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In this article, we discuss the strategy designed by a private oncology group to offer patients access to new technologies and treatments via a recently created research program, and we describe how the patient journey was the motivation for developing standard assistance flows and processes to integrate areas of care. The increase in Brazilians’ life expectancy has raised the incidence of cancer, and it is now the second leading cause of death. Because it is a multifactorial disease, cancer treatment has several challenges. We elected to approach cancer research using a strategic program to obtain national attention and visibility. Starting in 2007, the initial project included three phases: phase I, diagnosis of units in major metropolitan areas; phase II, project design, with a central-office operation model; and phase III, implementation, with launch and integration of research activities at selected units. The foundation of the program was the construction of departmental and interdepartmental flows, standard operating processes, and guidelines (regulatory, ethical, legal, and financial). Recruitment of qualified professionals was another critical, successful determinant. The benefits of an additional central office include improved research-project distribution. Another advantage of the program is attracting and retaining trained professionals with alternative direct or indirect sources of revenue. We increased our corporate and academic partnerships, adhered to deadlines and noted an improvement in turnaround times, and we increased clinical staff engagement and motivation. Some barriers continue to challenge the program's continued expansion, including Brazilian regulatory authority approval, tax inefficiency, and a growing demand for qualified professionals. Research sites offering high-quality care are a reality in Brazil; they offer multiple lines of treatment in the public and private sectors.

PURPOSE COVID-19 has affected cancer care worldwide. Clinical trials are an important alternative for the treatment of oncologic patients, especially in Latin America, where trials can be the only opportunity for some of them to access novel and, sometimes, standard treatments. METHODS This was a cross-sectional study, in which a 22-question survey regarding the impact of the COVID-19 pandemic on oncology clinical trials was sent to 350 representatives of research programs in selected Latin American institutions, members of the Latin American Cooperative Oncology Group. RESULTS There were 90 research centers participating in the survey, with 70 of them from Brazil. The majority were partly private or fully private (n = 77; 85.6%) and had confirmed COVID-19 cases at the institution (n = 57; 63.3%). Accruals were suspended at least for some studies in 80% (n = 72) of the responses, mostly because of sponsors' decision. Clinical trials' routine was affected by medical visits cancelation, reduction of patients' attendance, reduction of other specialties' availability, and/or alterations on follow-up processes. Formal COVID-19 mitigation policies were adopted in 96.7% of the centers, including remote monitoring and remote site initiation visits, telemedicine visits, reduction of research team workdays or home office, special consent procedures, shipment of oral drugs directly to patients' home, and increase in outpatient diagnostic studies. Importantly, some of these changes were suggested to be part of future oncology clinical trials' routine, particularly the ones regarding remote methods, such as telemedicine. CONCLUSION To our knowledge, this was the first survey to evaluate the impact of COVID-19 on Latin American oncology clinical trials. The results are consistent with surveys from other world regions. These findings may endorse improvements in clinical trials' processes and management in the postpandemic period.

Background The aim of this study was to carry out a descriptive analysis of the somatic genetic profile and co‐occurring mutations of non‐small cell lung cancer (NSCLC) samples from patients tested with comprehensive genomic profiling (CGP). Methods This was a retrospective cross‐sectional study of patients diagnosed with NSCLC from 2013 to 2018 in Brazil and whose samples were submitted to CGP (FoundationOne or FoundationACT) using either tumor or circulating tumor DNA (ctDNA) from plasma. Results We recovered 513 CGP results from patients, 457 (89.1%) of which were from tumors and 56 (10.9%) from plasma. The median age of patients was 64 years old, of which 51.6% were males. TP53 mutations were identified in 53.6% of tumor samples, KRAS mutations in 24.2%, EGFR activating mutations were detected in 22.5%, STK11 mutations in 11.6%, PIK3CA mutations in 8.8%, ALK rearrangements in 5.4%, BRAF mutations in 5.2%, and ERBB2 alterations in 4.9%. The most commonly comutated gene was TP53. TP53 p.R337H was observed in 4.3% of samples and was associated with somatic mutations in EGFR and ERBB2 (P, This is the first report of the prevalence of driver mutations in Brazilian NSCLC patients using comprehensive genomic profiling.

