Brazilian National Cancer Institute Research Articles

Epidemiological profile of neuroendocrine tumors in adults in Brazil.

Neuroendocrine tumors (NETs) are a set of diseases that originate from neuroendocrine cells, which comprises a diffuse endocrine system present in various organs of the body. These tumors are more frequent in the gastrointestinal tract (70%) and the bronchopulmonary system (20%-30%). A NET incidence rate of 1-5 per 100,000 inhabitants has been estimated for several European countries and the USA employing 20 years of data. However, no comprehensive studies on this rare neoplasm are available in Brazil. In this context, the aim of this study was to characterize the epidemiological NET profile in the country. This is a retrospective descriptive observational study based on data from Hospital Cancer Records available at the Brazilian National Cancer Institute and the São Paulo Oncocentro Foundation. Demographic, clinical and treatmentrelated variables were analyzed from selected cases employing descriptive statistics. A total of 15,859 cases were identified, most occurring in males (53.4%) and in individuals under 65 years old (63.3%). Small cell carcinoma was the most frequent histological type (46.7%). Bronchopulmonary tumors were the most frequent NETs, followed by pancreatic tumors, with cases mostly concentrated in high complexity centers in the Brazilian Southeast and treated mainly with surgery and chemotherapy, with over half of the patients diagnosed in advanced stages of the disease.

Abstract PO5-16-07: Unveiling the Landscape of PD-L1 Expression and Tumor-Infiltrating Lymphocyte Subtypes in Advanced Triple-Negative Breast Cancer

Abstract Background: Triple-negative breast cancer (TNBC) is known for its aggressive behavior with poor survival outcomes. Influenced by different expression levels of Programmed Death-Ligand 1 (PD-L1) and several subtypes of tumor-infiltrating lymphocytes (TILs), tumor microenvironment (TME) plays a crucial role in TNBC response to treatment and progression. Objective: To assess the prevalence and prognostic role of PD-L1 expression in advanced TNBC, defined as unresectable stage III or stage IV disease, in patients treated with a standard cytotoxic chemotherapy regimen. TILs composition was also evaluated as an exploratory objective. Methods: The internal database of the Brazilian National Cancer Institute was queried out for women diagnosed and treated with advanced TNBC from January 2018 to December 2022. Formalin-fixed paraffin-embedded samples of a maximum of four years old were analyzed. PD-L1 expression using 22C3 pharmDX assay was estimated through combined positive score (CPS) dichotomization (CPS < 10 vs. CPS≥10). Tissue microarrays comprising the samples of biopsies were subjected to immunohistochemistry, targeting specific markers including CD3, CD4, CD8, CD56, CD68, CD117, FOXP3, PD-1, the immune cell profiles were carefully examined and their correlation with the PD-L1 CPS was determined. Results: A total of 150 patients were included. The expression of PD-L1 was undetermined in 2 cases. The median age was 51.5 years (IQR 41.8-60.2) and 20.9% of the cases had CPS≥10. Most patients were < 65 years (73.0%), were postmenopausal (56.8%) and belonged to non-white ethnicity (70.3%). Postmenopausal women predominated in the CPS≥10 subgroup (74.2%) (Table 1). No significant differences in demographic characteristics and clinicopathological variables were observed based on PD-L1 subgroups, 117 patients (79.1%) had CPS < 10, with 91 (77.8%) being de novo stage IV metastatic disease. CD3+ (p=0.037), CD4+ (p=0.005) and CD8+ (p=0.001) TILs had higher expression in tumors with PD-L1 CPS≥10 (Table 2). According to the treatment received, almost half of the patients only received first-line chemotherapy (47%), as the following second line was applied to 28.8% of the total group. The third and fourth lines were administered in 12.9% and 9.1% of patients, respectively. Only 2 patients went through five palliative chemotherapy lines, and only one received up to 6 treatment lines. Between the subgroups CPS≥10 versus CPS < 10 no statistically significant differences were observed in the median progression-free survival (PFS) (5.1 vs. 5.0 months, p=0.89) and overall survival (OS) (8.7 vs. 8.8 months, p=0.6). Conclusion: This study offers insights into the expression patterns of PD-L1 and TILs subtypes in advanced TNBC cases in Brazil. PD-L1 CPS did not influence survival outcomes for this cohort of patients treated with cytotoxic chemotherapy only. The composition of TILs subtypes within the TME appears to vary based on PD-L1 CPS. Table 1. Advanced TNBC population characteristic by CPS (Nf148). Table 2. Tumor Infiltrating Lymphocytes characterization (CD3, CD4, CD8, CD56, CD68, CD 117, FOXP3 and PD-1) and its correlation with CPS status. Citation Format: Alexssandra Lima Siqueira dos Santos, Jesse Lopes da Silva, Lucas Zanetti de Albuquerque, Antônio Lucas Araújo Neto, Cecília Ferreira da Silva, Luana Aguiar Mesquita Cerva, Isabele Ávila Small, Cicera Pimenta Marcelino, Paula de Mendonça Batista, Maria Aparecida do Carmo Rego, Maria Amélia Carlos Souto Maior Borba, Andreia Cristina de Melo. Unveiling the Landscape of PD-L1 Expression and Tumor-Infiltrating Lymphocyte Subtypes in Advanced Triple-Negative Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-16-07.

