Trabalhos Científicos

Introduction: Datopotamab duruxtecan (Dato-DXd) is a monoclonal antibody conjugated to a potent topoisomerase I inhibitor, targeting TROP2. Currently, Dato-DXd is employed in the treatment of certain malignancies, including non-small cell lung cancer (NSCLC). The use of this medication, in this context, has brought promising results in objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), along with favorable safety and tolerability profiles, positioning it as an alternative to systemic chemotherapy. Objective: To review the clinical effects of Dato-DXd in NSCLC, as well as to provide data on OS, PFS, response rate, and adverse events. Method: This is a literature review whose content was obtained from the PubMed and LILACS databases, using the following search strategy: the MeSH descriptors "datopotamab deruxtecan" and "Lung cancer" were used, and the Boolean operator "and" was included between them. The search was conducted on August 10, 2024. In PubMed, nine articles were found, while no studies were identified in LILACS. All articles that had a title and abstract consistent with the studied topic were included. Works that were not published in English were excluded. Thus, a sample of 9 articles was reached (n=9). Results: The phase III TROPION-Lung01 trial, which randomized 604 patients with NSCLC into two arms, one to receive Dato-DXd 6mg/kg and the other to Docetaxel 75 mg/m2 every 3 weeks, with a median follow-up of 12.9 months, favoring the Dato-DXd arm, presenting PFS of 5.5 months versus 3.6 months (HR 0.63 - 95% CI 0.51-0.79), with statistical significance (p-value 0.004). The multicenter phase I TROPION-PanTumor01 trial, which included 180 patients with NSCLC, revealed that Dato-DXd, generally used in the third-line of therapy, presented manageable side effects, such as nausea (64% of patients), mucositis/stomatitis (60%), fatigue (28%) and alopecia (42%), with interstitial lung disease or pneumonitis in 6% of patients. Only 10% required dose reduction, and 14% had to discontinue the drug. The same study reported an OS of 11.4 months (95% CI, 7.1 to 20.6 months) and an ORR of 26%. Conclusion: There was promising antitumor activity of Dato-DXd as monotherapy and a manageable safety profile in patients with advanced NSCLC, previously treated with several lines, still obtaining encouraging results.

INTRODUCTION: Mammography is crucial for identifying neoplastic lesions at early stages, allowing for early breast cancer diagnosis and reducing associated mortality rates.METHODOLOGY: A cross-sectional descriptive quantitative study was conducted to assess the incidence of neoplastic breast lesions in Paraíba. Data collection used TABNET tools with access to the DATASUS database from January 2019 to July 2024, as well as the Ministry of Health’s mortality information system (SIM) database from January 2019 to July 2022. The target population consisted of women who had mammograms during this period. Analyzed variables included age, diagnostic findings, and mortality in Paraíba. Incidence rates were calculated based on 347,651 patients who underwent exams between 2019 and 2024, assessing parameters such as the number of mammograms per year, prevalent findings, and age groups by service location.RESULT: For women aged 40 to 60, there was a 2.4% decrease in the number of exams from 2019 to 2022. During this period, worse prognosis mammographic findings increased by 15%, with cancerous lesions and Category 3 findings being most prominent. Additionally, there was an 8.9% increase in mortality rates for this age group.CONCLUSION: The temporal overlap of decreased exam rates, increased worse prognosis findings, and rising mortality rates for breast neoplasms in women aged 40 to 60 in Paraíba underscores the health impact of reduced screening policies and worsening quality of life due to delayed cancer diagnosis. There is an urgent need for increased governmental efforts to promote breast health among women in Paraíba.

