Detection of Tumor DNA in Bronchoscopic Fluids in Peripheral NSCLC: A Proof-of-Concept Study.

Introduction: DNA genotyping from plasma is a useful tool for molecular characterization of NSCLC. Nevertheless, the false-negative rate justifies the development of methods with higher sensitivity, especially in difficult-to-reach peripheral lung tumors. Methods: We aimed at comparing molecular analysis from the supernatant of guide sheath flush fluid collected during radial-EndoBronchial UltraSound (r-EBUS) bronchoscopy with plasma sampling and tumor biopsies in patients with peripheral NSCLC. The DNA was genotyped using high-throughput sequencing or the COBAS mutation test. There were 65 patients with peripheral lung tumors subjected to concomitant sampling of guide sheath flush supernatant, plasma tumor DNA, and tumor biopsy and cytology using r-EBUS. There were 33 patients (including 24 newly diagnosed with having NSCLC) with an identifiable tumor mutation in the primary lesion selected for the comparative analysis. Results: Guide sheath flush-based genotyping yielded a mutation detection rate of 61.8% (17 of 24 mutated EGFR, one of two ERBB2, one of one KRAS, one of one MAP2K, one of four MET, and zero of one STK11), compared with 33% in plasma-based genotyping (p = 0.0151). Furthermore, in eight of 34 r-EBUS without tumor cells on microscopic examination, we were able to detect the mutation in four paired guide sheath flush supernatant, compared with only two in paired plasma. Conclusion: The detection of tumor DNA in the supernatant of guide sheath flush fluid collected during r-EBUS bronchoscopy represents a sensitive and complementary method for genotyping NSCLC.

Assessment of endobronchial ultrasound-guided bronchoscopy (EBUS) intranodal forceps biopsy added to EBUS 19-gauge transbronchial needle aspiration: A blinded pathology panel analysis.

BACKGROUND: Endobronchial ultrasound-guided (EBUS) transbronchial needle aspiration (TBNA) has significantly improved the diagnostic workup for intrathoracic lymphadenopathies. More recently, EBUS intranodal forceps biopsy (IFB) has been developed in an attempt to maximize diagnostic yield by providing additional tissue. In this study, we aimed to assess the improvement of diagnostic yield with EBUS-TBNA combined with EBUS-IFB, compared to EBUS-TBNA alone. METHODS: Consecutive patients who had 19-G EBUS-TBNA and EBUS-IFB from August 30, 2018, to September 28, 2021, were included. Four senior pathologists retrospectively analyzed, independently and blindly, first, only the EBUS-TBNA samples (cell block), then, at least 1 month later, both samples from EBUS-TBNA and from EBUS-IFB together. RESULTS: Fifty patients were included in the study and 52 lymph nodes were analyzed. Diagnostic yield was 77% (40/52) for EBUS-TBNA alone and 94% (49/52) when combined with EBUS-IFB (p = 0.023). Malignancy was diagnosed with EBUS-TBNA combined with EBUS-IFB in 25/26 cases (96%), versus 22/26 (85%) with EBUS-TBNA alone (p = 0.35); and 4/5 (80%) versus 2/5 (40%) for lymphoma specifically. Kappa interobserver agreement was 0.92 for EBUS-IFB and 0.87 for EBUS-TBNA alone. Nonmalignant condition was diagnosed with EBUS-TBNA combined with EBUS-IFB in 24/26 cases (92%), versus 18/26 (69%) for EBUS-TBNA alone (p = 0.07). CONCLUSION: The use of EBUS-IFB combined with 19-G EBUS-TBNA improves the mediastinal lymph node diagnostic yield However the benefit appears to be mainly restricted to nonmalignant histology.

French practical guidelines for the diagnosis and management of idiopathic pulmonary fibrosis - 2021 update. Full-length version.

BACKGROUND: Since the latest 2017 French guidelines, knowledge about idiopathic pulmonary fibrosis has evolved considerably. METHODS: Practical guidelines were drafted on the initiative of the Coordinating Reference Center for Rare Pulmonary Diseases, led by the French Language Pulmonology Society (SPLF), by a coordinating group, a writing group, and a review group, with the involvement of the entire OrphaLung network, pulmonologists practicing in various settings, radiologists, pathologists, a general practitioner, a health manager, and a patient association. The method followed the "Clinical Practice Guidelines" process of the French National Authority for Health (HAS), including an online vote using a Likert scale. RESULTS: After a literature review, 54 guidelines were formulated, improved, and then validated by the working groups. These guidelines addressed multiple aspects of the disease: epidemiology, diagnostic procedures, quality criteria and interpretation of chest CT scans, lung biopsy indication and procedures, etiological workup, methods and indications for family screening and genetic testing, assessment of the functional impairment and prognosis, indication and use of antifibrotic agents, lung transplantation, management of symptoms, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are intended to guide the diagnosis and practical management of idiopathic pulmonary fibrosis.

