J Cancer Res Clin Oncol
April 2024
Purpose: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil.
View Article and Find Full Text PDFIntroduction: Bladder microbiota dysbiosis has been associated with several urological disorders. However, dysbiosis markers in bladder cancer have not been identified and little is known about the effect of Bacillus Calmette-Guérin (BCG) intravesical therapy on the bladder microbiota. In this study, we compared the bladder microbiota of patients with non-muscle-invasive bladder cancer (NMIBC) undergoing BCG therapy to nononcological controls.
View Article and Find Full Text PDFInt J Mol Sci
October 2023
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).
View Article and Find Full Text PDFBackground: Patients with advanced hepatocellular carcinoma (HCC) and poor liver function lack effective systemic therapies. Low-energy electromagnetic fields (EMFs) can influence cell biological processes via non-thermal effects and may represent a new treatment option.
Methods: This single-site feasibility trial enrolled patients with advanced HCC, Child-Pugh A and B, Eastern Cooperative Oncology Group 0-2.
PD-L1 (CD274) amplification occurs in a small subset of malignancies and may predict anti-PD-1/PD-L1 immunotherapy responsiveness. We hypothesized that both copy number (CN) and focality of cancer-related PD-L1 amplifications impact protein expression, and, thus, analyzed solid tumors that underwent comprehensive genomic profiling between March 2016 and February 2022 at Foundation Medicine. PD-L1 CN alterations were detected using a comparative genomic hybridization-like method.
View Article and Find Full Text PDFJCO Precis Oncol
January 2023
Introduction: Germ-cell tumors (GCTs) are the most common malignancy in young men. There is a paucity of data on GCTs in developing countries. LACOG 0515 study aimed to evaluate clinical characteristics and treatment outcomes in patients with GCTs from Brazilian cancer centers.
View Article and Find Full Text PDFCancers (Basel)
November 2022
Purpose: Solid tumors harboring tumor mutational burden (TMB) ≥10 mutations per megabase (mut/Mb) received agnostic approval for pembrolizumab. This work aims to analyze the somatic mutational profile’s influence on the outcomes of patients with TMB-high tumors treated with immune checkpoint inhibitors (ICIs). Methods: This post-hoc analysis evaluated clinical and molecular features of patients with solid tumors treated with ICIs that could be either monoclonal antibody directed against programmed cell death protein-1 or monoclonal antibody directed against programmed cell death ligand 1 (anti-PD-1/anti-PD-L1), monoclonal antibody directed against cytotoxic T lymphocyte-associated antigen (anti-CTLA-4) or a combined treatment regimen including one anti-PD-1/anti-PD-L1 and one anti-CTLA-4 (ICIs combination).
View Article and Find Full Text PDFIntroduction: Non-metastatic, castration-resistant prostate cancer (nmCRPC) is an important clinical stage of prostate cancer, prior to morbidity and mortality from clinical metastases. In particular, the introduction of novel androgen-receptor signaling inhibitors (ARSi) has changed the therapeutic landscape in nmCRPC. Given recent developments in this field, we update our recommendations for the management of nmCRPC.
View Article and Find Full Text PDFBackground: 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.
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.
J Med Econ
March 2021
Background: Considering clinical benefits of new combination therapies for metastatic renal-cell carcinoma (mRCC), this study aims to calculate the number needed to treat (NTT) and the cost of preventing an event (COPE) for pembrolizumab plus axitinib (P + A), and nivolumab plus ipilimumab (N + I) as first-line treatments, from the Brazilian private perspective.
Methods: Overall survival (OS) and progression-free survival (PFS) data for intermediate- and poor-risk groups were obtained from KEYNOTE-426 and CHECKMATE-214 trials for P + A and N + I, respectively, versus sunitinib as mRCC first-line treatment.
Results: Considering a 12-month time horizon, 6 patients should be treated with P + A to prevent one death with sunitinib use, resulting in a COPE of 3,773,865 BRL.
The cyclin pathway may confer resistance to standard treatments but also offer novel therapeutic opportunities in prostate cancer. Herein, we analyzed prostate cancer samples (majority metastatic) using comprehensive genomic profiling performed by next-generation sequencing (315 genes, >500× coverage) for alterations in activating and sensitizing cyclin genes (CDK4 amplification, CDK6 amplification, CCND1, CCND2, CCND3, CDKN2B [loss], CDKN2A [loss], SMARCB1), androgen receptor (AR) gene, and coalterations in genes leading to cyclin inhibitor therapeutic resistance (RB1 and CCNE1). Overall, cyclin sensitizing pathway genomic abnormalities were found in 9.
