Kader Chouahnia

Upfront association of carboplatin plus pemetrexed in patients with brain metastases of lung adenocarcinoma

Approximately 10% of patients with non-small cell lung cancer (NSCLC) have brain metastases at the time of diagnosis. When surgical resection is not possible, whole brain radiotherapy is the standard of care, with a cerebral response rate of approximately 30%. We report our experience with an upfront association of carboplatin and pemetrexed (areas under the curve, 5 and 500 mg/m(2), respectively), every 3 weeks, in 30 patients presenting with newly diagnosed brain metastases and NSCLC. Cerebral MRIs were performed every 6-9 weeks. The radiologic response rates were assessed according to Response Evaluation Criteria in Solid Tumors. Overall survival was also determined. Twenty-six patients were evaluable for response, and the objective cerebral response rate (complete and partial response) in the intent-to-treat population was 40% (12 of 30 patients). Event-free survival was 31 weeks, and median overall survival was 39 weeks. The upfront association of carboplatin plus pemetrexed allows simultaneous treatment of cerebral and systemic disease in patients with NSCLC with newly diagnosed brain metastases and appears to be particularly interesting in terms of radiologic response and overall survival. Further clinical studies are warranted.

Cardiovascular toxicity of anti-angiogenic drugs

Anti-angiogenic targeted therapies are now major tools in the management of solid tumors. Briefly, one can distinguish between monoclonal antibodies such as bevacizumab directed against vascular endothelial growth factor (VEGF) and small molecules such as those targeted against receptors with tyrosine-kinase activity. Soon after they were marketed, these drugs showed cardiovascular toxicities, such as hypertension, left ventricular systolic dysfunction, heart failure and conduction abnormalities. The most frequent cardiovascular side effect of targeted therapies is hypertension, but the most life-threatening is QT prolongation with its risk of torsade de pointe and sudden cardiac death. Since the incidence of different types of cardiovascular side effects following targeted therapies varies across studies—and despite the fact that several meta-analyses attempted to summarize available information—those side effects are still not well identified. In addition, their reversibility is not precisely known. This review aims to present and discuss the various cardiovascular toxicities of anti-angiogenic targeted therapies for cancer.

18F-FDG PET-Derived Textural Indices Reflect Tissue-Specific Uptake Pattern in Non-Small Cell Lung Cancer

Purpose Texture indices (TI) calculated from 18F-FDG PET tumor images show promise for predicting response to therapy and survival. Their calculation involves a resampling of standardized uptake values (SUV) within the tumor. This resampling can be performed differently and significantly impacts the TI values. Our aim was to investigate how the resampling approach affects the ability of TI to reflect tissue-specific pattern of metabolic activity. Methods 18F-FDG PET were acquired for 48 naïve-treatment patients with non-small cell lung cancer and for a uniform phantom. We studied 7 TI, SUVmax and metabolic volume (MV) in the phantom, tumors and healthy tissue using the usual relative resampling (RR) method and an absolute resampling (AR) method. The differences in TI values between tissue types and cancer subtypes were investigated using Wilcoxon’s tests. Results Most RR-based TI were highly correlated with MV for tumors less than 60 mL (Spearman correlation coefficient r between 0.74 and 1), while this correlation was reduced for AR-based TI (r between 0.06 and 0.27 except for RLNU where r = 0.91). Most AR-based TI were significantly different between tumor and healthy tissues (pvalues <0.01 for all 7 TI) and between cancer subtypes (pvalues<0.05 for 6 TI). Healthy tissue and adenocarcinomas exhibited more homogeneous texture than tumor tissue and squamous cell carcinomas respectively. Conclusion TI computed using an AR method vary as a function of the tissue type and cancer subtype more than the TI involving the usual RR method. AR-based TI might be useful for tumor characterization.

Impact of physical activity on cancer-specific and overall survival of patients with colorectal cancer.

Background. Physical activity (PA) reduces incidence of colorectal cancer (CRC). Its influence on cancer-specific (CSS) and overall survival (OS) is controversial. Methods. We performed a literature-based meta-analysis (MA) of observational studies, using keywords “colorectal cancer, physical activity, and survival” in PubMed and EMBASE. No dedicated MA was found in the Cochrane Library. References were cross-checked. Pre- and postdiagnosis PA levels were assessed by MET. Usually, “high” PA was higher than 17 MET hour/week. Hazard ratios (HRs) for OS and CSS were calculated, with their 95% confidence interval. We used more conservative adjusted HRs, since variables of adjustment were similar between studies. When higher PA was associated with improved survival, HRs for detrimental events were set to <1. We used EasyMA software and fixed effect model whenever possible. Results. Seven studies (8056 participants) were included, representing 3762 men and 4256 women, 5210 colon and 1745 rectum cancers. Mean age was 67 years. HR CSS for postdiagnosis PA (higher PA versus lower) was 0.61 (0.44–0.86). The corresponding HR OS was 0.62 (0.54–0.71). HR CSS for prediagnosis PA was 0.75 (0.62–0.91). The corresponding HR OS was 0.74 (0.62–0.89). Conclusion. Higher PA predicted a better CSS. Sustained PA should be advised for CRC. OS also improved (reduced cardiovascular risk).