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.

About 4% to 7% of the non–small-cell lung cancer patients have anaplastic lymphoma kinase (ALK) rearrangements, and specific targeted therapies improve patients' outcomes significantly. ALK gene fusions are detected by immunohistochemistry or fluorescent in situ hybridization as gold standards in South America. Next-generation sequencing–based assays are a reliable alternative, able to perform simultaneous detection of multiple events from a single sample. We analyzed 4240 non–small-cell lung cancer samples collected in 37 hospitals from Chile, Brazil, and Peru, where ALK rearrangements were determined as part of their standard of care (SofC) using either immunohistochemistry or fluorescent in situ hybridization. A subset of 1450 samples was sequenced with the Oncomine Focus Assay (OFA), and the concordance with the SofC tests was measured. An orthogonal analysis was performed using a real-time quantitative PCR echinoderm microtubule-associated protein-like 4-ALK fusion detection kit. ALK fusion prevalence is similar for Chile (3.67%; N = 2142), Brazil (4.05%; N = 1013), and Peru (4.59%; N = 675). Although a comparison between OFA and SofC assays showed similar sensitivity, OFA had significantly higher specificity and higher positive predictive value, which opens new opportunities for a more specific determination of ALK gene rearrangements.

12108 Background: CIA has been reported as the most disturbing adverse event of cancer treatment by most women receiving chemotherapy. Many strategies have been tested to minimize CIA, among which scalp cooling has proven high effectiveness. However, discontinuation rates of this technology vary from 3% to 13%, mostly due to headache, cold sensation and pain. EHW could be used to mitigate these side effects, produce heat on demand and a warming sensation. The primary objective of this study is to evaluated the impact of EHW device on the general comfort of breast cancer patients while on scalp cooling during chemotherapy treatment. Methods: Patients were randomly assigned to EHW use or observation. Thermal, sensory and general comfort were measured with pragmatic questionnaires after each chemotherapy infusion: neutral or hot as favorable thermal responses; comfortable and very comfortable as favorable sensory responses; finally, favorable outcomes in both thermal and sensory comfort questionnaires defined a positive result on the general comfort. We evaluated the impact of age (≤ or > 50 years), alopecia (grade 0 or 1/2), chemotherapy regimen (with or without taxanes) and EHW use (yes or no) in the different comfort scales using Logistic Regression (LR) models. Results: Forty women with early or locally advanced breast cancer were assigned to EHW (n = 20) or observation (n = 20) during neo(adjuvant) chemotherapy. Median age was 53 years, 67.5% concluded university education, 52.5% had comorbidities. Most patients had stage II disease (55%), largely ER/PR+ HER2- disease (67.5%), followed by triple negative (22.5%), and HER2+ (10%). Most frequent regimen was ACdd-Tdd (42.5%). Thirty-one patients (77.5%) continued scalp cooling during entire chemotherapy regimen (alopecia < grade 3). A favorable thermal response was seen in 79% of EHW applications as compared to 50% in control arm (odds ratio [OR] 3.79, P

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

Lung cancer is one of the most incident types of cancer and a leading cause of cancer mortality in Brazil. We reviewed the current status of lung cancer by searching relevant data on prevention, diagnosis, and treatment in the country. This review highlights several issues that need to be addressed, including smoking control, patient lack of awareness, late diagnosis, and disparities in the access to cancer health care facilities in Brazil. We propose strategies to help overcome these limitations and challenge health care providers, as well as the society and governmental representatives, to work together and to take a step forward in fighting lung cancer. RESUMO O câncer de pulmão é um dos tipos de câncer com maior incidência e uma das principais causas de mortalidade por câncer no Brasil. Revisamos a situação atual do câncer de pulmão por meio de pesquisa de dados relevantes a respeito de prevenção, diagnóstico e tratamento no país. Esta revisão mostra várias questões que precisam de atenção, tais como controle do tabagismo, educação dos pacientes, desconhecimento por parte dos pacientes, diagnóstico tardio e desigualdade de acesso ao tratamento de câncer no Brasil. Propomos estratégias para ajudar a superar essas limitações e desafiamos os profissionais de saúde, a sociedade e os representantes do governo a trabalhar em conjunto e dar um passo à frente na luta contra o câncer de pulmão.

