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

The standard treatment of locally advanced rectal cancer comprises neoadjuvant chemoradiation followed by total mesorectal excision. This strategy provides low local recurrence rate, however distant recurrence is still an issue and may impact on survival rates. Novel approaches in the neoadjuvant setting have been tested to improve early and late outcomes, as well as to reduce treatment-related toxicity and morbidity. In this review, we discuss the current literature of neoadjuvant treatment in locally advanced rectal cancer, including total neoadjuvant methods, protocols for radiation delivery, chemotherapy regimen and efforts to add novel targeted therapies, selective withdrawal of surgery or radiotherapy, and future perspectives. Moreover, we highlight relevant issues that have emerged with these new treatment possibilities.

Aims: To assess non-small-cell lung cancer (NSCLC) patient-centered outcomes in the real world. Methods: This is a prospective study of NSCLC patients treated at a private cancer care institution in Brazil between 2014 and 2019. Results: The report comprises 337 patients. Advanced stage was associated with higher symptom burden – fatigue (p = 0.03), pain (p

Introduction We analyzed the prevalence of non–small-cell lung cancer (NSCLC) with a programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) of ≥ 50% and compared the results with the existing data from clinical trials and databases from other countries. Materials and Methods The Latin American Cooperative Oncology Group and Grupo Brasileiro de Oncologia Toracica performed a retrospective, cross-sectional study from August 2017 to April 2018. PD-L1 expression was collected from pathology reports from 5 laboratories in Brazil. All tests were sponsored by the pharmaceutical industry on request from the treating medical oncologist. PD-L1 expression was assessed by immunohistochemistry. The variables were summarized as absolute and relative frequencies or the median and interquartile range. Pearson's χ2 test was used to compare the TPS categories stratified by sex, age, and histologic type. All analyses were performed with SAS, version 9.4, and were deemed statistically significant at P Results A total of 1512 patients were included in the present study. Their median age was 66 years. Most patients were men (56.02%), and the most common histologic type was adenocarcinoma (58.04%); 109 tumors (11.31%) had EGFR mutations and 34 (3.64%) had ALK gene rearrangements. Overall, 56.54% had a PD-L1 TPS Conclusion The prevalence of high PD-L1 expression among the Brazilian NSCLC samples was lower than previously described in other countries, which could affect the number of patients who might be candidates for immunotherapy alone.

A novel EGFR-tyrosine kinase inhibitor (TKI), osimertinib, has marked efficacy in patients with EGFR-mutated lung cancer. However, some patients show intrinsic resistance and an insufficient response to osimertinib. This study showed that osimertinib stimulated AXL by inhibiting a negative feedback loop. Activated AXL was associated with EGFR and HER3 in maintaining cell survival and inducing the emergence of cells tolerant to osimertinib. AXL inhibition reduced the viability of EGFR-mutated lung cancer cells overexpressing AXL that were exposed to osimertinib. The addition of an AXL inhibitor during either the initial or tolerant phases reduced tumor size and delayed tumor re-growth compared to osimertinib alone. AXL was highly expressed in clinical specimens of EGFR-mutated lung cancers and its high expression was associated with a low response rate to EGFR-TKI. These results indicated pivotal roles for AXL and its inhibition in the intrinsic resistance to osimertinib and the emergence of osimertinib-tolerant cells.

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

e18621 Background: Major improvements in breast cancer (BC) treatments have led to a significant increase in overall survival. Quality of life (QoL) is one of the main goals of cancer treatment and patient-centered outcomes are measured in almost all randomized clinical trials, but real-world data are lacking in the literature. Methods: This is a prospective, multicenter, observational study of female BC patients, without prior systemic treatment, treated between 2012 and 2019 in private healthcare in Sao Paulo and Rio de Janeiro, Brazil. QoL was assessed by EQ-5D-5L and EORTC-QLQ-BR23 at baseline, 3, 6, 9 and 12 months. All measures were presented as means and analyzed according to staging and subtypes using the Kruskal-Wallis test. A linear mixed model was used to assess the changes in the mean scores over time. Results were reported as increments relative to the baseline category, using 95% confidence intervals and p values. Results: A total of 1,372 female BC patients were evaluated, with a median age at diagnosis of 53.8 years. Stage 0, I, II, III and IV were diagnosed in 11%, 36%, 31%, 16% and 3% of the patients, respectively. Among the five dimensions of the EQ-5D-5L questionnaire, at baseline, the main reported problem was anxiety/depression, in which 37.1% and 19.5% reported slight and moderate symptoms, respectively. In the EQ VAS (visual analogue scale), patients stage III and IV had significantly lower score at baseline, 77.1 and 69.7 respectively, compared to stage I and II, 79.5 and 79.2 respectively (p = 0.016). Despite the high symptom burden at baseline, patients with metastatic BC had the most significant improvement after treatment, with 8.85 points difference at 12 months in absolute values from baseline (p = 0.005). Among EORTC-QLQ-BR23 measures, the baseline scores were similar between all stages, except for more “breast symptoms” in stage III patients, and more “systemic therapy” symptoms and better “sexual functioning” for stage IV patients, compared with early stages (p < 0.005). When we assess the impact of surgical treatment over time, patients undergoing lumpectomy had a better perception of “body image”, and axillary dissection led to more “arm symptoms” after 12 months. Similarly, radiotherapy enhanced “breast symptoms” and patients treated with chemotherapy had significantly more “systemic therapy” side effects compared with other treatments. Conclusions: In our population, patients with stage III/IV BC had worse baseline health perception, but those with metastatic disease had the greatest improvement over time, due to the benefit of systemic treatment. Patients undergoing chemotherapy, mastectomy, and radiation therapy reported worse QoL and long-term side effects. Early diagnosis and access to treatments with fewer side effects should be our future goals.

