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To compare the outcomes of patients with low-risk gestational trophoblastic neoplasia (GTN) treated with standard 8-day methotrexate/folinic acid (MTX/FA) versus modified regimen.Retrospective cohort study of patients with low-risk GTN followed at Rio de Janeiro Federal University, from January/1990-December/2017 with standard 8-day MTX/FA or modified regimen (MTX administered on the 8th day rather than 7th) to avoid treatment on the weekend.From 937 patients with low-risk GTN, 538 were treated with standard MTX/FA and 98 patients received modified regimen. Both groups were comparable in age (p = .749), antecedent pregnancy (p = .221), time to initiate chemotherapy (p = .926), hCG pretreatment level (p = .112) and WHO/FIGO prognostic risk score (p = .723). Patients treated with modified MTX/FA had twice of cases of metastatic lung disease compared with the standard regimen (22.5% vs 10.6%; p = .002). The rate of remission (p = .999), number of cycles to remission in the first-line (p = .966), chemoresistance (p = .500), time to switch to second-line therapy (p = .176), need for multiagent chemotherapy (p = .084), relapse (p = .122) or death (p = .475) was the same for both MTX/FA regimen. However, although patients receiving modified MTX/FA required a higher total number of remission cycles (6 vs 5 cycles; p = .004) and longer time to remission (19 vs 16 weeks; p .001) when compared with the standard regimen, these variables showed no significant differences after multivariate logistic regression adjusted for lung metastasis.The modified 8-day MTX/FA regimen didn't compromise oncologic outcomes for women with low-risk GTN. This regimen appears to be an acceptable alternative to standard 8-day MTX/FA when treatment on weekend isn't an option.

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).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.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.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.

A pesquisa clínica pode ser definida como qualquer investigação que tem como participante os seres humanos e tem como objetivo descobrir ou verificar os efeitos farmacodinâmicos, farmacológicos e clínicos, além de outros efeitos, dos produtos investigados.

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/m2 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.

Background Low socioeconomic status, increasing age, and poor lifestyle behaviors are associated with poor survival in patients with oral cavity squamous cell carcinoma (OCSCC). To determine the overall survival (OS) and the risk of OCSCC death by tumor subsite. Material and Methods A retrospective cohort study of OCSCC patients diagnosed from 2007 to 2009 and treated at a single cancer center in Rio de Janeiro, Brazil. Patient information was obtained from the Hospital Cancer Registry (HCR) database and complemented by individual search of physical and electronic medical records. Descriptive statistics of population characteristics were computed. OS was estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards regression analyses were used to estimate the risk of death by tumor subsite. Results Seven hundred and three patients with OCSCC were identified. Most patients were men (77.4%) with low levels of education (67.5%), who drank (73.9%) and smoked (79.7%). The most prevalent tumor site was the tongue (45.4%), 73.4% of patients had advanced (clinical stage III or IV) OCSCC at diagnosis and 74.1% died during follow-up. For the entire cohort, the OS was 39.1% at two years and 27.9% at five years. The median survival time was 1.4 years (95%CI: 1.2‒1.5). Non-operative treatment (HR: 3.11; 95%CI: 2.26‒4.29; p 60 years at diagnosis (HR: 1.37; 95%CI: 1.15‒1.64; p

PURPOSE Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer death worldwide. Platinum agents and fluoropyrimidines are the main compounds used in the first-line setting for advanced GC. Given the activity of fluorouracil (FU) bolus, the PFL protocol, a chemotherapy regimen combining cisplatin, FU bolus, and leucovorin, was incorporated at the Brazilian National Cancer Institute, because this schedule does not require hospitalization or infusion pumps. This study aims to evaluate the outcomes of PFL in the first-line setting for patients with advanced GC. MATERIALS AND METHODS This was a retrospective cohort study evaluating patients with advanced GC treated in the first-line setting with cisplatin 80 mg/m2 on day 1 and FU bolus 400 mg/m2 plus leucovorin 20 mg/m2 on days 1, 8, 15, and 22 every 4 weeks, from January 2008 to December 2014. RESULTS A total of 109 patients were enrolled. The median number of cycles received per patient was four (one to 11). Complete responses were achieved in 6.4% and partial responses in 14.7%. Median progression-free survival was 6.3 months (95% CI, 5.08 to 7.58 months) and median overall survival was 8.3 months (95% CI, 6.79 to 9.87 months). Thirty-four (31.2%) patients were alive in 1 year. Grade 3 and 4 adverse events were experienced by 26.6% and 3.7% of patients, respectively, with dose reduction necessary in 9.1%. CONCLUSION PFL is active in advanced GC and could be an alternative for FU continuous infusion protocols in institutions with limited resources and/or low budget, which is the reality in many nations all over the world.