View Article and Find Full Text PDFTumor mutational burden (TMB) reflects cancer mutation quantity. Mutations are processed to neo-antigens and presented by major histocompatibility complex (MHC) proteins to T cells. To evade immune eradication, cancers exploit checkpoints that dampen T cell reactivity.
View Article and Find Full Text PDFIntroduction: 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.
Background: We describe the landscape of cyclin and interactive gene pathway alterations in 190,247 solid tumors.
Methods: Using comprehensive genomic profiling (315 genes, >500× coverage), samples were analyzed for alterations in activating/sensitizing cyclin genes (CDK4 amplification, CDK6 amplification, CCND1, CCND2, CCND3, CDKN2B [loss], CDKN2A [loss], SMARCB1), hormone genes (estrogen receptor 1 [ESR1], androgen receptor [AR]), and co-alterations in genes leading to cyclin inhibitor therapeutic resistance (RB1 and CCNE1).
Results: Alterations in at least one cyclin activating/sensitizing gene occurred in 24% of malignancies.
J Cancer Res Clin Oncol
July 2020
Purpose: The outcome of RCC has improved considerably in the last few years, and the treatment options have increased. LACOG-GU and LARCG held a consensus meeting to develop guidelines to support the clinical decisions of physicians and other health professionals involved in the care of RCC patients.
Methods: Eighty questions addressing relevant advanced RCC treatments were previously formulated by a panel of experts.
Hundreds of trials are being conducted to evaluate combination of newer targeted drugs as well as immunotherapy. Our aim was to compare efficacy and safety of combination versus single non-cytotoxic anticancer agents. We searched PubMed (01/01/2001 to 03/06/2018) (and, for immunotherapy, ASCO and ESMO abstracts (2016 through March 2018)) for randomized clinical trials that compared a single non-cytotoxic agent (targeted, hormonal, or immunotherapy) versus a combination with another non-cytotoxic partner.
View Article and Find Full Text PDFIntroduction: Recently, new oncology therapies were developed using a biomarker for patient selection. In the era of cancer genomics, this paradigm is expected to increase. Most cytotoxic chemotherapies and other oncological treatments were historically approved without a biomarker.
View Article and Find Full Text PDFTher Adv Urol
September 2019
Background: Renal cell cancer (RCC) is one of the 10 most common cancers in the world, and its incidence is increasing, whereas mortality is declining only in developed countries. Therefore, two collaborative groups, The Latin American Oncology Cooperative Group-Genitourinary Section (LACOG-GU) and the Latin American Renal Cancer Group (LARCG), held a consensus meeting to develop this guideline.
Methods: Issues (134) related to the treatment of RCC were previously formulated by a panel of experts.
Anti-EGFR antibodies are a standard care for advanced -wild type colorectal cancers. Circulating tumor DNA (ctDNA) monitoring during therapy can detect emergence of mutant clones and early resistance to therapy. We describe a 61-years-old man presenting a metastatic and recurrent rectal cancer treated with different chemotherapy regimens.
View Article and Find Full Text PDFBackground: The phosphatidylinositol 3-kinase (PI3K) pathway is frequently altered in cancer. This report describes the landscape of PI3K alterations in solid tumors as well as co-alterations serving as potential resistance/attenuation mechanisms.
Methods: Consecutive samples were analyzed in a commercial Clinical Laboratory Improvement Amendment-certified laboratory using comprehensive genomic profiling performed by next-generation sequencing (315 genes).
Integr Cancer Ther
December 2018
Immunotherapies are becoming increasingly important in the treatment armamentarium of a variety of malignancies. Immune checkpoint inhibitors are the most representative drugs receiving regulatory approval over the past few years. In a recent study published in Clinical Cancer Research, we demonstrated that these agents are being developed faster than other prior anticancer therapies.
View Article and Find Full Text PDFImmune checkpoint inhibitors have unique toxicities and response kinetics compared with cytotoxic and gene-targeted anticancer agents. We investigated the impact of innovative/accelerated immunotherapy drug development/approval models on the accuracy of safety and efficacy assessments by searching the FDA website. Initial phase I trials for each agent were reviewed and safety and efficacy data compared with that found in later trials leading to regulatory approvals of the same agents.
View Article and Find Full Text PDFBackground Both MET and c-SRC are important mediators of cancer progression and there is cross talk between the two molecules. Preclinical studies have demonstrated combination of MET and c-SRC inhibitors is effective in multiple cancer types. Methods We analyzed the safety and efficacy of administering a c-SRC inhibitor (dasatinib) in combination with a MET inhibitor (crizotinib) in a two-arm concurrent phase I study.
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