9035 Background: In the Phase 3 POSEIDON study in 1L mNSCLC, adding T to D+CT resulted in statistically significant improvements in PFS and OS vs CT. No new safety signals were identified and treatment discontinuations due to treatment-related AEs (TRAEs) were similar for the T+D+CT and D+CT arms (15.5% and 14.1%). Here we present details of AEs and their management. Methods: 1013 pts with EGFR/ ALK wild-type mNSCLC were randomized 1:1:1 to 1L T+D+CT, D+CT or CT. Safety was assessed in all treated pts. Results: 330, 334 and 333 pts received T+D+CT, D+CT and CT; 78%, 82% and 74% received at least 4 cycles of platinum-based CT. The most common grade 3/4 TRAEs were hematologic (anemia in 17%, 15% and 20% of pts in the T+D+CT, D+CT and CT arms and neutropenia in 16%, 13% and 12%) and most were managed using standard approaches per local practice; 22%, 18% and 16% of pts received colony stimulating factors and 22%, 21% and 26% received blood transfusions. All grade immune-mediated AEs (imAEs) occurred in 34%, 19% and 5% of pts in the T+D+CT, D+CT and CT arms; a higher incidence of diarrhea/colitis, dermatitis/rash and endocrinopathies was seen with the addition of T to D+CT (Table). Grade 3/4 imAEs occurred in 10%, 7% and 2% of pts in the T+D+CT, D+CT and CT arms, and serious imAEs in 10%, 6% and 1%; imAEs led to discontinuation of any study treatment in 6%, 4% and 0.6%, and led to death in 0.6%, 0.3% and 0%. Most imAEs were low grade and manageable with systemic corticosteroids (received by 26%, 13% and 4% of pts in the T+D+CT, D+CT and CT arms) or endocrine therapy (12%, 8% and 1%). Median time from first dose to onset of imAEs (TTO) was generally > 60 days and the majority of non-endocrine imAEs resolved (Table). Conclusions: In POSEIDON, the safety profile of all regimens was manageable per standard guidelines and in line with the known profiles of D, T+D and CT; the most common grade 3/4 TRAEs were those typically associated with CT. As expected, more imAEs occurred with T+D+CT than D+CT, but the incidence of grade 3 or 4 imAEs, imAE-related deaths and treatment discontinuations due to imAEs was generally similar in the IO arms. T+D did not compromise the ability to administer planned CT. Clinical trial information: NCT03164616. [Table: see text]

Background: KRAS is the most frequently mutated oncogene in cancer, however efforts to develop targeted therapies have been largely unsuccessful. Recently, two small-molecule inhibitors, AMG 510 and MRTX849, have shown promising activity in KRAS G12C-mutant solid tumors. The current study aims to assess the molecular profile of KRAS G12C in colorectal (CRC) and non-small-cell lung cancer (NSCLC) tested in a clinical certified laboratory.Methods: CRC and NSCLC samples submitted for KRAS testing between 2017 and 2019 were reviewed. CRC samples were tested for KRAS and NRAS by pyrosequencing, while NSCLC samples were submitted to next generation sequencing of KRAS, NRAS, EGFR, and BRAF. Results: The dataset comprised 4,897 CRC and 4,686 NSCLC samples. Among CRC samples, KRAS was mutated in 2,354 (48.1%). Most frequent codon 12 mutations were G12D in 731 samples (15.2%) and G12V in 462 (9.6%), followed by G12C in 167 (3.4%). KRAS mutations were more frequent in females than males (p=0.003), however this difference was exclusive of non-G12C mutants (pConclusions: KRAS G12C presents in frequencies higher than several other driver mutations, represent a large volume of patients in absolute numbers. KRAS testing should be considered in all CRC and NSCLC patients, independently of clinical or demographic characteristics.

