Homologous recombination deficiency is a marker of response to poly(ADP-ribose) polymerase inhibitors in different cancer types including ovary, prostate, and pancreatic cancer. To date, no report ...about poly(ADP-ribose) polymerase inhibitors has been published on cervical cancer.
Here we present the case of a patient with cervical cancer treated in this setting. A 49-year-old woman diagnosed with International Federation of Obstetricians and Gynecologists stage 2018 IIIC2 locally advanced undifferentiated cervical cancer received first-line chemoradiotherapy followed by carboplatin, paclitaxel, and bevacizumab with partial response. Because of a family history of cancers, the patient was tested and found positive for a pathogenic BRCA1 germline and somatic mutation, which motivated bevacizumab plus olaparib maintenance treatment. A simple hysterectomy was performed after 2 years stable disease; pathological report showed complete pathological response, and 12 months follow-up showed no recurrence.
Poly(ADP-ribose) polymerase inhibitors could be an alternative maintenance treatment for patients with persistent advanced cervical cancer previously treated with platinum, especially when familial history of cancers is reported. Clinical trials using poly(ADP-ribose) polymerase inhibitors for advanced cervical cancer are warranted.
Patients who carry the BReast Cancer 1 or 2 (BRCA) gene mutations have an underlying hereditary predisposition for breast and ovarian cancers. These deleterious genetic mutations are the most common ...ones implicated in hereditary breast and ovarian cancers. Oncogenetic counselling plays a key role in identifying patient for BRCA testing and for mutation identification. BRCA1/2 carriers have to be followed up regularly and may justify breast and/or adnexal prophylactic surgery, according to the French National Cancer Institute guidelines (INCa). Poly- (DNA-riboses) polymerases inhibitors, notably olaparib, have a major role in the management of epithelial ovarian cancer in patients with BRCA mutation and many studies are ongoing to expand their indications in a near future.
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Background: Head and neck squamous cell carcinoma (HNSCC) is the fourth cause of death by cancer in France. For metastatic patients, the standard first line treatment is the ...EXTREME regimen. However, a lot of these patients have a poor performance status (PS) and/or several comorbidities making them unfit for this regimen. We have treated them with carboplatin and cetuximab (simplified EXTREME regimen) since 2007. The aim of this study is to assess the efficacy and tolerance of this regimen in this frail population. Methods: We retrospectively reviewed the medical charts of all patients treated with simplified EXTREME regimen for recurrent or metastatic HNSCC in three French academic hospitals between 2007 and 2017. The primary endpoint was overall survival (OS) and secondary endpoints were progression free survival (PFS), overall response rate (ORR), identification of prognostic factors, and toxicity. Results: 103 patients were included with a median age of 63 y.o., 60% had a PS 0-1 and 40% a PS 2-3. With a median follow-up of 30.2 months, median OS was 7.2 months and median PFS 3.7 months. ORR was 39% and 24% of patients had disease stabilization. On univariate analysis, a PS of 2 or more was significantly associated with a worse OS (median OS 10.1 months if PS 0-1 versus 4.6 months if PS 2-3; HR = 1.68; 95%CI = 1.11-2.57; p = 0.01). Acute grade 3-4 hematologic and non-hematologic toxicity rates were 25.2% and 27.2%, respectively, with 11.8% of thrombopenia, 9.7% of neutropenia, 10% of skin toxicity, and 12.6% of asthenia. Patients with grade 1 or more skin toxicity had a higher ORR (HR = 3.44; 95%CI = 1.16-10.23; p = 0.03) and a prolonged OS (HR = 0.37; 95%CI = 0.23-0.58; p < 0.0001) and PFS (HR0.29; 95%CI = 0.19-0.47; p < 0.0001). During treatment, 29% of patients had a pain decrease, 13.5% a gain of weight, and 17.2% an improvement in PS. Conclusions: This is the largest cohort of patients treated with simplified EXTREME for HNSCC. Simplified EXTREME was well tolerated in this frail population with a high ORR. Patients with a good PS had prolonged survival. Interestingly, skin toxicity of any grade was significantly correlated with treatment efficacy.
