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S.G. Rapetti



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    P3.08 - Poster Session 3 - Radiotherapy (ID 199)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P3.08-006 - Respiratory function changes after stereotactic ablative radiotherapy (SABR) in stage I non-surgical NSCLC: preliminary results from a single institution prospective study. (ID 1017)

      09:30 - 09:30  |  Author(s): S.G. Rapetti

      • Abstract

      Background
      Stereotactic Ablative Radiotherapy (SABR) is an alternative to surgery in patients with early stage non-small cell lung cancer (NSCLC) inoperable for medical co-morbidities (mainly cardiovascular or respiratory diseases) or who refuse surgery. We performed a prospective evaluation of lung function parameters, treatment-related radiological and clinical toxicity in a cohort of patients treated with SABR.

      Methods
      We prospectively recruited 26 patients from July 2012 to May 2013. All patients had a histological or cytological diagnosis of NSCLC (n=20) or a lung lesion in dimensional growth with PET positivity (SUV>2.5) (n=6). All patients had stage IA– IB and were judged unfit for surgery or refused it. Each patient did a 4D-TC with slice of 2.5mm/2.5mm, treatment consisted of a single Volumetric Modulated Arc Therapy and the fractionation schedule was dependent on tumor location. Pulmonary toxicity was assessed through the execution of pulmonary function tests and on chest Computed Tomografy (CT). All tests were synchronously performed before treatment and at regular intervals after SABR (the first control at 45 days, then every 90 days until progression). Lung function parameters were obtained performing spirometry, body plethysmography, determination of the diffusion lung capacity of carbon monoxide (DLCO) and arterial blood gas analysis.

      Results
      Of 26 patients enrolled, 17 performed the first evaluation at 45 days, 5 at 135. At 45 days the total lung capacity (TLC) slightly decreased from 5.87±1.50 Liters (L) to 5.62±1.42 (t=1.87; NS), whereas VC, FEV~1~ and FEV~1~/VC ratio showed minimal changes. At 135 days TLC in the 5 patients who ultimate this step showed a slight recovery to 5.75±1.75 L. The pulmonary diffusion capacity for carbon monoxide (D~L~CO), corrected for hemoglobin (Hb) levels, significantly decreased from 14.4±4.9 to 12.9±5.2 (mL min[-1]·mmHg[-1]) at 45 days (p<0.019) with a slight recovery at 135 day to 13.9±2.7. When D~L~CO was corrected for the measured Alveolar Volume (D~L~CO/VA) the change was not significant. The difference between plethysmographic TLC and the dilution VA (TLC-VA) increased at 45 days from 1.24±0.7 to 1.49±0.8 L, suggesting an increase in ventilation inhomogeneity of the lung. Arterial oxygen pressure decreased from 75.8±7.2 to 71.6±10.4 mmHg (p=0.056 NS) and the variation correlated with TLC-VA (r=-0.72, p<0.001) and DLCO variations (r=-0.67, p<0.03). We observed a low toxicity profile during the first evaluation at 45 days, with only 1 RTOG grade 2 and 1 grade 3 post actinic pneumonia, both treated with systemic corticosteroids. Only three patients reported fatigue as the only adverse event. At the first radiological re-evaluation we didn’t observe any progression disease, with a 59% rate of partial response.

      Conclusion
      Preliminary findings suggest that no major changes in lung function can be detected at 45 days after SABR. A slight reduction in D~L~CO can be observed, and this could reflect a transitory increase in pulmonary ventilation inhomogeneity caused by RT rather than a direct membrane damage. Study prosecution will hopefully clear the physiopathological evolution at several months after SABR, and further analyses will be carried out investigating for a potential correlation with radiological toxicity and dosimetric profiles.

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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 - 09:30  |  Author(s): S.G. Rapetti

      • 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.

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    P3.19 - Poster Session 3 - Imaging (ID 181)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Imaging, Staging & Screening
    • Presentations: 1
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      P3.19-015 - Should core biopsy with larger needle replace FNAB in assessing lung masses? (ID 2331)

      09:30 - 09:30  |  Author(s): S.G. Rapetti

      • Abstract

      Background
      The distinction between SCLC and NSCLC has been recently replaced by a more detailed re-classification. As 70% of patients with LC are still not eligible for surgery, tumor characterization is often based on needle biopsy. For the management of lung masses (LM), the availability of adequate samples is critical not only for pathological diagnosis, but also for additional molecular studies. In this context, our aim was to evaluate the safety and accuracy of image-guided core biopsies (CB) in our last 4-year series.