Gestational trophoblastic neoplasia (GTN) is a rare tumor that originates from pregnancy that includes invasive mole, choriocarcinoma (CCA), placental site trophoblastic tumor and epithelioid trophoblastic tumor (PSTT/ETT). GTN presents different degrees of proliferation, invasion and dissemination, but, if treated in reference centers, has high cure rates, even in multi-metastatic cases. The diagnosis of GTN following a hydatidiform molar pregnancy is made according to the International Federation of Gynecology and Obstetrics (FIGO) 2000 criteria: four or more plateaued human chorionic gonadotropin (hCG) concentrations over three weeks; rise in hCG for three consecutive weekly measurements over at least a period of 2 weeks or more; and an elevated but falling hCG concentrations six or more months after molar evacuation. However, the latter reason for treatment is no longer used by many centers. In addition, GTN is diagnosed with a pathological diagnosis of CCA or PSTT/ETT. For staging after a molar pregnancy, FIGO recommends pelvic-transvaginal Doppler ultrasound and chest X-ray. In cases of pulmonary metastases with more than 1 cm, the screening should be complemented with chest computed tomography and brain magnetic resonance image. Single agent chemotherapy, usually Methotrexate (MTX) or Actinomycin-D (Act-D), can cure about 70% of patients with FIGO/World Health Organization (WHO) prognosis risk score ≤ 6 (low risk), reserving multiple agent chemotherapy, such as EMA/CO (Etoposide, MTX, Act-D, Cyclophosphamide and Oncovin) for cases with FIGO/WHO prognosis risk score ≥ 7 (high risk) that is often metastatic. Best overall cure rates for low and high risk disease is close to 100% and > 95%, respectively. The management of PSTT/ETT differs and cure rates tend to be a bit lower. The early diagnosis of this disease and the appropriate treatment avoid maternal death, allow the healing and maintenance of the reproductive potential of these women.

This narrative review describes implementation, current status and perspectives of a pharmacogenomic (PGx) program at the Brazilian National Cancer Institute (INCA), targeting the cancer chemotherapeutic drugs – fluoropyrimidines, irinotecan and thiopurines. This initiative, designed as a research project, was supported by a grant from the Brazilian Ministry of Health. A dedicated task force developed standard operational procedures from recruitment of patients to creating PGx reports with dosing recommendations, which were successfully applied to test 100 gastrointestinal cancer INCA outpatients and 162 acute lymphoblastic leukemia pediatric patients from INCA and seven other hospitals. The program has been subsequently expanded to include gastrointestinal cancer patients from three additional cancer treatment centers. We anticipate implementation of routine pre-emptive PGx testing at INCA but acknowledge challenges associated with this transition, such as continuous financing support, availability of trained personnel, adoption of the PGx-informed prescription by the clinical staff and, ultimately, evidence of cost–effectiveness.

Aims: The current study aims to present epidemiologic changes and clinical aspects of Merkel cell carcinoma (MCC) in Brazil. Methods: Data were collected from the Brazilian Population-Based Cancer Registries (2000–2015) and Hospital-Based Cancer Registries (2000–2017). Results: The average age-standardized incidence rates significantly increased in men between the years 2000 (0.31/1,000,000) and 2015 (1.21/1,000,000), with an annual percentage change of 9.4 (95% CI: 4.7–14.4; p 60 years (82.2%), White (67.6%) and diagnosed at stages III or IV (50.5%). Conclusions: A key aspect of public health promotion is to understand the incidence and morbidity of MCC.

Objective 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.

Numerous factors have been identified to influence susceptibility to SARS-CoV-2 infection and disease severity. Cancer patients are more prone to clinically evolve to more severe COVID-19 conditions, but the determinants of such a more severe outcome remain largely unknown. We have determined the full-length SARS-CoV-2 genomic sequences of cancer patients and healthcare workers (HCW; non-cancer controls) by deep sequencing and investigated the within-host viral quasispecies of each infection, quantifying intrahost genetic diversity. Naso- and oropharyngeal SARS-CoV-2+ swabs from 57 cancer patients and 14 healthcare workers (HCW) from the Brazilian Cancer Institute were collected in April–May 2020. Complete genome amplification using ARTIC network V3 multiplex primers was performed followed by next-generation sequencing. Assemblies were conducted in Geneious R11, where consensus sequences were extracted and intrahost single nucleotide variants (iSNVs) were identified. Maximum likelihood phylogenetic analysis was performed using PhyMLv.3.0 and lineages were classified using Pangolin and CoV-GLUE. Phylogenetic analysis showed that all but one strain belonged to clade B1.1. Four genetically linked mutations known as the globally dominant SARS-CoV-2 haplotype (C241T, C3037T, C14408T and A23403G) were found in the majority of consensus sequences. SNV signatures of previously characterized Brazilian genomes were also observed in most samples. Another 85 SNVs were found at a lower frequency (1.4–19.7%). Cancer patients displayed a significantly higher intrahost viral genetic diversity compared to HCW (p = 0.009). Intrahost genetic diversity in cancer patients was independent of SARS-CoV-2 Ct values, and was not associated with disease severity, use of corticosteroids, or use of antivirals, characteristics that could influence viral diversity. Such a feature may explain, at least in part, the more adverse outcomes to which cancer/COVID-19 patients experience., Author Summary Cancer patients are more prone to clinically evolve to more severe COVID-19 conditions, but the determinants of such a more severe outcome remain largely unknown. In this study, phylogenetic and variation analysis of SARS-CoV-2 genomes from cancer patients and non-cancer healthcare workers at the Brazilian National Cancer Institute were characterized by deep sequencing. Viral genomes showed signatures characteristic of Brazilian viruses, consistent with the hypothesis of local, community transmission rather than virus importation from abroad. Despite most genomes in patients and healthcare workers belonging to the same lineage, intrahost variability was higher in cancer patients when compared to non-cancer counterparts. The intrahost genomic diversity analysis presented in our study highlights the relaxed evolution of SARS-CoV-2 in a vulnerable population of cancer patients. The high number of minor variations can result in the selection of immune escape variants, resistance to potential drugs, and/or increased pathogenicity. The impact of this higher intrahost variability over time warrants further investigation.