Introduction: To an effective evaluation of hereditary predisposition to cancer, it’s necessary to have a detailed personal and family history, of at least three generations from maternal and paternal sides, to be able to suspect the diagnosis of one or more syndrome of hereditary cancer even before of molecular tests, in addition to understanding the biopsychosocial needs of each patient Objective: Show the benefits gathered in a cancer genetics risk assessment clinics after the implantation of nursing consultation prior to the first medical evaluation. Methodology: Analysis of the proposed operational procedure to implantation and following up of procedures carried out over a week to guarantee agreement. Results: All patients scheduled to the first evaluation of cancer genetics risk assessment received a link to answer questions about personal and family history, followed by orientation to go through an online appointment with the nurse navigator before the first evaluation with a clinical geneticist. Prior to the nursing appointment, the nurse prepares the patient's pedigree with the information received. During the consultation he validates the information, in addition to seeking further details about the history and evaluating the patient in his biopsychosocial aspects. The main gain was an increased precision of the pedigree for consultation with the geneticist. With the guidance of the nurse, patients sought the information necessary for medical consultation. During the nursing appointment, it was also possible to identify patients who needed help obtaining health insurance coverage and the urgency of each case, facilitating patient flow. Another indirect gain was the patient's bond with their care team. Conclusion: The specialist nurse is an essential component for cancer genetics risk assessment. The nursing consultation prior to the first medical evaluation is one moment in which this professional can contribute to counseling, within their responsibilities, participating in data collection and patient education process, promoting gains in the quality of care.

Introduction: Breast cancer is the most common type of cancer among women in Brazil, second only to non-melanoma skin cancer. In the case of advanced disease, even without a curative perspective, there are treatment options that aim not only to increase survival but also to relieve symptoms and improve or maintain quality of life. It is well established in the literature that patients with advanced disease who have not received prior treatments, express hormonal receptors, and are postmenopausal benefit from the addition of an aromatase inhibitor (AI) with a CDK4/6 inhibitor. Objectives: To analyze progression-free survival and the safety of using AI combined with ribociclib (a CDK4/6 inhibitor) over 18 months in a group of 25 patients with metastatic luminal breast cancer in the first line of treatment. Methods: This is an observational, longitudinal, retrospective study designed to evaluate progression-free survival and the safety of using ribociclib combined with AI in hormone receptor-positive, HER2-negative metastatic breast cancer patients in the first line of treatment at a public institution in Belo Horizonte, Minas Gerais, Brazil. Recruitment occurred in 2023, selecting 25 patients who had not been exposed to other systemic treatments in a metastatic setting and who agreed to participate in a partnership with Novartis, which committed to providing ribociclib to the 25 selected patients until disease progression, toxicity, or incorporation of the technology into the public health system. Data were collected anonymously from medical records, following the ethical principles defined by Resolution 196/96 on research involving human subjects in Brazil. Results: The analysis included 24 female patients and 1 male patient, with a mean age of 56 years. After 18 months of follow-up, 16 patients (64%) continued using the therapeutic strategy, 6 patients (24%) experienced disease progression, and 3 patients (12%) had dose-limiting toxicities. Of the 16 patients currently on ribociclib, 9 (56.25%) are using 600 mg of the drug, and 7 (43.75%) have had dose reductions due to adverse effects, primarily afebrile neutropenia. No hepatic or QT interval toxicities were recorded. Conclusion: The use of ribociclib combined with AI has proven to be a safe and beneficial therapeutic addition in controlling advanced breast cancer, with data consistent with previous randomized studies in a real-world setting

INTRODUCTION: The need for a palliative care (PC) team in oncology reference centers rises in the sphere of Brazilian public health and increasingly, the population and health professionals unite in favor of a humanitarian philosophy that aims to provide care to affected individuals diseases that represent a potential threat to life. OBJECTIVE: The study aims to develop a conceptual map for the implementation of a hospital palliative care service in a High Complexity Oncology Treatment Unit (UNACON) of a public hospital in the northern region of the state of Rio Grande do Sul, in addition to presenting a bibliographical review on the topic, assisting in a possible future scenario of implementing this service METHODS: Through a retrospective, observational, analytical and descriptive study, through the collection and quantitative and descriptive analysis of data, collected through the Hospital Cancer Registry (HCR), in the public domain, of cancer patients receiving care at the UNACON location under study between 2015-2020. For data description, calculation of absolute and relative frequencies of categorical variables was additionally used, in addition to analysis of variance, in which p values lower than 0.05 were considered significant. The program used was SPSS, version 23. RESULTS: According to the mapping of PC services in Brazil, the majority of these services were concentrated in the Southwest region (58%), Northeast (20%) and South region (14%) and the majority of PC centers recently started their activities between 2011 -2018. Epidemiological data related to UNACON in a study between 2015 and 2020, reveal that the average age range of care remains constant, with the highest range demonstrated in the period of 64,14 years in 2015. There were fluctuations between hospital records depending on the number of patients: 1.138, 1.045, 1.031, 1,002 and 1.047 between 2015-2020. Furthermore, only in 2018 was the number of cases by gender of care higher for females, n=506 and n=496 for males, and the general percentage throughout the study period of female individuals was 47,9% and males of 52,1%. CONCLUSION: Thus, it can be inferred that a researched institution presents sufficient criteria to include a PC service, together with its UNACON, corroborating the quality of life of patients. However, several challenges must be overcome, such as scientific improvement and hospital management in the context under study.

