Contribution à l'étude du test des micronoyaux en tant que biomarqueur de cancer

Comprendre la nature et l évolution des évènements qui surviennent lors d une exposition à un ou plusieurs agents carcinogènes et entraînent l émergence d une pathologie comme le cancer est un des grands challenges de la recherche en épidémiologie moléculaire. Un lien direct a été établi entre les anomalies chromosomiques et le cancer. La notion d'instabilité génomique doit être estimée dès lors que les premières étapes du processus carcinogénique sont amorcées. Ainsi, pour appréhender au mieux le risque de cancer, ces dernières années ont vu naître un regain d'intérêt dans l'étude de biomarqueurs de l'instabilité génomique, évènement intermédiaire se situant entre une exposition à un composé carcinogène et le développement ultime de la maladie cancéreuse. Dans notre étude, nous avons donc analysé les relations entre, d'une part, un biomarqueur connu (le test des micronoyaux sur lymphocytes T), d'autre part, des données cliniques et environnementales de 31 patients cancéreux, avant tout traitement. Nous avons par ailleurs analysé les corrélations entre les micronoyaux et les anticorps anti-P53 circulants chez ces mêmes patients. Une analyse qualitative des mutations chromosomiques générant des micronoyaux consécutivement à des évènements tantôt aneugènes, tantôt clastogènes, a été réalisée au moyen du test des micronoyaux associé à l'hybridation in situ fluorescente (FISH) par sondes pancentromériques. Les principaux résultats mettent à nouveau en évidence une fréquence anormalement élevée de lymphocytes micronucléés (18,5 ). Nous observons la présence chez 26 % des patients des anticorps anti-P53 circulants. Les patients présentant une exposition globale ont un taux particulièrement élevé de lymphocytes micronucléés (22,1 ) par rapport aux patients non exposés (14,1 ). L analyse qualitative des lymphocytes micronucléés montre que les taux de micronoyaux acentromériques, centromériques et multi- centromériques sont approximativement 2 fois plus élevés. Ainsi, il est possible que les anomalies clastogéniques élevées chez les patients cancéreux soient le reflet d une exposition à des génotoxiques directs ou consécutifs à des cassures double brin non réparées de l ADN. Une nette prédominance des phénomènes aneugéniques (70%) est observée. La perte d'un chromosome entier semble donc être l'événement prédominant dans la formation de ces micronoyaux. Il est intéressant d'observer que, d une part, 50% des micronoyaux contiennent plusieurs chromosomes et, d autre part, les deux tiers des micronoyaux centromériques contiennent plusieurs chromosomes. Dès lors, la plupart des évènements aneugéniques conduisant à la formation de micronoyaux implique plusieurs chromosomes. Il apparaît également remarquable que la perte de multiples chromosomes au sein d une même cellule conduit plus fréquemment à la formation d un seul micronoyau multi-centromérique plutôt qu à plusieurs micronoyaux mono-centromériques. Par ailleurs, les cellules trinucléées sont plus fréquentes chez les patients cancéreux que chez les témoins mais la différence n est pas significative. La plupart des évènements aneugéniques semblent résulter des dysfonctionnements cellulaires au niveau des centrosomes. En conclusion, les micronoyaux observés dans les lymphocytes circulants des patients porteurs de cancer sont le reflet essentiellement des anomalies chromosomiques de nombre. Les événements clastogéniques sont donc importants; toutefois les évènements aneugéniques surviennent fréquemment dans ces cellules. Dès lors, les mutations chromosomiques et génomiques sont impliquées dans l'instabilité génomique. Actuellement, les relations causales entre carcinogenèse et évènements aneugènes et/ou clastogènes restent encore à préciser.AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Illness representations and quality of life in French patients suffering from lung cancer

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Body image and psychological distress in women with breast cancer: a French online survey on patients' perceptions and expectations