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.

Objectives: Prospective studies comparing poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors with standard-of-care (SOC) chemotherapy (CT) in patients (pts) with relapsed ovarian cancer (OC) are currently limited. ARIEL4 (NCT02855944) is a phase III, randomized, open-label, international, multicenter study of the efficacy and safety of rucaparib vs SOC CT as treatment for PARP-inhibitor naive pts with relapsed high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer, who had a deleterious BRCA1/2 (BRCA) mutation and had received ≥2 prior CT regimens. Methods: Pts were randomized 2:1 to oral rucaparib 600 mg twice daily or SOC CT and stratified based on progression-free interval (≥1 to Results: A total of 233 pts were randomized to rucaparib and 116 to CT (visit cutoff Sep 30, 2020); 179 (51.3%) had platinum-resistant, 96 (27.5%) had partially platinum-sensitive, and 74 (21.2%) had fully platinum-sensitive disease. A total of 23 pts (6.6%) with BRCA reversion mutations and 1 pt without a BRCA mutation were excluded from the efficacy population. Median PFS was significantly longer with rucaparib vs CT in both the efficacy and ITT populations (Table). In an exploratory analysis of pts with BRCA reversion mutations, median PFS was shorter with rucaparib (n=13) vs CT (n=10); 2.9 vs 5.5 months, hazard ratio 2.769 (95% CI, 0.989–7.755). ORR was not significantly different between the rucaparib and CT arms in both populations (Table). Adverse events were consistent with the known safety profiles of rucaparib and CT. Download : Download high-res image (119KB) Download : Download full-size image Conclusions: Patients with BRCA-mutated advanced, relapsed OC who received rucaparib had a significant improvement in PFS vs SOC CT. No new safety signals were identified. This is the first prospective report from a randomized trial demonstrating that the presence of a BRCA reversion mutation predicts for primary resistance to rucaparib.

Background Brazil is a country of continental dimensions with great potential for the development of clinical studies across the whole territory to tackle the needs of the population. It is therefore important to obtain the national profile of clinical trials in order to identify local strengths and weaknesses in terms of productivity and study application. Thus, this paper aims to highlight the profiles of clinical studies on cancer developed and sponsored by hospitals, institutes, universities and international institutions in Brazil between 1997 and 2015. Methods This is a retrospective and analytical study in which the content analysis method of Laurence Bardin was used. Data were collected from the clinicaltrials.gov database, where 783 clinical studies on cancer prevention, diagnosis and treatment were found; 188 (24 %) of these corresponded to national initiatives and 595 (76 %) to international initiatives. Results The results show an increase in the number of national clinical studies, in particular phase III studies. There is a clear absence of national clinical studies focusing on the development of new chemical and biotechnological products in oncology. Conclusion The results indicate a regional imbalance in the distribution of national and international clinical trials. Policy summary The present study aims to improve understanding of the profile of clinical studies registered in Brazil and to draw attention to the improvements needed in the health sector's productivity to address the national demand.

PURPOSEThe COVID-19 pandemic remains a public health emergency of global concern. Determinants of mortality in the general population are now clear, but specific data on patients with cancer remain limited, particularly in Latin America.MATERIALS AND METHODSA longitudinal multicenter cohort study of patients with cancer and confirmed COVID-19 from Oncoclínicas community oncology practice in Brazil was conducted. The primary end point was all-cause mortality after isolation of the SARS-CoV-2 by Real-Time Polymerase Chain Reaction (RT-PCR) in patients initially diagnosed in an outpatient environment. We performed univariate and multivariable logistic regression analysis and recursive partitioning modeling to define the baseline clinical determinants of death in the overall population.RESULTSFrom March 29 to July 4, 2020, 198 patients with COVID-19 were prospectively registered in the database, of which 167 (84%) had solid tumors and 31 (16%) had hematologic malignancies. Most patients were on active systemic therapy or radiotherapy (77%), largely for advanced or metastatic disease (64%). The overall mortality rate was 16.7% (95% CI, 11.9 to 22.7). In univariate models, factors associated with death after COVID-19 diagnosis were age ≥ 60 years, current or former smoking, coexisting comorbidities, respiratory tract cancer, and management in a noncurative setting ( P < .05). In multivariable logistic regression and recursive partitioning modeling, only age, smoking history, and noncurative disease setting remained significant determinants of mortality, ranging from 1% in cancer survivors under surveillance or (neo)adjuvant therapy to 60% in elderly smokers with advanced or metastatic disease.CONCLUSIONMortality after COVID-19 in patients with cancer is influenced by prognostic factors that also affect outcomes of the general population. Fragile patients and smokers are entitled to active preventive measures to reduce the risk of SARS-CoV-2 infection and close monitoring in the case of exposure or COVID-19-related symptoms.