Purpose Molecular classification of endometrial cancer (EC) has emerged as a key approach to individualize therapy and define prognostic outcomes. This study aimed to implement the traditional ProMisE classification in a Brazilian population, compared with a molecular setting of ProMisE biomarkers, and evaluate its impact on patients’ prognosis. Patient and Methods A prospective cohort of 114 patients with primary EC treated at Barretos Cancer Hospital (BCH) between October 2020 and December 2022 was conducted. Pathology diagnosis, staging, treatment, and follow-up data were collected. The traditional ProMisE methodology was carried out by POLE hotspot sequencing and immunohistochemistry (IHC) for p53 and mismatch repair (MMR) proteins. We further evaluate the MMR and TP53 status by molecular approach, namely microsatellite instability (MSI) by PCR-based and TP53 mutation analysis by next-generation sequencing (NGS). The results of the 4 molecular groups in both methodologies were compared regarding agreement accuracy and survival outcomes. Results Among the 114 cases, the traditional ProMisE groups were: POLEmut 15.8%, MMRd 28.1%, p53abn 27.2%, and no specific molecular profile (NSMP) 28.9%. Considering the molecular classification approach, we observed a POLEmut group of 15.8%, MSI group of 23.7%, TP53 mutation of 27.2%, and NSMP of 33.3%. Importantly, both traditional and molecular ProMisE approaches were associated with significant distinct outcomes, with POLEmut patients exhibiting a better prognosis, whereas the p53abn/TP53 mutated having a worse survival time. Conclusion We reported for the first time the Brazilian profile of the ProMisE classification of endometrial cancer and demonstrated the prognostic impact of the traditional and molecular ProMisE classification on patient outcomes.

Introduction: The term "cancer survivor" can have various meanings in the literature. Most commonly, a cancer survivor refers to anyone who has been diagnosed with cancer¹,². There are over 32 million cancer survivors worldwide, and this number is expected to continue growing. However, both human and institutional resources are limited and must be used rationally and optimally. Given this duality, our initial plan was to develop an institutional protocol for the safe discharge of patients from specialized primary care settings. Thus, this integrative review aims to examine the current literature on transitional care from the oncology care team’s perspective. Objective: To examine the current literature on transitional care from the perspective of the oncology care team. Method: An integrative review of articles from the LILACS and BDENF/BVS, MEDLINE/PubMed, and Scopus databases was conducted using the descriptors "Cancer survivor," "Transitional Care," and "Primary Care." Eligible articles were reviewed to synthesize findings. The review followed the five stages of integrative review methodology: problem formulation, literature search, data evaluation, data analysis, and presentation. Results: The initial search yielded 29 articles. One duplicate article was removed, and 28 articles were subjected to a title and abstract review. Only 14 articles met the inclusion criteria. Conclusion: Transitions of care between cancer specialists and primary care physicians (PCPs) require ongoing improvement. The transition is a complex process during which patients, the oncology care team, and the primary care team may face unpredictability, partly due to the lack of evidence-based models. Barriers include the need for improved communication, knowledge/information sharing, financial toxicity, and resources for quality survivorship care. A survivorship care plan could enhance communication between cancer specialists and PCPs, improve survivors' receipt of cancer-related care, reduce costs, and support preventive care. Advancements in survivorship care education may lead to more effective care coordination and smoother transitions in the future.