Surgical, oncologic, and obstetric outcomes of radical trachelectomy in early-stage cervical cancer: results from a retrospective cohort study at Brazil National Cancer Institute.

to analyze oncological, obstetrical, and surgical results of young early-stage cervical cancer patients who underwent radical trachelectomy (RT) surgery and wished to maintain their fertility. a retrospective cohort study was carried out concerning cases attended at the Brazilian National Cancer Institute Gynecology Oncology Service. Patients who underwent RT between January 2005 and January 2021 were included. A total of 32 patients with median age of 32 years old, 62.5% of whom were nulliparous, were assessed. Concerning cancer type, 65.6% squamous cell carcinoma (SCC) cases, 31.2% adenocarcinoma cases and 3.1% adenosquamous carcinoma cases were verified. Stage IA2 was evidenced in 12.5% of the patients and stage IB < 4cm in 87.5%. Regarding surgical approaches, 68.25% of the patients underwent vaginal RT (VRT), 18.75%, abdominal RT (ART), 9.3%, the robotic radical trachelectomy (RORT) and 3.1%, video laparoscopy radical trachelectomy (VLRT). The median number of removed lymph nodes was 14, with only two detected as positive. Two cases of positive surgical margins were noted. A total of 3.1% intraoperative and 31.25% postoperative complications were observed, with cervical stenosis being the most common. The recurrence rate of the study was 3.1%, with a median follow-up time of 87 months, where 3.1% deaths occurred. The pregnancy rate of the study was 17.85% (5/28), with 54.5% evolving to live births and 45.5% evolving to abortion. Radical trachelectomy is a feasible procedure presenting good oncological results and acceptable pregnancy rates.

Differential survival of Brazilian patients with diffuse large B-cell lymphoma with and without HIV infection.

Combinatorial antiretroviral therapy provided improvement of HIV patients' immune function and a decrease in the incidence of non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is one of the most common NHL forms affecting HIV+ patients. The present study aimed to evaluate the impact of HIV infection on the prognosis of patients treated for DLBCL in a reference cancer treatment center in Brazil. A retrospective case-control study was developed with patients followed-up at the Brazilian National Cancer Institute, in which 243 DLBCL patients (91 HIV+ and 152 HIV-) were enrolled. HIV- controls were matched to HIV+ according to date of cancer diagnosis, clinical staging, primary cancer treatment and date of birth. Sociodemographic and cancer treatment data were extracted from medical charts. Kaplan-Meier analyses were carried out to estimate survival, while univariate and multiple Cox regression analyses were used to determine factors associated with mortality. A total of 98 deaths were observed in a 5-year period after cancer diagnosis. A negative association of HIV infection with both overall and disease-specific survival 1 year after cancer diagnosis was observed [hazard ratio (HR) = 1.98 and 1.96, respectively]. The negative association with HIV infection with disease-specific survival remained significant for a 5-year period after cancer diagnosis (HR = 1.53). HIV viral load above 1000 copies/ml at study entry was also associated with shorter overall and cancer-specific survival. HIV infection negatively impacted prognosis and mortality of DLBCL patients irrespective of cancer-related clinical factors.

The Usefulness of an Online Simplified Screening Questionnaire (SSQ) in Identifying Work-Related Cancers.