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

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in cervical tumors, being correlated with adverse clinical outcomes. EGFR may be activated by a diversity of mechanisms, including transactivation by G-protein coupled receptors (GPCRs). Studies have also shown that platelet-activating factor (PAF), a pro-inflammatory phospholipid mediator, plays an important role in the cancer progression either by modulating the cancer cells or the tumor microenvironment. Most of the PAF effects seem to be mediated by the interaction with its receptor (PAFR), a member of the GPCRs family. PAFR- and EGFR-evoked signaling pathways contribute to tumor biology; however, the interplay between them remains uninvestigated in cervical cancer. In this study, we employed The Cancer Genome Atlas (TCGA) and cancer cell lines to evaluate possible cooperation between EGFR, PAFR, and lysophosphatidylcholine acyltransferases (LPCATs), enzymes involved in the PAF biosynthesis, in the context of cervical cancer. It was observed a strong positive correlation between the expression of EGFR × PAFR and EGFR × LPCAT2 in 306 cervical cancer samples. The increased expression of LPCAT2 was significantly correlated with poor overall survival. Activation of EGFR upregulated the expression of PAFR and LPCAT2 in a MAPK-dependent fashion. At the same time, PAF showed the ability to transactivate EGFR leading to ERK/MAPK activation, cyclooxygenase-2 (COX-2) induction, and cell migration. The positive crosstalk between the PAF-PAFR axis and EGFR demonstrates a relevant linkage between inflammatory and growth factor signaling in cervical cancer cells. Finally, combined PAFR and EGFR targeting treatment impaired clonogenic capacity and viability of aggressive cervical cancer cells more strongly than each treatment separately. Collectively, we proposed that EGFR, LPCAT2, and PAFR emerge as novel targets for cervical cancer therapy.

Anti-programmed death-1 agents are an established option for advanced melanoma, but the anti-programmed death-ligand 1 (anti-PD-L1) antibody atezolizumab, an agent approved for the treatment of multiple solid tumors, was not previously evaluated. This phase 1b study cohort (NCT03178851; cohort C) evaluated first-line atezolizumab 1,200 mg every 3 weeks in adults with BRAF

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

Cancer patients suffer from worse coronavirus disease-2019 (COVID-19) outcomes. Whether active oncologic treatment is an additional risk factor in this population remains unclear. Therefore, here we have conducted a systematic review and meta-analysis to summarize the existing evidence for the effect of active oncologic treatment on COVID-19 outcomes.Systematic search of databases (PubMed, Embase) was conducted for studies published from inception to July 1, 2020, with a subsequent search update conducted on 10 October 2020. In addition, abstracts and presentations from major conference proceedings (ASCO, ESMO, AACR) as well as pre-print databases (medxriv, bioxriv) were searched. Retrospective and prospective studies reporting clinical outcomes in cancer patients with laboratory confirmation or clinical diagnosis of COVID-19 and details of active or recent oncologic treatment were selected. Random-effects model was applied throughout meta-analyses. Summary outcome measure was the pooled odds ratio (OR) of death for active cancer therapy versus no active cancer therapy for each of the following modalities: recent surgery, chemotherapy, targeted therapy, immunotherapy, or chemoimmunotherapy.Sixteen retrospective and prospective studies (3558 patients) were included in the meta-analysis. Active chemotherapy was associated with higher risk of death compared to no active chemotherapy (OR, 1.60, 95% CI, 1.14-2.23). No significant association with risk of death was identified for active targeted therapy, immunotherapy, chemoimmunotherapy, or recent surgery. Meta-analysis of multivariate adjusted OR of death for active chemotherapy was consistently associated with higher risk of death compared to no active chemotherapy (OR, 1.42, 95% CI, 1.01-2.01).Active chemotherapy appears to be associated with higher risk of death in cancer patients with COVID-19. Further research is necessary to characterize the complex interactions between active cancer treatment and COVID-19.

PURPOSE Little 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. METHODS Incidence, 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. RESULTS From 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. CONCLUSION A 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.