Introduction: Breast cancer is one of the most prevalent forms of global cancer, being especially common among women. In 2015, the National Cancer Institute (INCA) published guidelines for early detection of breast cancer in Brazil. Besides that, the diagnosis still occurs in advanced stages and the mortality rates remain high. This raises questions regarding the limits imposed by the current protocol of the Ministry of Health, that advocates the start of screening for breast cancer only from the age of 50. Objectives: Analyze the epidemiological aspects of the incidence of breast cancer incidence in Brazil between 2019 and 2023 and to question the effectiveness of the conventional age for screening. Methodology: The study is a descriptive epidemiological analysis, using data from DATASUS (TABNET) between the years 2019 and 2023. The age group was used as a parameter to assess the incidence of breast cancer in Brazil. Results: Between 2019 and 2023, 65,385 cases of breast cancer were reported in Brazil. The highest incidence was observed in the age groups of 50 to 54 years (13.5%), 55 to 59 (13.4%) and 60 to 64 (12.6%), with a gradual increase in cases from adolescence until the peak in the mentioned ages. A decrease in incidence was observed after the age of 65, but cases remain prevalent in older ages. In the age group of 45 to 49 years, 8,103 cases (12.3%) were recorded, a relevant incidence for an age group not included in the Ministry of Health's screening protocol. There were also 6,605 cases (10.1%) in the age group of 40 to 44 years and 3,851 cases (5.8%) in the age group of 35 to 39 years. Conclusion: The incidence of breast cancer in Brazil over the past five years has shown a significant increase among women under the age of 49, who are currently not included in the mandatory screening guidelines set by the Ministry of Health. This study observed a marked and relevant increase in the age group of 40 to 49 years, despite the predominance of cases among those aged 50 to 54, followed by a decrease in incidence in those over 65 years. In this context, it is reasonable to consider that early breast cancer screening, before the age recommended by the Ministry of Health, which starts at 50, would be beneficial for the Brazilian population. Including younger women in the screening protocol could improve early detection and treatment of the disease.

INTRODUCTION: Cancer is one of the major malignant diseases that significantly impacts global public health and exhibits complex patterns of incidence and mortality. Over the past 10 years, cancer incidence in Brazil has shown significant variations influenced by age and sex. Therefore, it is crucial to conduct a comprehensive analysis of the data related to cancer incidence in Brazil. OBJECTIVE: To analyze and understand data related to cancer incidence in Brazil over a 10-year period, based on the data provided by DataSUS. The goal is to quantify, examine, and compare the variations according to age group, geographical region, and sex through epidemiological analysis. METHODOLOGY: Data available from the DataSUS Tabnet from 2019 to 2023 were collected. The data selection criteria included those related to sex and age group available during the same period. RESULTS: From 2019 to 2023, 1.676.147 cases of breast cancer were recorded in Brazil. The highest incidence was observed in the age groups of 60 to 64 years (13.2%), 65 to 69 years (12.9%), and 55 to 59 years (11.7%), with a gradual increase in cases from adolescence to the highest rates in these age ranges. There was a decline in incidence after age 69, although cases remained prevalent in older ages. Notably, 315.908 cases (7.4%) were recorded between 45 and 49 years, 252.956 cases (5.9%) between 40 and 44 years, and 191.775 cases (4.5%) between 35 and 39 years — age groups not included in the mandatory screening by the Ministry of Health. CONCLUSION: Over the past five years, there has been a significant increase in breast cancer cases among women under 49 in Brazil, an age group currently not covered by the mandatory screening by the Ministry of Health. The highest incidence occurs between 50 and 54 years, followed by a decrease in cases among those over 65. These data suggest that early screening, before age 50, could be beneficial for the population, allowing not only for detection but also for more effective interventions.