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...

Purpose To compare the effectiveness and side effects of methadone and morphine as first-line treatment with opioids for cancer pain. Patients and Methods Patients in international palliative care clinics with pain requiring initiation of strong opioids were randomly assigned to receive methadone (7.5 mg orally every 12 hours and 5 mg every 4 hours as needed) or morphine (15 mg sustained release every 12 hours and 5 mg every 4 hours as needed). The study duration was 4 weeks. Results A total of 103 patients were randomly assigned to treatment (49 in the methadone group and 54 in the morphine group). The groups had similar baseline scores for pain, sedation, nausea, confusion, and constipation. Patients receiving methadone had more opioid-related drop-outs (11 of 49; 22%) than those receiving morphine (three of 54; 6%; P = .019). The opioid escalation index at days 14 and 28 was similar between the two groups. More than three fourths of patients in each group reported a 20% or more reduction in pain intensity by day 8. The proportion of patients with a 20% or more improvement in pain at 4 weeks in the methadone group was 0.49 (95% CI, 0.34 to 0.64) and was similar in the morphine group (0.56; 95% CI, 0.41 to 0.70). The rates of patient-reported global benefit were nearly identical to the pain response rates and did not differ between the treatment groups. Conclusion Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain.

Veno-occlusive disease (VOD) of the liver remains a major complication after hematopoietic stem cell transplantation (SCT). VOD is thought to develop after hepatic endothelial cells are damaged by high-dose chemotherapy or radiation, causing microthrombosis in hepatic venules. However, the precise mechanisms leading to VOD are not well defined, and a diagnosis is often difficult to establish. It is also difficult to predict which patients are most likely to develop VOD. Elevated levels of homocysteine (HC) have been associated with thrombosis, and prothrombin fragment 1 + 2 (F1 + 2) is a measurable marker for coagulation. Therefore, we performed a prospective cohort study to determine if HC or F1 + 2 levels could be used to predict the development of VOD prior to SCT, or to help establish a diagnosis of VOD in association with other clinical parameters. Plasma levels of these factors were measured before conditioning and serially for 21 days after SCT in 42 consecutive patients undergoing SCT. Eleven of 26 allogeneic SCT recipients developed VOD, whereas no autologous SCT recipient (n = 16) developed VOD (p = 0.008). In patients who developed VOD, HC levels were consistently higher than those seen in non-VOD patients after day 7 of SCT. Patients with VOD also had higher levels of F1 + 2 after SCT, although this marker was less consistently elevated over time. A logistic regression model that evaluated all serial measures of HC and F1 + 2 showed a moderate sensitivity and specificity in diagnosing VOD in allogeneic SCT patients, but neither marker was useful to predict development of VOD when tested prior to SCT.

Chemokines and their receptors are broadly expressed in different tissues and are involved in diverse biologic processes. Gene inactivation studies have shown that both stromal cell derived factor-1 (SDF-1) and chemokine receptor 4 (CXCR4) are essential for B lymphopoiesis. However, it is not yet clear by which mechanisms B lymphopoiesis is affected. In the present study, we have examined CXCR4 expression and function on primary B cells representing sequential stages of development (eg, pro-B, pre-B, immature, and mature B cells) in fetal and adult bone marrow. The expression of CXCR4 was observed to be sinusoidal. Expression was highest on pre-B cells, decreased as cells developed into immature B cells, and then increased again upon transition to the mature B-cell stage. The corresponding ligand SDF-1 was shown to trigger vigorous cell signaling and migration responses, which are restricted to early lineage B cells. The responsiveness to SDF-1 was markedly decreased for immature and mature B cells despite relatively high levels of CXCR4 expression. Thus, the diminished responsiveness to SDF-1 by more mature B cells was determined to be disproportionate to the level of CXCR4 expression. These findings raise the possibility that CXCR4 function is differentially controlled during B lymphopoiesis and may be relevant to the compartmentalization of B-cell precursors in the bone marrow.

