In the past few years, we have witnessed the consolidation of "immunotherapy" as an effective and viable way of treating cancer. Therapeutic intervention using monoclonal antibodies targeting molecules that modulate the immune response, or immune co-receptors, broadened the clinical benefit expectations for patients affected by melanoma, lung cancer and several other neoplasms. As an example, cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) blockers have been recently incorporated into clinical practice after approvalby the regulatory agencies in several countries, including Brazil, and new combination modalities for the engagement of the immune system are currently being studied. Nonetheless, immune activation, especially of T-lymphocytes, carries the risk of triggering responses towards healthy tissues, which are manifested as immune-mediated adverse events. In this context, learning the safety profile of these drugs and the stepwise management of adverse events is crucial. Over the next years, a rise in indications is expected, and consequently, consistent incorporation into the oncological practice and an increase in the number of treated patients are likely to occur. Therefore, the purpose of this guideline is to discuss the range of toxicities related to the use of immune co-receptor blockers and the strategies that allow their early diagnosis and proper management.
Keywords: Immunotherapy; CTLA-4 antigen; Programmed cell death 1 receptor; Antibodies, monoclonal
OBJECTIVE: In the USA there will be a shortage of medical oncologists by 2020. In Europe, a recent study showed that almost all analyzed countries will reach the estimated need. However, no data on this subject is available for Brazil, a developing country with a high cancer incidence. The aim of this study was to predict the Brazilian scenario for 2020. The number of practicing medical oncologists was obtained through Federal Council of Medicine in August 2014.
METHODS: Data on cancer incidence (excluding non-melanoma skin cancer) since 2008 were obtained from Brazilian National Cancer Institute (INCA).
RESULTS: Cancer incidence estimates for year 2020 were analyzed assuming a stable increase between 2014 and the subsequent years. Ratios of new cancer cases versus number of medical oncologists were calculated for 2014 and for 2020 per each Brazilian region. Based on the variation ratio per year, the Brazilian cancer incidence in 2020 is estimated to be 393,75/100,000 compared with 289,44/100,000 in 2014. The number of medical oncologists in Brazil will increase by 2020 in comparison to 2014, especially due to the growth of training vacancies. There will still be a heterogeneous distribution of medical oncologists through the different Brazilian regions and also a high number of patients per MO.
CONCLUSION: The more critic region to oncology care seems to be the Midwest. This survey shows the need of a monitoring and planning program in oncology assistance in all Brazilian regions.
Keywords: Neoplasms/epidemiology; Physicians; Medical hole; Brazil
BACKGROUND: DNA repair genes play a key role in maintaining genomic stability and integrity. DNA repair gene polymorphisms, such as X-ray repair cross-complementing group 1 and 3 genes (XRCC1 and XRCC3), are implicated to contribute to carcinogenesis.
OBJECTIVE: In this study, we investigated the correlation between cervical cancer risk and XRCC1 (Arg194Trp and Arg399Gln) and XRCC3 (Thr241Met) genetic variants.
METHODS: A case-control study of 77 cases of cervical cancer (including 70 carcinoma and 7 adenocarcinoma) and 73 normal women was performed. Three single nucleotide polymorphisms (SNPs) (XRCC1, and XRCC3) were genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).
RESULTS: Genotype frequencies of were similar between cases and controls: (XRCC1 - Arg194Trp [C-T]): CC 60(77.9%), CT 16(20.8%) e TT 1(1.3%) in cases and CC 57(78,1%), CT 16(21,9%) e TT 0(0%) in controls (p=1.00); (XRCC1 - Arg399Gln [G-A]): GG 13(16.9%), GA 28(36.4%) e AA 36(46.8%) in cases and GG 10(13,7%), GA 47(64,4%), AA 16(21,9%) in controls (p=0.01); (XRCC3 - Thr241Met [C-T]): CC 43(55,8%), CT 28(36,4%), TT 6(7,8%) in cases and CC 36(48,6%), CT 30(41,7%), TT 7(9,7%) in controls, (p=0.74). We found association XRCC1(Arg399Gln) and the risk for cervical cancer as a protective factor [OR = 0.20; IC=0.05-0.73, p=0.02] and found no association between XRCC1 (Arg194Trp) and XRCC3 (Thr241Met) polymorphisms and the risk of cervical cancer in our study.
CONCLUSION: Our results showed that there was positive correlation between the genetic variation Arg399Gln in XRCC1 gene and the susceptibility to cervical carcinoma in the studied population.
Keywords: XRCC1; XRCC3; Polymorphism, genetic; Papillomaviridae; Uterine cervical neoplasms
The identification of prognostic and predictive biomarkers may personalize antineoplastic therapy to intending to greater survival, reduction of relapse and quality of life for patients diagnosed with glioblastoma. We currently have several applicants for potential biomarkers studied in laboratories in preclinical phases, and their use in the clinical still lacks better elucidation of the real benefit as molecular targets. MicroRNAs are potential biomarkers, in addition to other molecular characteristics, of methylation and genomic expression responsible for the development and feature of glioblastoma. Gene signature has been helping in stratification into subgroups, in alterations in pathological classifications, and with great therapeutic potential.
Keywords: Glioblastoma; MicroRNAs; Radiotherapy; MGMT; IDH-1 mutation