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.

Radial-EBUS and virtual bronchoscopy planner for peripheral lung cancer diagnosis: How it became the first-line endoscopic procedure.

BACKGROUND: Various advanced bronchoscopy methods have been developed to reach peripheral lung lesions (PLL). In a large cohort, we aimed to assess a standardized procedure of first-line radial-endobronchial ultrasound (r-EBUS) and virtual bronchoscopy planner for the diagnosis of peripheral lung cancer. METHODS: This retrospective, single center study included patients who had r-EBUS-guided bronchoscopy for the diagnosis of a PLL between 2008 and 2019. Cases without a final diagnosis of cancer or follow-up were excluded. RESULTS: Between 2008 and 2019, 2735 patients had a r-EBUS procedure, among whom 1627 had a final diagnosis of cancer and were included in the present study. Over the 12-year study period, r-EBUS became the first-line endoscopic procedure to assess PLL (25% as first-line bronchoscopy in 2008 vs. 92% in 2019). The frequency of the bronchus sign decreased from 2009 to 2019 (100% to 80%; p = 0.001), whereas US visualization of the lesion remained stable (88%). The median number of biopsies increased from two (2008 to 2014) to four (2015 to 2019) (p < 0.0001), with the same diagnostic efficiency (74% total and 80% when a bronchus sign was present). Of the 651 adenocarcinomas, molecular analysis was possible in 86%. PD-L1 expression analysis was possible in 81% of cases. During the study period, the lifetime of the radial probe increased from 57 procedures to 77 procedures/probe. CONCLUSION: Because r-EBUS and VB planner is easy to perform under local anesthesia, inexpensive and efficient it can be used as a first-line procedure to assess peripheral lung cancer.

How Bronchoscopic Dye Marking Can Help Minimally Invasive Lung Surgery.

In the era of increasing availability of high-resolution chest computed tomography, the diagnosis and management of solitary pulmonary nodules (SPNs) has become a common challenging clinical problem. Meanwhile, surgical techniques have improved, and minimally invasive approaches such as robot- and video-assisted surgery are becoming standard, rendering the palpation of such lesions more difficult, not to mention pure ground-glass opacities, which cannot be felt even in open surgery. In this article, we explore the role of bronchoscopy in helping surgeons achieve successful minimally invasive resections in such cases.

Prognostic value of total tumour volume, adding necrosis to metabolic tumour volume, in advanced or metastatic non-small cell lung cancer treated with first-line pembrolizumab.

BACKGROUND: Metabolic tumour volume (MTV) measured on fluorodeoxyglucose F18 (FDG) positron emission tomography coupled with computed tomography (PET/CT) is a prognostic factor of advanced non-small cell lung cancer (NSCLC) treated by first-line immunotherapy. However, these tumours are often necrotic and the necrosis, which is hypometabolic in PET FDG, is not included in the MTV. The aim of this study was to evaluate the prognostic value of total tumour volume (TTV), adding necrotic tumour volume (NTV) to metabolic tumour volume (MTV). METHODS: We retrospectively included 65 patients with NSCLC treated with pembrolizumab as monotherapy. All patients had a pretreatment FDG PET/CT. PET/CT measured parameters were MTV, NTV and TTV. Clinical, biological and tumour parameters were also retrieved. Receiver operator characteristics (ROC) analysis was performed and overall survival at 1 year was studied using Kaplan-Meier and uni/multivariate Cox analysis. RESULTS: In the ROC analysis, MTV, NTV, TTV, age at diagnosis, polynuclear blood neutrophil, derived neutrophil/leukocyte ratio (dNLR), and haemoglobin had an area under the curve (AUC) significantly higher than 0.5. In Kaplan-Meier analysis, prognosis was worse for patients with high MTV (p = 0.02), high TTV (p = 0.003), high NTV (p = 0.014), low haemoglobin (p < 0.001), older people (p = 0.002), neutrophil polynucleosis (p < 0.001) and dNLR (p = 0.022). All these parameters, except age and neutrophil polynucleosis, were significant prognostic factors in univariate Cox analysis (p < 0.05). In a stepwise multivariate Cox analysis focused on PET parameters, the only significant parameter was TTV (HR = 3.66, p = 0.002) and in a stepwise multivariate Cox analysis exploring all the parameters, a model combining TTV, performance status and brain metastasis was found (p = 0.002). CONCLUSIONS: TTV and NTV measured on pretreatment FDG PET/CT are significant prognosis factor for stage III-IV NSCLC treated by pembrolizumab and TTV could have a higher prognostic value than MTV.