Human Transplantation of a Biologic Airway Substitute in Conservative Lung Cancer Surgery

BACKGROUND Pneumonectomies for lung cancer are associated with a high postoperative mortality, especially when right-sided, after neoadjuvant radiochemotherapy, and in patients over 70 years of age. Preliminary studies in our laboratory have shown that aortic grafts could be valuable airway substitutes. We report the first human bronchial transplantation of a cryopreserved aortic allograft used as a biologic airway substitute to prevent a pneumonectomy for lung cancer. METHODS The procedure was performed in a high-risk 78-year old patient with an extensive right bronchopulmonary malignant tumor pretreated with chemotherapy. After a complete resection of the lung cancer using an upper bilobectomy with lymph node removal, mobilization procedures did not allow for a primary end-to-end bronchial anastomosis. A stent-supported cryopreserved aortic allograft from a certified tissue bank was interposed to restore the bronchial continuity with sparing of the lower lobe. RESULTS The postoperative course was eventful for a supraventricular arrhythmia leading to mild pulmonary edema that resolved using standard medical therapy, and a right lower lobe atelectasis with bacterial colonization that required fiberoptic bronchoscopies in addition to antibiotic treatment. A 1-year postoperative evaluation found a well-functioning reimplanted lower lobe with no complications related to the cryopreserved aortic allograft or the stent. The patient recovered to his baseline activity with a satisfying health-related quality of life. CONCLUSIONS We demonstrate the feasibility of this surgical innovation to prevent the high-risk procedure of pneumonectomy in a single case. If confirmed in larger series of selected patients, it could bring new perspectives in conservative lung cancer surgery.

Fluorine 18 fluorodeoxyglucose PET/CT volume-based indices in locally advanced non-small cell lung cancer: prediction of residual viable tumor after induction chemotherapy.

PURPOSE To study whether volume-based indices of fluorine 18 fluorodeoxyglucose positron emission tomographic (PET)/computed tomographic (CT) imaging is an accurate tool to predict the amount of residual viable tumor after induction chemotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS This study was approved by institutional review board with waivers of informed consent. Twenty-two patients with locally advanced NSCLC underwent surgery after induction chemotherapy. All had pre- and posttreatment FDG PET/CT scans. CT largest diameter, CT volume, maximum standardized uptake value (SUVmax), mean SUV (SUVmean), metabolic tumor volume (TV), and total lesion glycolysis of primary tumor were calculated. Changes in tumor measurements were determined by dividing follow-up by baseline measurement (ratio index). Amounts of residual viable tumor, necrosis, fibrous tissue, inflammatory infiltrate, and Ki-67 proliferative index were estimated on resected tumor. Correlations between imaging indices and histologic parameters were estimated by using Spearman correlation coefficients or Mann-Whitney tests. RESULTS No baseline or posttreatment indices correlated with percentage of residual viable tumor. TV ratio was the only index that correlated with percentage of residual viable tumor (r = 0.61 [95% confidence interval: 0.24, 0.81]; P = .003). Conversely, SUVmax and SUVmean ratios were only indices correlated with Ki-67 (r = 0.62 [95% confidence interval: 0.24, 0.82]; P = .003; and r = 0.60 [95% confidence interval: 0.21, 0.81]; P = .004, respectively). Total lesion glycolysis ratio was moderately correlated with residual viable tumor (r = 0.53 [95% confidence interval: 0.13, 0.78]; P = .01) and with Ki-67 (r = 0.57 [95% confidence interval: 0.18, 0.80]; P = .006). No ratios were correlated with presence of inflammatory infiltrate or foamy macrophages. CONCLUSION TV and total lesion glycolysis ratios were the only indices correlated with residual viable tumor after induction chemotherapy in locally advanced NSCLC.