Investigating the nature of physiological traits potentially related to fitness is important towards a better understanding of how species and/or populations may respond to selective pressures ...imposed by contrasting environments. In northern species in particular, the ability to mobilize energy reserves to compensate for the low external energy intake during winter is crucial. However, the phenotypic and genetic bases of energy reserve accumulation and mobilization have rarely been investigated, especially pertaining to variation in strategy adopted by different populations. In the present study, we documented variation in several energy reserve variables and estimated their quantitative genetic basis to test the null hypothesis of no difference in variation at those traits among three strains of brook charr (Salvelinus fontinalis) and their reciprocal hybrids. Our results indicate that the strategy of winter energy preparation and mobilization was specific to each strain, whereby (1) domestic fish accumulated a higher amount of energy reserves before winter and kept accumulating liver glycogen during winter despite lower feeding; (2) Laval fish used liver glycogen and lipids during winter and experienced a significant decrease in condition factor; (3) Rupert fish had relatively little energy reserves accumulated at the end of fall and preferentially mobilized visceral fat during winter. Significant heritability for traits related to the accumulation and use of energy reserves was found in the domestic and Laval but not in the Rupert strain. Genetic and phenotypic correlations also varied among strains, which suggested population-specific genetic architecture underlying the expression of these traits. Hybrids showed limited evidence of non-additive effects. Overall, this study provides the first evidence of a genetically based—and likely adaptive—population-specific strategy for energy mobilization related to overwinter survival.
Discriminating between genetic and environmental causes of phenotypic variation is an essential requirement for understanding the evolutionary potential of populations. However, the extent to which ...genetic variation differs among conspecific groups and environments during ontogeny has rarely been investigated. In this study, the genetic basis of body mass was measured in three divergent strains of brook charr (Salvelinus fontinalis) in different rearing environments and at different time periods. The results indicate that body mass was a heritable trait in all strains but that the level of heritability greatly differed among strains. Moreover, heritability estimates of each strain varied differently according to environmental rearing conditions, and cross-environments correlations were all significantly lower than unity, indicating strain-specific patterns of genotype-environment interactions. Heritability estimates also varied throughout ontogeny and decreased by 50% from 9 to 21 months of age. This study highlights the divergence in genetic architecture and evolutionary potential among these strains and emphasizes the importance of considering the strain-specific potential of the response to selection according to environmental variation.
We studied the link between T-cell activation, differentiation and senescence phenotypes and non-AIDS-related comorbidities in HIV-suppressed patients.
Patients included in the ANRS CO3 Aquitaine ...Cohort were consecutively enrolled in this cross-sectional study between October 2011 and May 2013 called Chronic Immune Activation and Senescence (CIADIS) study.
We summarized immune markers CD4 and CD8 activation (DR), differentiation (naive and terminally differentiated memory T cells), and senescence (CD57CD28) in a weighted immune score by principal component analysis called CIADIS. Previously described Veterans Aging Cohort Study (VACS) index and immune risk profile (IRP) scores were calculated. We used adjusted logistic regression to assess the association between the CIADIS score and the presence of at least three non-AIDS-defining comorbidities.
Of 876 patients with an undetectable viral load, 73.4% were men and median age was 50.5 years interquartile range (IQR) 44.7-56.7 years. Median CD4 T-cell count was 579/μl (IQR 429-759 cells/μl), and median duration of HIV viral suppression was 5.3 years (IQR 2.3-8.7). The weighted CIADIS score was associated with at least three comorbidities (odds ratio 1.3 for 1 SD more, 95% confidence interval 1.0, 1.6) independently of age, sex, AIDS stage, and the Veterans Aging Cohort Study score. The CIADIS and the immune risk profile scores were significantly associated with at least three comorbidities in adjusted models restricted to patients younger than 60 years. None of the tested scores were associated with at least three comorbidities in patients older than 60 years.
The weighted CIADIS score based on activation, senescence, and differentiation markers might help physicians identifying patients at a higher risk for non-AIDS-related comorbidities.
Three strains of brook trout Salvelinus fontinalis (domestic D, Laval L, and Rupert R) and their reciprocal hybrids were reared from 7 to 21 months of age in three different environments (indoor, ...constant temperature conditions; indoor, seasonal temperature variations; and outdoor, seasonal temperature variations) to test for the occurrence of heterosis in important life history traits of interest for production (body mass, length, condition factor, the absence of early sexual maturation, and survival). For each cross, body mass, length, and mortality were measured at regular intervals and sexual maturity was assessed in age‐1+ fish (21 months of age). We found evidence for heterosis in mass and length that varied according to strain, cross direction in reciprocal hybrids, developmental stage, or environment; no significant outbreeding depression was detected for these traits. Heterosis expression for weight varied from 4.9% to 23.8% depending on the hybrids and environments. We found that one out of five reciprocal hybrids tested (LfemaleRmale) expressed heterosis at each age stage throughout the experiment in the three environments while the other four had mixed results. No evidence for heterosis was observed for sexual maturity and survival. These results not only provide one of the first clear pieces of evidence for the occurrence of heterosis in salmonids but also illustrate the complex nature and the unpredictability of this phenomenon.
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