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S. Demichelis



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    P1.23 - Poster Session 1 - Tobacco Control, Prevention and Chemoprevention (ID 162)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Prevention & Epidemiology
    • Presentations: 1
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      P1.23-001 - The real role of health care professionals in providing smoking cessation counselling among lung cancer patients: preliminary data (ID 1051)

      09:30 - 16:30  |  Author(s): S. Demichelis

      • Abstract

      Background
      According to the World Health Organization, one hundred million deaths were caused by tobacco in the 20th century and the expectation for 2030 is equal to 10 million deaths. Lung cancer is the leading cause of cancer death and in the United States cigarette smoking is responsible for an estimated 90% of all lung cancers. About 50% of lung cancer patients are current smokers at the time of diagnosis and 11 to 48% of all smokers continue to smoke. Parsons et al. in a review of 10 studies suggest that smoking cessation after early stage lung cancer diagnosis improves prognostic outcomes and, despite evidences that smoking cessation is related with more effective treatment, reduced chemotherapy and radiotherapy toxicities and a better prognosis, the belief prevails that treating tobacco dependence is less important than the other therapeutic approaches.

      Methods
      122 lung cancer patients referring to the Thoracic Oncology Unit of the S. Luigi Hospital in Orbassano – Italy (31% of the total number of patients referring to this center in this period of time) were prospectively and sequentially evaluated from 02/01/2013 to 30/05/2013. In order to collect data, a dedicated 15 question-anonymous survey was developed with the aim to understand if smoker or former smoker patients had received information by health professionals, about smoking cessation before or after the diagnosis, which reaction they had and which actions were adopted for quitting smoking.

      Results
      The median age of participants was 65 years or more, 75% were men, 25% women. 27% were smokers, 73% former smokers. Among active smokers, most patients (87.8%) reduced the number of cigarettes after being diagnosed. 45.4% of patients report not to have received information on smoking cessation by the healthcare professionals and among patients who received it, the majority (84.2%) declared a good or very good ability of health workers to understand the difficulty of quitting smoking. About 76% considers positively the action of health care providers and a little percentage reports a warning and paternalistic attitude of them. 67.7% of patients who attempted to quit smoking, state the sudden termination as the most effective measure, more than the gradual reduction of cigarettes. Analyzing anti-smoking techniques or therapies adopted, most patients declare not to resort to such methods: only 25% started using electronic cigarettes, 5.5% has used a nicotine replacement treatment, 4.1% is attending an antismoking clinic.

      Conclusion
      The analysis of the study results underline that most lung cancer patients are interested in smoking cessation programs and although many of them receive advice and assistance by healthcare workers, the recourse to the use of techniques, drugs or access to specific clinic is very low. In Italy there are few centers offering counseling for smoking cessation, while in UK, Norway and Netherlands innovative interventions are available and oncology nurses are essential in the identification of and intervention with patients who struggle with this dependence. This is a pivotal experience and other Italian and Spanish centers are already been involved in the questionnaire collection to get more complete and heterogeneous results

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    P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.06-013 - Genetic profiling of lung cancer in young adults patients: early data assessment using Next-Generation Sequencing. (ID 1189)

      09:30 - 16:30  |  Author(s): S. Demichelis

      • Abstract

      Background
      In 3% of cases, lung cancer is diagnosed in patients younger than 45 years. The epidemiology, biology and clinical history of young lung cancer patients is generally different from the adult counterpart: the higher percentage of mutations has the potential to influence both tolerability and response to treatment with consequent impact on quality of life and survival. The biomolecular characterization of the disease in this subgroup will allow the design of clinical studies dedicated to young patients, that will lead to the identification of specific items that are not deducible from trials opened to the general adult population. In this study, Next-Generation Sequencing (NGS) technology has been applied to archival tissue samples to enhance tumor-specific genomic profile knowledge in this selected cohort of young patients (pts).

      Methods
      A retrospective analysis has been performed at the Thoracic Unit of San Luigi Hospital from January 2007 to March 2013, collecting 13 lung cancer-diagnosed pts (10 completely sequenced; in 3 cases the analysis is ongoing), aged between 15-39 years. Genomic DNA was extracted by microdissected formalin-fixed and paraffin embedded (FFPE) tumor samples of all pts and by lymphocytes of three healthy controls (ctrl). Amplicons NGS libraries for 46 oncogenes included in the Ion Torrent Cancer Panel were generated, following manufacture guidelines, and sequenced in Personal Genome Machine (PGM) Ion Torrent instrument. Variant Caller included in Torrent Suite Software was used to identify mutations.