To obtain a history of occupational exposure in the workplace, the questionnaire is one of the main sources of information. The aim of this study was to develop an online questionnaire using the REDCap data management platform based on the Work-Related Cancer Surveillance Guidelines, reported by the Brazilian National Cancer Institute. Several issues were taken into consideration for its routine application. It should be simple, easy, capable of being applied in a short time and used in the clinical setting of collecting information on the occupational history of the cancer patient. Consequently, this could enable the compulsory notification of work-related cancer. The questionnaire was developed based on questions about the use of and exposure to carcinogenic factors at work and due to smoking. An entirely electronic version of the cancer patient interview was performed using tablets. The online questionnaire was applied at the Barretos Cancer Hospital, Barretos, to newly diagnosed patients from July 2016 to 2018. A total of 1063 patients were included, and 550 indicated positively when asked "Do you work, or have you worked with this substance and/or in this function?/job?" Of these potentially notified patients, 38 subsequently had compulsorily reported work-related cancer. Another important result of this study was the creation and development of a website. In conclusion, we developed an online tool that could facilitate hospital routines, contributing to generating data for the compulsory notification of work-related cancer and triggering investigations and surveillance actions in Brazil.

Abstract 1216: Virome characterization in different types of non-Hodgkin lymphoma

Abstract Non-Hodgkin's lymphoma (NHL) is a heterogeneous group of lymphoid tissue neoplasms, with different clinical, genetic and morphological aspects. It is the most common form of hematological malignancy worldwide. In addition to risk factors, some infectious agents cause or are related to the risk of developing NHL. These include Epstein Barr virus (EBV), human herpes virus 8, human T-cell lymphotropic virus type 1, human immunodeficiency virus, hepatitis C virus, and the H. pylori. Overall, cancer attributable to infections accounted for 15.4% of new cases in 2012, and this number may increase due to improvements in molecular methodologies. Recently, other infectious agents have been associated with NHL, such as human pegivirus and cutavirus. Although factors related to immune function and the infectious agents described play a relevant role in the etiology of NHL, these factors do not explain most cases, suggesting that others factors or infectious agents could be involved in NHL development. Identifying possible pathogens associated with NHL and understanding the cancer-infectious agents relationship is essential for the development of prevention and screening aproaches. The aim of this study is to characterize the viral composition of the tumor microbiome in different types of NHL. Tumor tissue samples from NHL stored at the Brazilian National Cancer Institute were processed for viral DNA and RNA extraction. The viral nucleic acids were prepared for 19 samples with the Nextera XT kit and sequenced on an Illumina MiSeq platform. Virus identification analyses were performed by comparing the sequences obtained with viral sequences in the GenBank database through the BLASTX tool. Most samples were from diffuse large B cell lymphoma (DLBCL; n = 11), followed by marginal zone and follicular lymphoma (three cases each), and small lymphocytic and non-B, non-T cell lymphoma (one case each). A median of 46% of the obtained reads mapped to the human genome. Among the remaining reads, four viral families were identified: Anelloviridae, Flaviviridae, Herpesviridae and Papillomaviridae. EBV, a herpervirus associated with different types of NHL, was found in one gastric DLBCL. Anelloviridae reads included only the genus Alphatorquevirus and were found in five DLBCL. This virus family has a ubiquitous presence, without any clinical manifestation so far described in humans. However, anellovirus viral load has been associated with the subject’s immune status. Different human papillomaviruses from the Alpha, Beta and Gamma genera were found in six samples, comprising follicular lymphoma and DLBCL. The flavivirus human pegivirus was found in one DLBCL. Some recent studies associated this later virus with risk of lymphoma. In summary, this study describes the viral diversity found in NHL, showing the presence of viruses not yet associated with this neoplasia. Additional studies are warranted to clarify the role of these viruses in the etiology of NHL. Citation Format: Juliana D. Siqueira, Esmeralda A. Soares, Marcelo A. Soares. Virome characterization in different types of non-Hodgkin lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1216.

