Georges Sebbane

Comparison of the efficacy and safety of single-agent and doublet chemotherapy in advanced non-small cell lung cancer in the elderly: A meta-analysis

BACKGROUND In patients with advanced non-small cell lung cancer (NSCLC) aged more than 70 years, the benefit-to-risk ratio of doublet chemotherapy vs single-agent is not established. METHODS We performed a meta-analysis (MA), with a PubMed query using keywords simultaneously (Randomized controlled trial, Aged, Anti-neoplastic combined chemotherapy protocols/therapeutic use, Carcinoma, Non-small cell lung/drug therapy). Abstracts from ASCO, WCLC, and ESMO proceedings were reviewed. Articles were also obtained by cross-checking references. Third-generation agents (gemcitabine, vinorelbine, paclitaxel, docetaxel) in combination with or without platinum were included. The efficacy outcomes were Overall Response Rate (ORR) and 1-Year Overall Survival (OS). We used EasyMA software and a random-effect model in case of heterogeneity. RESULTS This MA comprised 10 studies including 2605 patients (mean age 74; 1866 men and 620 women; 654 stage IIIB and 1677 stage IV; 839 squamous cell cancers, 968 adenocarcinomas, 521 other pathological types). One-year OS (including the last trial by Abe) did not significantly improve for doublets compared with single-agents (HR 0.92; 95% Confidence Interval or CI: 0.82-1.03) whereas it improved significantly before inclusion of this last study, when the study by Quoix et al., the most favorable to doublets, was included. However, doublet chemotherapy significantly improved ORR after inclusion of Abe study (HR 1.51; 1.22-1.86; p<0.001). OS was not significantly improved, neither by doublets including platinum (HR 0.90, 0.70-1.16), nor by those without platinum (HR 0.94, 0.84-1.07). ORR, but not OS, was improved by doublets including a taxane (docetaxel and paclitaxel) (HR 1.72; 1.28-2.33) except for paclitaxel with a significant OS and ORR benefit. All-grade neutropenia thrombocytopenia and anemia were significantly more frequent with doublets than with single-agents (HR 1.26, 1.15-1.39; 1.75, 1.11-2.77 and 1.33, 1.17-1.52 respectively). Grade 3/4 thrombocytopenia and anemia but not neutropenia were significantly more frequent with doublets (HRs 2.13, 1.01-4.49 and 1.84, 1.29-2.63 respectively). CONCLUSION Compared with single-agents, doublets significantly improved ORR but not OS. They induced significantly more frequent thrombocytopenia and anemia. The benefit-to-risk ratio of doublets in advanced NSCLC might be more favorable than that of single agents, based on ORR but not OS.

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.

Impaired mobility, depressed mood, cognitive impairment and polypharmacy are independently associated with disability in older cancer outpatients: The prospective Physical Frailty in Elderly Cancer patients (PF-EC) cohort study

OBJECTIVE To assess the prevalence of disability and the oncologic factors associated with disability in older outpatients with cancer. MATERIALS AND METHODS The Physical Frailty in Elderly Cancer patients (PF-EC) study (France) is a prospective bicentric observational cohort study. Two hundred and ninety outpatients with cancer were included. A cross-sectional analysis of oncologic factors and geriatric variables associated with disability that were collected using a comprehensive geriatric assessment (CGA) was conducted. Disability was defined as impairment in activities of daily living (ADL) and/or instrumental activities of daily living (IADL), simplified to four items. Univariate and multivariate logistic models of disabled patients were performed. The three final multivariate models were compared using the area under the receiver operating characteristic curve (AUC/ROC) of the logistic model. RESULTS The mean age was 80.6years, and 51% of the patients were women with various types of cancer. The prevalence of disability was 67.6%. No oncologic factors (cancer site, cancer extension) were associated with disability. Impaired mobility, poor functional status, depressive mood, cognitive impairment and polypharmacy were independently associated with disability (P<0.05). The AUC/ROC of the final models was similar. CONCLUSION Disability was highly prevalent in older cancer outpatients before cancer treatment but was not associated with oncologic factors. Impaired mobility, depressed mood, cognitive impairment and polypharmacy were the geriatric variables significantly and independently associated with disability. Identifying these factors prior to cancer treatment could enable the implementation of corrective actions to improve patient autonomy before treatment and during follow-up.

