 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Increased global cancer incidence rates have led to a growing demand for cancer diagnosis and treatment, as well as basic and clinical research on the subject. The expansion of clinical cancer trials beyond the borders of highly developed countries has aided the arrival of these assessments in South American countries. In this context, this study's objective is to highlight clinical cancer trial profiles developed and sponsored by pharmaceutical companies and conducted in South American countries from 2010 to 2020., Methods: This study comprises descriptive and retrospective research conducted following a search for clinical trials (phases I, II and III), registered at clinicaltrials.gov, carried out in Latin American countries and sponsored by pharmaceutical companies ("Argentina", "Brazil", "Chile", "Peru", "Colombia", "Ecuador", "Uruguay", "Venezuela", "Paraguay", "Bolivia"), registered between 1 January 2010 and 31 December 2020. A total of 1451 clinical trials were retrieved, of which 200 trials unrelated to cancer were excluded and 646 duplicates were removed, leading to a final total of 605 clinical trials employing qualitative and quantitative analyses., Results: A 122% increase in the number of clinical trial registrations from 2010 to 2020 was noted, with a prevalence of phase III studies (431 trials of a total of 605). Lung (119), breast (100), leukemia (42), prostate (39) and melanoma (32) were the main cancers tested for new drugs., Conclusions: The data reported herein indicate the need for strategic basic and clinical research planning that considers South American epidemic cancer profiles.

Purpose: This study aimed to describe the clinical and demographic profile of cervical cancer patients exploring risk factors for prolonged use of opioids., Methods: The database of the Brazilian National Cancer Institute was queried out and 214 women with cervical cancer diagnosed between January 2014 and December 2015 who underwent isolated external beam radiation therapy (EBRT) or chemoradiotherapy (CRT) with complete response were included. Patients who no longer used opioids 6 months after completion of radiation therapy were classified as stoppers; patients who continued using opioids were non-stoppers. Variables were comparatively evaluated as risk factors for prolonged use of opioids., Results: The median age was 49.4 years. Most women were non-white (64.5%) and had ECOG Performance Status (PS) ≥ 1 (76.6%), International Federation of Gynecology and Obstetrics (FIGO) stage II-III (84.1%), and squamous cell carcinoma (82.7%). Smoking and alcohol consumption rates were, respectively, 44.9% and 39.7%. The median time from diagnosis to the onset of EBRT was 111 days (interquartile range 66.2). Most patients underwent CRT (88.8%). The rate of non-stoppers was 65.0%. By multivariate analysis, prescription of strong opioids (p = 0.005) and disease recurrence (p < 0.001) were suggested as independent factors for prolonged use of opioids., Conclusion: The rate of prolonged use of opioids after radiotherapy is alarming. Prescription of strong opioids and disease recurrence might be independent risk factors for its persistent use., Implications for Cancer Survivors: These results reveal an unmet and urgent need to implement public multiprofessional support programs with well-established protocols for dependence withdrawal, as well as stricter national measures of control in opioid prescription., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Uterine 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 Findings: The 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, <10%), 6 (10.5%) showed moderate (score 2, between 10-50%), and 14 (24.6%) showed strong L1CAM staining (score 3, ≧50%). dMMR occurred in 3 (5.3%) cases. The p53 was aberrantly expressed in 15 (26.3%) tumors. CDX2 was positive in 3 (5.3%) patients. The three-year progression-free survival (PFS) rate in the general population of the study was 21.2% (95% CI: 11.7-38.1) and the three-year overall survival (OS) rate was 29.4% (95% CI: 18.1-47.6). By multivariate analysis, the presence of metastases and CDX2-positive were significantly associated with poorer PFS (p < 0.001 and p = 0.002, respectively) and OS (p < 0.001 and p = 0.009, respectively)., Conclusion: The 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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 da Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (Copyright © 2023 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