Abstract 1903: Esophageal cancer clinical and socioeconomic aspects in Brazil: Inequalities affect patients from diagnosis to prognosis

Abstract Esophageal cancer is the sixth most incident and the fifth most lethal cancer among men in Brazil. Advanced stages at presentation, unsatisfactory therapeutic results, as well as high recurrence and mortality rates reflect the disease limited knowledge and highlights the need for new strategies aiming at better patient care. In this study, we evaluated a retrospective cohort of 850 esophageal cancer cases enrolled at the Brazilian National Cancer Institute (INCA) from 2012 to 2016. Patients’ sociodemographic and clinical characteristics were compared between the most frequent histological types (adenocarcinoma - EAC and squamous cell carcinoma - ESCC), and variables associated with advanced presentation at diagnosis, offering curative treatments, response to therapy and overall survival (OS) were evaluated. Relative to EAC, patients with ESCC were younger (p=0.007); more frequently non-white (p&amp;lt;0.001); most often did not have a partner (p&amp;lt;0.001); showed lower education levels (p&amp;lt;0.001); and were more frequently smokers and drinkers (p&amp;lt;0.001). The frequency of patients not receiving any treatment was higher among ESCC (40.8%) relative to EAC (32.6%) (p=0.003). Furthermore, potentially curative treatments (surgery or trimodal treatment) were more commonly offered to EAC patients (p&amp;lt;0.001). ESCC patients showed a median OS of 7.4 months (6.7 - 8.0 months) relative to 10.3 months (8.4 - 12.1 months) among EAC patients (p &amp;lt;0.001). When analyzing specific histologic tumor types, variables associated with EAC stages I and II were female sex (p=0.016); non-metropolitan origin; and non-alcoholic (p=0.048). Also, in EAC, higher education levels (p&amp;lt;0.001) were associated with curative treatments. EAC OS was significantly and independently associated with tumor stage at diagnosis (p=0.001) and curative treatments (p&amp;lt;0.001). In ESCC, early diagnosis was associated with white skin color (p=0.031) and occurrence of second primary tumors (p&amp;lt;0.001). Curative treatments were more commonly offered to ESCC patients who had a partner (p=0.028); higher education levels (p=0.010); and who were non-drinkers (p=0.042). Chemoradiotherapy resistance was associated with smoking (p=0.001) and low body mass index (p=0.028) among ESCC cases, while OS was significantly and independently associated with smoking (p=0.002) and staging (p&amp;lt;0.001). In summary, sociodemographic and clinical characteristics affected outcomes and special attention should be given to modifiable risk factors such as smoking and nutritional status. In addition, our study evidenced how social aspects are inextricably linked to health outcomes, and efforts should be made to minimize this gap. Citation Format: Rachele Grazziotin Reisner, Flávia Nascimento de Carvalho, Luis Felipe Ribeiro Pinto, Sheila Coelho Soares-Lima. Esophageal cancer clinical and socioeconomic aspects in Brazil: Inequalities affect patients from diagnosis to prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1903.

Abstract OT2-22-02: Sequencing of anthracyclines and taxanes during neoadjuvant therapy of locally advanced HER2-negative breast cancer (NEOSAMBA Study/LACOG 0419)