Patients accessing the public health system often present with more advanced stages of breast cancer at diagnosis and appear to have a worse prognosis. The present study aimed to identify the profile of breast cancer patients accessing the Unified Health System (Sistema Unico de Saude; SUS) Oncology Service in Rio de Janeiro, Brazil, as well as their histopathological and immunohistochemical characteristics, access to treatment, and percentage of deaths during the evaluated period. Patients with a diagnosis of breast cancer confirmed by histopathology and immunohistochemistry between January 2022 and September 2023 were included in the study. Patient data were recorded in Microsoft Excel spreadsheets and analyzed for the frequency of observed variables. The percentage of deaths that occurred during the studied period was recorded in February 2024. The study included 106 patients with confirmed breast cancer diagnoses, 105 of which were females with mean age of 59 years. Most patients (52.83%) were at stage III (p<0.0001), followed by stage II (27.3%), stage IV (12.26%), and stage 0 (4.7%). The most common type of breast cancer was invasive carcinoma of no special type (73.6%), followed by lobular (10.5%), micropapillary (6.6%), mucinous (2.8%), cribriform (0.9%), and metaplastic (0.9%). The remaining patients had in situ carcinoma (4.7%). Half of the patients had luminal B subtype (p<0.0001), followed by luminal A (22.7%), triple-negative (11.3%), triple-positive (9.4%), and HER2-enriched (6.6%). The majority of patients (53.7%) received neoadjuvant or adjuvant chemotherapy, whereas 13.2% received palliative chemotherapy and 33% did not receive any chemotherapy. All luminal patients received hormonal treatment, except those at stage 0 (in situ). All ten triple-positive patients and four of the seven HER2-enriched patients were treated with HER2 blockers. Five patients died (4.7%) during the studied period, four of which were stage IV and receiving palliative chemotherapy. Most patients had luminal B and stage III breast cancer, indicative of a worse prognosis in terms of response to therapies. Nonetheless, access to the hormonal and anti-HER2 drug therapies available through SUS likely had a positive impact on the short- and medium-term follow-up of these patients. Early diagnosis of breast cancer and facilitated access to specialized public health services can result in long-term benefits and cost reductions for the country.

Introduction: Cancer registries are essential for epidemiological analyses, public health planning and quality of care evaluation. Most of its data come from hospital-based cancer registries. In Brazil, following National Cancer Institute and World Health Organization standards, basic sociodemographic characteristics on these databases originate from administrative records. Brazil has a regulation for filling out the race/skin color question in health information system forms since 2017. Racial disparity in cancer care and outcomes is one of the greatest challenges that Brazil faces. A great amount of information and analyses to understand and deal with this disparity comes from secondary data as cancer registries. Objective: To compare self-reported skin color to race/skin color reported in the same patient's hospital cancer registry. Methods: This is a cross-sectional study of breast cancer patients. A review of electronic medical records was performed including all patients whose treatment for breast cancer began in 2022/23. Skin color self-reported data was obtained from a cancer center retrospective cohort study that analyzed time between diagnostic and first treatment. Results: We retrieved 176 cases where women self-reported skin color. Mean age was 61, ranging between 27 and 87 years old. Concordant data was seen in 86,9% of the records. In this sample, 40 patients (22,7%) self-reported as black (the aggregation definition of the IBGE Brazilian categories for “preto” and “pardo”), even though only 15,9% was registered as non-white patients. Among the 23 discordant color identification, 56,5% was a misclassification of black patients to white. There was just one patient that was classified the other way around, she self-reported to be white and it was registered as “Pardo”. The discordant data left was inside the black category (“preto” to “pardo” and vice-versa). Discussion: We found almost 7% of relevant discordance rate. This is different from American and English studies, whose records and self-reported data did not agree on around 5% of cases. The precision of this data is crucial to study disparity in cancer care. Although this is a small, selected sample, probably, it represents the race/skin color information quality on cancer registries. Understanding the source of inconsistency is extremely relevant to improve sociodemographic information in medical records. More Brazilian studies are necessary to confirm these results.

Introduction: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer characterized by erythema, edema, and skin changes such as nipple inversion and peau d'orange. These symptoms are primarily due to the presence of numerous dermal tumor emboli that obstruct lymphatic drainage. Despite the distinct symptomatology between IBC and non-IBC, the molecular differences between these two forms of breast cancer remain largely unexplored. The Advanced Glycation End Product Receptor (AGER/RAGE) is a transmembrane receptor overexpressed in various cancers, is associated with epithelial-to-mesenchymal transition, and has been implicated in breast cancer pathogenesis. The overexpression of AGER is linked to rapid tumor progression and metastasis. Objective: To measure and compare the levels of AGER expression in patients with IBC and non-IBC. Method: Indirect immunofluorescence was analyzed in 35 samples (19 IBC and 16 non-IBC). Both sample types were stained with DAPI, which binds to the nuclear area, and an anti-AGER monoclonal antibody, which binds to the receptor. Four fields were selected for each sample, and AGER expression was quantified as a percentage of the immunofluorescence intensity area. The expression data and clinicopathological parameters were compared, including the prognostic values of these biomarkers. The transcriptomic data of IBC and non-IBC microarray data from the Gene Expression Omnibus repository (GEO) were used to investigate the expression of AGER genes. Results: Tumor samples from IBC patients showed higher AGER immunoexpressions than the non-IBC group and were associated with obesity and Ki-67 expression (p <0.05). AGER expression in IBC versus non-IBC was also statistically associated with triple-negative molecular subtypes. External validation by analyzing three external GEO datasets confirmed the higher expression of AGER in IBC than in non-IBC samples. Conclusion: Overall, tumor samples from IBC patients showed higher AGER expressions than other breast cancer types.