The objective of this review is to address the barriers limiting access to next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) for metastatic nonsquamous non-small cell lung cancer in Brazil and to propose its implementation in practice. A selected panel of lung cancer experts was provided with relevant prompts to address at a conference; a paper was then compiled on the topic. The authors propose specific and realistic recommendations for implementing access to ctDNA NGS. Further, the authors address all barriers and impediments mentioned within this review. There is a great need to increase ctDNA NGS for cancer care in Brazil. Adapting the current cancer testing framework is essential to expanding the use of this tool.

OBJECTIVES: To evaluate the molecular testing and treatment patterns in a retrospective cohort of newly diagnosed treatment-naïve patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). METHODS: This is an observational retrospective cohort study conducted across 10 cancer centers in Brazil. Treatment-naïve patients with locally advanced or metastatic NSCLC were enrolled from January to December 2014. The following data were collected from the medical records of patients from diagnosis until the last record (death, loss to follow-up, or the end of the maximum follow-up period): demographics; medical history; smoking status; disease characteristics; previous treatments; and molecular testing patterns and results. The overall survival (OS) was also estimated. Results: A total of 391 patients from 8 different Brazilian states were included, with a median age of 64.1 years (23.7-98.7), with most patients being males (60.1%). The smoking status of 74.2% of patients was a ‘former’ or ‘current smoker’. Stage IV NSCLC at diagnosis was observed in 82.4% of patients, with 269 of them (68.8%) presenting adenocarcinoma (ADC). Among the stage IV ADC patients, 54.0% were referred for molecular testing. Among the patients with an available epidermal growth factor receptor (EGFR) mutation status, 31 (24.0%) were EGFR-positive. The first-line treatment was a platinum-based chemotherapy for 98 patients (25.1%), while non-platinum-based regimens were used in 54 patients (13.8%). OS data were available for 370 patients, with a median OS of 10.8 months. Never smokers had a significantly higher median OS versus current or former smokers (14.6 versus 9.1 months; log-rank p=0.003). Among the patients for whom molecular testing data were available, those with EGFR-positive results had a longer median OS (34.6 versus 12.8 months; log-rank p=0.003). Conclusion: Our findings provide relevant information for prescribers and policy decision-makers by highlighting the unmet needs of patients and the importance of molecular testing in newly diagnosed locally advanced or metastatic lung adenocarcinoma. We also highlight the respective EGFR-tyrosine kinase inhibitor treatment when the result is positive and the areas in which further efforts are required to grant access to effective treatment.

The regional diversity of the genomics of non–small cell lung cancer (NSCLC) is an intriguing topic. Yet, little is known about the baseline factors—either genetic or environmental—that lead to different patterns of NSCLC-related mutations, except for tobacco-associated carcinogens. In a recent publication by Carrot-Zhang and colleagues (1), the authors presented very interesting data on patients from Colombia and Mexico and highlighted a plausible relationship between Native American genetic ancestry and somatic mutations in EGFR . The authors concluded “that while controlling for global ancestry, local ancestry is associated with mutations in EGFR and KRAS , providing the first example, to our knowledge, of a germline influence” for targetable somatic events in lung cancer (1). To further the community discussion of this important topic we would like …

Background Developing countries like Brazil often present a dichotomous health care system, where patients may be treated in either public or private institutions that differ substantially in terms of level of access to diagnostic and therapeutics procedures. Herein, we present the first report of a comprehensive study to assess real-world data in breast cancer patients treated in the private health care in Brazil. Methods This is a prospective study of breast cancer patients treated in a private health care institution, comprising six unities in Rio de Janeiro and surroundings. Eligible patients were at least 18 years old and had a histology-proven diagnosis of breast cancer between July 2012 and November 2016. For this analysis, only female patients with an invasive component were included. Patients with prior malignancies and those who initiated therapy in other institutions were excluded. Patients or relatives were contacted by telephone to ensure that all information was annotated. Data quality was certified by regular monitoring. This study was approved by the local Research Ethics Committee. Results One thousand three hundred and ninety patients were enrolled. One hundred sixty were excluded in this analysis, 11 due to male gender and 151 with exclusively in situ carcinoma. The report comprises 1230 female patients, predominantly diagnosed in early (79.0% stages I-II) or locally advanced (16.1% stage III) stages. One thousand thirty-three (84.0%) patients had hormone receptor (HR)-positive tumors, and 185 (15.0%) were HER2 positive. One hundred twenty-six (10.2%) cases were triple negative. The primary tumor was resected in 89.0% of times, most often through breast-conserving surgery (55.1%). Axillary lymph nodes were assessed in 83.4% of cases, and 32.0% required complete axillary dissection. Chemotherapy was used in 61.3% of cases, and radiation therapy in 59.6%. Patients with locally advanced disease received more aggressive therapy than patients with early stage (higher rates of mastectomy, axillary dissection and chemotherapy use). After a median follow up of 22.5 months (95% CI, 21.09-23.90), 54 (4.4%) deaths were reported. The estimated 2-year overall survival (OS) was 95.3%. 2-year OS was significantly longer among patients with stages I-II (97.9% and 97.5%, respectively) than in stages III and IV (89.4% and 69.5%, respectively) (p Conclusion To our knowledge, this is the most comprehensive and best-annotated study in breast cancer patients treated in the private health care in Brazil. More oncological interventions were used in advanced stages, reflecting international recommendations, but also a need to pursue early diagnoses, where outcome is optimal despite less aggressive therapy. Outcomes are favorably similar to the current literature from developed countries in all stages. The data provided helps comprehending the current scenario of breast cancer presentation and treatment in Brazil, and may serve as a foundation to guide resource allocation in the years to come. Citation Format: Boukai A, Gonçalves AC, Andrade PM, Carvalho N, Almeida T, Lemos F, Padoan M, Teich NS, Araujo LH. Outcome of breast cancer patients treated in the private health care in Brazil [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-25.