Abstract Background: Breast cancer (BC) is the most frequent cancer in women in Brazil, with more than 60,000 cases estimated annually. Forty percent of patients present with stages III and IV and neoadjuvant chemotherapy (NACT) remains the mainstay of treatment for locally advanced breast cancer (LABC). Taxanes usually follow anthracyclines in breast cancer neo/adjuvant treatment, likely because of their later introduction into clinical practice. However, the potential impact of alternative sequencing remains to be studied. A single-center phase II randomized clinical trial conducted in the Brazilian National Cancer Institute showed an improvement in overall survival with taxane-first compared with anthracycline-first sequencing in HER2-negative LABC (Bines J et al, The Oncologist 2020). As a taxane-before-anthracycline sequence carries neither an incremental cost nor increased toxicity, the optimal sequencing of these agents could have significant implications for clinical practice. To confirm this finding, we are currently conducting a multicenter randomized phase III trial comparing a taxane followed by an anthracycline-based regimen with the reverse sequence in the neoadjuvant setting. Trial Design: This randomized, open-label, phase III trial will be conducted in 15 research centers in Brazil. It was approved by the local ethics committee in 2020 and is registered in Clinicatrials.gov with the identifier NCT04540692. Women with HER2-negative LABC are randomized in a 1:1 ratio to anthracycline-before-taxane (AC-T arm) or taxane-before-anthracycline (T-AC arm), stratified by hormone receptor status (positive vs. negative) and axillary lymph node status (N0 vs. N+). The anthracycline-based therapy recommended in this trial is AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) every three weeks for four cycles, whilst the taxane-based therapy is either weekly paclitaxel 80 mg/m2 weekly for 12 weeks, paclitaxel 175 mg/m2 every three weeks, or docetaxel 75-100 mg/m2 every three weeks. The use of carboplatin concomitantly with taxane for triple-negative tumors and dose-dense regimens is allowed following institutional guidelines. Further therapies (surgery, radiotherapy, and endocrine therapy) are performed according to the physicians’ discretion. Tumor samples are collected and stored for translational studies. Eligibility: Inclusion criteria: women ≥18 years of age; histologically confirmed HER2-negative breast cancer (by ASCO/CAP guidelines); stage ≥ IIB (if TNBC) or ≥ III (if HR-positive); PS ECOG 0-2 and adequate organ function. Exclusion criteria: previous use of anti-cancer therapies; bilateral BC and pregnancy. Specific Aims: The primary objective is invasive disease-free survival (iDFS). Secondary objectives include pathological complete response (pCR) rates, overall survival (OS) and safety. Statistical Methods: Considering an unicaudal type I error of 0.05, a type II error of 0.2, and an estimated iDFS of 50% in 5 years in the control arm, a total of 227 evaluable patients should be included per arm to demonstrate a HR of 0.7 favoring the taxane-first arm. Estimating a dropout rate of 10%, 494 patients will need to be included in the study. Present Accrual and Target Accrual: A total of 9 sites of 15 planned are activated. The first patient was enrolled on January 12, 2021, and as of June 24, 2022, a total of 113 patients have been accrued. The target goal of 494 patients is expected to be achieved by 2025 and initial study results will be reported by 2026. Funding: Brazilian Health MInistry, Programa Nacional de Apoio à Atenção Oncológica (PRONON), NUP 25000.183207/2019-50. Acknowledgements: CURA Project, SAS. Citation Format: Tomás Reinert, Cristiano P. Souza, Pedro Liedke, Gustavo Werutsky, Laura Testa, Vivian Antunes, Carlos Barrios, Vivian Vasconcelos, Heloísa Resende, Geraldo Silva Queiroz, Gisah Guilgen, Yeni Nerón, Lilian Arruda Bastos, Sabina Aleixo, Daniel Cubero, Maria Cristina F. Magalhães, Ana Coradazzi, Daniela Galvão B. de Oliveira, João S. Nunes, Rafaela G. Jesus, Gustavo Gössling, José Bines. Sequencing of anthracyclines and taxanes during neoadjuvant therapy of locally advanced HER2-negative breast cancer (NEOSAMBA Study/LACOG 0419) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-22-02.

Minor Salivary Gland Cancer of the Head and Neck: A Review of Epidemiologic Aspects, Prognostic Factors, and Outcomes.

Minor salivary gland carcinomas (MiSGC) of the head and neck are a group of rare cancers with significant heterogeneity in histological types and with variable clinical behavior. This study aims to clarify the incidence, epidemiology, predictive factors, and outcome-based survival in a large cohort of patients treated at the Brazilian National Cancer Institute (BNCI) over a 20-year period by comparing and associating the results of current articles on the world stage. The difficulty in developing an algorithm of treatment is due to the low number of cases when evaluated in a single institution and the variety of histological subtypes that have different behaviors and different treatments according to each anatomical location. We reviewed the experience of tertiary centers for the treatment of head and neck cancer and epidemiological studies from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute of the USA. The lack of consensus on the management of MiSGC requires further knowledge about the biological behaviors of these tumors, as the identification of predictive factor of failure and survival to adequate treatment intensity. The growing collaboration of different centers publishing their experience allows us to unify these samples to reach concrete conclusions about these tumors.

Avaliação pós-comercialização de um produto trocável similar ao anastrozol em pacientes brasileiras com câncer de mama

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

Contribution of public oral pathology services to the diagnosis of oral and oropharyngeal cancer in Brazil.

