Safety and oncological effectiveness after desensitization in patients with previous hypersensitivity reactions to chemotherapy.

INTRODUCTION: Taxanes and platinum are first-line treatments in gynecological tumors with high rates of hypersensitivity reactions (HSRs), leading to discontinuation of treatment. Desensitization involves induction of temporary tolerance to previously sensitized medications. The aims of this study are to describe HSRs to paclitaxel and carboplatin and evaluate the safety and effectiveness of desensitization protocols in gynecological cancer patients. METHODS: Original, retrospective, descriptive, analytical study, approved by Bioethics and Research Committee, included >18-year-old patients with gynecological tumors experiencing HSRs to first-line chemotherapy. Patients underwent 3-bag-12-step desensitization. RESULTS: 174 desensitization (95 paclitaxel, 79 carboplatin) in 33 female patients, mean age 45.5 years (18-71y). Cancer diagnosis: breast 8 (24.2%), ovarian 14 (42.2%), endometrial 2 (6.1%) and cervix 9 (27.2%). HSR occurred in paclitaxel during cycles 1-2 and in carboplatin after 6 cycles. The most frequently seen HSR symptom was cardiovascular with paclitaxel (94.7%), and cutaneous (93.3%) with carboplatin. Three-bags 12-steps desensitization protocol (initial dilution 1:100) in 5.67hrs. All patients reached total dose desensitization: 82% with no reaction, 12% mild, 6% moderate and 0% severe reaction. Mean disease-free interval and progression-free interval in months (m): breast cancer 29 m and 14 m, ovarian 22 m and 9 m, endometrial 40 m and cervical cancer: 67.5 m and 27 m. Twenty-five patients (73.5%) are still alive. CONCLUSION: HSRs to paclitaxel manifest in the first 1-2 cycles and to carboplatin after 6 cycles. Symptoms include cardiovascular, atypical neuromuscular and urticaria. Changing treatment lines impacts prognosis. Our study revealed that ovarian cancer patients undergoing desensitization protocols achieved longer progression-free intervals. All patients successfully reached total dose desensitization. This study provides evidence of the effectiveness and safety of desensitization and promising perspective for continuing first-line treatment with HSRs.

Analysis of the pathogenic variants of BRCA1 and BRCA2 using next-generation sequencing in women with familial breast cancer: a case-control study.

BACKGROUND: Pathogenic variants (PVs) of BRCA genes entail a lifetime risk of developing breast cancer in 50-85% of carriers. Their prevalence in different populations has been previously reported. However, there is scarce information regarding the most common PVs of these genes in Latin-Americans. This study identified BRCA1 and BRCA2 PV frequency in a high-risk female population from Northeastern Mexico and determined the association of these mutations with the patients' clinical and pathological characteristics. METHODS: Women were divided into three groups: aged ≤ 40 years at diagnosis and/or risk factors for hereditary breast cancer (n = 101), aged > 50 years with sporadic breast cancer (n = 22), and healthy women (n = 72). Their DNA was obtained from peripheral blood samples and the variants were examined by next-generation sequencing with Ion AmpliSeq BRCA1 and BRCA2 Panel using next-generation sequencing. RESULTS: PVs were detected in 13.8% group 1 patients (BRCA1, 12 patients; BRCA2, 2 patients). Only two patients in group 2 and none in group 3 exhibited BRCA1 PVs. Variants of uncertain significance were reported in 15.8% patients (n = 16). In group 1, patients with the triple-negative subtype, PV frequency was 40% (12/30). Breast cancer prevalence in young women examined in this study was higher than that reported by the National Cancer Institute Surveillance, Epidemiology (15.5% vs. 5.5%, respectively). CONCLUSIONS: The detected BRCA1 and BRCA2 PV frequency was similar to that reported in other populations. Our results indicate that clinical data should be evaluated before genetic testing and highly recommend genetic testing in patients with the triple-negative subtype and other clinical aspects.

High-grade endometrial stromal sarcoma as the initial presentation of an adult patient with Peutz-Jeghers Syndrome: a case report.