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., Competing Interests: GC received: grants or had contracts from Novartis, Merck Sharp & Dohme, Pfizer, Roche/Genentech, Bristol Myers Squibb, Array, Springer, Grupo Español de Melanoma; consulting fees from Merck Sharp & Dohme, Novartis, Bristol Myers Squibb, Roche/Genentech; honoraria for presentations from Novartis, Merck Sharp & Dohme, Pfizer, Roche, Bristol Myers Squibb, Array, Springer, and Grupo Español de Melanoma; support for attending meetings from Novartis, Merck Sharp & Dohme, Bristol Myers Squibb, Roche; payment for board participation from Novartis, Merck Sharp & Dohme, Bristol Myers Squibb, Roche/Genentech. AM’s institution received grants from Clovis Oncology, Regeneron, Merck Sharp & Dohme, Bristol Myers Squibb, GlaxoSmithKline, AstraZeneca, Novartis, Amgen, and Roche for clinical trials. AM received payment for lectures from Merck Sharp & Dohme, Bristol Myers Squibb, GlaxoSmithKline, AstraZeneca, Novartis, Roche, Sanofi. Advisory Board participation from Merck Sharp & Dohme, Bristol Myers Squibb, GlaxoSmithKline, AstraZeneca, Novartis, Roche. RS received: consulting fees from Merck Sharp & Dohme and L’Oreal; payment for presentations from Merck Sharp & Dohme, Bristol Myers Squibb, Sanofi Genzyme, Pfizer, Merck Serono, Novartis; support from Bristol Myers Squibb for expert testimony; support for attending meetings from Sanofi Genzyme and Merck Sharp & Dohme. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Salman, de Melo, Rico-Restrepo, Rodriguez, Russi, Schmerling, Zambrano and Cinat.)

Background: Endometrial cancer is of increasing concern in several countries, including Brazil, in part because of an ageing population, declines in fertility, and the increasing prevalence of obesity. Although endometrial tumors had lagged behind other cancer types in terms of treatment improvements, molecular characterization of these tumors is paving the way for novel therapies and an expansion of the therapeutic arsenal. We aimed to help medical oncologists who manage patients with recurrent or metastatic endometrial cancer in the Brazilian healthcare setting., Methods: The panel, composed of 20 medical oncologists, convened in November 2021 to address 50 multiple-choice questions on molecular testing and treatment choices. We classified the level of agreement among panelists as (1) consensus (≥75% choosing the same answer), (2) majority vote (50% to <75%), or (3) less than majority vote (<50%)., Results: Consensus was present for 25 of the 50 questions, whereas majority vote was present for an additional 23 questions. Key recommendations include molecular testing for every patient with recurrent/metastatic endometrial cancer; choice of first-line treatment according to microsatellite instability and HER2, with the addition of programmed death ligand 1 (PD-L1) and hormone receptors (HRs) for second-line therapy; carboplatin and paclitaxel as the preferred option in first-line treatment of HER2-negative disease, with the addition of trastuzumab in HER2-positive disease; pembrolizumab plus lenvatinib as a key option in second line, regardless of HER2, PD-L1 or HRs; and various recommendations regarding treatment choice for patients with distinct comorbidities., Conclusion: Despite the existing gaps in the current literature, the vast majority of issues addressed by the panel provided a level of agreement sufficient to inform clinical practice in Brazil and in other countries with similar healthcare environments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 de Andrade, Guimarães, de Melo, Nogueira-Rodrigues, Gomes, Scaranti, Maia, Morelle, Santos, Souza, de Freitas, Callegaro Filho, Paulino, Júnior, Pimenta, Santos, de Almeida, Souza, Cabral and Maluf.)