This study aimed to evaluate the contribution of oral and maxillofacial pathology laboratories (OMPLs) in Brazilian public universities to the diagnosis of lip, oral cavity, and oropharyngeal squamous cell carcinoma (SCC). A cross-sectional study was performed using biopsy records from a consortium of sixteen public OMPLs from all regions of Brazil (North, Northeast, Central-West, Southeast, and South). Clinical and demographic data of patients diagnosed with lip, oral cavity, and oropharyngeal SCC between 2010 and 2019 were collected from the patients' histopathological records. Of the 120,010 oral and maxillofacial biopsies (2010-2019), 6.9% (8,321 cases) were diagnosed as lip (0.8%, 951 cases), oral cavity (4.9%, 5,971 cases), and oropharyngeal (1.2%, 1,399 cases) SCCs. Most cases were from Brazil's Southeast (64.5%), where six of the OMPLs analyzed are located. The predominant profile of patients with lip and oral cavity SCC was Caucasian men, with a mean age over 60 years, low schooling level, and a previous history of heavy tobacco consumption. In the oropharyngeal group, the majority were non-Caucasian men, with a mean age under 60 years, had a low education level, and were former/current tobacco and alcohol users. According to data from the Brazilian National Cancer Institute, approximately 9.9% of the total lip, oral cavity, and oropharyngeal SCCs reported over the last decade in Brazil may have been diagnosed at the OMPLs included in the current study. Therefore, this data confirms the contribution of public OMPLs with respect to the important diagnostic support they provide to the oral healthcare services extended by the Brazilian Public Health System.

FLEXIBILITY OF FISH PROBES IN MONITORING IAMP21 ACUTE LYMPHOBLASTIC LEUKEMIA: STUDY OF FOUR BRAZILIAN CHILDREN

Intrachromosomal Amplification of chromosome 21 (iAMP21) is an independent outcome indicator in B-cell Precursor ALL (BCP-ALL). IAMP21 is characterized by multiple RUNX1 copies in blast cells, and comprises 2% of children with BCP-ALL. It was first detected during routine screening for ETV6-RUNX1 fusion by FISH. This disease features protocol-dependent outcomes. For example, in pediatric patients, iAMP21-ALL presents poor outcomes when standard therapy is used. Although, when children receive intensive treatment, they usually show lower relapse risk and improved survival. Thus, the early detection of iAMP21 is crucial to guide therapeutic strategies. In this regard, FISH probes may provide a rapid and effective screening, being a valuable ally for banding cytogenetics. In this work, we describe the clinical and molecular data of four pediatric patients with BCP-ALL iAMP21, showing the importance of RUNX1-RUNX1T1 and ETV6-RUNX1 FISH probes in screening this high-risk entity. This collaborative study included four children with BCP-ALL iAMP21. The peripheral blood and Bone Marrow (BM) samples were referred to the cytogenetics laboratory at the Brazilian National Cancer Institute between 2013 and 2021. We performed G-banding and FISH experiments in interphase nuclei and metaphase spreads. We used commercial Locus-Specific (LSI) ETV6-RUNX1, RUNX1-RUNX1T1, and centromeric 13/21 FISH probes. Using the FISH technique with LSI ETV6-RUNX1 and RUNX1-RUNX1T1 probes, we identified the derivative chromosome 21 and the precise number of RUNX1 signals for each patient. It also helped disclose whether the RUNX1 amplifications were intra- and or extrachromosomal. The intrachromosomal amplification of chromosome 21 is an uncommon high-risk chromosomal aberration in pediatric B-ALL. iAMP21 can be elusive, sometimes escaping detection by banding cytogenetics. Thus, confirmation by molecular techniques is necessary. Besides, recent studies suggest a relapse risk associated with therapy intensity, emphasizing the importance of a rapid and early detection of iAMP21 for appropriate risk stratification and therapeutic intervention. The FISH approach used through our experimental design has proved efficient in the early detection of iAMP21 in all patients. Importantly, it helped determine the diagnosis of iAMP21 48 hours after initial diagnosis. Our approach can also be valuable in monitoring patients for Minimal Residual Disease (MRD). According to the literature, those who continuously present MRD should be eligible for BM transplantation. In summary, the flexibility of FISH probes enabled the rapid detection of this high-risk neoplasm. Besides, the precise characterization of iAMP21, including the aberrant chromosomes 21 and extra RUNX1 signals, was important to guide treatment strategies and the monitoring of patients. In addition, we reinforce the importance of investigating the heterogeneity of iAMP21 marker chromosomes, their molecular complexity, and genomic association with disease progression. Novel genetic findings may provide valuable information about this entity, which could open perspectives regarding novel therapeutic approaches for children with BCP-ALL iAMP21.

Trends in the incidence of malignant central nervous system tumors in Brazil, 2000-2015.