Anti-PD1/PD-L1 Immunotherapy for Non-Small Cell Lung Cancer with Actionable Oncogenic Driver Mutations.

Anti-PD1/PD-L1 immunotherapy has emerged as a standard of care for stage III-IV non-small cell lung cancer (NSCLC) over the past decade. Patient selection is usually based on PD-L1 expression by tumor cells and/or tumor mutational burden. However, mutations in oncogenic drivers such as EGFR, ALK, BRAF, or MET modify the immune tumor microenvironment and may promote anti-PD1/PD-L1 resistance. In this review, we discuss the molecular mechanisms associated with these mutations, which shape the immune tumor microenvironment and may impede anti-PD1/PD-L1 efficacy. We provide an overview of the current clinical data on anti-PD1/PD-L1 efficacy in NSCLC with oncogenic driver mutation.

An improved assay for detection of theranostic gene translocations and MET exon 14 skipping in thoracic oncology.

Theranostic translocations may be difficult to detect by routine techniques, especially when specimens are exiguous. We recently demonstrated in a series of translocated lung adenocarcinomas that LD-RT-PCR (ligation-dependent reverse transcription polymerase chain reaction) assay could identify ALK, ROS1 and RET rearrangements with 64% sensitivity and 100% specificity. Here, we report an upgraded version of this assay used in a routine prospective cohort of lung carcinomas. Newly diagnosed lung carcinomas referred to the Rouen molecular platform between 15/05/2018 and 15/05/2019 for ALK and ROS1 IHC, genotyping (SNaPshot© +/- high-throughput genotyping) and sometimes FISH (standard routine process) were tested prospectively in parallel with the LD-RT-PCR assay designed to detect at one go ALK, ROS1 and RET translocations and MET exon 14 skipping. 413 tumors from 396 patients were included. LD-RT-PCR had a global sensitivity of 91.43% (standard routine process: 80%), with a specificity of 100%. It detected 15/18 ALK and 4/4 ROS1 translocated tumors, but also 6/6 tumors with MET exon 14 skipping retrieved by genotyping. In addition, it retrieved 7 alterations missed by the routine process, then confirmed by other means: 5 MET exon 14 skipping and 2 RET translocated tumors. Finally, it allowed to deny an effect on MET exon 14 skipping for 8 mutations detected by routine genotyping. We successfully implemented LD-RT-PCR in routine analysis. This technique is cheap, fast, sensitive, specific, and easily upgradable (e.g., NTRK translocations), but still requires IHC to be performed in parallel. Owing to its advantages, we recommend considering it, in parallel with IHC and genotyping, as an excellent cost-effective alternative, for the systematic testing of lung adenocarcinoma, to FISH and to more expensive and complex assays such as RNA-seq.

Virtual Bronchoscopy Planner and Radial-EBUS Guided Biopsy for Organizing Pneumonia Diagnosis.