Numerous factors have been identified to influence susceptibility to SARS-CoV-2 infection and disease severity. Cancer patients are more prone to clinically evolve to more severe COVID-19 conditions, but the determinants of such a more severe outcome remain largely unknown. We have determined the full-length SARS-CoV-2 genomic sequences of cancer patients and healthcare workers (HCW; non-cancer controls) by deep sequencing and investigated the within-host viral quasispecies of each infection, quantifying intrahost genetic diversity. Naso- and oropharyngeal SARS-CoV-2+ swabs from 57 cancer patients and 14 healthcare workers (HCW) from the Brazilian Cancer Institute were collected in April–May 2020. Complete genome amplification using ARTIC network V3 multiplex primers was performed followed by next-generation sequencing. Assemblies were conducted in Geneious R11, where consensus sequences were extracted and intrahost single nucleotide variants (iSNVs) were identified. Maximum likelihood phylogenetic analysis was performed using PhyMLv.3.0 and lineages were classified using Pangolin and CoV-GLUE. Phylogenetic analysis showed that all but one strain belonged to clade B1.1. Four genetically linked mutations known as the globally dominant SARS-CoV-2 haplotype (C241T, C3037T, C14408T and A23403G) were found in the majority of consensus sequences. SNV signatures of previously characterized Brazilian genomes were also observed in most samples. Another 85 SNVs were found at a lower frequency (1.4-19.7%). Cancer patients displayed a significantly higher intrahost viral genetic diversity compared to HCW (p = 0.009). Intrahost genetic diversity in cancer patients was independent of SARS-CoV-2 Ct values, and was not associated with disease severity, use of corticosteroids, or use of antivirals, characteristics that could influence viral diversity. Such a feature may explain, at least in part, the more adverse outcomes to which cancer/COVID-19 patients experience.Author SummaryCancer patients are more prone to clinically evolve to more severe COVID-19 conditions, but the determinants of such a more severe outcome remain largely unknown. In this study, phylogenetic and variation analysis of SARS-CoV-2 genomes from cancer patients and non-cancer healthcare workers at the Brazilian National Cancer Institute were characterized by deep sequencing. Viral genomes showed signatures characteristic of Brazilian viruses, consistent with the hypothesis of local, community transmission rather than virus importation from abroad. Despite most genomes in patients and healthcare workers belonging to the same lineage, intrahost variability was higher in cancer patients when compared to non-cancer counterparts. The intrahost genomic diversity analysis presented in our study highlights the relaxed evolution of SARS-CoV-2 in a vulnerable population of cancer patients. The high number of minor variations can result in the selection of immune escape variants, resistance to potential drugs, and/or increased pathogenicity. The impact of this higher intrahost variability over time warrants further investigation.

Objective: To evaluate the association of sociodemographic, clinical, and pathological factors with response and survival in triple negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy (NACT). Methods: Clinical-pathological and sociodemographic data were obtained from medical records of 235 eligible women with TNBC diagnosed between 2010 and 2014 undergoing NACT and surgery at the Brazilian National Cancer Institute. They have been assessed for pathological complete response (pCR), event-free survival (EFS), and overall survival (OS). Both univariate and multivariate Cox regression analyses were performed. Results: The median follow-up was 64.3 months. Most patients had advanced clinical stage (III: 85.1%; cT3/T4: 86.4%; cN1-3: 74.4%) and high-grade tumors (72.1%). Clinical staging (III vs II, adjusted hazard ratio [HR] = 2.95, P = .012) significantly influenced the pCR rate. Alcohol intake negatively influenced EFS (adjusted HR = 1.67, P = .006) and OS (adjusted HR = 1.89, P = .005). Women with pCR showed better EFS (crude HR = 0.15, P Conclusion: Clinical stage III were associated with lower response rate and worse survival. Alcohol intake, pCR, and burden of post-NACT residual disease have shown considerable influence on survival outcomes.

Melanoma is considered the most lethal skin cancer and its incidence has increased during the past decades. About 10 % of cases are classified as hereditary melanoma. Genetic predisposition usually manifests itself clinically as early onset and multiple cutaneous melanomas. Several genes have been identified as involved to melanoma susceptibility, some of them still with unknown clinical relevance. Beyond melanoma, the affected families are also more prone to develop other malignancies, such as pancreatic cancer. The identification of risk families and involved genes is of great importance, since different forms of oncological surveillance are recommended. However, well established guidelines to standardize both the selection of individuals and the genetic panel to be requested are still lacking. Given the importance of the genetic counseling and testing in the context of clinical suspicion of hereditary melanoma, this paper aims to review the literature regarding genetic panel indications worldwide.

Introdução: A doença do enxerto contra o hospedeiro crônica (DECHc) é a principal causa de morbimortalidade após o transplante alogênico de células-tronco hematopoiéticas (TCTH-alo). Relato do Caso: Acompanhamento odontológico de paciente do sexo masculino, 59 anos, com diagnóstico inicial de leucemia mieloide aguda, submetido ao TCTH-alo em maio de 2017. No D+ 224, o paciente evoluiu para um quadro de DECHc acometendo a pele, a cavidade oral e o trato gastrointestinal, porém com dentes ainda hígidos. No D+ 392, o paciente queixou-se de boca seca, e foram observadas lesões orais, sialometria de 0,024 mL/min e evolução de lesões cariosas nos dentes 17, 15, 22, 25, 27, 38, 45 e 46. No D+ 560, o paciente ainda estava com DECHc oral e houve progressão das cáries em inúmeros dentes. Tratamento e Resultados: O manejo terapêutico adotado consistiu na utilização de diamino fluoreto de prata pela propriedade cariostática com redução da odontalgia e, posteriormente, foram realizadas as restaurações dentárias. Além disso, o paciente foi orientado em relação à dieta, à manutenção da higiene oral e ao uso de lubrificante oral na tentativa de amenizar a xerostomia. Conclusão: Observou-se, neste caso clínico, que o diamino fluoreto de prata foi eficaz no controle da evolução da cárie e redução da odontalgia no paciente adulto. É evidente a importância da capacitação dos cirurgiões-dentistas no que diz respeito ao conhecimento sobre a utilização de cariostáticos em pacientes com alterações na qualidade e quantidade de saliva como os pacientes com DECHc oral.