In Brazil, 5870 new cases of malignant central nervous system tumors (MCNST) were estimated for men and 5220 for women for each year of the 2020-2022 triennium. The objective of this study was to analyze incidence rate trends and compare demographic characteristics of new MCNST cases according to tumor topographies in Brazil from 2000 to 2015. This study comprises an analytical cross-sectional assessment of secondary databases extracted from the Brazilian National Cancer Institute (INCA) website. Data comprised new neoplasm cases of meninges (C70), brain (C71), spinal cord, cranial nerves, and other central nervous system parts (C72) retrieved from 23 population-based cancer registries. A descriptive analysis was performed. Crude and age-adjusted incidence rates were calculated. Linear trends were calculated using a linear least squares regression for adjusted incidence rates versus time. A total of 24 986 new MCNST cases were recorded. The main topography was the brain (91.5%). Except for meninges tumors, where 62.4% of the cases were observed in women, MCNST cases were more frequent among men concerning the other evaluated topographies. All 3 topographies occurred predominantly in adult patients aged from 40- to 64-year-old. Between 2000 and 2015, incidence rates ranged from 5.12 to 4.95 (a 1.4% increase of per year; 95% CI -4.0 to 6.8; P = .584) in men and from 4.35 to 3.61 (a 3.1% increase per year; 95% CI -1.7 to 8.0; P = .189). The most frequent topography was the brain. Incidence rates of MCNST remained relatively stable over time in both sexes.

Incidence and risk factors associated with the development of metastatic spinal cord compression due to bone metastasis in women with cervical cancer.

The aim of this study was to determine the incidence and factors associated with the development of metastatic spinal cord compression (MSCC) after cervical cancer (CC). This retrospective cohort of 3551 women with CC who underwent treatment at the Brazilian National Cancer Institute were included in the study. Clinical and sociodemographic variables were obtained from the Hospital Cancer Registry and from hospital records. A descriptive study of the population was carried out, using means and standard deviations or frequencies and percentages. The Kaplan-Meier curve was used to identify annual incidence rates. Associations between the independent variables and the outcome (MSCC) were evaluated by a univariate analysis, applying crude and adjusted odds ratios (aOR) assuming 95% confidence intervals. The MSCC incidence was of 1.5% (n = 51), associated to advanced staging (aOR = 2.65, 95% CI: 1.45-4.85, p = 0.001) and initial treatment with concomitant chemotherapy and radiotherapy (aOR = 4.40, 95% CI: 1.74-11.13, p = 0.002). Our findings revealed the incidence and factors associated with MSCC, indicating a subset of patients who may be potential targets for the prevention and early treatment of this condition, indicating unprecedented and relevant data for the Brazilian epidemiological scenario due to the high CC incidence rates.

Impact of microvascular invasion on 5-year overall survival of resected non-small cell lung cancer.

ABSTRACTObjectives:Non-small cell lung cancer (NSCLC) is an incidental and aggressive type of cancer. Although curative treatment can be offered, the recurrence rate is relatively high. Identifying factors that have a prognostic impact may guide changes in the staging system and recommendations for adjuvant therapy. The aim of this study was to evaluate the impact of microvascular invasion on the 5-year overall survival (OS) of patients with resected NSCLC treated at a reference cancer center. Methods:This retrospective, observational cohort study included patients diagnosed with early-stage NSCLC (clinical stages I-IIIA), treated with curative-intent surgery at the Brazilian National Cancer Institute between 2010 and 2016. Results:The dataset comprised 91 surgical patients, mostly females and white, with a mean age of 62 years (range between 29-83). Cases were distributed as stages I, II, and III in 55%, 29%, and 16%. Adenocarcinoma was the predominant histological subtype (67%), and microvascular invasion was present in 25% of the patients. The 5-year OS probability was 60% (95% CI, 48.3-68.9). Among all characteristics, advanced stages (p = 0.001) and the presence of microvascular invasion (p< 0.001) were related to a worse 5-year OS. After adjusting for age group and pathological stage, the presence of microvascular invasion was associated with a 4-fold increased risk of death (HR 3.9, 95% CI, 1.9-8.2). Conclusion:The presence of microvascular invasion was an independent factor related to worse survival and, therefore, should be routinely assessed in resected specimens.