Cervical cancer (CC) is a worldwide problem, especially in low- and middle-income countries, where patients are often diagnosed with locally advanced disease. Until recently, all chemotherapy drugs achieved low ORR and 12-month overall survival (12- month OS) for advanced CC after failure for platinum compounds. Advances in systemic therapy with immunotherapy, targeted therapy, and antibody-drug conjugates (ADC) have leveraged the 12-month OS limit. Recently, immunotherapy (pembrolizumab) has become the standard of care in first-line advanced CC combined with platinum and taxane and in second-line after platinum doublet failure., Competing Interests: Conflict of interest The authors declare no potential., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To analyze the epidemiological profile and the specific survival of patients diagnosed with tongue squamous cell carcinoma at the National Cancer Institute (INCA)., Materials and Methods: Hospital Cancer Registry System Data and Mortality Information from 2007 to 2009 were retrieved in a retrospective cohort study of patients diagnosed with tongue squamous cell carcinoma. Specific survival was estimated using the Kaplan-Meier method. The association between independent variables and the risk of death was explored in a Cox proportional hazards regression model., Results: A total of 346 patients were eligible, mostly male (77.5%), smokers (87.6%), with alcohol consumption (80.9%), with low education (65.6%), advanced staging at the time of diagnosis (71.1%), and presenting a high mortality rate (72.5%). In total, 44.5% of patients underwent a surgical approach alone or associated with another treatment modality, of which 85.1% of patients underwent neck dissection and 90.1% had free surgical margins. Specific survival was 40.6% in two years and 31.2% in five years., Conclusion: The 5-year specific survival was considered worse in individuals over 60 years, and who did not undergo surgical treatment or had surgery associated with another treatment, compared to patients undergoing isolated surgery., (© 2021 Wiley Periodicals LLC.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Viana, Curty, Furtado, Singh, Bendall, Viola, de Melo, Soares and Moreira.)

Glyphosate excessive use is reported in Brazilian citrus orchards, whereas there is speculation about its consequences and the published studies are contradictory and inconclusive. This study aimed to describe the possible harmful effects by simulating glyphosate drift directly to the leaves of ∼4-yr-old citrus plants. As major results, glyphosate doses >360 g ae ha -1 increased the shikimate accumulation in leaves (up to 2.3-times above control), which was increased after a second glyphosate application (up to 3.5-times above control), even after a 240-d interval. Interestingly, shikimate accumulation was occasionally related to a dose-response of the herbicide at specific times; however, the doses had their accumulation peak on determined dates. These accumulations were directly correlated to reduced net photosynthesis even months after the glyphosate sprays. Quantum productivity based on electron transport through the photosystem II and apparent electron transport reductions up to 17% were also observed during the entire experiment course. Similarly, quantum productivity based on CO 2 assimilation of glyphosate sprayed leaves decreased up to four times compared to the control after the second application. Glyphosate doses >360 g ae ha -1 increased stomatal conductance and transpiration as the carboxylation efficiency decreased, evidencing a carbon drainage in the Calvin-Benson cycle. These metabolic and physiological disturbances suggest possible photooxidative damage and an increase in photorespiration, which may be a mitigation strategy by the citrus plants to glyphosate effects, by the cost of reducing the citrus fruit yield (up to 57%). It is concluded that glyphosate phytotoxicity damages citrus plants over time due to chronic disturbances in the shikimate pathway and photosynthesis, even when there are no symptoms. This study is the first report to demonstrate how glyphosate damages citrus trees beyond the shikimate pathway., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rodrigo Martinelli reports financial support was provided by Coordination of Higher Education Personnel Improvement. Fernando Alves de Azevedo reports financial support was provided by State of Sao Paulo Research Foundation. Dirceu de Mattos Jr reports financial support was provided by State of Sao Paulo Research Foundation. Fernando Alves de Azevedo reports financial support was provided by National Council for Scientific and Technological Development., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., (© 2022. The Author(s).)

Introduction: Due 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., Methods: The 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., Results: Consensus 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., Conclusion: The development of guidelines focusing on areas of the world facing more severe resource limitations may improve medical practice and patient care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Maluf, Zibetti, Paulino, de Melo, Racy, Ferrigno, Uson Junior, Ribeiro, Moretti, Sadalla, Nogueira Rodrigues, Carvalho, Baiocchi, Callegaro-Filho and Angioli.)

