The Clinical and Molecular Profile of Lung Cancer Patients Harboring the R337H Germline Variant in a Brazilian Cancer Center: The Possible Mechanism of Carcinogenesis.

In southern and southeastern Brazil, the founder variant c.1010G>A (R337H) has been previously documented with a prevalence of 0.3% within the general population and linked to a heightened incidence of lung adenocarcinomas (LUADs).

Real-world treatment outcomes in HR+ HER2- metastatic breast cancer patients treated with CDK4/6 inhibitors: Results from a reference center in Brazil.

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have been recently developed and introduced into clinical practice.

Methods: We retrospectively analyzed data from patients with confirmed HR+/HER2 metastatic breast cancer treated with hormonal therapy in combination with ribociclib (R), palbociclib (P), or abemaciclib (A).

Outcomes: median progression-free survival (mPFS), time to treatment discontinuation (mTTD), and objective response rate (ORR).

Cost-effectiveness analysis of Oncotype DX from a Brazilian private medicine perspective: a GBECAM multicenter retrospective study.

Background: Oncotype DX (ODX) is a validated assay for the prediction of risk of recurrence and benefit of chemotherapy (CT) in both node negative (N0) and 1-3 positive nodes (N1), hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer (eBC). Due to limited access to genomic assays in Brazil, treatment decisions remain largely driven by traditional clinicopathologic risk factors. ODX has been reported to be cost-effective in different health system, but limited data are available considering the reality of middle-income countries such as Brazil.

Genomic and biological study of fusion genes as resistance mechanisms to EGFR inhibitors.

The clinical significance of gene fusions detected by DNA-based next generation sequencing remains unclear as resistance mechanisms to EGFR tyrosine kinase inhibitors in EGFR mutant non-small cell lung cancer. By studying EGFR inhibitor-resistant patients treated with a combination of an EGFR inhibitor and a drug targeting the putative resistance-causing fusion oncogene, we identify patients who benefit and those who do not from this treatment approach. Through evaluation including RNA-seq of potential drug resistance-imparting fusion oncogenes in 504 patients with EGFR mutant lung cancer, we identify only a minority of them as functional, potentially capable of imparting EGFR inhibitor resistance.

Unique fusion is associated with marked response to crizotinib in lung adenocarcinoma.

Chromosomal rearrangements involving the c-ros oncogene 1 () gene define a subset of non-small cell lung cancers highly sensitive to small-molecule tyrosine kinase inhibitors. However, little is known about the impact of different fusion partners on tyrosine kinase inhibitor efficacy. We herein describe a case of a 26-year-old never-smoker patient from southern Africa with metastatic lung adenocarcinoma driven by - fusion, who had a pronounced and durable response to crizotinib.

Cardiovascular toxicity following immune checkpoint inhibitors: A systematic review and meta-analysis.

Background: Immune checkpoint inhibitors may be associated with multiple immune-related toxicities. Cardiovascular adverse effects are underreported in clinical trials.

Methods: We conducted a systematic review and meta-analysis to evaluate cardiovascular adverse effects incidence among patients with solid tumors receiving immune checkpoint inhibitors in randomized clinical trials and the relative risk of presenting these effects compared to placebo or best supportive care.

Identification of the p.R337H Variant in Tumor Genomic Profiling Should Prompt Consideration of Germline Testing for Li-Fraumeni Syndrome.

Purpose: Li-Fraumeni syndrome (LFS) is rare in the worldwide population, but it is highly prevalent in the Brazilian population because of a founder mutation, p.R337H, accounting for 0.3% of south and southeastern population.

Impressive response to dabrafenib, trametinib, and osimertinib in a metastatic EGFR-mutant/BRAF V600E lung adenocarcinoma patient.

The survival outcomes of the FLAURA trial support osimertinib as the new standard of care for untreated patients harboring activating mutations in the epidermal growth factor receptor (EGFR). Despite the initial response, disease progression invariably occurs. Although uncommon, BRAF V600E mutation arises as a unique mechanism of resistance, and thus far, no prospective studies are available to support concurrent EGFR/BRAF blockade.

SARS-CoV-2 testing for asymptomatic adult cancer patients before initiating systemic treatments: a systematic review.

Introduction: Cancer patients may have a higher risk of severe events and unfavourable outcomes in the setting of COVID-19. This review addresses the question of whether to test asymptomatic cancer patients before initiating systemic cancer treatments.

Methods: This systematic review was conducted based on the PRISMA framework.

COVID-19 in a patient with advanced Merkel cell carcinoma receiving immunotherapy.

Little is known about the 2019 novel coronavirus disease (COVID-19) course and outcomes in patients receiving immunotherapy. Here we describe a metastatic Merkel cell carcinoma patient with a severe acute respiratory syndrome coronavirus 2 infection while receiving pembrolizumab. A 66-year-old man, with a metastatic Merkel cell carcinoma receiving pembrolizumab, presented with fever.

Alectinib activity in chemotherapy-refractory metastatic RET-rearranged non-small cell lung carcinomas: A case series.

Objectives: to report outcomes of four cases of chemo-refractory RET-rearranged non-small cell lung carcinomas (NSCLCs) treated with alectinib in a single center.

Materials And Methods: we retrospectively assessed and reported the activity and tolerability of alectinib 600 mg twice daily in advanced and chemo-refractory RET-rearranged NSCLC patients treated in a Brazilian institution. Identification of RET rearrangements was performed using the FoundationOne® next-generation sequencing (NGS) platform.

