Hypnosis associated with 3D immersive virtual reality technology during bronchoscopy under local anesthesia.

Background: Patients undergoing flexible bronchoscopy under local anesthesia usually experience anxiety before and during the procedure. Different non-pharmacological techniques, including music and hypnosis, are used to distract patients' attention, and to reduce anxiety. The new technique "virtual reality hypnosis (VRH)", defined as a hypnotic induction suggestion delivered by personalized virtual reality software, can generate a simulation of a lifelike environment. No study has described the use of VRH during bronchoscopy. The objective is to investigate the anxiety reducing effect and the satisfaction of patients, physicians, and nurses using VRH during bronchoscopy. Methods: VRH was proposed to all patients who experienced anxiety before undergoing flexible bronchoscopy under local anesthesia. Local anesthesia was performed using 5% lidocaine spray only. No sedation was used. After the procedure, patients, physicians and nurses filled a standardized satisfaction form. Results: Twenty consecutive patients who reported pre-procedure anxiety were included. The sex ratio was 16 women/4 men, the median age was 65 years. Eight patients (40%) had undergone a previous bronchoscopy under local anesthesia. The median duration of the procedure was 10 minutes, and all procedures were completed. The median level of anxiety of patients decreased from 9/10 before the procedure to 4/10 during the procedure. The median satisfaction rate regarding the use of VRH was 10/10. All patients agreed to use VRH again in case of a new bronchoscopy procedure. Conclusions: This preliminary report has shown that VRH was useful to reduce patients' anxiety during bronchoscopy under local anesthesia. VRH was easily implemented in the routine practice.

Endoscopic follow-up of low-grade precancerous bronchial lesions in high-risk patients: long-term results of the SELEPREBB randomised multicentre trial.

BACKGROUND: 3-9% of low-grade preinvasive bronchial lesions progress to cancer. This study assessed the usefulness of an intensive bronchoscopy surveillance strategy in patients with bronchial lesions up to moderate squamous dysplasia. METHODS: SELEPREBB (ClinicalTrials.gov NCT00213603) was a randomised study conducted in 17 French centres. After baseline lung computed tomography (CT) and autofluorescence bronchoscopy (AFB) to exclude lung cancer and bronchial severe squamous dysplasia or carcinoma in situ (CIS), patients were assigned to standard surveillance (arm A) with CT and AFB at 36 months or to intensive surveillance (arm B) with AFB every 6 months. Further long-term data were obtained with a median follow-up of 4.7 years. RESULTS: 364 patients were randomised (A: 180, B: 184). 27 patients developed invasive lung cancer and two developed persistent CIS during the study, with no difference between arms (OR 0.63, 95% CI 0.20-1.96, p=0.42). Mild or moderate dysplasia at baseline bronchoscopy was a significant lung cancer risk factor both at 3 years (8 of 74 patients, OR 6.9, 95% CI 2.5-18.9, p<0.001) and at maximum follow-up (16 of 74 patients, OR 5.9, 95% CI 2.9-12.0, p<0.001). Smoking cessation was significantly associated with clearance of bronchial dysplasia on follow-up (OR 0.12, 95% CI 0.01-0.66, p=0.005) and with a reduced risk of lung cancer at 5 years (OR 0.15, 95% CI 0.003-0.99, p=0.04). CONCLUSION: Patients with mild or moderate dysplasia are at very high risk for lung cancer at 5 years, with smoking cessation significantly reducing the risk. Whereas intensive bronchoscopy surveillance does not improve patient outcomes, the identification of bronchial dysplasia using initial bronchoscopy maybe useful for risk stratification strategies in lung cancer screening programmes.

A simple endoscopic method with radial endobronchial ultrasonography for low-migration rate coil-tailed fiducial marker placement.