INDUCTION: chemotherapy (IC) followed by chemoradiation (CRT) is an attractive approach in high-risk locally advanced rectal cancer. Additionally, ASA has shown potential to improve outcomes alongside CRT in rectal cancer. The ICAR trial aimed to evaluate the safety and efficacy of IC followed by CRT with or without ASA on MRI tumor response., Methods: Single-center, double-blind, randomized phase II trial to evaluate induction treatment with CAPOX, followed by capecitabine-based chemoradiotherapy with ASA (arm 1) or placebo (arm 2) in high-risk stage II-III rectal adenocarcinoma staged by MRI. The primary endpoint was MRI tumor regression grade (mrTRG). Secondary endpoints were pathological response, surgical outcomes, postoperative complications, treatment tolerance, DFS, and OS., Results: Between January 2018 and August 2019, 27 patients were eligible, 25 (92.5%) completed IC, and 23 patients were randomly assigned (12 to ASA group; 11 to placebo group). In the ASA arm, 3 pts (25%) presented distant disease progression at restaging. Seven patients (30.4%) had cCR after neoadjuvant treatment. All 13 patients submitted to surgery after neoadjuvant treatment underwent R0 resections except for 1 patient with positive CRM, and 12 patients (92.3%) had sphincter preservation. After a median follow-up of 34.9 months, the 2-year DFS was 83.1% and 3-year OS was 81.5%., Conclusion: There was good compliance in both treatment arms and encouraging cCR rate. ASA during CRT was safe but failed to improve on MRI tumor response. The study was closed due to the absence of benefits., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Nearly 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., Methods: The 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%., Results: Consensus 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., Discussion: The 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Maluf, Dal Molin, de Melo, Paulino, Racy, Ferrigno, Uson Junior, Ribeiro, Moretti, Sadalla, Nogueira-Rodrigues, Carvalho, Baiocchi, Callegaro-Filho and Abu-Rustum.)

Grumixama ( Eugenia brasiliensis Lam.) is a native fruit of the Brazilian Atlantic Forest, belonging to the Myrtaceae family, which designatesthe most significant number of species with food potential. It stands out due to its phytochemical characteristics because of the presence of polyphenols and volatile organic compounds. Volatile compounds are substances released by foods that give off an aroma and influence flavor. Solid-phase microextraction is a technique that allows for low-cost, fast, and solvent-free extraction, has an affinity for numerous analytes, and is easily coupled to gas chromatography. The objectives of this work were to evaluate the efficiency of different fibers of SPME (solid-phase microextraction) in the extraction of volatile organic compounds from grumixama pulp; optimize a method for extraction time, temperature, and sample weight; and to determine the characteristic volatile profile of this fruit. For the extraction of volatile compounds, three fibers of different polarities were used: polar polyacrylate (PA) fibers, divinylbenzene/carboxyne/polydimethylsiloxane (DVB/CAR/PDMS) semipolar fibers, and polydimethylsiloxane/divinylbenzene (PDMS/DVB). Fourteen volatile organic compounds (VOCs) were identified by DVB/CAR/PDMS, six by PA, and seven by PDMS/DVB through solid-phase microextraction in the headspace mode (SPME-HS). Considering the total number of compounds identified, regardless of the fiber used, and the optimization of the method, Eugenia brasiliensis presented sesquiterpene fractions (85.7%, 83.3%, and 85.7% of total VOCs) higher than the monoterpene fractions (14.3%, 16.7%, and 14.3%) for DVB/CAR/PDMS, PA, and PDMS/DVB, respectively in its composition. In addition, it was possible to verify that the fiber DVB/CAR/PDMS presented a better efficiency due to the larger chromatographic area observed when the grumixama pulp was subjected to conditions of 75 °C, 2.0 g, and an adsorption time of 20 min.