Introduction: Lung cancer is the most common cancer diagnosed worldwide (excluding nonmelanoma skin cancer) and is the leading cause of global cancer related deaths. In Brazil, it is the fourth most common cancer, with an estimated 32.560 new cases a year. A lack of standardization in systemic cancer therapy among patients in the public health system can lead to inequalities in outcomes. Objective: This study aims to identify differences in systemic cancer therapy comparing treatment protocols among institutions and with the protocol recommended by the Brazilian Ministry of Health (MS), the World Health Organization (WHO), Essential Medicines List, the Magnitude of Clinical Benefit Scale (MCBS) from the European Society for Medical Oncology (ESMO) guidelines. Methods: Between September 2023 and January 2024, a national cross-sectional study was conducted by requesting systemic lung cancer therapy protocols from all public cancer centers, using Brazil’s Freedom of Information Law (Law nº 12.527/2011). Results: A total of 95 responses from all five regions cancer centers were received and 43 regarding lung cancer protocols. In the adjuvant setting of patients with NSCLC without driver mutation, the treatments offered are 100% adequate considering availability of chemotherapy, but only 6% of the cancer centers offer immunotherapy. In the setting of definitive treatment with concomitant chemoradiation, none of the centers offer immunotherapy, but all of them offer the proper chemotherapy regimens. In the metastatic setting, 100% of the centers comply with the chemo regimens, and 51% of the centers offer targeted therapies for EGFR mutations, and 2% for ALK fusion (treatments that exclude 2nd or 3rd generation drugs, such as Osimertinib, Alectinib or Brigantinib). Furthermore, no center reported offering treatment with targeted therapies for molecular alterations including ROS-1, RET, MET, HER-2, BRAF, NTRK and KRAS G12C. Conclusion: Within the context of outdated guidelines by the Ministry of Health, cancer centers do offer all chemotherapy drugs. Only half of the centers offer the recommended EGFR-targeted therapy. Immunotherapy, not yet recommended by the MH or by WHO-EML but universally recommended by international guidelines such as ESMO, has very limited availability among the cancer centers. The observed inequality contradicts one of the cornerstones of the Brazilian public health system and warrants further discussion of this issue.

Introduction: The C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have been employed for prognostic evaluation. Here, we aimed to analyze the association between inflammatory biomarkers and sociodemographic, clinical as well as anthropometric variables in women with stage I-III, breast cancer during the first and third cycles of outpatient chemotherapy. Methods: A prospective study was conducted at a reference oncological hospital in Brazil, involving women aged ≥18 years, diagnosed with breast cancer in stages I-III and receiving outpatient chemotherapy. Descriptive and bivariate statistical analyzes were carried out. Results: CRP levels were elevated as early as the 1st cycle of chemotherapy, remaining consistent in the 3rd cycle of treatment. Conversely, NLR and PLR exhibited averages below the recommended levels but increased over the course of chemotherapy. Variables such as self-reported race, waist circumference, Body Mass Index, tricipital skinfold thickness, and corrected arm circumference showed an association with CRP. NLR was associated with marital status, staging, TNM classification, diabetes, and corrected arm muscle area. Conclusion: Assessing systemic chronic inflammatory markers in the bloodstream can offer valuable insights into the role of inflammation during breast cancer chemotherapy treatment.