BACKGROUND: Fiducial markers (FMs) are useful for tracking small peripheral lung nodules (PLN) before stereotactic radiotherapy, but migration over the course of treatment may result in inaccurate dosing to the tumor. To minimize FM migration, coil-tailed FMs have been designed. Our objective was to assess both the feasibility of radial endobronchial ultrasonography (r-EBUS) placement and the migration rate of coil-tailed FMs. METHODS: In this retrospective study, we included patients who received r-EBUS guided placement of coil-tailed FMs for PLN <25 mm from June 2015 to May 2018. We introduced the FM into the nodule with the use of bronchial brush, without fluoroscopy. RESULTS: Thirty patients had r-EBUS guided placement of a coil-tailed FM before stereotactic radiation therapy. Nodule's median long- and short-axis diameters were 15 mm (8-25 mm) and 8 mm (5-20 mm), respectively; short diameter of 27 nodules (90%) was less than 15 mm. All nodules were reached and visualized with r-EBUS, with an ultrasound (US) signal showing a centered or tangential probe in 26 and 4 cases, respectively. No immediate complication was reported. Twenty-three patients had stereotactic radiation therapy within a median time of 29 days (14-126 days). No FM migration occurred between r-EBUS placement and radiotherapy. Pre-treatment planning and 3-month follow-up CT scans showed that all FMs stayed in direct contact with the lesions. CONCLUSIONS: r-EBUS is a safe procedure for the placement of nitinol coil FMs, which have a low migration rate.

Characteristics of Lung Cancer in Patients Younger than 40 Years: A Prospective Multicenter Analysis in France.

OBJECTIVES: The aim of this study was to describe the demographic and clinico-pathological characteristics of lung cancer in patients younger than 40 years. MATERIALS AND METHODS: This was a prospective study performed within the Groupe Français de Pneumo-Cancérologie. Consecutive patients diagnosed with lung cancer before the age of 40 years were eligible. Data on demographics, medical history, clinico-pathological characteristics, treatment and overall survival were analysed. RESULTS: In total, 146 patients were included from January 2011 to December 2013. Median age was 38 years (IQR: 34-40). Women accounted for 41%. Main histological type was adenocarcinoma (77%). Only 3% had a prior history of cancer, but a family history (first- or second-degree relatives) of cancer was reported in 80 (55%) patients; 85 and 50% were current or past smokers of tobacco and cannabis, respectively; 82% had stage IIIB/IV at diagnosis. Median overall survival was 15.3 (95% CI: 8.1-24.0) months in the whole population, 10.3 (95% CI: 12.5-14.2) months in stage IV and 15 (95% CI: 8.7-35.2) months in stage III. One- and two-year overall survival rates were 57% (95 CI: 49-65) and 31.5% (95 CI: 27-43), respectively. Compared to smokers, non-smokers were significantly younger and more often females. Median overall survival was not statistically different between smokers and non-smokers.

Assessment of Per-Endoscopic Placement of Fiducial Gold Markers for Small Peripheral Lung Nodules < 20 mm Before Stereotactic Radiation Therapy.

BACKGROUND: Stereotactic radiotherapy is used to treat peripheral lung cancer in inoperable patients. Placement of fiducial gold markers (FMs) is crucial for tracking small lesions that are not visible on chest radiographs. Our objective was to assess endoscopic FM placement in small peripheral lung nodules (PLNs) that are not trackable using automated tracking software. METHODS: All patients benefiting from virtual bronchoscopy and radial endobronchial ultrasonography (R-EBUS)-guided placement of FMs for PLNs < 20 mm were included. After confirmation by biopsy sampling, a gold-seed FM was inserted into the nodule using a bronchial brush, without the use of fluoroscopy. The performance and complications of the procedure were recorded. RESULTS: From May 2010 to June 2015, FMs were placed in the PLNs of 54 consecutive patients, 34 of whom presented with a nodule < 20 mm. Seventy-six percent of the procedures were performed using local anesthesia on an outpatient basis. The median long- and short-axis diameters of nodules were 15 mm (9-20 mm) and 11 mm (6-20 mm), respectively, with 31 of 34 nodules exhibiting a short axis of < 15 mm. In 23 cases (79%), histologic samples were obtained during the procedure that allowed FM placement. Migration occurred in six cases, including two in the hours following the procedure. FMs were in place and visible on CT imaging performed 3 months after radiation therapy in 80% of cases. No complications were reported. CONCLUSIONS: Diagnosis of peripheral nodules < 20 mm and FM placement using R-EBUS are efficient and safe in a single procedure.

Multidisciplinary Tumor Board Decision Making for Postoperative Radiotherapy in Thymic Epithelial Tumors: Insights from the RYTHMIC Prospective Cohort.