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 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.

e13600 Background: The COVID-19 infection was declared pandemic in March 2020. Since then, multiple studies have attempted to correlate clinical factors with risk of complications from COVID-19, including cancer. However, cancer patients are underrepresented in clinical trials and the results vary between different cohorts. Methods: We conducted a multicentre retrospective study, based on systematic review of medical records, including nine cancer centers, located in five different Brazilian cities. Patients were diagnosed with COVID-19 through RT-PCR between March 15, 2020 and August 13 , 2020. Poisson regression models were then used to test for an association between clinical characteristics and severity of COVID-19 infections. Results: 102 patients had data collected for analysis, 85 (83.3%) of whom were hospitalized due to complications from COVID-19 infection. The median age was 65.8 years, most were female patients (61.8%) and white (73,5%). 78.4% had a performance status of 0-1, and the most common cancer subtypes were gastrointestinal (30.4%), breast (22.6%) and hematological (13.7%). Almost 40% of population had stage IV disease. Mortality rate for all hospitalized patients was 36.5%, while for those admitted to the ICU it was 68.4%. Key univariable risk factors for mortality included age (RR 1.03), ECOG ≥ 2 (RR 1.83), hypertension (RR 1.72), lung metastasis (RR 1.67), and lymphocytes ≤ 1000 admission (RR 2.40). At the multivariable analysis, the risk factors were also age (RR 1.02), primary lung cancer (RR 2.61), lung metastasis (RR 2.86), and coronary disease (RR 3.76). Conclusions: Despite the high mortality of patients hospitalized with COVID-19, our data are compatible with other cohorts. Cancer patients must be carefully monitored in pandemic periods of infectious diseases.

Introduction: The molecular classification of cancer through next generation sequencing has transformed drug development towards the molecularly guided era of precision medicine. Genomic sequencing technologies have enabled a complex characterization of an individual’s cancer genome, and selection of genomically matched treatment.Areas covered: Herein, we discuss how genomic sequencing strategies have been used in oncology to tailor targeted therapies in precision medicine programs. We highlight clinically applicable sequencing technologies, modern clinical trial designs, and novel concepts like tumor heterogeneity, liquid biopsies, and immune-oncology.Expert commentary: There remain numerous challenges to evolve precision oncology into a reality in cancer care. Improving sequencing platforms, educating technical personnel and clinicians, defining clinical utility, and exploring novel perspectives are key steps in this process.

We appreciate Dr. Sekine’s interest on the topic of genomic differences of non-small cell lung cancer (NSCLC) in ethnically distinct populations. In his commentary to Journal of Thoracic Disease (1), Dr. Sekine points the lack of comprehensive studies in this matter, and reviews the extant data. As described in his review, minority groups like African Americans (AA) are often underrepresented in relevant studies like the Lung Cancer Mutation Consortium (LCMC) (2) and The Cancer Genome Atlas (TCGA) (3), wherein most patients are self-reported as Whites.