WOS:000430419700007Background Altered body image caused by alopecia, loss of eyebrows or eyelashes, or mastectomy is a major source of psychological distress in women with breast cancer. Objective To identify and to assess patients' perceptions and expectations regarding altered body image. Method Opinion survey conducted among patients treated for breast cancer and member of French online support groups. Anonymous online self-administered survey sent to women with breast cancer. Results 85% of the women interviewed experienced alopecia during treatment and 67% of them loss of eyebrows or eyelashes. About half of patients suffering alopecia and loss of eyebrows or eyelashes reported fearing what others think. Mastectomy was experienced by 84% of the women in our study, but only 32% of them reported fearing what others think. 87% of our study cohort received information about the possibility of adverse events. 70, 56, and 60% of women felt helped by information they receive d for the management of alopecia, loss of eyebrows or eyelashes, or mastectomy, respectively. Conclusion This study confirms that altered body image is a critical psychosocial issue for women with breast cancer. Effective information can be a source of reassurance and may constitute one of the most important sources of emotional support

Prognostic Value of the B12/CRP Index in Older Systemically Treatable Cancer Patients

International audienceBackground: While comprehensive geriatric assessment (CGA) in older patients treated for cancer assesses several related domains, it does not include standardized biological tests. The present study aimed to: (1) assess the prognosis value of the B12/CRP index (BCI) in a population of systemically treatable older patients with cancer and (2) analyze the association between BCI value and pre-existing geriatric frailty. Method: We conducted a retrospective observational study between January 2016 and June 2020 at Marseille University Hospital. All consecutive cancer patients aged 70 years and over before initiating systemic therapy were included. Results: Of the 863 patients included, 60.5% were men and 42.5% had metastatic stage cancer. Mean age was 81 years. The low-BCI group (≤10,000) had a significantly longer survival time than the mid-BCI (10,000 40,000) groups (HR = 0.327, CI95% [0.26–0.42], p-value = 0.0001). Mid- and high-BCI (BCI > 40,000) values were associated with impaired functional status and malnutrition. Conclusion: A BCI > 10,000 would appear to be a good biological prognostic factor for poor survival times and pre-existing geriatric impairment in older cancer patients before they initiate systemic treatment

Impact of care pathway for nursing home residents treated for cancer: ONCO-EHPAD study

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Outcome According to Elective Pelvic Radiation Therapy in Patients With High-Risk Localized Prostate Cancer: A Secondary Analysis of the GETUG 12 Phase 3 Randomized Trial

International audiencePURPOSE:The role of pelvic elective nodal irradiation (ENI) in the management of prostate cancer is controversial. This study analyzed the role of pelvic radiation therapy (RT) on the outcome in high-risk localized prostate cancer patients included in the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG) 12 trial.METHODS AND MATERIALS:Patients with a nonpretreated high-risk localized prostate cancer and a staging lymphadenectomy were randomly assigned to receive either goserelin every 3 months for 3 years and 4 cycles of docetaxel plus estramustine or goserelin alone. Local therapy was administered 3 months after the start of systemic treatment. Performance of pelvic ENI was left to the treating physician. Only patients treated with primary RT were included in this analysis. The primary endpoint was biochemical progression-free survival (bPFS).RESULTS:A total of 413 patients treated from 2002 to 2006 were included, of whom 358 were treated using primary RT. A total of 208 patients received pelvic RT and 150 prostate-only RT. Prostate-specific antigen (PSA) concentration, Gleason score, or T stage did not differ according to performance of pelvic RT; pN+ patients more frequently received pelvic RT than pN0 patients (P<.0001). Median follow-up was 8.8 years. In multivariate analysis, bPFS was negatively impacted by pN stage (hazard ratio [HR]: 2.52 [95% confidence interval [CI]: 1.78-3.54], P<.0001), Gleason score 8 or higher (HR: 1.41 [95% CI: 1.03-1.93], P=.033) and PSA higher than 20 ng/mL (HR: 1.41 [95% CI: 1.02-1.96], P=.038), and positively impacted by the use of chemotherapy (HR: 0.66 [95% CI: 0.48-0.9], P=.009). There was no association between bPFS and use of pelvic ENI in multivariate analysis (HR: 1.10 [95% CI: 0.78-1.55], P=.60), even when analysis was restricted to pN0 patients (HR: 0.88 [95% CI: 0.59-1.31], P=.53). Pelvic ENI was not associated with increased acute or late patient reported toxicity.CONCLUSIONS:This unplanned analysis of a randomized trial failed to demonstrate a benefit of pelvic ENI on bPFS in high-risk localized prostate cancer patients

Androgen deprivation therapy plus docetaxel and estramustine versus androgen deprivation therapy alone for high-risk localised prostate cancer (GETUG 12): a phase 3 randomised controlled trial