INTRODUCTION: Thymic epithelial tumors (TETs) are rare intrathoracic malignancies for which surgery represents the mainstay of the treatment. Current practice for postoperative radiotherapy (PORT) is highly variable, and there is a lack of prospective, high level evidence. Réseau Tumeurs Thymiques et Cancer (RYTHMIC) is the nationwide network for TETs in France. Established in 2012, it prospectively collects data on all TET patients, for whom management is discussed at a national multidisciplinary tumor board (MTB). We assessed whether PORT decisions at the MTB were in accordance with RYTHMIC guidelines and ultimately implemented in patients. METHODS: All consecutive patients for whom PORT was discussed at the MTB from 2012 to 2015 were identified from the RYTHMIC prospective database, and a complete review of their medical records was performed. RESULTS: A total of 274 patients, including 243 with thymoma (89%) and 31 with thymic carcinoma (11%), were analyzed. The decision of the MTB was in accordance with guidelines in 221 patients (92%) of the 241 with stage I or III TET. An MTB decision to deliver PORT was made for 117 patients (43%). PORT was ultimately initiated in 101 patients. The most frequent reason for not delivering PORT was excessive (>3 months) delay after surgery. Dose-volume constraints defined by the International Thymic Malignancy Interest Group were followed in all but four patients. CONCLUSION: Our data provide a unique insight into the decision-making process for PORT in TETs, highlighting the need for systematic discussion at an expert MTB, while stressing the value of current available guidelines.

Use of a Comprehensive Geriatric Assessment for the Management of Elderly Patients With Advanced Non-Small-Cell Lung Cancer: The Phase III Randomized ESOGIA-GFPC-GECP 08-02 Study.

PURPOSE: Comprehensive geriatric assessment (CGA) is recommended to assess the vulnerability of elderly patients, but its integration in cancer treatment decision making has never been prospectively evaluated. Here, in elderly patients with advanced non-small-cell lung cancer (NSCLC), we compared a standard strategy of chemotherapy allocation on the basis of performance status (PS) and age with an experimental strategy on the basis of CGA. PATIENTS AND METHODS: In a multicenter, open-label, phase III trial, elderly patients ≥ 70 years old with a PS of 0 to 2 and stage IV NSCLC were randomly assigned between chemotherapy allocation on the basis of PS and age (standard arm: carboplatin-based doublet if PS ≤ 1 and age ≤ 75 years; docetaxel if PS = 2 or age > 75 years) and treatment allocation on the basis of CGA (CGA arm: carboplatin-based doublet for fit patients, docetaxel for vulnerable patients, and best supportive care for frail patients). The primary end point was treatment failure free survival (TFFS). Secondary end points were overall survival (OS), progression-free survival, tolerability, and quality of life. RESULTS: Four hundred ninety-four patients were randomly assigned (standard arm, n = 251; CGA arm, n = 243). Median age was 77 years. In the standard and CGA arms, 35.1% and 45.7% of patients received a carboplatin-based doublet, 64.9% and 31.3% received docetaxel, and 0% and 23.0% received best supportive care, respectively. In the standard and CGA arms, median TFFS times were 3.2 and 3.1 months, respectively (hazard ratio, 0.91; 95% CI, 0.76 to 1.1), and median OS times were 6.4 and 6.1 months, respectively (hazard ratio, 0.92; 95% CI, 0.79 to 1.1). Patients in the CGA arm, compared with standard arm patients, experienced significantly less all grade toxicity (85.6% v 93.4%, respectively P = .015) and fewer treatment failures as a result of toxicity (4.8% v 11.8%, respectively; P = .007). CONCLUSION: In elderly patients with advanced NSCLC, treatment allocation on the basis of CGA failed to improve the TFFS or OS but slightly reduced treatment toxicity.

Epidemiology and treatment costs of bone metastases from lung cancer: a French prospective, observational, multicenter study (GFPC 0601).

INTRODUCTION: The aim of this prospective, observational, multicenter study was to examine the epidemiology and management costs of bone metastatic disease (BMD) in patients with lung cancer. METHODS: The analysis included all patients with BMD from lung cancer diagnosed between May 2006 and May 2007 in 40 centers. We analyzed their management and the direct costs of BMD from the health care provider's perspective, using a Markov model. Skeletal-related event (SRE) was defined as pathological fractures, spinal cord compression, or hypercalcemia (clinical SRE [cSRE]) for an initial analysis; a second analysis included palliative radiotherapy and surgery (therapeutic SRE [tSRE]). RESULTS: Among the 554 patients enrolled (62 ± 11 years, 76.5% males, 69.3% performance status 0/1, 91% non-small cell lung cancer), 24.7% had a cSRE and 26.7% a tSRE at baseline and 9% and 39% during follow-up, respectively; 81.8% received at least one chemotherapy cycle. The median survival time was 5.8 months, and the 1- and 2-year survival rates were 22% and 7%, respectively; there was no significant difference in overall survival between the patients with and without SRE at enrollment. The main BMD treatments were opiate therapy (77.7%), biphosphonates (52.3%), radiotherapy (42.1%), and surgery (9.2%). The mean monthly BMD treatment costs in euros were €190, €374, and €4672 for asymptomatic patients, symptomatic patients, and patients with SRE, respectively. The average first-year BMD management cost in euros was €3999 ± 4135 (95% confidence interval: 374-15,886), and 49.5% of this cost was attributable to patients with SRE. CONCLUSIONS: This analysis confirms the poor prognosis of BMD from lung cancer and underlines the burden of SRE in overall treatment costs.

