A model-strengthened imaging biomarker for survival prediction in EGFR-mutated non-small-cell lung carcinoma patients treated with tyrosine kinase inhibitors

International audienceNon-small-cell lung carcinoma is a frequent type of lung cancer with a bad prognosis. Depending on the stage, genomics, several therapeutical approaches are used. Tyrosine Kinase Inhibitors (TKI) may be successful for a time in the treatment of EGFR-mutated non-small cells lung carcinoma. Our objective is here to propose a survival assessment as their efficacy in the long run is challenging to evaluate. The study includes 17 patients diagnosed as of EGFR-mutated non-small cell lung cancer and exposed to an EGFR-targeting TKI with 3 computed tomography (CT) scans of the primitive tumor (one before the TKI introduction and two after). An imaging biomarker based on the texture heterogeneity evolution between the first and the third exams is derived and computed from a mathematical model and patient data. Defining the overall survival as the time between the introduction of the TKI treatment and the patient death, we obtain a statistically significant correlation between the overall survival and our imaging marker (p = 0:009). Using the ROC curve, the patients are separated into two populations and the comparison of the survival curves is statistically significant (p = 0:025). The baseline exam seems to have a significant role in the prediction of response to TKI treatment. More precisely, our imaging biomarker defined using only the CT scan before the TKI introduction allows to determine a first classification of the population which is improved over time using the imaging marker as soon as more CT scans are available. This exploratory study leads us to think that it is possible to obtain a survival assessment using only few CT scans of the primary tumor

Hospitalisations non programmées des patients des services de médecine oncologique de l'Institut Bergonié

BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Prévention et sevrage tabagique chez les adolescents (à propos de 9 cas)

BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Quantitative mathematical modeling of clinical brain metastasis dynamics in non-small cell lung cancer

Brain metastases (BMs) are the largest disabling site for non-small cell lung cancers, but are only visible when sizeable. Individualized prediction of the BM risk and extent is a major challenge for therapeutic decision. This study assesses mechanistic models of BM apparition and growth against clinical imaging data.We implemented a quantitative computational method to confront biologicallyinformed mathematical models to clinical data of BMs. Primary tumor growth parameters were estimated from size at diagnosis and histology. Metastatic dissemination and growth parameters were fitted to either population data of BM probability (n=183 patients) or longitudinal measurements of number and size of visible BMs (63 size measurements in two patients). Pre-clinical phases from first cancer cell to detection were estimated to 2.1-5.3 years. A model featuringdormancy was best able to describe the longitudinal data, as well as BM probability as a function of primary tumor size at diagnosis. It predicted first appearance of BMs at 14-19 months pre-diagnosis. Model-informed predictions of invisible cerebral disease burden could be used to inform therapeutic intervention

Nutritional advice in older patients at risk of malnutrition during treatment for chemotherapy: a two-year randomized controlled trial.

We tested the effect of dietary advice dedicated to increase intake in older patients at risk for malnutrition during chemotherapy, versus usual care, on one-year mortality.We conducted a multicentre, open-label interventional, stratified (centre), parallel randomised controlled trial, with a 1∶1 ratio, with two-year follow-up. Patients were aged 70 years or older treated with chemotherapy for solid tumour and at risk of malnutrition (MNA, Mini Nutritional Assessment 17-23.5). Intervention consisted of diet counselling with the aim of achieving an energy intake of 30 kCal/kg body weight/d and 1.2 g protein/kg/d, by face-to-face discussion targeting the main nutritional symptoms, compared to usual care. Interviews were performed 6 times during the chemotherapy sessions for 3 to 6 months. The primary endpoint was 1-year mortality and secondary endpoints were 2-year mortality, toxicities and chemotherapy outcomes.Between April 2007 and March 2010 we randomised 341 patients and 336 were analysed: mean (standard deviation) age of 78.0 y (4·9), 51.2% male, mean MNA 20.2 (2.1). Distribution of cancer types was similar in the two groups; the most frequent were colon (22.4%), lymphoma (14.9%), lung (10.4%), and pancreas (17.0%). Both groups increased their dietary intake, but to a larger extent with intervention (p<0.01). At the second visit, the energy target was achieved in 57 (40.4%) patients and the protein target in 66 (46.8%) with the intervention compared respectively to 13 (13.5%) and 20 (20.8%) in the controls. Death occurred during the first year in 143 patients (42.56%), without difference according to the intervention (p = 0.79). No difference in nutritional status changes was found. Response to chemotherapy was also similar between the groups.Early dietary counselling was efficient in increasing intake but had no beneficial effect on mortality or secondary outcomes. Cancer cachexia antianabolism may explain this lack of effect.ClinicalTrials.gov NCT00459589

Main baseline characteristics of participants in the trial.

<p>ECOG PS: Eastern Cooperative Oncology Group performance status.</p><p>Main baseline characteristics of participants in the trial.</p

Two-year mortality and other outcomes.

<p>Two-year mortality and other outcomes.</p

Flowchart of participant progression through a randomized controlled trial of nutritional intervention in older patients at risk of malnutrition.

<p>Flowchart of participant progression through a randomized controlled trial of nutritional intervention in older patients at risk of malnutrition.</p

Dietary intake the day before each cycle during the chemotherapy period.

<p>Data are presented as mean and 95% CI, or proportion. Total dietary intake was analyzed with mixed models: increase of total intake at the second visit in both groups (UC+NI, P<0.0001; **UC, P = 0.02), with higher increased in UC+NI compared to UC, P<0.01.</p

Two-year mortality according to groups UC and UC+NI. N = 336.

<p>Comparisons were performed with Cox model adjusted on recruiting centres.</p