Background: Tumor mutational burden (TMB) is currently under investigation as a biomarker for predicting response to anti-cancer immunotherapy. TMB can be defined as the number of somatic nonsynonymous mutations per Mb in a cancer genome, therefore DNA artifacts could lead to inaccurate measurements. Cytosine deamination (C:G>T:A) is a well-known phenomenon in formalin-fixed, paraffin-embedded (FFPE) samples, producing errors in next-generation sequencing (NGS). Herein, we measured TMB in FFPE samples using two comprehensive NGS panels for routine diagnostics implementation. Methodology: TMB assessment was performed on FFPE samples by amplicon-based target enrichment on Thermo Fisher's Oncomine™ Tumor Mutation Load (OTML; n=9) and/or hybrid capture-based on Illumina's TruSight™ Oncology 500 Assay (TSO500; n=8), according to manufacturer's instructions. TMB values were compared for uracil-DNA glycosylase (UDG) treatment prior to PCR amplification and enrichment method. Samples were also compared according to their previous results in a clinically-certified NGS and an in-house microsatellite instability (MSI) assay. TMB >=10 mutations/Mb was considered high, and MSI >=20% was considered unstable. Results and Discussion: The concordance between TMB values for OTML and TSO500 was 75% (n=4) and 62.5% (n=8) with and without UDG treatment, respectively. UDG reduced artifactual C:G>T:A for both enrichment approaches, reinforcing its presence in FFPE DNA; however, there was no alterations on TMB results for both methods (TSO500 n=5; OTML n=7). C:G>T:A variants could be successfully filtered by low allelic frequency (60), leading to TMB overestimation (>350), which could not be corrected even after UDG treatment and manufacture's bioinformatic adjustment. Interestingly, the same samples presented low TMB values for TSO500. Samples with low deamination rates were not influenced by UDG treatment or bioinformatics adjustment regardless of enrichment method. TMB values from a certified NGS was completely concordant for TSO500 (n=4) but only 25% for OTML (n=4). MSI was fully concordant between certified NGS and TSO500 (n=4) and between in-house method and TSO500 (n=4) (value not analyzed by OTML assay). No QC parameter predicted differences between high and low deaminated samples. Conclusions: NGS enrichment methods strongly influenced TMB assessment. Hybrid-based capture showed better performance than amplicon-based. UDG treatment and higher allelic frequency cutoff could minimize false positives at variant calling level, although no significant effect could be observed for general TMB values. Future experiments should cover other alternatives to distinct FFPE DNA damages. Citation Format: Michele A. Pereira, Feliciana L. Marinho, Joice P. Silva, Renato Puga, Maíra C. Freire, Mariana R. Monteiro, Rafael L. Guedes, Luiz H. Araujo. Tumor mutational burden is affected by next-generation sequencing enrichment method in highly deaminated samples from solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1996.

e15066 Background: Obesity is linked to an increased risk of cancer development. The excess of body fatness seems to be associated with alterations in hormonal, metabolic and inflammatory pathways, that may lead to activation of the carcinogenesis process. Previous studies suggested this obesity pro-inflammatory state could improve ICI clinical efficacy. Methods: Baseline characteristics and clinical outcomes were retrospectively collected from advanced cancer patients of any primary site, and treated with ICI in our institution. The BMI was determined for all pts and categorized into 2 groups: obese (BMI≥30) and non-obese (BMI < 30). Primary outcomes were the association of BMI category with overall survival (OS) and progression free survival (PFS) assessed by log-rank statistic, and both were stratified by sex, age, treatment agent and primary tumor site using the Cox-regression. Secondary outcome was the association of BMI with objective response rate (ORR). Results: We collected data from 448 advanced cancer pts - 192 (43%) as normal weight, 159 (36%) as overweight, 78 (17%) as obese and 19 (4%) as underweight. A total of 370 pts (83%) were included in the non-obese group (BMI < 30) and 78 (17%) patients in the obese group (BMI≥30). The majority of pts (387 - 84%) received anti-PD-1/anti-PD-L1; 128 pts (28%) were treated at 1st line and 200 pts (44%) at 2nd line. The obese group experienced longer mOS than the non-obese group - 21.8 months (95% CI NR - NR) vs. 14.9 months (95% CI 8.3 -21.5); HR = 0.82, (95% CI 0.57-1.18, P = 0.28). However, this was not statistically significant and even after stratification. The obese group had an inferior mPFS than the non-obese group - 4.7 months (95% CI 3.8- 5.7) vs. 5.3 months (95% CI 3.45-7.15); - HR = 0.99, (95% CI 0.76 -1.30), P = 0.95. There was no significative difference in mPFS and ORR according to BMI. Conclusions: Although study did not report an improved OS among high BMI pts treated with ICI, our results suggested a trend in survival benefit. The BMI should be explored as a stratification variable in the design of prospective trials with advanced cancer pts and ICI treatment.