A 46-year-old female presents with a pelvic mass and is diagnosed as having a high-grade endometrial stromal sarcoma. During surgery, she is noted to have areas of intussusception of the small bowel secondary to large hamartomatous polyps. The patient had a previous history of small bowel obstruction secondary to what had been thought to be hyperplastic polyps but represented hamartomatous polyps on further review. Additional examination revealed the presence of subtle hyperpigmented macules on the fingers leading to a diagnosis of Peutz-Jeghers Syndrome (PJS). The diagnosis was confirmed by the presence of a germ-line STK11 mutation. Immunohistochemistry analysis of the tumor showed decreased expression of STK-11 as compared to one of the patient's hamartomatous polyps. Next generation sequencing of the tumor specimen failed to demonstrate a "second hit" somatic mutation in STK-11. This case represents the first case of endometrial stromal sarcoma associated with PJS and illustrates the importance of increased awareness of this condition among oncologists. PJS is associated with dysregulation of the mTOR pathway; treatment with an mTOR inhibitor was not effective in this case.

Identification of Germline Variants in Patients with Hereditary Cancer Syndromes in Northeast Mexico.

Hereditary cancer syndromes (HCS) are genetic diseases with an increased risk of developing cancer. This research describes the implementation of a cancer prevention model, genetic counseling, and germline variants testing in an oncologic center in Mexico. A total of 315 patients received genetic counseling, genetic testing was offered, and 205 individuals were tested for HCS. In 6 years, 131 (63.90%) probands and 74 (36.09%) relatives were tested. Among the probands, we found that 85 (63.9%) had at least one germline variant. We identified founder mutations in BRCA1 and a novel variant in APC that led to the creation of an in-house detection process for the whole family. The most frequent syndrome was hereditary breast and ovarian cancer syndrome (HBOC) (41 cases with BRCA1 germline variants in most of the cases), followed by eight cases of hereditary non-polyposic cancer syndrome (HNPCC or Lynch syndrome) (with MLH1 as the primarily responsible gene), and other high cancer risk syndromes. Genetic counseling in HCS is still a global challenge. Multigene panels are an essential tool to detect the variants frequency. Our program has a high detection rate of probands with HCS and pathogenic variants (40%), compared with other reports that detect 10% in other populations.

Real-World Evidence: Multicenter Efficacy and Toxicity Analysis of Nintedanib With Docetaxel as Second-Line Treatment in Mexican Patients With Advanced Lung Adenocarcinoma.

PURPOSE: The LUME-Lung 1 study has brought consistent evidence of the effective use of nintedanib in lung adenocarcinoma as a second line of treatment; however, differences among ethnicities have been found in some studies. METHODS: This was a retrospective review among 21 medical centers of 150 patients with a confirmed diagnosis of lung adenocarcinoma, included in a compassionate use program of nintedanib from March 2014 to September 2015. The current study aimed to analyze the effectiveness of nintedanib in combination with docetaxel in the Mexican population, using progression-free survival rate and the best objective response to treatment by RECIST 1.1 as a surrogate of effectiveness. In addition, we examined the toxicity profile of our study population as a secondary end point. RESULTS: After exclusion criteria, only 99 patients met the criteria for enrollment in the current study. From the total study population, 53 patients (53.5%) were male and 46 (46.5%) were female, with an average age of 60 years and stage IV as the most prevalent clinical stage at the beginning of the compassionate use program. A total of 48 patients (48.5%) had partial response; 26 (26.3%), stable disease; 4 (4%), complete response; and 16 (16.2%), progression; and 5 (5%) were nonevaluable. We found a median progression-free survival of 5 months (95% CI, 4.3 to 5.7 months). The most common grade 3 or 4 adverse reactions were fatigue (14%) and diarrhea (13%). CONCLUSION: Nintedanib, as part of a chemotherapy regimen, is an effective option with an acceptable toxicity profile for advanced lung adenocarcinoma after first-line treatment progression.