Patient: Female, 45-year-old Final Diagnosis: Endometrial cancer Symptoms: Abdominal discomfort • abdominal distension Medication: — Clinical Procedure: Hormone therapy • surgery removal Specialty: Oncology Objective: Rare co-existance of disease or pathology Background: Carcinoma arising from an endometriosis-associated abdominal wall scar is a rare entity, with only a few case reports published in the literature. The management is very controversial due to on its own rarity, and there are no specific guidelines. Treatment with a multidisciplinary team is important to achieve the best outcome. Case Report: We report the case of a 45-year-old woman diagnosed with a growing painless lesion in the right lower quadrant. We decided to perform Tru-Cut biopsy of the abdominal wall lesion, but unfortunately the pathological report was inconclusive at that time. Due to the presence of a highly suspicious lesion, the gynecologic oncologist together with the plastic surgeon and connective tissue surgeon decided to perform a wide resection of the abdominal wall along with hysterectomy and salpingo-oophorectomy. The final pathology report demonstrated endometriosis associated with an endometrioid adenocarcinoma grade II in the abdominal wall tumor. She was restaged with new imaging exams before the definition of the best adjuvant treatment, which showed suspicious bilateral inguinal and right axillary (1.9 cm) lymph nodes, with no other sites of metastatic disease. She was treated with megestrol acetate 160 mg/daily for 8 months, with a partial response. Conclusions: Carcinoma arising from an endometriosis-associated abdominal wall scar is a rare entity, and there are no no specific treatment guidelines. Such patients must be assessed by a multidisciplinary team for decision making. Options for adjuvant and palliative treatment for endometrial cancer are generally used for the treatment of this entity. The main purpose of this article is to report this rare presentation and perform a review of the literature about diagnosis, clinical presentation, treatment, and prognosis.

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).

The current research aimed to understand melanoma epidemiology in Brazil and to evaluate temporal trends in incidence and mortality. The data came from Brazilian Hospital Cancer Registries, Population Based Cancer Registries, and the National Mortality Information System from 2000 to 2014. Descriptive statistics were used for epidemiological and clinical characteristics. To describe trends in change in incidence and mortality rates, the Average Annual Percentage Change (AAPC) was calculated. Between 2000 and 2013, in men, the median incidence rate rose from 2.52 to 4.84, with an AAPC of +21.5% [95% confidence interval (CI): 15.4-28] and in women from 1.93 to 3.22 per 100 000, with an AAPC of +13.9% (95% CI: 8.1-20). Regarding mortality, between 2000 and 2014, the rates went from 0.85 to 0.9 per 100 000 for men (AAPC=+0.8, 95% CI: 0.4-1.1) and from 0.56 for 0.53 per 100 000 for women (AAPC=-0.1, 95% CI: -0.2 to 0). From the database, a total of 28 624 patients with melanoma were included. Most of the patients were females (51.9%), White (75%) and with stage I or II (53.2%). Sex, ethnicity, education level, geographical area of the cancer center, topography, histology, time between diagnosis and treatment, and early death were significantly associated with distant metastases. Brazil is a large country with a very young population and a low rate of melanoma incidence and prevalence that should increase over the years. Understanding the trends attributed to melanoma is important for behavioral counseling interventions that focus on promoting skin cancer prevention.

Immuno-therapeutics have revolutionized the field of oncology. The Brazilian cancer population would unquestionably benefit from an increase in the availability of cost-effective immuno-oncologic drugs. The challenge is how to incorporate these into the toolbox of health professionals, given the complexity and inequities of the Brazilian healthcare system, limiting financial resources and numerous health needs. We provide a series of recommendations that are likely to improve access and reduce the cost of these important medications. Nonetheless, there are numerous challenges that must be overcome if the entire Brazilian cancer population is to benefit from this remarkable advancement in health care.

The aim of the study was to investigate if there was an association between intraoperative NSAID use and recurrence or survival. A cohort of patients who underwent sentinel lymph node biopsy for the treatment of cutaneous melanoma was retrospectively recruited. After applying inclusion and exclusion criteria, 516 were included (NSAIDs = 307). The 10-year melanoma-specific survival was 63.2%. Log-rank test showed no statistically significant differences in time to treatment failure, melanoma-specific survival, disease-free survival, and overall survival between the study groups. The current study did not support the use of intraoperative NSAIDs in preventing death or recurrence in patients with melanoma.