404 Background: Patients with germ cell tumors (GCT) that relapse after first-line platinum-based chemotherapy can still be successfully rescued with second-line regimens. High-dose chemotherapy has shown favorable outcomes, and is a preferred option in most instances. Herein, we argued if conventional-dose chemotherapy (CDCT) could also be an alternative in selected patients. Methods: We performed a retrospective observational study, analyzing medical data of 57 GCT male patients treated with salvage chemotherapy after relapse to first-line platinum-based treatment from 2000 to 2015 at the Brazilian National Cancer Institute. Results: The median age was 28 years (range 15 to 49). 26 patients (46%) were Afro-Brazilian, 45 (79%) were non-seminoma, and 53 (93%) had primary testis tumors. 14 patients (25%) had bone, liver or brain metastasis at relapse, and in 35 (61%) the progression-free interval (PFI) after first-line was < 3months. The International Prognostic Factors Study Group (IPFSG) risk classification at relapse for very-low/low, intermediate and high/very-high risk were 8 (14%), 25 (44%), 24 (42%), respectively. After a median follow-up of 8 years, the 2-year PFS was 30% (95% IC, 20 % to 45 %) and the 2-year overall survival (OS) was 34% (95% IC, 23% to 49%). PFI < 3m after first-line (HR 2,38; p 1000 at relapse (HR 2,38, p

Secretory carcinoma, described as mammary analog secretory carcinoma, is a recently described tumor of salivary glands that is defined by its histologic, immunophenotypic, and genetic similarities to the secretory breast carcinoma and is characterized by ETV6 translocation. The first description of mammary analog secretory carcinoma was reported by Skalova et al. in 2010. Retrospective studies showed that some tumors of salivary glands such as acinic cell carcinoma, low-grade salivary duct carcinoma, adenocarcinoma/cystadenocarcinoma not otherwise specified (NOS), and low-grade mucoepidermoid carcinoma were misdiagnosed. The purpose of this study is to review the literature showing the differential characteristics among these tumors and secretory carcinoma, highlighting how to perform the correct diagnosis, giving the patients the right treatment and improving their prognosis. Potential target therapy is also approached.

New cases of the novel coronavirus disease 2019 (COVID-19), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continue to rise worldwide following the declaration of a pandemic by the World Health Organization (WHO). The current pandemic has completely altered the workflow of health services worldwide. However, even during this critical period, patients with other diseases, like cancer, need to be properly treated. A few reports have shown that mortality due to SARS-CoV-2 is higher in elderly patients and those with other active comorbidities, including cancer. Patients with lung cancer are at risk of pulmonary complications from COVID-19, and as such, the risk/benefit ratio of local and systemic anticancer treatment has to be considered. For each patient, several factors, including age, comorbidities, and immunosuppression, as well as the number of hospital visits for treatment, can influence this risk. The number of cases is rising exponentially in Brazil, and it is important to consider the local characteristics when approaching the pandemic. In this regard, the Brazilian Thoracic Oncology Group has developed recommendations to guide decisions in lung cancer treatment during the SARS-CoV-2 pandemic. Due to the scarcity of relevant data, discussions based on disease stage, evaluation of surgical treatment, radiotherapy techniques, systemic therapy, follow-up, and supportive care were carried out, and specific suggestions issued. All recommendations seek to reduce contagion risk by decreasing the number of medical visits and hospitalization, and in the case of immunosuppression, by adapting treatment schemes when possible. This statement should be adjusted according to the reality of each service, and can be revised as new data become available.

Purpose Middle-income countries like Brazil often have a dichotomous health care system in which patients may be treated in either public or private institutions that differ substantially in terms of level of access to diagnostic and therapeutic procedures. Patients and Methods This was a prospective, observational study to assess real-world data in 1,230 female patients with breast cancer who were treated in a private health care institution between 2012 and 2016 in Brazil. Results Breast cancer in these patients mostly was diagnosed at early (79.0% stages I or II) or locally advanced (16.1% stage III) stages. The primary tumor was resected in 89.0% of cases, most often through breast-conserving surgery (55.1%). Patients with locally advanced disease received more aggressive therapy (eg, higher rates of mastectomy, axillary dissection and chemotherapy use) than patients with early-stage disease. The estimated 2-year overall survival (OS) was 95.3%. Survival was significantly longer among patients with stage I or II disease (2-year OS, 97.9% and 97.5%, respectively) than those with stage III or IV disease (89.4% and 69.5%, respectively; P < .01). Tumor grade was also correlated with OS in the overall cohort ( P = .05); triple-negative status was only prognostic for patients with stage III disease ( P < .01). Conclusion The data provided aid understanding of the current scenario of breast cancer presentation and treatment in the Brazilian private health care system and may serve as a foundation to guide resource allocation. Our results reinforce the need to pursue adequate access to cancer care in low- and middle-income countries to optimize patient outcome.