      Results
      Twenty-two non-synonymous, 3 frameshifts, 3 stop-gain and 55 synonymous somatic sequence variations were found in 10 young adult patients (allelic frequency ≥ 10%). Excluding synonymous mutations, the most frequently altered genes in patients were TP53 (7 mutations; 25%), followed by EGFR and KDR (5 mutations; 18%), PI3K (3 mutations; 11%), KIT (7 mutations; 14%), FGFR3-ABL1-MET-ATM-RB1-SMO (1 mutation; 3.6%). Furthermore, 14 of these mutations are annotated in SIFT or in PolyPhen databases as “mutations that could damage affected protein”. Overall, we identified 28 mutations annotated in COSMIC database, among which the most frequent were COSM149673, COSM28026 and COSM6223-COSM22413 with 5,4 and 2 counts, respectively. We also found 93 SNPs in our cohort, including the most frequent rs7688609, rs1873778 and rs1050171 with 13 counts (10 pts; 3 ctrl) followed by rs1800861 (9 pts; 3ctrl); rs41115 (8 pts; 2ctrl); rs1870377 (4 pts; 1ctrl); rs3822214 (2 pts; 2ctrl); rs3729687 (2 pts; 1ctrl); rs2228230 (2 pts) and rs3730358-rs3135898 (1 pt; 1ctrl).

      Conclusion
      The development of new biological techniques, such as the next-generation sequencing, could allow to collect a wide number of mutations. From these preliminary results, some interesting data have been discovered concerning SNPs or mutations. This pivotal retrospective analysis is the basis for the ongoing prospective collection. A better definition of molecular-genetic pattern in this selected young population of patients could increase the knowledge about the lung cancer etiology and suggest age-related new trials design.

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    P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.11-041 - Treatment with crizotinib in patients with IV stage non-small cell lung cancer (NSCLC) with ALK translocation: a single institution experience. (ID 2961)

      09:30 - 16:30  |  Author(s): S. Demichelis

      • Abstract

      Background
      Crizotinibis is a MET inhibitor, having also an activity on ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene 1) pathways. The ALK translocation is described in 4% of NSCLC and these patients (pts) benefit from crizotinib therapy with a response rate (RR) ranging from 51 to 61%.The drug is already approved by FDA and EMA; in Italy crizotinib is available in first line within controlled clinical trials and, until April 2013, within expanded access program (EAP).

      Methods
      From June 2010 to February 2013, 155 pts with advanced NSCLC were analyzed for Alk translocation using fluorescence in situ hybridization (FISH) at our institution. The selection criteria were: adenocarcinoma histology, never or ex smoker, EGFR status WT. Main pts characteristics were: 59% males, median age 57,5 years (range 26-76), 77 former smoker (76 pts for more than 15 years). Tissue samples were available from primary tumor and metastases in 78 and 22%, respectively, having 73% of cases with cytological material. In 23,2% of the specimens Alk rearrangement was not evaluable due to poor quality and/or quantity issues.

      Results
      Among the 155 pts, 22 (14%) are ALK translocated: 19 were treated within PROFILE clinical trials and 3 patients in the EAP. 20 pts are currently evaluable for response and toxicity: 6 of them received crizotinib as first-line treatment, the others in subsequent lines. The response rate was equal to 70%. The total number of administered cycles is 235.The reduction of the dose (7% of cycles) was necessary in two pts: in 1 case due to bradicardia and fatigue G3 (in first line treatment) and in the other one due to neutropenia G3 (in second line).The observed toxicities were mostly grade 1-2 (fatigue 47%, bradycardia 5,8%, visual disorder 5,8%, anemia 29%, neutropenia 18% and nausea 12%); grade 3-4 was less common. The temporary cessation of treatment was required in 3 pts (range 4-15 days) for grade 3-4 toxicity (mostly neutropenia plus fatigue). No drug interruption for unacceptable toxicity was reported. The most common progression sites were brain (37%) and bone (27%).

      Conclusion
      The introduction of a selection criteria (such as negative EGFR status) leads on an increase of our cases of Alk traslocated pts compared to literature data; this selection is moreover recommended in diagnostic algorithm recently proposed by the Italian Expert Panel (Marchetti A et al, JTO 2013). Efficacy and tolerability profile are consistent with published data.