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

Diagnostic performance of gait speed, G8 and G8 modified indices to screen for vulnerability in older cancer patients: the prospective PF-EC cohort study

BACKGROUND The diagnostic performance of tools used to screen vulnerability in older cancer patients varies widely. We assessed the diagnostic performance of gait speed (GS) for assessing vulnerability in such patients. METHODS All consecutive outpatients 65 years and older were referred for geriatric oncology assessment (GA) before a therapeutic decision between November 2013 and April 2016 in a bicentric observational and prospective cohort study. Vulnerability was defined as impaired score on at least one of the 6 domains of the GA. GS and the G8 index and G8 modified index were assessed at the first geriatric oncology visit during the GA. Sensitivity, specificity, positive and negative predictive value and positive and negative likelihood ratio were estimated. The accuracy of the three tools was analysed by the area under the receiver operating characteristic curve (AUC). RESULTS Among 269 included patients (mean [SD] age, 81.3 years [5.9]; 55% women, 94.4% solid tumors; 39.4% with metastasis), 252 (93.7%) had impaired GA. With the GS threshold of 1 m/s, sensitivity was 79.4% (95% CI, 73.8-84.2), specificity 64.7% (38.3-85.8), and AUC 82.0 (74.0-90.0). The corresponding values for the G8 index were 90.1% (85.7-93.5), 35.3% (14.2-61.7), and 79.0 (70.0-88.0) and G8 modified index were 89.3% (84.8-92.8), 64.7% (38.3-85.8), and 84.0 (74.0-92.0). CONCLUSIONS GS < 1 m/s with a single measure could be used as a new screening tool for detecting vulnerability in older cancer outpatients. This first external validation of the G8 modified index was very good.Background The diagnostic performance of tools used to screen vulnerability in older cancer patients varies widely. We assessed the diagnostic performance of gait speed (GS) for assessing vulnerability in such patients. Methods All consecutive outpatients 65 years and older were referred for geriatric oncology assessment (GA) before a therapeutic decision between November 2013 and April 2016 in a bicentric observational and prospective cohort study. Vulnerability was defined as impaired score on at least one of the 6 domains of the GA. GS and the G8 index and G8 modified index were assessed at the first geriatric oncology visit during the GA. Sensitivity, specificity, positive and negative predictive value and positive and negative likelihood ratio were estimated. The accuracy of the three tools was analysed by the area under the receiver operating characteristic curve (AUC). Results Among 269 included patients (mean [SD] age, 81.3 years [5.9]; 55% women, 94.4% solid tumors; 39.4% with metastasis), 252 (93.7%) had impaired GA. With the GS threshold of 1 m/s, sensitivity was 79.4% (95% CI, 73.8-84.2), specificity 64.7% (38.3-85.8), and AUC 82.0 (74.0-90.0). The corresponding values for the G8 index were 90.1% (85.7-93.5), 35.3% (14.2-61.7), and 79.0 (70.0-88.0) and G8 modified index were 89.3% (84.8-92.8), 64.7% (38.3-85.8), and 84.0 (74.0-92.0). Conclusions GS < 1 m/s with a single measure could be used as a new screening tool for detecting vulnerability in older cancer outpatients. This first external validation of the G8 modified index was very good.

32. Un myxofibrosarcome de haut grade de la cuisse chez une patiente âgée

Fiche Situations de soins : Madame M., âgee de 80 ans, est hospitalisee en medecine geriatrique pour une perte d’autonomie en lien avec l’evolution d’une masse tumorale de la cuisse gauche. L’aspect clinique de cette tumeur rare des tissus mous est exemplaire. (R.E.)

P.10 Evaluation of standard chemo-radiotherapy in older patients with locally advanced non-small cell lung cancer (NSCLC) enrolled in a multicenter randomized phase II study

Background: More than half of cancers occur after the age of 65 and this should grow progressively. Unfortunately elderly people are rarely included in therapeutic surveys and in screening tests, so they miss optimal treatment of their cancer (surgery, chemotherapy, radiotherapy) most of the time. At the Ambroise Pare academic hospital, a 440 beds urban hospital, a geriatric intervention team (GIT) has been created since February 2004. One of its aims is to help others specialists to assess the better treatment for their patients. Patients: In 3 years, 2800 evaluations were done by the GIT in the whole hospital, 234 on inpatients of the pneumology department. On those, 53 were hospitalised for the diagnosis or the treatment of a cancer. Results: Patients average age was 80±6 years old, 53% were female. The mini-GDS was positive in 53% and a time and space disorientation was observed in 41%. 67% patients had cognitive troubles, with high risk of falls for 86%. In 28%, patients received a chemotherapy. In the end, 4 groups of patients could be observed “primary” (2%) who will have an optimal treatment “intermediate” (37%) at whom will be proposed an adjusted treatment “secondary”(50%) who will have a symptomatic treatment “near death” (11%) with palliative care Conclusion: This collaboration have afforded us to identify better patients likely to receive an optimal treatment. The main contribution of the EIG in this collaboration was to afford a fast geriatric assessment to the others physicians in order to make up one’s mind to the best treatment.