Introduction: Since the Human Genome Project, the volume of Omics data has required complex in silico analyses strategies, as the data volume exceeds human analytical capacity. The literature reflects a growing number of genomic and transcriptomic information derived from robust databases, guiding clinically relevant hypotheses. However, there is no standardization or defined methodological strategies, complicating the interpretation, validation and comparison of results from different groups. Objective: To propose an integrated in silico workflow using open databases, aiming to standardize the analysis of the transcriptome of solid tumors in a translational research laboratory linked to graduate programs in Human Pathology and Oncology. Methods: An integrated workflow was established for transcriptome analysis using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Data analysis algorithms were selected via the collaborative platform GitHub, and the R environment was employed for the in silico study. Results: Guided by clinical questions, two experienced oncologists selected and curated the available databases in TCGA and GEO. Transcriptome data (RNASeq) were downloaded into the R environment, followed by the identification of differentially expressed genes (DEG), using the Limma and/or DESeq2 packages, subsequently grouped into weighted gene co-expression networks (WGCNA and GeneXPress). Functions related to gene communities were obtained through gene ontology on the DAVID, KEGG, and Medscape platforms. The integrated analysis between the gene signature and aspects of the tumor microenvironment was conducted on the CIBERSORT and TIMER platforms, which provide relevant data on immune cells, tumor and non-tumor gene expression. Additionally, the study of predicted protein interaction networks was conducted using the String platform, identifying the most relevant proteins within each previously described community of interest. Conclusion: The establishment of a coherent omics data analysis workflow allows for the standardization of transcriptome and tumor microenvironment studies across various solid tumors, utilizing information obtained from cancer databases. This has significant implications for the reproducibility, consistency, and applicability of results, promoting transparency and generating new hypotheses that guide complementary studies, thereby expanding relevant scientific knowledge for clinical practice.

Background: There is a growing emphasis on the application of interdisciplinarity approaches in the treatment of breast cancer, especially for patients with some degree of frailty that interferes with therapeutic implementation. Although the studies have limitations due to different methodologies, they reinforce the importance of collaborative teams in individualized and humanized patient care. Objective: To identify the clinical characteristics of breast cancer patients assessed by the interdisciplinarity team through the institutional therapeutic oncological frailty risk protocol. Method: Observational Retrospective Cohort Study involved 190 patients diagnosed with breast cancer between January and December 2023, treated at a Brazilian oncology health service. Demographic data, staging and treatment intention were collected from records. Descriptive analysis of the study population was carried out by determining central tendency and dispersion measures for continuous variables and frequency distribution for categorical variables.The therapeutic oncology fragility risk was assessed using an institutional protocol that used the tools of subjective Patient-Produced Global Assessment (reduced ASG-PPP) plus strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F), Hospital Anxiety and Depression Scale (HADS), pharmaceutical questionnaire on essential medications and assessment of the need for portacath, respectively by the nutrition, psychology, pharmacy and nursing sectors, where each analysis could receive a score 0 (no risk) or 1 (with risk). The sum of the scores provided a frailty risk score, with up to 2 being considered low risk and > 2 being high risk. All sectors monitored high-risk patients together; low-risk patients were monitored as needed. Results:Of the 190 patients, two were male. 68.4% were aged ≥ 50 years, and 62.8% were overweight. The majority of patients (64.5%) had stages I and II. Twenty patients were undergoing palliative treatment. 82.7% of stage III and IV patients obtained a low-risk score. Conclusion: Interestingly, the study demonstrated that our interdisciplinarity institutional protocol for assessing the risk of therapeutic oncology frailty did not reveal that advanced/metastatic clinical staging was a variable that directly correlated with a frailty risk score in daily practice. It strengthened the use of pre-established standard metrics for the integrative assessment of these patients.