Introduction: The mutational profile of non–small-cell lung cancer (NSCLC) has become an important tool in tailoring therapy to patients, with clear differences according to the population of origin. African Americans (AAs) have higher lung cancer incidence and mortality than Caucasians, yet discrepant results have been reported regarding the frequency of somatic driver mutations. We hypothesized that NSCLC has a distinct mutational profile in this group. Methods: We collected NSCLC samples resected from self-reported AAs in five sites from Tennessee, Michigan, and Ohio. Gene mutations were assessed by either SNaPshot or next generation sequencing, and ALK translocations were evaluated by fluorescence in situ hybridization. Results: Two hundred sixty patients were included, mostly males (62.3%) and smokers (86.6%). Eighty-one samples (31.2%) were squamous cell carcinomas. The most frequently mutated genes were KRAS (15.4%), epidermal growth factor receptor ( EGFR, 5.0%), PIK3CA (0.8%), BRAF, NRAS, ERBB2, and AKT1 (0.4% each). ALK translocations were detected in two nonsquamous tumors (1.7%), totaling 61 cases (23.5%) with driver oncogenic alterations. Among 179 nonsquamous samples, 54 (30.2%) presented a driver alteration. The frequency of driver alterations altogether was lower than that reported in Caucasians, whereas no difference was detected in either EGFR or KRAS mutations. Overall survival was longer among patients with EGFR mutations. Conclusions: We demonstrated that NSCLC from AAs has a different pattern of somatic driver mutations than from Caucasians. The majority of driver alterations in this group are yet to be described, which will require more comprehensive panels and assessment of noncanonical alterations.

Purpose Technologic advances have enabled the comprehensive analysis of genetic perturbations in non–small-cell lung cancer (NSCLC); however, African Americans have often been underrepresented in these studies. This ethnic group has higher lung cancer incidence and mortality rates, and some studies have suggested a lower incidence of epidermal growth factor receptor mutations. Herein, we report the most in-depth molecular profile of NSCLC in African Americans to date. Methods A custom panel was designed to cover the coding regions of 81 NSCLC-related genes and 40 ancestry-informative markers. Clinical samples were sequenced on a massively parallel sequencing instrument, and anaplastic lymphoma kinase translocation was evaluated by fluorescent in situ hybridization. Results The study cohort included 99 patients (61% males, 94% smokers) comprising 31 squamous and 68 nonsquamous cell carcinomas. We detected 227 nonsilent variants in the coding sequence, including 24 samples with nonoverlapping, classic driver alterations. The frequency of driver mutations was not significantly different from that of whites, and no association was found between genetic ancestry and the presence of somatic mutations. Copy number alteration analysis disclosed distinguishable amplifications in the 3q chromosome arm in squamous cell carcinomas and pointed toward a handful of targetable alterations. We also found frequent SMARCA4 mutations and protein loss, mostly in driver-negative tumors. Conclusion Our data suggest that African American ancestry may not be significantly different from European/white background for the presence of somatic driver mutations in NSCLC. Furthermore, we demonstrated that using a comprehensive genotyping approach could identify numerous targetable alterations, with potential impact on therapeutic decisions.

Purpose To compare single-agent pemetrexed (P) versus the combination of carboplatin and pemetrexed (CP) in first-line therapy for patients with advanced non–small-cell lung cancer (NSCLC) with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2. Patients and Methods In a multicenter phase III randomized trial, patients with advanced NSCLC, ECOG PS of 2, any histology at first and later amended to nonsquamous only, no prior chemotherapy, and adequate organ function were randomly assigned to P alone (500 mg/m2) or CP (area under the curve of 5 and 500 mg/m2, respectively) administered every 3 weeks for a total of four cycles. The primary end point was overall survival (OS). Results A total of 205 eligible patients were enrolled from eight centers in Brazil and one in the United States from April 2008 to July 2011. The response rates were 10.3% for P and 23.8% for CP (P = .032). In the intent-to-treat population, the median PFS was 2.8 months for P and 5.8 months for CP (hazard ratio [HR], 0.46; 95% CI, 0.35 to 0.63; P < .001), and the median OS was 5.3 months for P and 9.3 months for CP (HR, 0.62; 95% CI, 0.46 to 0.83; P = .001). One-year survival rates were 21.9% and 40.1%, respectively. Similar results were seen when patients with squamous disease were excluded from the analysis. Anemia (grade 3, 3.9%; grade 4, 11.7%) and neutropenia (grade 3, 1%; grade 4, 6.8%) were more frequent with CP. There were four treatment-related deaths in the CP arm. Conclusion Combination chemotherapy with CP significantly improves survival in patients with advanced NSCLC and ECOG PS of 2.

Some proteins, canonically not associated with amyloid diseases, can aggregate into amyloid-like fibrils under special conditions. Our group hypothesized that stressful cancer microenvironment might induce the formation of insoluble deposits of p53 mutant protein. A cohort of 28 non-small cell lung cancer (NSCLC) patients was used to test the aforementioned hypothesis. Tumor specimens were assessed for TP53 mutations using DNA sequencing and for amyloid formation by Congo red staining. TP53 mutations were present in 57% of patients, whereas no amyloid deposits were detected in tissue sections under polarized light microscopy. Mutant p53 proteins are not associated with the appearance of amyloid-like fibrils in NSCLC samples, and DNA sequencing remains the standard method to detect such abnormality.

e21140Background: Immune checkpoint inhibitors improved outcomes of patients with advanced non-small cell lung cancer (NSCLC). KEYNOTE-024 trial demonstrated that immunotherapy was superior to plat...