Background: Few prospective studies have compared poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors to chemotherapy for the treatment of BRCA1-mutated or BRCA2-mutated ovarian carcinoma. We aimed to assess rucaparib versus platinum-based and non-platinum-based chemotherapy in this setting., Methods: In this open-label, randomised, controlled, phase 3 study (ARIEL4), conducted in 64 hospitals and cancer centres across 12 countries (Brazil, Canada, Czech Republic, Hungary, Israel, Italy, Poland, Russia, Spain, Ukraine, the UK, and the USA), we recruited patients aged 18 years and older with BRCA1-mutated or BRCA2-mutated ovarian carcinoma, with an Eastern Cooperative Oncology Group performance status of 0 or 1, and who had received two or more previous chemotherapy regimens. Eligible patients were randomly assigned (2:1), using an interactive response technology and block randomisation (block size of six) and stratified by progression-free interval after the most recent platinum-containing therapy, to oral rucaparib (600 mg twice daily) or chemotherapy (administered per institutional guidelines). Patients assigned to the chemotherapy group with platinum-resistant or partially platinum-sensitive disease were given paclitaxel (starting dose 60-80 mg/m 2 on days 1, 8, and 15); those with fully platinum-sensitive disease received platinum-based chemotherapy (single-agent cisplatin or carboplatin, or platinum-doublet chemotherapy). Patients were treated in 21-day or 28-day cycles. The primary endpoint was investigator-assessed progression-free survival, assessed in the efficacy population (all randomly assigned patients with deleterious BRCA1 or BRCA2 mutations without reversion mutations), and then in the intention-to-treat population (all randomly assigned patients). Safety was assessed in all patients who received at least one dose of assigned study treatment. This study is registered with ClinicalTrials.gov, NCT02855944; enrolment is complete, and the study is ongoing., Findings: Between March 1, 2017, and Sept 24, 2020, 930 patients were screened, of whom 349 eligible patients were randomly assigned to rucaparib (n=233) or chemotherapy (n=116). Median age was 58 years (IQR 52-64) and 332 (95%) patients were White. As of data cutoff (Sept 30, 2020), median follow-up was 25·0 months (IQR 13·8-32·5). In the efficacy population (220 patients in the rucaparib group; 105 in the chemotherapy group), median progression-free survival was 7·4 months (95% CI 7·3-9·1) in the rucaparib group versus 5·7 months (5·5-7·3) in the chemotherapy group (hazard ratio [HR] 0·64 [95% CI 0·49-0·84]; p=0·0010). In the intention-to-treat population (233 in the rucaparib group; 116 in the chemotherapy group), median progression-free survival was 7·4 months (95% CI 6·7-7·9) in the rucaparib group versus 5·7 months (5·5-6·7) in the chemotherapy group (HR 0·67 [95% CI 0·52-0·86]; p=0·0017). Most treatment-emergent adverse events were grade 1 or 2. The most common grade 3 or worse treatment-emergent adverse event was anaemia or decreased haemoglobin (in 52 [22%] of 232 patients in the rucaparib group vs six [5%] of 113 in the chemotherapy group). Serious treatment-emergent adverse events occurred in 62 (27%) patients in the rucaparib group versus 13 (12%) in the chemotherapy group; serious adverse events considered related to treatment by the investigator occurred in 32 (14%) patients in the rucaparib group and six (5%) in the chemotherapy group. Three deaths were considered to be potentially related to rucaparib (one due to cardiac disorder, one due to myelodysplastic syndrome, and one with an unconfirmed cause)., Interpretation: Results from the ARIEL4 study support rucaparib as an alternative treatment option to chemotherapy for patients with relapsed, BRCA1-mutated or BRCA2-mutated ovarian carcinoma., Funding: Clovis Oncology., Competing Interests: Declaration of interests RK has received institutional funding from Clovis Oncology for this clinical trial; reports clinical trial grants from Merck Sharp & Dohme; has served as a consultant for Basilea Pharmaceutica and Shattuck Pharma; has received honoraria from Clovis Oncology, AstraZeneca, GlaxoSmithKline, and Incyte; received travelling support from AstraZeneca, GlaxoSmithKline, and Sierra Oncology; has served on data safety monitoring boards or advisory boards for Clovis Oncology, AstraZeneca, BeiGene, Eisai, GlaxoSmithKline, Incyte, iTeos Therapeutics, PharmaMar, and Roche. AF is currently at P A Herzen Cancer Research Institute, Moscow, Russia and delcares no competing interests. ACdM has received institutional funding from Clovis Oncology for this cl.inical trial; reports institutional clinical trial grants from Amgen, AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Regeneron, and Roche; has received honoraria for lectures from AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Roche, and Sanofi; has served on advisory boards for AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, and Roche. YS has received honoraria from AstraZeneca, Merck Sharp & Dohme, and Roche. NC reports grants from AstraZeneca and Roche; has served as a consultant for Clovis Oncology, AstraZeneca, BIOCAD, Eisai, GlaxoSmithKline, Immunogen, Merck Sharp & Dohme/Merck, Mersana, Oncxerna, Pfizer, Pharmamar, Roche, Takeda, and Tesaro; has received honoraria from Clovis Oncology, AstraZeneca, Eisai, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, and Tesaro; received traveling support from Tesaro; and has served on data safety monitoring boards or advisory boards for Clovis Oncology, AstraZeneca, BIOCAD, Eisai, GlaxoSmithKline, Immunogen, Merck Sharp & Dohme/Merck, Mersana Therapeutics, OncXerna, Pfizer, PharmaMar, Roche, Takeda, and Tesaro. DL has received institutional funding from Clovis Oncology for this clinical trial; reports institutional research grants from Clovis Oncology, GlaxoSmithKline, and Merck Sharp & Dohme; has served as a consultant for Merck Serono and ParmaMar; has served on advisory boards for Amgen, AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme, and PharmaMar; has received travelling support from AstraZeneca, GlaxoSmithKline, PharmaMar, and Roche; has served on data safety monitoring committee for Novartis; and has served on the board of directors for the Gynecological Cancer Academy, the Gynecological Cancer InterGroup, and Multicenter Italian Trials in Ovarian Cancer and Gynecologic Malignancies. GS reports grants and research support from Merck Sharp & Dohme Italia SRL; has served as a consultant for Tesaro Bio Italy SRL and Johnson & Johnson; and has received honoraria and served on a speakers' bureau for Clovis Oncology Italy SRL. DC has served as a consultant for Akeso Biopharma, AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme, Novocure, Roche, Seagen, and SOTIO. DT, KKL, KM, and SG are employees of Clovis Oncology, and have stock and stock options. AMO reports institutional research grants from AstraZeneca; has served on an advisory board (uncompensated) for GlaxoSmithKline; has served on advisory boards and steering committees (uncompensated) for Clovis Oncology and AstraZeneca; and has served as a principal investigator on investigator-initiated trials for Clovis Oncology, AstraZeneca, and GlaxoSmithKline. All other authors declare no competing interests. Authors received writing support from Clovis Oncology during the conduct of the study. RK is currently at the Department of Oncology, Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London, UK. AL is currently at the Department of Oncology, Almazov National Medical Research Center, Saint Petersburg, Russia. DL is currently at Gynecologic Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Sarcomas 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 Methods: We 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., Results: From 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., Conclusion: This 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., Competing Interests: Celso Abdon MelloConsulting or Advisory Role: Daichii Sankyo Andreia Cristina de MeloHonoraria: MSD Oncology, Novartis, BMS BrazilSpeakers' Bureau: BMS Brazil, MSD OncologyResearch Funding: Roche (Inst), MSD Oncology (Inst), BMS Brazil (Inst), Novartis (Inst), Clovis Oncology (Inst), AstraZeneca (Inst)Travel, Accommodations, Expenses: MSD OncologyNo other potential conflicts of interest were reported.

Copaiba oleoresin has been related to properties including healing and anti-inflammatory effects, making it a potential candidate to treat oral lesions. We aimed to define the benefits related to the anti-inflammatory and healing capacity of Copaiba-based formulations on the oral cavity. This is a systematic review, conducted in PubMed, Web of Science, Scopus, Embase, Scielo, Cochrane Library, BVS, and Google Scholar databases selecting full articles in English, Portuguese, or Spanish, until March 3 rd , 2021. Pre-clinical, clinical, or randomized clinical trials, cohort and case-control in vivo studies were included; studies with other designs, in vitro, and those that did not match the PICO question were excluded (PROSPERO: CRD42021244938). Data was collected and synthesized descriptively through a specific form. The risk of bias was evaluated by SYRCLE's RoB Tool. So, five studies were included. Two reported beneficial wound healing effects, such as early reduction in the wound area and greater immature bone formation in the rats' mandibles; and two related benefic anti-inflammatory effects, like reduced acute inflammatory reaction and more advanced tissue repair stage, early formation of collagen fibrils, with greater quantity, thickness and better organization, and more expressive anti-inflammatory activity, reduction of the edema intensity and the CD68 + macrophages concentration. Based on the articles, benefits related to the wound healing and anti-inflammatory effects in the oral cavity of rats treated with Copaiba oleoresin were suggested. However, due to the limited data, future studies are necessary, especially clinical ones., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)