Cost-effectiveness of second-line chemotherapy for non-small cell lung cancer: an economic, randomized, prospective, multicenter phase III trial comparing docetaxel and pemetrexed: the GFPC 05-06 study.

BACKGROUND: There are few data on the cost-effectiveness of second-line chemotherapies for non-small cell lung cancer (NSCLC). The objective of this phase III, randomized, multicenter, prospective study was to compare the cost-effectiveness of docetaxel and pemetrexed, two widely used drugs. METHODS: We compared, from a payer's perspective, the directs costs and effectiveness of docetaxel (75 mg/m, arm A) and pemetrexed (500 mg/m, arm B) administered every 3 weeks to NSCLC patients who had progressed after first-line platinum-based chemotherapy. Monthly health utilities (based on disease states: responding, stable or progressive, and grade 3/4 toxicities) were derived from the literature. Costs were prospectively assessed. RESULTS: One hundred fifty patients were enrolled between February 2006 and June 2008. The patients in the docetaxel and pemetrexed arms had similar clinical characteristics and treatment efficacy (respective objective response rates 10.7% and 12%; median progression-free survival times 2.8 and 2.5 months; median survival times 8.0 and 6.4 months, respectively). Grade 3/4 toxicities were significantly less frequent with pemetrexed (52.0% versus 33.3%, p = 0.02). Docetaxel was associated with lower treatment-period costs (€9709 ± €6272 versus €13,436 ± €6508, p < 0.001). Docetaxel had a more favorable cost-utility ratio than pemetrexed. When compared with best supportive care, the cost-utility was €32,652/quality-adjusted life year for docetaxel and €40,980/quality-adjusted life year for pemetrexed. CONCLUSION: Second-line treatment for NSCLC is more cost-effective with docetaxel than with pemetrexed. Both strategies have acceptable cost-effectiveness ratios compared with commonly used and reimbursed regimens for advanced NSCLC.

Molecular predictive factors for progression of high-grade preinvasive bronchial lesions.

RATIONALE: The outcome of precancerous bronchial lesions is not well known, and their management is subject to controversy. Many molecular alterations are present in preinvasive lesions, but none has been assessed to predict the evolution of the lesions. OBJECTIVES: To analyze the outcome of high-grade precancerous lesions according to their molecular profile. METHODS: Twenty-three severe dysplasia and 31 carcinoma in situ (CIS) lesions in 37 patients were monitored using repeated autofluorescence bronchoscopy over a 12-year period. Microdissection and polymerase chain reaction analysis were performed on paraffin tissue sections to assess loss of heterozygosity (LOH) and microsatellite instability on chromosome 3p, 5q, and 9p. Histology and molecular status at baseline were compared between 7 lesions that became invasive, 11 that relapsed after treatment, 17 that were eradicated with local treatment, and 19 that spontaneously regressed. MEASUREMENTS AND MAIN RESULTS: Ninety-four percent of lesions that progressed or relapsed were CIS at baseline, whereas 79% of spontaneously regressing lesions were severe dysplasia (P < 0.0001). 3p and 9p LOH was more frequent in CIS than in severe dysplasia (P = 0.03). In the whole group of lesions as well as in the CIS group, 3p LOH was strongly associated with progression (P < 0.0001 and P = 0.02, respectively). Microsatellite instability was not associated with the outcome of the lesions. A therapeutic strategy based on the presence of 3p or 9p LOH would have led to overtreatment of six lesions but would have missed only 1 among the 18 progressing lesions. CONCLUSIONS: Baseline histology and 3p LOH analysis appear to be useful in predicting the outcome of high-grade precancerous lesions.