Introdução: O câncer de mama é a neoplasia mais incidente no sexo feminino com 48.930 novos casos estimados em 2006, no Brasil. Os principais sítios de metástases são: ossos, pele, linfonodos, pulmões, pleura, fígado e cérebro. Metástases gástricas são raras e pouco citadas na literatura, sendo o câncer de mama o segundo principal responsável. À endoscopia digestiva alta, apresentam-se mais comumente sob a forma de infiltração intramural difusa, assemelhando-se à linite plástica, e predominam em tumores do tipo lobular. A comparação histológica dos espécimes é obrigatória, porém a imunoistoquímica também pode ser útil. O prognóstico é ruim, visto que a doença metastática raramente se restringe ao estômago. O tratamento é paliativo e inclui quimioterapia, terapia hormonal e radioterapia. Relato de caso: Paciente com câncer de mama em tratamento adjuvante com anastrozol apresentou-se ao serviço com queixa de plenitude gástrica e emagrecimento. Havia massa endurecida em epigástrio, dolorosa à palpação profunda. Ao exame endoscópico, observou-se lesão infiltrante, comprometendo o fundo e metade proximal do corpo gástrico. Foi verificado carcinoma ductal com áreas secretoras de muco e células em "anel de sinete" metastático para o estômago; CK7 positivo, CK20 e receptor hormonal negativos. Sem evidência de doença em outros focos, a paciente foi tratada com seis ciclos de docetaxel, obtendo-se resposta patológica gástrica completa. Discussão: Apesar de rara, a metástase gástrica é causa de considerável morbidade em pacientes com câncer de mama e pode responder ao tratamento sistêmico apropriado.

Background: Although clinical studies have shown promise for targeting PD1/PDL1 signaling in non–small cell lung cancer (NSCLC), the regulation of PDL1 expression is poorly understood. Here, we show that PDL1 is regulated by p53 via miR-34. Methods: p53 wild-type and p53-deficient cell lines (p53–/– and p53+/+ HCT116, p53-inducible H1299, and p53-knockdown H460) were used to determine if p53 regulates PDL1 via miR-34. PDL1 and miR-34a expression were analyzed in samples from patients with NSCLC and mutated p53 vs wild-type p53 tumors from The Cancer Genome Atlas for Lung Adenocarcinoma (TCGA LUAD). We confirmed that PDL1 is a direct target of miR-34 with western blotting and luciferase assays and used a p53R172HΔg/+K-rasLA1/+ syngeneic mouse model (n = 12) to deliver miR-34a–loaded liposomes (MRX34) plus radiotherapy (XRT) and assessed PDL1 expression and tumor-infiltrating lymphocytes (TILs). A two-sided t test was applied to compare the mean between different treatments. Results: We found that p53 regulates PDL1 via miR-34, which directly binds to the PDL1 3’ untranslated region in models of NSCLC (fold-change luciferase activity to control group, mean for miR-34a = 0.50, SD = 0.2, P < .001; mean for miR-34b = 0.52, SD = 0.2, P = .006; and mean for miR-34c = 0.59, SD = 0.14, and P = .006). Therapeutic delivery of MRX34, currently the subject of a phase I clinical trial, promoted TILs (mean of CD8 expression percentage of control group = 22.5%, SD = 1.9%; mean of CD8 expression percentage of MRX34 = 30.1%, SD = 3.7%, P = .016, n = 4) and reduced CD8+PD1+ cells in vivo (mean of CD8/PD1 expression percentage of control group = 40.2%, SD = 6.2%; mean of CD8/PD1 expression percentage of MRX34 = 20.3%, SD = 5.1%, P = .001, n = 4). Further, MRX34 plus XRT increased CD8+ cell numbers more than either therapy alone (mean of CD8 expression percentage of MRX34 plus XRT to control group = 44.2%, SD = 8.7%, P = .004, n = 4). Finally, miR-34a delivery reduced the numbers of radiation-induced macrophages (mean of F4-80 expression percentage of control group = 52.4%, SD = 1.7%; mean of F4-80 expression percentage of MRX34 = 40.1%, SD = 3.5%, P = .008, n = 4) and T-regulatory cells. Conclusions: We identified a novel mechanism by which tumor immune evasion is regulated by p53/miR-34/PDL1 axis. Our results suggest that delivery of miRNAs with standard therapies, such as XRT, may represent a novel therapeutic approach for lung cancer.