Objective The aim of this systematic review was to describe the epidemiology, diagnostic criteria, differential diagnosis, treatment, prognostic factors, and treatment outcomes of secretory carcinoma. Study Design A comprehensive search of Lilacs, PubMed, Science Direct, and Web of Science databases was conducted to identify all case reports, letter to the editor, and histopathologic reclassifications regarding salivary gland secretory carcinoma published in English, Spanish, French, and Portuguese. Results The final analysis included 119 studies, which totaled 642 secretory carcinoma diagnoses, with 239 case reports and 403 diagnostic reclassifications, mostly in the United States. The age range was 5 to 87 years, and cases were predominantly in males (58.7%) and mostly affecting the parotid glands (73.7%). The disease usually presents as a slow-growing, painless mass. The main differential diagnosis is acinic cell carcinoma, and the tumor is usually treated with surgery. The prognosis is considered favorable, although there have been reports of local recurrences, distant metastases, and deaths. Conclusions It is important that clinicians become aware of this salivary gland neoplasm and report clinical data, clinical course, management and long-term follow-up. There is an urgent need to conduct more clinical trials, especially on tropomyosin receptor kinase (TRK) inhibitors and other potential target therapy modalities.

Objectives Compare marital status, household income and labor activity at diagnosis and at 1-year follow-up among cervical cancer (CC) patients in Brazil. Methods LACOG 0215 EVITA is a prospective observational study, within 16 Brazilian sites, including 18 years-old, newly diagnosed, stage I to IV invasive CC patients. We present data collected at baseline and at 1-year follow-up regarding demography, histology, stage, marital status, household income and labor activity. Variables were compared using Chi-square test. Results 593 patients were included in this analysis. 75 (12.6%) were diagnosed in stage I, 452 (76.2%) II-III and 66 (11.2%) IV. Mean age at diagnosis was 57.0, 56.4 and 50.5 years respectively. Squamous cell carcinoma was the most frequent histology. 34.2% of stage I, 30.6% of stage II-III and 24.6% of stage IV patients had 9 or more years of education. About 95% patients had a previous pregnancy history. At 1-year follow-up there was a decrease in the proportion of married patients in stage II-III patients only (53.3% to 47.5%; p-value Conclusions CC may impact patients personal and work life long after diagnosis, even in those diagnosed with curable disease. In this cohort, stage II-III CC face more risk of divorce and job losses. Social support following diagnosis and treatment is essential for CC patients.

Mucosal melanomas are primary malignant neoplasias originated from melanocytes within mucous membranes in any part of mucosal surface lining, more commonly, in the nasal cavity and accessory sinuses, oral cavity, lips, pharynx, vulvar, vaginal, cervix and anorectal mucosa. Epidemiology data regarding mucosal melanomas in Brazil is scarce, hence the motivation to conduct this research paper. The χ2 test was used to compare categorical variables. Forward stepwise logistic regression method was used in the multivariate analysis to identify independent predictors of early death. A total of 801 patients were included in the analysis. Surgical resection is frequently the first approach to primary tumours (65.3%), even though the utility of lymph node surgery and radiation therapy is not well established. Advanced stage was observed in more than two thirds of patients. Early death was observed in 28.3%. MM cases with regional or distant metastases as well as those located in unusual locations had almost 4 times more risk for early death. Besides that, MM located in lips, oral cavity and pharynx and those receiving chemotherapy had 2 times more risk of early death.

IntroductionCutaneous 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 analysisThe 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 disseminationEthics approval is not required as we analyse data from previously reported studies.PROSPERO registration numberCRD42018114918.

Objectives This study aim was to review cases of acinic cell carcinoma (the main differential diagnosis of secretory carcinoma) that were diagnosed and treated at the National Cancer Institute of Brazil (INCA) between 1996 and 2016. The primary objective was to identify underdiagnosed cases of secretory carcinoma via a clinical, immunopathological and molecular reassessment. Materials and methods This is a cross sectional study, with retrospective data collection from medical records and histological specimen review, with staining for periodic acid-Schiff (PAS) and PAS with diastase, immunohistochemistry for S-100, mammaglobin, and DOG-1, and droplet digital RT-PCR for ETV6-NTRK3. The Research Ethics Committee approved this study, and the patients allowed their participation through informed consent. Results Eighty-three cases of acinic cell carcinoma were diagnosed and treated in the specified period at INCA, of which, seven had their diagnosis changed to secretory carcinoma. Conclusion The present study adds seven cases of secretory carcinoma to the literature, contributing to a better understanding of the epidemiological, histological, immunohistochemical and molecular characteristics of this recently described tumor. Also, the use of a comprehensive diagnostic approach, including immunohistochemical and molecular methods, along with classical morphological studies, allowed the reclassification of acinic cell carcinoma to secretory carcinoma.