Revue généraleLes métastases cérébrales des cancers bronchiques non à petites cellules : vers une prise en charge homogèneManagement of brain metastases from non-small cell lung carcinoma

INTRODUCTION In France, approximately 30,000 new patients per year develop brain metastases (BM), most of them resulting from a lung cancer. STATE OF THE ART Surgery and radiosurgery of all the BM must be considered when possible. In other cases, whole brain radiotherapy remains the standard of care. PERSPECTIVES The role of chemotherapy, poorly investigated so far, should be revisited. CONCLUSION This review focused on BM secondary to a non-small cell lung carcinoma.

Les métastases cérébrales des cancers bronchiques non à petites cellules : vers une prise en charge homogène

INTRODUCTION In France, approximately 30,000 new patients per year develop brain metastases (BM), most of them resulting from a lung cancer. STATE OF THE ART Surgery and radiosurgery of all the BM must be considered when possible. In other cases, whole brain radiotherapy remains the standard of care. PERSPECTIVES The role of chemotherapy, poorly investigated so far, should be revisited. CONCLUSION This review focused on BM secondary to a non-small cell lung carcinoma.

Géfitinib et méningite carcinomateuse d'un carcinome bronchique non à petites cellules (CBNPC)

Resume Introduction Une meningite carcinomateuse est une complication majeure dans le CBNPC. Malgre le traitement par radiotherapie associee ou non a une chimiotherapie intra-thecale ou systemique, le pronostic reste tres reserve. Observations Nous rapportons l’observation d’une patiente non tabagique atteinte d’un adenocarcinome bronchique de type bronchiolo-alveolaire, presentant un meningite carcinomateuse compliquant l’evolution de sa maladie 3 ans apres le diagnostic de la tumeur primitive. Le traitement par gefitinib est initie apres une radiotherapie cerebrale devant la persistance d’un syndrome meninge. Ce traitement a permis une reponse clinique en moins de 3 semaines, et le maintien de cette reponse pendant 9 mois. Conclusion Le gefitinib peut entrainer une amelioration symptomatique sur la meningite carcinomateuse dans le CBNPC. Il merite d’etre evalue dans cette indication vu l’absence de toute therapeutique classique reellement active.

Feasibility of Bioengineered Tracheal and Bronchial Reconstruction Using Stented Aortic Matrices

Importance Airway transplantation could be an option for patients with proximal lung tumor or with end-stage tracheobronchial disease. New methods for airway transplantation remain highly controversial. Objective To establish the feasibility of airway bioengineering using a technique based on the implantation of stented aortic matrices. Design, Setting, and Participants Uncontrolled single-center cohort study including 20 patients with end-stage tracheal lesions or with proximal lung tumors requiring a pneumonectomy. The study was conducted in Paris, France, from October 2009 through February 2017; final follow-up for all patients occurred on November 2, 2017. Exposures Radical resection of the lesions was performed using standard surgical techniques. After resection, airway reconstruction was performed using a human cryopreserved (−80°C) aortic allograft, which was not matched by the ABO and leukocyte antigen systems. To prevent airway collapse, a custom-made stent was inserted into the allograft. In patients with proximal lung tumors, the lung-sparing intervention of bronchial transplantation was used. Main Outcomes and Measures The primary outcome was 90-day mortality. The secondary outcome was 90-day morbidity. Results Twenty patients were included in the study (mean age, 54.9 years; age range, 24-79 years; 13 men [65%]). Thirteen patients underwent tracheal (n = 5), bronchial (n = 7), or carinal (n = 1) transplantation. Airway transplantation was not performed in 7 patients for the following reasons: medical contraindication (n = 1), unavoidable pneumonectomy (n = 1), exploratory thoracotomy only (n = 2), and a lobectomy or bilobectomy was possible (n = 3). Among the 20 patients initially included, the overall 90-day mortality rate was 5% (1 patient underwent a carinal transplantation and died). No mortality at 90 days was observed among patients who underwent tracheal or bronchial reconstruction. Among the 13 patients who underwent airway transplantation, major 90-day morbidity events occurred in 4 (30.8%) and included laryngeal edema, acute lung edema, acute respiratory distress syndrome, and atrial fibrillation. There was no adverse event directly related to the surgical technique. Stent removal was performed at a postoperative mean of 18.2 months. At a median follow-up of 3 years 11 months, 10 of the 13 patients (76.9%) were alive. Of these 10 patients, 8 (80%) breathed normally through newly formed airways after stent removal. Regeneration of epithelium and de novo generation of cartilage were observed within aortic matrices from recipient cells. Conclusions and Relevance In this uncontrolled study, airway bioengineering using stented aortic matrices demonstrated feasibility for complex tracheal and bronchial reconstruction. Further research is needed to assess efficacy and safety. Trial Registration clinicaltrials.gov Identifier: NCT01331863