Bevacizumab-associated osteonecrosis of the femur and tibia.

Osteonecrosis is a multifactorial process that can affect different skeletal structures of the body. Osteonecrosis of the jaw associated with bevacizumab, steroids and bisphosphonates, alone or in combination, is a well-documented phenomenon. There are few cases of involvement of the appendicular skeleton.

The role of histone deacetylase inhibitors in metastatic breast cancer.

Histone deacetylase inhibitors (HDACi) are a relatively new class of drug that plays an important role in the epigenetic and non-epigenetic regulation in cancer, inducing death, apoptosis and cell cycle arrest in cancer cells. Although HDACi are approved only for hematologic malignancies, there are several trials in the breast cancer setting with promising results. In this review, we summarize the latest studies with HDACi in breast cancer from the emerging data in the translational research until its possible applicability in the clinical practice.

Lung cancer in Brazil.

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.

Next-generation Sequencing-based genomic profiling: Fostering innovation in cancer care?

Objectives: With the development of next-generation sequencing (NGS) technologies, DNA sequencing has been increasingly utilized in clinical practice. Our goal was to investigate the impact of genomic evaluation on treatment decisions for heavily pretreated patients with metastatic cancer.

Methods: We analyzed metastatic cancer patients from a single institution whose cancers had progressed after all available standard-of-care therapies and whose tumors underwent next-generation sequencing analysis.

Radiotherapy for a breast cancer patient with Schnitzler syndrome: Report of acute toxicity and early follow-up.

This article provides description about acute toxicity and early follow-up of one patient treated for breast cancer and Schnitzler syndrome. There are no previously reported cases exploring this interaction on medical literature. The expected radiodermitis to occur in the region treated with radiotherapy along with urticarial-like lesions might be challenging in view of the interaction between symptoms and therapeutic measures.

Acquired Pulmonary Arteriovenous Fistula within Metastasis from Choriocarcinoma: A Case Report.

Choriocarcinoma is a highly malignant neoplasm arising from the trophoblast of a human pregnancy, which may have distant spread to multiple organs, particularly to the lung. We report a case of a pulmonary arteriovenous fistula that developed after chemotherapy within a choriocarcinoma metastasis. A 24-year-old female with a history of uterine choriocarcinoma presented with multiple hypervascular pulmonary nodules on the initial chest computed tomography (CT) scan, consistent with lung metastases.

Sequential liquid biopsies reveal dynamic alterations of EGFR driver mutations and indicate EGFR amplification as a new mechanism of resistance to osimertinib in NSCLC.

Osimertinib is an EGFR-T790M-specific TKI, which has demonstrated impressive response rates in NSCLC, after failure to first-line anti-EGFR TKIs. However, acquired resistance to osimertinib is also observed and the molecular mechanisms of resistance are not yet fully understood. Monitoring and managing NSCLC patients who progressed on osimertinib is, therefore, emerging as an important clinical challenge.

Selecting postoperative adjuvant systemic therapy for early stage breast cancer: A critical assessment of commercially available gene expression assays.

Risk stratification of patients with early stage breast cancer may support adjuvant chemotherapy decision-making. This review details the development and validation of six multi-gene classifiers, each of which claims to provide useful prognostic and possibly predictive information for early stage breast cancer patients. A careful assessment is presented of each test's analytical validity, clinical validity, and clinical utility, as well as the quality of evidence supporting its use.

Bevacizumab as first-line therapy in advanced non-small-cell lung cancer: a brazilian center experience.

Objectives: Bevacizumab has been approved by the US Food and Drug Administration as a first-line therapy for metastatic non-small-cell lung cancer (NSCLC), in combination with carboplatin and paclitaxel. A single Latin American center experience was reviewed to determine the safety and efficacy of adding bevacizumab to first-line chemotherapy in a local population.

Methods: We retrospectively identified patients with non-squamous NSCLC treated with bevacizumab plus chemotherapy combinations as first-line chemotherapy between July 1, 2006, and January 30, 2011, at Sirio Libanes Hospital in Sao Paulo, Brazil.

Assessment of quality of life in advanced non-small-cell lung cancer: an overview of recent randomized trials.

Background: Health-related quality of life (HRQOL) parameters are often used as secondary endpoints in advanced non-small-cell lung cancer (NSCLC). We assessed the frequency and correlates of both usage and gain in HRQOL endpoints in NSCLC phase III trials.

Methods: We searched PubMed for phase III trials on systemic anticancer therapies for NSCLC published between 1/98 and 12/09 in 13 leading journals.

Assessment of quality of life in advanced breast cancer. An overview of randomized phase III trials.

Background: Health-related quality of life (HRQOL) parameters are often used as end points in phase III trials in advanced breast cancer. The frequency and correlates of significant gains in HRQOL have not been assessed.

Methods: To evaluate the contemporary role for HRQOL assessment in advanced breast cancer, we searched PubMed for the main and companion papers reporting the results of phase III trials on systemic antineoplastic therapies published between 1/98 and 7/09 in 11 leading journals.

Management of anemia in cancer patients.

Cancer-related anemia adversely affects quality of life and is associated with reduced overall survival. The correction of anemia in cancer patients has the potential to improve treatment efficacy and increase survival. A large number of studies demonstrate that treatment of anemia in cancer patients using erythropoiesis-stimulating agents (ESAs) significantly increases hemoglobin levels, decreases transfusion requirements and improves quality of life, predominantly by reducing fatigue.