Advances in our understanding of the molecular defects underlying this leukemia have led to novel therapeutic approaches that have not only altered the natural history of the disease but also apparently effected cures in some patients. The next step may be to offer the possibility of a cure to all patients. Allogeneic bone marrow and T cell transplantation shows promise in this regard.

Purpose Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. A randomized, double-blind, placebo-controlled phase IIB trial assessed sorafenib with capecitabine for locally advanced or metastatic human epidermal growth factor receptor 2 (HER2) –negative breast cancer. Patients and Methods Patients were randomly assigned to first- or second-line capecitabine 1,000 mg/m2 orally twice a day for days 1 to 14 of every 21-day cycle with sorafenib 400 mg orally twice a day or placebo. The primary end point was progression-free survival (PFS). Results In total, 229 patients were enrolled. The addition of sorafenib to capecitabine resulted in a significant improvement in PFS versus placebo (median, 6.4 v 4.1 months; hazard ratio [HR], 0.58; 95% CI, 0.41 to 0.81; P = .001) with sorafenib favored across subgroups, including first-line (HR, 0.50; 95% CI, 0.30 to 0.82) and second-line (HR, 0.65; 95% CI, 0.41 to 1.04) treatment. There was no significant improvement for overall survival (median, 22.2 v 20.9 months; HR, 0.86; 95% CI, 0.61 to 1.23; P = .42) and overall response (38% v 31%; P = .25). Toxicities (sorafenib v placebo) of any grade included rash (22% v 8%), diarrhea (58% v 30%), mucosal inflammation (33% v 21%), neutropenia (13% v 4%), hypertension (18% v 12%), and hand-foot skin reaction/hand- foot syndrome (HFSR/HFS; 90% v 66%); grade 3 to 4 toxicities were comparable between treatment arms except HFSR/HFS (44% v 14%). Reasons for discontinuation in the sorafenib and placebo arms included disease progression (63% v 82%, respectively), adverse events (20% v 9%, respectively), and death (0% v 1%, respectively). Conclusion Addition of sorafenib to capecitabine improved PFS in patients with HER2-negative advanced breast cancer. The dose of sorafenib used in this trial resulted in unacceptable toxicity for many patients. A phase III confirmatory trial has been initiated with a reduced sorafenib dose.

When interleukin-2 (IL-2) binds to the IL-2 receptor (IL2-R) on activated T cells, a soluble portion of the receptor (sIL2-R) is released. After allogeneic bone marrow transplantation (BMT), the serum concentration of sIL2-R may, therefore, be a useful surrogate marker for T cell activation that results in acute graft-versus-host disease (aGVHD). To determine if the sIL2-R concentration is a useful marker to help establish a diagnosis of aGVHD, serial sIL2-R concentrations were measured weekly for 4 weeks in 43 patients after allogeneic BMT. Grafts were from HLA-matched siblings (n = 33), 5/6 HLA-matched siblings (n = 3) or matched unrelated donors (n = 7). GVHD prophylaxis included cyclosporine A (CSA)/methotrexate (MTX) (n = 25), solumedrol/CSA (n = 15), or T cell depletion (n = 3). Twenty-three patients developed aGVHD (Grade I, 7; Grade II, 12; Grade III, 4) a median of 28 days after transplant. There was a significant association between a clinical diagnosis of aGVHD and an increase in the sIL2-R concentration (p < 0.001). The mean percent increase (+/-SE) over baseline for patients with a clinical diagnosis of aGVHD was 294% (+/-57%) by week 2 (n = 12), 431% (+/-116%) by week 3 (n = 14), and 650% (+/-315%) by week 4 (n = 9) after BMT. For each 100% increase over baseline, the likelihood of having aGVHD increased by 18%. Six of 20 patients without aGVHD became critically ill and exhibited marked increases in sIL2-R concentrations, similar to patients with a clinical diagnosis of aGVHD who never became critically ill. Fourteen patients without aGVHD who did not become critically ill exhibited negligible increases of sIL2-R in 2- to 4-week period after BMT. These data suggest that serial measurements sIL2-R concentration are helpful in establishing the diagnosis of aGVHD, but are not useful in the most acutely ill patients.