Metabolic profile of patients with endometrial adenocarcinoma and association with tumor grade

ObjectiveTo describe the prevalence of metabolic syndrome and other metabolic indicators in patients with endometrial cancer and its association with tumor grade.MethodsThis is a cross-sectional study of patients with endometrial...

Prevalence of long-term opioid use after radiotherapy for cervical cancer in a Brazilian cancer center.

This study aimed to describe the clinical and demographic profile of cervical cancer patients exploring risk factors for prolonged use of opioids. 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 6months 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. The median age was 49.4years. 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 111days (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. 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. 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.

Preventing Uterine Cervix Cancer: The Clinical Meaning of Atypical Glandular Cells.

To determine the prevalence of the atypical glandular cells (AGCs) cytology and to analyze its clinical significance in different age ranges. Retrospective observational study using computerized data from the Brazilian National Cancer Institute, including women screened between January 2002 and December 2008. The women included were those with an AGC result who were properly followed-up with colposcopy and a second cytology. A total of 132,147 cytopathological exams were performed during the study period. Five-hundred and thirty-three (0.4%) women with AGC cytology were identified and, of these, 69.41% (370/533) were properly referred for colposcopy and a new cytology. Most of the women (79.2%) with a 1st or 2nd AGC cytology were between the ages of 25 and 54 years. The 2nd cytology demonstrated 67.6% (250/370) of normality, 24.5% (91/370) of squamous atypia, and 6.2% (23/370) of AGC, 0.8% (3/370) adenocarcinoma in situ and 0.8% (3/370) adenocarcinoma invasor. On biopsy of the women with a second AGC cytology, 43.4% (10/23) had normal histology, 43.4% (10/23) had squamous lesions, 8.7% (2/23) had invasive adenocarcinoma, and 1.2% (1/23) had an inconclusive report. All of the women with high-grade squamous intraepithelial lesion (HSIL) or invasive adenocarcinoma (respectively 5 and 2 patients), after a 2nd AGC cytology were 25 years old or older. The prevalence of the AGC cytology was low in the studied population. Most of the AGC cytology cases occurred in adult women between the ages of 25 and 54. Although most of the patients had normal histology after follow-up, several of them presented with squamous intraepithelial lesions or invasive adenocarcinoma.

The do-not-resuscitate-like (DNRL) order, a medical directive for limiting life-sustaining treatment in the end-of-life care of children with cancer: experience of major cancer center in Brazil.

In the last few decades, interest in palliative care and advance care planning has grown in Brazil and worldwide. Empirical studies are needed to reduce therapeutic obstinacy and medical futility in the end-of-life care of children with incurable cancer. The aim of this study was to investigate the effects of do-not-resuscitate-like (DNRL) orders on the quality of end-of-life care of children with incurable solid tumors at a cancer center in Brazil. A retrospective observational cohort study of 181 pediatric patients with solid tumors followed at the Pediatric Oncology Department of the Brazilian National Cancer Institute, Rio de Janeiro, Brazil, who died due to disease progression from 2009 to 2013. Medical records were reviewed for indicators of quality of end-of-life care, including overtreatment, care planning, and care at death, in addition to documentation of the diagnosis of life-limiting illness and the presence of a DNRL order. Data were summarized using descriptive statistics. Univariate and multivariate logistic regression analyses were used to examine associations between demographics, disease, treatment, and indicators of end-of-life care with a DNRL order. A documented DNRL order was associated with lower odds of dying in the intensive care unit or emergency room (80%), dying within 30days of endotracheal tube placement (80%), or cardiopulmonary resuscitation (CPR) administration at the time of death (96%). Placement of DNRL orders early in the disease process is critical in reducing futile treatment in pediatric patients with incurable cancer.

Radiotherapy Information System in Cancer Treatment Improvement: A Case Study at the Brazilian National Cancer Institute.

Radiotherapy is one of the main means of treating cancer patients. Its application has grown worldwide. Around 50% of all cancer patients should receive radiation. Brazil faces a shortage of radiotherapy treatment because of a lack of enough treatment units, equipment availability, well-trained staff, and fair reimbursement. The Radiotherapy Information System (RIS) implementation to manage information about patient scheduling is vital to improve the efficiency of care and reduce the waiting time to start cancer treatment. The information system deployed can be indicated as a disruptive innovation in the Brazilian public health system, considering the radical improvement in the cancer treatment process at the Brazilian National Cancer Institute.