BACKGROUND: The diagnosis of organizing pneumonia (OP) often requires histological confirmation. The aim of this retrospective study was to evaluate the diagnostic yield and complication rate of radial endobronchial ultrasound (r-EBUS) for OP. METHODS: All patients who had r-EBUS as a first diagnostic procedure for a peripheral pulmonary lesion at Rouen University Hospital, France, between April 2008 and December 2020 were included. Cases without a final diagnosis of OP or follow-up were excluded. Patients, lesions, and r-EBUS characteristics were retrospectively analyzed. RESULTS: 2735 r-EBUS procedures were performed, and 33 cases with final OP could be analyzed. Procedures were performed under local anesthesia in 28/33 cases (85%). Among the 33 final OP cases, 17 were considered cryptogenic, and 16 secondary. The lesions were patchy alveolar opacities in 23 cases (70%), masses or pulmonary nodules in 8 cases (24%), and diffuse infiltrative opacities in 2 cases (6%). A bronchus sign on CT scan was found in all cases. In 22 cases (67%), a histopathological diagnosis was obtained from the r-EBUS samples. In 4 cases (12%), histopathological diagnosis was made by surgery, and in 7 cases (21%) the diagnosis was made based on clinical, radiological, and evolution features. An ultrasound image was found in 100% (22/22) of cases in the r-EBUS positive (r-EBUS+) group vs. 60% (6/10) in the r-EBUS negative (r-EBUS-) group, respectively (p < 0.002). The diagnostic yield of r-EBUS for OP was 67% and increased to 79% (22/28) when an ultrasound image was obtained. The median time between CT scan and r-EBUS procedure was 14 days (3-94): 11.5 days in the r-EBUS+ group and 22 days in the r-EBUS- group (p < 0.0001). No severe complications were reported. CONCLUSION: r-EBUS, when performed shortly after a CT scan showing a bronchus sign, is an efficient and safe technique for OP diagnosis.

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.

Inhibition of ADAMTS-4 Expression in Olfactory Ensheathing Cells Enhances Recovery after Transplantation within Spinal Cord Injury.

Spinal cord injury (SCI) induces permanent loss of sensitive and motor functions below the injury level. To date, a wide variety of cells has been used as biotherapies to cure SCI in different animal paradigms. Specifically, olfactory ensheathing cells (OECs) is one of the most promising. Indeed, OECs have been shown to enhance recovery in many animal studies. Moreover, OECs transplantation has been applied to a paraplegic patient and have shown beneficial effects. However, it has been reported that the significant level of recovery varies among different patients. Therefore, it is of primary importance to enhance the regenerative efficiency of OECs for better translations. Recently, it has been shown that inhibiting ADAMTS4 expression in glial cells in vitro increases their synthesis of neurotrophic factors. We hypothesized that the expression of neurotrophic factors secreted by OECs can be increased by the deletion of ADAMTS4. Taking advantage of ADAMTS4-/- mouse line, we produce ADAMTS4 deficient primary OEC cultures and then we investigated their regenerative potential after SCI. By using quantitative polymerase chain reaction, bioluminescence imaging, measurement of locomotor activity, electrophysiological studies, and immunohistochemistry, our results show that ADAMTS4-/- olfactory bulb OEC (bOECs) primary cultures upregulate their trophic factor expression in vitro, and that the transplantation of ADAMTS4-/- bOECs in a severe SCI model increases functional recovery and tissue repair in vivo. Altogether, our study reveals, for the first time, that primary bOEC cultures transplantation can be potentialized by inhibition of the expression of ADAMTS4.

Scalable chemical synthesis of doped silicon nanowires for energy applications.

A versatile, low-cost and easily scalable synthesis method is presented for producing silicon nanowires (SiNWs) as a pure powder. It applies air-stable diphenylsilane as a Si source and gold nanoparticles as a catalyst and takes place in a sealed reactor at 420 °C (pressure <10 bar). Micron-sized NaCl particles, acting as a sacrificial support for the catalyst particles during NW growth, can simply be removed with water during purification. This process gives access to SiNWs of precisely controlled diameters in the range of 10 ± 3 nm with a high production yield per reactor volume (1 mg cm-3). The reaction was scaled up to 500 mg of SiNWs without altering the morphology or diameter. Adding diphenylphosphine results in SiNW n-type doping as confirmed by ESR spectroscopy and EDX analyses. The measured SiNW doping level closely follows the initial dopant concentration. Doping induces both an increase in diameter and a sharp increase of electrical conductivity for P concentrations >0.4%. When used in symmetric supercapacitor devices, 1% P-doped SiNWs exhibit an areal capacity of 0.25 mF cm-2 and retention of 80% of the initial capacitance after one million cycles, demonstrating excellent cycling stability of the SiNW electrodes in the presence of organic electrolytes.

A rationale for surgical debulking to improve anti-PD1 therapy outcome in non small cell lung cancer.

