Place of anti-EGFR therapy in older patients with metastatic colorectal cancer in 2020

International audienceAlmost half of the new cases of colorectal cancer concern patients aged ≥70 years. However, very few clinical trials have specifically included older patients. As a consequence, the treatment of these patients is controversial because the balance between clinical benefits and toxicities remains uncertain. In patients without comorbidities and with an ECOG performance score of 0-1, treatment indications are similar to those of younger patients. For frail patients, chemotherapy is possible, but a comprehensive geriatric assessment is recommended. Anti-EGFR (epidermal growth factor receptor) therapy is indicated either in combination with chemotherapy in the first-line or second-line setting or as monotherapy in the third-line setting (i.e., after failure of chemotherapy). For fit older patients, clinical trials that compared chemotherapy alone with doublet chemotherapy plus anti-EGFR in either first-line or second-line setting suggested that age is not an absolute contraindication for the use of this regimen. In frail patients, anti-EGFR monotherapy in the first-line, second-line or third-line setting has shown feasibility and antitumor activity and had mainly cutaneous toxicities that were easily managed. In any case, administration of treatment must be very cautious in older patients and the treatment dose needs to be adapted according to comorbidities

Chemotherapy in Old Women with Breast Cancer: Is Age Still a Predictor for Under Treatment?

International audienceBreast cancer affects mostly older women but there are no guidelines especially devoted to adjuvant chemotherapy for this population. In this context, this study was carried out in a population-based cohort of French elderly women with breast cancer, to check adherence to the existing national guidelines according to the women's age, taking into account the evolution of the situation over time for women requiring chemotherapy. Between October 2006 and December 2008, all consecutive women included in the French Health registry for a biopsy-proven primary nonmetastatic breast cancer, aged 65-80 years at diagnosis, and living in South Eastern France, were asked to participate in a cohort study. Medical information was collected from physicians. The study population was restricted to the 223 women who were recommended adjuvant chemotherapy according to national guidelines. Those who received chemotherapy were compared to those who did not receive this treatment. Among these 223 women 55% had received chemotherapy. Only three women refused the treatment. Less than 8% have had a geriatric assessment before treatment decision and only two were proposed to participate in a clinical trial. After adjustment for comorbidity score, tumor characteristics, socio-demographic characteristics, and year of diagnosis, increasing patient age was independently associated with decreased guideline concordance for adjuvant chemotherapy. Women aged 75-80 years received chemotherapy more than four times less often than women aged 65-74 years. However, the percentage of women who received chemotherapy increased from 33% to 58% between 2006 and 2008, in parallel with the setting up of Onco-Geriatric Coordination Units in the area. In France, chronological age remains a barrier to receive chemotherapy for older breast cancer women but the establishment of a formal collaboration between oncologists and geriatricians seems to be an effective way to improve care delivery in this population

Identification of genome specific markers in oilseed rape

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Extracting the A genome from oilseed rape

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Lung cancer in elderly patients: A retrospective analysis of practice in a single institution

International audienceIncidence of non-small cell lung cancer is increasing especially among elderly with about 40% arising in patients over 70 years old. Most of these elderly patients are under treated. Seventy-one patients with lung cancer over 70 years old were treated in Institut Paoli-Calmettes from January 2000 until December 2003 (male/female: 57/14). Median age was 75.5 years (70-92). OMS 0-1-2-3=4.2-60.6-25.4-4.2%, respectively. Comorbidities were represented by arterial hypertension, coronaropathy, cardiac failure, thrombo-embolism, respiratory failure, diabetes, vascular cerebral dysfunction, and renal failure. 29.6% of patients were without comorbidity, and 14.1% had at least three comorbidities. The averages of the Charlson comorbidity score and the Age-Charlson comorbidity score were 3.4 and 6.6, respectively. Histological characteristics: epidermoïd/adenocarcinoma/undifferentiated/small cells: 39.4%/26.8%/15.5%/9.9%. Most of them were advanced lung cancer: St IIIB=14 (19.7%) and St IV=37 (52.1%). Forty-six patients received chemotherapy (64.8%) with 40 patients (86.9%) with platin (carboplatin or cisplatin). The median number of treatment cycles was 4.1 (range 1-7). Two patients achieved complete response and 15 had partial response. The response rate was 39.6%. The 1-year survival rate was 48.5% and the estimated median survival time was 11 months (95%; 7-18 months) for all patients. The 1-year survival rate was 75% and 21.6% and the estimated median survival time was 25.9 months (95%; 12.6, ND) and 5.7 months (95%; 4.2-9.6) for stage IIIB and IV, respectively. Toxicities were judged acceptable with 19 hospitalizations after chemotherapy, for 16 patients who represent 34.8% of patients who received chemotherapy.Conclusions: Chemotherapy is feasible in elderly patients with lung cancer. Patients should be evaluated for chemotherapy based on their performance status and comorbidities especially with geriatric assessment rather than age alone. The chemotherapy with platinum seems to be tolerable and effective