      Methods
      480 consecutive patients (325 male; 33-87 y, mean 68; LM diameter 6-150 mm, m 37,4) underwent 439 CT-guided, 35 US-guided and 6 US+CT-guided lung biopsies. In 325/480 cases (68%) a CB was preferred due to the possible requirement of molecular studies. 275 CB were performed with >=18G tru-cut needle, 50 with <18G, both by a coaxial technique (inserted in a 1G larger styleted cannula). 1 to 6 sampling per patient (m 1.5) were performed. Adverse events (including major complications) were recorded and correlated with technical issues (namely, with needle size). To assess the accuracy of CB, surgical specimens, outcome of non-surgical therapy and follow-up imaging were considered as gold standards. Sensitivity, specificity, diagnostic accuracy and positive and negative predictive values of CB were calculated.

      Results
      81/325 (24.9%) adverse events occurred, but only 23 (7%) were major complications (MC) (22 pneumothorax and 1 hemothorax, requiring drainage and prolonged hospitalization). The incidence of MC wasn’t different between either CB and FNAB group (11/155, 7%), or larger and smaller CB needle size (20/275 vs. 3/50, p=n.s). Only the depth of the LM seemed to be significant as negative predictor for MC (p=.0061). Pathological diagnosis was of benign LM in 60 CB (18.4%), malignancy in 265 (81.5%). According to the above gold standard criteria, TP were 265, FN 13, TN 47, FP 0. Sensitivity, specificity and diagnostic accuracy were 95.3%, 100% and 96%, respectively. PPV was 100%, NPV 78.3%.

      Conclusion
      CB is as safe as FNAB in characterizing LM; particularly, needle size doesn’t impact on MC rate. CB is highly accurate in morphological characterization of LM, also providing additional tissue for molecular studies, when needed.

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    P3.24 - Poster Session 3 - Supportive Care (ID 160)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P3.24-009 - Histologic and genotypic evolution in lung cancer harboring mutations in the epidermal growth factor receptor (EGFR): a clinical case. (ID 708)

      09:30 - 09:30  |  Author(s): S.G. Rapetti

      • Abstract

      Background
      This is a clinical case of an EGFR-mutant Non-Small Cell Lung Cancer (NSCLC) with adenocarcinoma (ADC) histology: a subsequent diagnosis of high grade neuroendocrine small-cell lung cancer (SCLC) carrying an EGFR mutation was done at the first re-biopsy and further, a sarcomatous cancer was finally diagnosed. Recent publications were focused on drug-resistance mechanisms in patients with a specific biomolecular alteration re-biopsed after receiving the targeted therapy: in some cases morphologic and immunophenotypic changes were described. This finding suggests the possibility of "clonal resistance" with a selective pressure of some groups of cells, even if the histopathological features of these mechanisms have not yet been completely elucidated.

      Methods
      A 62-year-old caucasian man, with past smoking habit, presented with a 2-week history of cough and dyspnea. After a diagnosis of stage IV lung ADC, he received, on March 2010, 1st line treatment with cisplatin 75 mg/m2 plus pemetrexed 500 mg/m2 on Day 1 every 21 days, for 6 cycles. He achieved a partial response on computed tomography (CT) and a marked regression of his symptoms. On August 2011, a CT scan revealed a progressive disease (PD); he started treatment with Erlotinib plus ARQ-197/placebo within a clinical trial. As deemed by protocol, molecular analyses were performed on biopsy specimen at time of diagnosis, evidencing exon 21 – point mutation, p.Leu858Arg at EGFR mutational assessment. After 4 cycles, a local progressive disease was described by CT scan and a fibrobronchoscopic re-biopsy was performed in order to define the novel biomolecular profile at that time of the history of the disease. The histological evaluation highlighted a SCLC and molecular analyses confirmed the p.Leu858Arg mutation. Based on new histological diagnosis, he underwent chemotherapy with AUC6 carboplatin on Day 1 every 21 days plus etoposide 100 mg/m2 on Day 1,2,3 every 21 days, for a total of 6 cycles, until May 2012, achieving partial response at CT scan. On August 2012, because of radiological evidence of disease progression, he underwent chemotherapy with Cyclophosphamide 800 mg/m2, Doxorubicine 40mg/m2 and Vincristine 1mg/m2 on Day 1 every 21 days. After 3 cycles, he reported intense swelling in the supraclavicular right fossa and a fine needle aspiration of supraclavicular right lymphadenopathy was performed. The final pathological diagnosis was undifferentiated sarcoma cells (CK-,TTF1-, VIM+) . Patient died, on January 2013, because of worsening of clinical conditions.

      Results
      Not applicable

      Conclusion
      Many studies hypothesize that SCLC either evolved from the previously diagnosed NSCLC or that both arose from a common precursor. Further comparative molecular analysis of these histologically distinct tumors would be of value to better understand the potential role of EGFR in the evolution of lung cancer and the role of selection for an EGFR-mutant SCLC cell subclone as an unusual mechanism of acquired resistance to EGFR inhibitors in NSCLC.