Anti-PD1 immunotherapy has emerged as a gold-standard treatment for first- or second-line treatment of stage IV NSCLC, with response rates ranging from 10 to 60%. Strategies to improve the disease control rate are needed. Several reports suggested that debulking surgery enhances anti-tumor immunity. We aimed at examining tumor burden as a predictive factor of anti-PD1 tretment efficacy and to evaluate the role of cytoreductive surgery in anti-PD1 treated NSCLC. Immunocompetent DBA/2 mice engrafted with various amount of allogeneic lung squamous cancer KLN-205 cells were treated with anti-PD1 monoclonal antibody. Mice engrafted with two tumors also underwent a debulking surgery or a sham procedure. Tumor volume was monitored to assess treatment efficacy. Tumor infiltrating lymphocytes were assessed by flow cytometry. In a retrospective study of 48 stage IV NSCLC patients treated with Nivolumab who underwent a 18-FDG PETscan before treatment onset, the prognostic role of metabolic tumor volume was analysed. Anti-PD1 treatment effect was greater in mice bearing smaller tumors. Treatment with higher doses of anti-PD1 antibody did not improve the outcome, independently of the size of the tumor. In mice bearing 2 tumors, excision of 1 tumor improved the anti-PD1 treatment effect on the remaining tumor. In 48 NSCLC patients receiving anti-PD1 treatment, high metabolic tumor volume was associated with poor overall survival and the absence of clinical benefit. Treg infiltration, but not effector T cells, was positively correlated to tumor volume. Taken together, our results suggest that tumor volume is a predictive factor of anti-PD1 efficacy in NSCLC. Additionally, an experimental murine model suggests that tumor debulking may improve control of residual tumor.

Characteristics and outcome of patients set up on high-flow oxygen therapy at home.

BACKGROUND: High-flow oxygen therapy (HFOT) is increasingly used for acute respiratory failure. Few data support its use at home for the treatment of chronic respiratory failure. Our aim was to report the pattern of the use of long-term HFOT in our center and the outcome of patients setup on long-term HFOT. METHODS: A retrospective monocentric study including all patients setup on long-term HFOT between January 2011 and April 2018 in Rouen University Hospital was carried out. Patients were divided into two groups, patients with hypoxemic respiratory failure treated with nasal HFOT (nHFOT) and tracheotomized patients treated with tracheal HFOT (tHFOT). RESULTS: A total of 71 patients were established on long-term HFOT. Out of these 43 (61%) were included in the nHFOT group and 28 (39%) were included in the tHFOT group. In the nHFOT group, underlying respiratory diseases were interstitial lung disease (n = 15, 35%), pulmonary hypertension (n = 12, 28%), lung cancer (n = 9, 21%), and chronic airway disease (n = 7, 16%). In the tHFOT group, the number of admissions for exacerbation decreased by -0.78 per year (-2 to 0) (p = 0.045). In total, 51 (72%) patients were discharged to their homes and 20 (28%) went to a post-acute re-enablement facility. Median survival following HFOT was 7.5 months. Survival was significantly lower in the nHFOT group with a median survival of 3.6 months whereas median survival was not reached in the tHFOT group (p < 0.001). Monthly costs associated with home delivery of HFOT were €476 (296-533) with significant differences in costs between the nHFOT group of €520 (408-628) and costs in the tHFOT group of €296 (261-475) (p < 0.001). CONCLUSIONS: The use of long-term HFOT allows very severe patients to be discharged at a reasonable cost from acute care facilities. The reviews of this paper are available via the supplementary material section.

Prognostic value of post-induction chemotherapy 18F-FDG PET-CT in stage II/III non-small cell lung cancer before (chemo-) radiation.

INTRODUCTION: The purpose of our present study was to assess the prognostic impact of FDG PET-CT after induction chemotherapy for patients with inoperable non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS: This retrospective study included 50 patients with inoperable stage II/III NSCLC from January 2012 to July 2015. They were treated for curative intent with induction chemotherapy, followed by concomitant chemoradiation therapy or sequential radiation therapy. FDG PET-CT scans were acquired at initial staging (PET1) and after the last cycle of induction therapy (PET2). Five parameters were evaluated on both scans: SUVmax, SUVpeak, SUVmean, TLG, MTV, and their respective deltas. The prognostic value of each parameter for overall survival (OS) and progression-free survival (PFS) was evaluated with Cox proportional-hazards regression models. RESULTS: Median follow-up was 19 months. PET1 parameters, clinical and histopathological data were not predictive of the outcome. TLG2 and ΔTLG were prognostic factors for OS. TLG2 was the only prognostic factor for PFS. For OS, log-rank test showed that there was a better prognosis for patients with TLG2< 69g (HR = 7.1, 95%CI 2.8-18, p = 0.002) and for patients with ΔTLG< -81% after induction therapy (HR = 3.8, 95%CI 1.5-9.6, p = 0.02). After 2 years, the survival rate was 89% for the patients with low TLG2 vs 52% for the others. We also evaluated a composite parameter considering both MTV2 and ΔSUVmax. Patients with MTV2> 23cc and ΔSUVmax> -55% had significantly shorter OS than the other patients (HR = 5.7, 95%CI 2.1-15.4, p< 0.01). CONCLUSION: Post-induction FDG PET might be an added value to assess the patients' prognosis in inoperable stage II/III NSCLC. TLG, ΔTLG as well as the association of MTV and ΔSUVmax seemed to be valuable parameters, more accurate than clinical, pathological or pretherapeutic imaging data.