The poor lonesome Brassica napus A subgenome may not survive without its mate

International audienceWhole genome duplication (WGD) is recognized as a major force in plant evolution and speciation, resulting from both structural and/or functional alterations. These modifications occur in the first few generations following WGD events and continue during the lifespan of the polyploid species. To study the long-term evolutionary impact of allopolyploidy, previous studies have almost exclusively compared a present allotetraploid species with its current diploid progenitors. However, the diploid progenitors have independently evolved since the allotetraploid formation, preventing to fully understand its evolution. To circumvent this problem, another approach corresponding to the subgenome extraction, offers the unique opportunity to elucidate the long-term evolution in an allopolyploid context. Presently, one of the best model to determine the role of allopolyploidy in genome evolution corresponds to oilseed rape (Brassica napus, AACC, 2n=38), formed about 8,500 years ago from a cross between B. rapa (AA, 2n=20) and B. oleracea (CC, 2n=18). To identify the structural rearrangements that occurred since this allotetraploid formation, we performed two different strategies to extract its diploid AA component. For the 1st strategy, a cross between B. napus var. Darmor and B. rapa was realized to produce a triploid AAC F1 interspecific hybrid. This triploid was then backcrossed three times to B. napus and the AAC progenies were selected at each generation in order to obtain an almost pure B. napus A subgenome. We finally attempted to separate the AA and C components by selfing the last AAC plant but no AA plant was obtained. For the 2nd strategy, a cross between the initial AAC F1 hybrid and B. rapa was performed to generate AA plants. After four cycles of selfed and also backcrossed to B. napus, AA plants mainly containing the B. napus A subgenome were obtained. Using the 60k SNP Illumina micro array and the genome sequence of B. napus var. Darmor, we assessed the genomic structure of the last AA plants produced. They presented a lower proportion of B. napus A subgenome extracted than expected and some introgressions from the C subgenome. Our analyses revealed that the genomic regions from B. rapa conserved in diploid AA plants were not randomly distributed along the A subgenome, suggesting that the A subgenome may not survive without the C subgenome, most presumably due to the loss of one homoeologous copy since the formation of the allotetraploid B. napus

Can a lonesome poor A genome of Brassica napus survive at diploid stage?

International audienceBackground: There are two strategies available for understanding structural and/or functional modifications that took place during the stabilization of polyploid species. The first one allows assessment of events that arose immediately after the formation of a polyploid species by crossing and doubling its parental genomes in order to produce synthetic forms. The second one tries to elucidate the changes that occurred since the polyploid species was created by extracting in the polyploidy one of its parental genome.Objectives: In the present study, we tried to identify the structural rearrangements that occurred since the origin (about 8000 years ago) of oilseed rape (Brassica napus, AACC, 2n=38), which is a natural hybrid between B. rapa (AA, 2n=20) and B. oleracea (CC, 2n=18). To that purpose, we produced an original plant material in which the B. napus A subgenome was extracted. Methods: We used two methods to extract the diploid AA genome from B. napus. Firstly, AAC F1 interspecific hybrids (produced by crosses between B. napus var Darmor and B. rapa) were backcrossed three times to B. napus, and AAC plants were selected at each generation. Secondly, the initial AAC F1 hybrids were crossed to B. rapa and plants with AA genomes were selected for, selfed and also backcrossed to B. napus. After four cycles of such crossing, we selected AA plants with mainly the A genome of B. napus. Using the 60k SNP Illumina microarray and the sequence of B. napus genomes var Darmor, we assessed the genomic structure of the so far extracted B. napus A subgenome. Result: We found that the backcrosses of AAC F1 interspecific hybrids to B. napus (first strategy) could not permit to eliminate the C chromosomes by selfing since the progenies were male sterile. The second strategy allowed production of AA plants with a regular meiosis. We expected more than 68% of Darmor A genome in this plant. To validate this assessment, genomic structure was established by SNP analysis using markers specific of A genome of Darmor and of the B. rapa variety used in the initial crosses. The homozygous or heterozygous stage of each marker physically anchored was determined. Additionally, CDarmor genome regions introduced by homeologous recombination were characterized. Conclusions: From this original material, it will be possible to determine the comparative evolution of the A genome in a diploid and polyploid genetic background. The first data seem to indicate that rearrangements are too large and/or too frequent to obtain 100% A genome of B. napus at the diploid stage. However, functional analyses will allow identification of the rearrangement impacts