Introduction: Oxaliplatin (OXL), an antineoplastic agent and first-line treatment for metastatic colorectal cancer, is primarily associated with neurotoxicity, manifested as dose-limiting peripheral sensory neuropathy (PSN). Cannabinoid agonists have shown potential in preventing the development of PSN associated with OXL. However, to ensure therapeutic efficacy, it is necessary to investigate whether these agonists interfere with the antitumor effects of OXL. Objective: To evaluate the impact of cannabinoid agonists on the antitumor efficacy of OXL in vivo and in vitro using murine colorectal adenocarcinoma (CT26) cells. Methodology: Male Balb/c mice (CEUA No 16110422-0) were inoculated subcutaneously with CT26 cells and treated with WIN-55-212-2 (a non-selective cannabinoid agonist) and ACEA (a selective CB1 cannabinoid agonist), either alone or in combination with OXL. Tumor growth was assessed until day 12, and tumors were collected. PSN was evaluated using von Frey (VF) and acetone (TA) tests. CT26 cells were cultured in 96-well plates and treated with ascending concentrations of OXL, WIN, and ACEA. Synergism was assessed by combining OXL with ACEA and WIN. After 72 hours, cell viability was measured using the AlamarBlue assay. Results: WIN and ACEA inhibited the development of PSN, reducing mechanical allodynia by 133% and 100%, respectively (p<0.05), in the VF test, and cold allodynia by 40% and 67% (p<0.05), in the TA test. Only the ACEA+OXL-treated groups showed antitumor effects (79%; p<0.05). WIN treatment did not alter the effect of OXL and had no effect alone. In vitro, OXL reduced cell viability with an IC50 of 2.23 μM. Both agonists decreased cell viability, with IC50 values of 7.09 μM (WIN) and 49.46 μM (ACEA). Additionally, the IC50 of OXL+WIN was reduced to 1.48 μM, suggesting a synergistic effect. The ACEA+OXL combination consistently showed an inhibition rate above 75% at all concentrations, indicating strong synergism. Conclusion: WIN and ACEA exhibited antineuropathic effects in tumor-bearing animals. WIN reduced tumor cell growth in vitro but not in vivo, and in combination with OXL, enhanced its effect in vitro but not in vivo. ACEA alone did not show antitumor effects in vivo or in vitro, but when combined with OXL, it reduced tumor growth both in vitro and in vivo. These results are promising and suggest the need for further investigation into the use of cannabinoid agonists as adjuncts in colorectal cancer therapy with OXL.

Neoadjuvant chemoradiotherapy (nCRT) is the standard treatment for locally advanced rectal cancer (LARC), aimed at shrinking tumors and facilitating surgical resection. Recently, organ preservation has become an appealing strategy for managing rectal cancer. However, clinical and radiological features are poor predictors of response. Intratumoral genetic heterogeneity (ITGH) has emerged as a potential biomarker for assessing tumor response, and our previous studies have shown that ITGH increases following nCRT. Additionally, the effects of copy number alterations (CNAs) and structural variations (SVs) on LARC outcomes and their impact on ITGH estimation remain underexplored. In this retrospective study, we evaluated 72 patients with LARC, with pre-treatment tumor biopsy collected and subjected to whole exome sequencing. All patients received long-course nCRT with either 5FU-based chemotherapy or Capecitabine. Patients were categorized into three groups based on clinical outcomes: nCRT-Responders (n=16), nCRT-Not Responders (n=38), and nCRT-Not Responders Metastatic (n=18). We used (SNVs/Indels) data to measure ITGH using the MATH score, observing a significant association between low MATH scores and nCRT response (p≤0.05, Wilcoxon test), especially when comparing nCRT-Responders to non-metastatic nCRT-Not Responders. SV events, including translocations, duplications, deletions, and insertions, were identified using MANTA, while CNAs (gains and losses) were detected with the GATK pipeline. SVs and CNAs were not correlated with clinical outcomes (p>0.05, Wilcoxon test). We further investigated whether CNAs could affect the MATH score's association with clinical outcomes. To do this, we recalculated the MATH score using SNVs within and outside CNA regions individually and found no change in its association with clinical outcomes. Finally, we analyzed patients with non-metastatic clinical outcomes (n=53). Using ROC curve analysis, we determined the best MATH score threshold (34.04), with a sensitivity of 89% and specificity of 53% (AUC=0.67). Multivariate analysis with the clinical-radiological features shows that MATH-low is significantly associated with nCRT-R (OR:11.66; p=0.01). Our results show no correlation between CNAs and SVs events with clinical outcomes, that CNAs events do not impact ITGH, and suggest that the MATH score may help select patients for preoperative treatment, potentially achieving a complete response and enabling organ preservation.