The Path of Gallium from Chemical Bath into ZnO Nanowires: Mechanisms of Formation and Incorporation.

ZnO nanowires grown by chemical bath deposition (CBD) are of high interest, but their doping with extrinsic elements including gallium in aqueous solution is still challenging despite its primary importance for transparent electrodes and electronics, and for mid-infrared plasmonics. We elucidate the formation mechanisms of ZnO nanowires by CBD using zinc nitrate and hexamethylenetetramine as standard chemical precursors, as well as gallium nitrate and ammonia as chemical additives. A complete growth diagram, revealing the effects of both the relative concentration of gallium nitrate and pH, is gained by combining a thorough experimental approach with thermodynamic computations yielding theoretical solubility plots as well as Zn(II) and Ga(III) speciation diagrams. The role of Ga(OH)4- complexes is specifically shown as capping agents on the m-plane sidewalls of ZnO nanowires, enhancing their development and hence decreasing their aspect ratio. Additionally, the gallium incorporation into ZnO nanowires is investigated in detail by chemical analyses and Raman scattering. They show the predominant formation of gallium substituting for zinc atoms (GaZn) in as-grown ZnO nanowires and their partial conversion into GaZn-VZn complexes after postdeposition annealing under oxygen atmosphere. The conversion is further related to a significant relaxation of the strain level in ZnO nanowires. These findings reporting the physicochemical processes at work during the formation of ZnO nanowires and the related gallium incorporation mechanisms offer a general strategy for their extrinsic doping and open the way for carefully controlling their physical properties as required for nanoscale device engineering.

Sub-cutaneous Fat Mass measured on multislice computed tomography of pretreatment PET/CT is a prognostic factor of stage IV non-small cell lung cancer treated by nivolumab.

Introduction: Our aim was to explore the prognostic value of anthropometric parameters in patients treated with nivolumab for stage IV non-small cell lung cancer (NSCLC). Methods: We retrospectively included 55 patients with NSCLC treated by nivolumab with a pretreatment 18FDG positron emission tomography coupled with computed tomography (PET/CT). Anthropometric parameters were measured on the CT of PET/CT by in-house software (Anthropometer3D) allowing an automatic multi-slice measurement of Lean Body Mass (LBM), Fat Body Mass (FBM), Muscle Body Mass (MBM), Visceral Fat Mass (VFM) and Sub-cutaneous Fat Mass (SCFM). Clinical and tumor parameters were also retrieved. Receiver operator characteristics (ROC) analysis was performed and overall survival at 1 year was studied using Kaplan-Meier and Cox analysis. Results: FBM and SCFM were highly correlated (ρ = 0.99). In ROC analysis, only FBM, SCFM, VFM, body mass index (BMI) and metabolic tumor volume (MTV) had an area under the curve (AUC) significantly higher than 0.5. In Kaplan-Meier analysis using medians as cut-offs, prognosis was worse for patients with low SCFM (<5.69 kg/m2; p = 0.04, survivors 41% vs 75%). In Cox univariate analysis using continuous values, BMI (HR = 0.84, p= 0.007), SCFM (HR = 0.75, p = 0.003) and FBM (HR = 0.80, p= 0.004) were significant prognostic factors. In multivariate analysis using clinical parameters (age, gender, WHO performance status, number prior regimens) and SCFM, only SCFM was significantly associated with poor survival (HR = 0.75, p = 0.006). Conclusions: SCFM is a significant prognosis factor of stage IV NSCLC treated by nivolumab.