5517 Background: In ARIEL4 (NCT02855944), rucaparib significantly improved the primary endpoint of progression-free survival (PFS) vs chemotherapy (CT) in patients with advanced, relapsed ovarian carcinoma (OC) harboring a deleterious BRCA1/2 (BRCA) mutation (median PFS 7.4 [95% CI 7.3–9.1] vs 5.7 [5.5–7.3] months; hazard ratio (HR) 0.64 [95% CI 0.49–0.84]; P=0.001). This prespecified exploratory analysis investigated the effect of platinum sensitivity on the efficacy of rucaparib vs CT in ARIEL4. Methods: Patients were randomized 2:1 to oral rucaparib 600 mg twice daily or CT and stratified based on progression-free interval (≥1 to 2; patients with fully platinum-sensitive disease received investigator’s choice of platinum-based CT (single-agent carboplatin or cisplatin, or platinum doublet). Patients could crossover from CT to rucaparib following radiologic disease progression. Efficacy endpoints were explored in patients with a confirmed BRCA mutation (patients with a reversion mutation were excluded), based on the randomization strata of platinum sensitivity. Results: The visit cutoff date was September 30, 2020. PFS and objective response rates (ORR) per RECIST v1.1 for rucaparib vs CT across subgroups are presented in the Table. The most common treatment-emergent adverse events in the rucaparib group were anemia/decreased hemoglobin (platinum-resistant patients: rucaparib 47% vs CT 40%; partially platinum-sensitive patients: 63% vs 27%; fully platinum-sensitive patients: 58% vs 20%) and nausea (52% vs 21%; 51% vs 23%; 60% vs 68%). In the intent-to-treat population, 74/116 (64%) patients in the CT group crossed over to receive rucaparib: 39/59 (66%) with platinum-resistant, 25/31 (81%) with partially platinum-sensitive, and 10/26 (38%) with fully platinum-sensitive disease. Conclusions: Results from this exploratory subgroup analysis suggest that rucaparib is a reasonable treatment option for heavily pretreated patients across all platinum sensitivity subgroups. Safety was consistent with prior rucaparib studies. Clinical trial information: NCT02855944. [Table: see text]

1558 Background: COVID-19 is a challenge for clinical decision-making in cancer patients and the allocation of healthcare resources. An accurate prognosis prediction to effectively triage patients is needed, especially in the community oncology practice. Methods:Nationwide cohort from Oncoclínicas Brazil was used to validate previously developed multivariable logistic regression (mLR) model (Ferrari et al, JCO GO 2021) and to construct a machine learning Random Forest (RF) algorithm as predictor of 30-day mortality after SARS-CoV-2 detection by RT-PCR in cancer patients diagnosed in an outpatient setting. To find the most important baseline clinical determinants of early COVID-19-related death via Gini index, a RF with 100,000 trees was trained in 75% of the dataset, and the performance was assessed in the remaining 25%. We then compared the accuracy of different models in terms of sensitivity, specificity and area under the receiver operating characteristics curves (AUC). Results:From March to December 2020, 533 patients with COVID-19 were prospectively registered in the database. Median age was 60 years (19-93) and 67% were female. Most frequent cancers were breast in 34%, hematological in 16%, and gastrointestinal in 15%. Comorbidities were common (52%), as was current/former smoking history (17%). Most patients were on active systemic therapy or radiotherapy (84%) in the advanced or metastatic disease setting (55%). The overall mortality rate was 15% (CI95% 12%-18%). We validated the original mLR model trained in the first 198 patients: management in a non-curative setting (odds ratio [OR] 3.7), age ≥ 60 years (OR 2.3), and current/former smoking (OR 1.9) were significant predictors of death in the expanded cohort. Presence of comorbidities (OR 1.9) also defined poor outcome in the updated mLR model, which yielded low sensitivity (74%), specificity (68%) and AUC (0.78). With RF modeling, the most significant predictors of 30-day death after COVID-19 (in decreasing order) were older age, treatment of advanced or metastatic disease, tumor type (respiratory tract, brain and unknown primary cancers had higher mortality), COVID-related symptom burden at baseline evaluation and treatment regimen (immunotherapy combinations had higher mortality). The RF model demonstrated high sensitivity (89%), specificity (88%) and AUC (0.96). Conclusions:The results highlight the possibility that machine learning algorithms are able to predict early mortality after COVID-19 in cancer patients with high accuracy. The proposed prediction model may be helpful in the prompt identification of high-risk patients based on clinical features alone, without having to wait for the results of additional tests such as laboratory or radiologic studies. It can also help prioritize medical resources and redefine vaccination strategies. A web-based mortality risk calculator will be created for clinical decision support.

Cervical carcinomas are almost universally associated with high-risk human papillomavirus (HPV) infections, and are a leading cause of cancer death in women worldwide. Since the late 1990s, when a spate of studies reported the benefit of cisplatin-based chemotherapy, there had been a dearth of clinical trials in cervical cancer (CC). More effective therapies in locally advanced and recurrent or metastatic CC are an urgent clinical need. In the era of molecular oncology one should look beyond conventional chemoradiation and chemotherapy for locally advanced and advanced CC. The fact that the initiating oncogenic insult, infection with a high-risk HPV and viral oncoprotein expression is common to almost all CC offers unique opportunities for disease control. Diverse biologic pathways with an implication in the development and progression of CC are being explored. For the first time, increase in overall survival has recently been obtained for advanced CC patients with a target drug, the antiangiogenic agent bevacizumab, and durable complete responses after HPV-targeted adoptive T cell therapy in metastatic CC patients were achieved. In this review, we will summarize molecular aspects of HPV infection focusing on potential targets to stop the carcinogenic process, present updated drug development data, and discuss challenges and prospects for the future.