International audienceBACKGROUND:Early risk-stratified chemotherapy is a standard treatment for breast, colorectal, and lung cancers, but not for high-risk localised prostate cancer. Combined docetaxel and estramustine improves survival in patients with castration-resistant prostate cancer. We assessed the effects of combined docetaxel and estramustine on relapse in patients with high-risk localised prostate cancer.METHODS:We did this randomised phase 3 trial at 26 hospitals in France. We enrolled patients with treatment-naive prostate cancer and at least one risk factor (ie, stage T3-T4 disease, Gleason score of ≥8, prostate-specific antigen concentration >20 ng/mL, or pathological node-positive). All patients underwent a staging pelvic lymph node dissection. Patients were randomly assigned (1:1) to either androgen deprivation therapy (ADT; goserelin 10·8 mg every 3 months for 3 years) plus four cycles of docetaxel on day 2 at a dose of 70 mg/m(2) and estramustine 10 mg/kg per day on days 1-5, every 3 weeks, or ADT only. The randomisation was done centrally by computer, stratified by risk factor. Local treatment was administered at 3 months. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was relapse-free survival in the intention-to-treat population. Follow-up for other endpoints is ongoing. This study is registered with ClinicalTrials.gov, number NCT00055731.FINDINGS:We randomly assigned 207 patients to the ADT plus docetaxel and estramustine group and 206 to the ADT only group. Median follow-up was 8·8 years (IQR 8·1-9·7). 88 (43%) of 207 patients in the ADT plus docetaxel and estramustine group had an event (relapse or death) versus 111 (54%) of 206 in the ADT only group. 8-year relapse-free survival was 62% (95% CI 55-69) in the ADT plus docetaxel and estramustine group versus 50% (44-57) in the ADT only group (adjusted hazard ratio [HR] 0·71, 95% CI 0·54-0·94, p=0·017). Of patients who were treated with radiotherapy and had data available, 31 (21%) of 151 in the ADT plus docetaxel and estramustine group versus 26 (18%) of 143 in the ADT only group reported a grade 2 or higher long-term side-effect (p=0·61). We recorded no excess second cancers (26 [13%] of 207 vs 22 [11%] of 206; p=0·57), and there were no treatment-related deaths.INTERPRETATION:Docetaxel-based chemotherapy improves relapse-free survival in patients with high-risk localised prostate cancer. Longer follow-up is needed to assess whether this benefit translates into improved metastasis-free survival and overall survival.FUNDING:Ligue Contre le Cancer, Sanofi-Aventis, AstraZeneca, Institut National du Cancer

Patients' self-assessment versus investigators' evaluation in a phase III trial in non-castrate metastatic prostate cancer (GETUG-AFU 15)

BACKGROUND: Toxicity, which is a key parameter in the evaluation of cancer treatments, can be underestimated by clinicians. We investigated differences between patients and physicians in reporting adverse events of androgen deprivation therapy (ADT) with or without docetaxel in a multicentre phase III trial in non-castrate metastatic prostate cancer. METHODS: The 385 patients included were invited to complete a 26-symptom questionnaire 3 and 6months after the start of treatment, among which eighteen symptoms were also assessed by physicians, reported in medical records and graded using the Common Toxicity Criteria of the National Cancer Institute. Positive and negative agreements as well as Kappa concordance coefficients were computed. FINDINGS: Data were available for 220 and 165 patients at 3 and 6months respectively. Physicians systematically under-reported patients' symptoms. Positive agreement rates (at respectively 3 and 6months) for the five most commonly reported symptoms were: 61.0% and 64.3% hot flushes, 50.0% and 43.6% fatigue, 29.4% and 31.1% sexual dysfunction, 24.4% and 14.4% weigh gain/loss, 16.7% and 19.3% for joint/muscle pain. For symptoms most frequently reported as disturbing or very disturbing by patients, the clinicians' failure to report them ranged from 50.8% (hot flushes) to 89.5% (joint/muscle pain) at 3months, and from 48.2% (hot flushes) to 88.4% (joint/muscle pain) at 6months. INTERPRETATION: Physicians often failed to report treatment-related symptoms, even the most common and disturbing ones. Patients' self-evaluation of toxicity should be used in clinical trials to improve the process of drug assessment in oncology. FUNDING: French Health Ministry and Institut National du Cancer (PHRC), Sanofi-Aventis, Astra-Zeneca, and Amgen