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R. Ramos



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    P1.05 - Poster Session with Presenters Present (ID 457)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Early Stage NSCLC
    • Presentations: 1
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      P1.05-004 - Surfactant Protein C is a Prognostic Marker in Resected Non-Small Cell Lung Cancer (ID 4393)

      14:30 - 15:45  |  Author(s): R. Ramos

      • Abstract
      • Slides

      Background:
      The lung cancer cells express genes involved in key points of the lung development. The objective of this study was to determine the prognostic value of expression of embryonic markers in tumour tissue samples from patients with surgically-treated non-small cell lung cancer (NSCLC).

      Methods:
      Study based on 129 primary tumour samples from 102 patients with surgically-treated NSCLC (99% R0) and 27 lung samples. Expression of the following markers was evaluated by mRNA RT-qPCR assay: CEACAM5, FGFR2b, FRS2, MYCN, SFTPC, SHH, SHP2, and SOX17 in the tumour and lung samples. Statistical analyses included chi-squared tests, non-parametric tests, Kaplan Meier curves, log-rank and Cox regression tests.

      Results:
      Patients' characteristics were: mean age 67 ± 8 years, squamous carcinoma (49%), adenocarcinoma (43%), pathological staging: I: 56%, II: 32%, III: 11% and IV: 1%. 18% received adjuvant chemotherapy, 1% radiotherapy and 7% both. CEACAM5 and MYCN were overexpressed in tumour samples related to lung samples (p<0,05), FGFR2b showed similar expression and FRS2, SFTPC, SHH, SHP2 and SOX17 were underexpressed (p<0,05). The squamous carcinomas expressed more FGFR2b, FRS2 and SFTPC (p<0,10), while adenocarcinomas expressed more CEACAM5 (p>0,05). Lymph node involvement was associated with SHH underexpression (p<0,05), intratumoral vascular invasion with CEACAM5 or FGFR2b underexpression (p<0,05) and relapse with SHH (p<0,05) or SFTPC (p=0,09) underexpression. Kaplan-Meier curves of SFTPC were plotted in figure 1. Underexpression of SFTPC in the tumour sample was associated with a 7-fold (7.3; 1.3-40.9) greater active risk of recurrence and a nearly 5-fold (4.9; 1.04-23.2) greater risk of death. Underexpression of SHP2 was associated with a shorter disease-free survival interval (DFS) and overall survival (OS) (p=0.055). Overexpression of FGFR2b or SHH was associated with longer DFS and OS (p<0.05; for SHH, p=0.07 for OS). Combining markers did not provide any additional information. Figure 1



      Conclusion:
      Underexpression of SFTPC in tumour samples was independently associated with worse prognosis.

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    P2.03b - Poster Session with Presenters Present (ID 465)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P2.03b-044 - Treatment Outcome and the Role of Primary Tumor Therapy in a Cohort of Patients with Synchronous Oligometastatic NSCLC (ID 6089)

      14:30 - 15:45  |  Author(s): R. Ramos

      • Abstract
      • Slides

      Background:
      Although long-term survival was observed in selected patients (pts) with oligometastatic non-small cell lung cancer, the current treatment for those pts remains controversial. This retrospective study aimed to determine the characteristics and the outcome of pts with synchronous oligometastatic NSCLC (SOM-NSCLC) treated in a single center.

      Methods:
      SOM was defined as thoracic disease along with ≤3 metastatic lesions. We identified 90 pts in our database that qualified as SOM-NSCLC treated from 2007-2015 at the Catalan Institute of Oncology. Overall Survival (OS) was plotted using Kaplan Meier method, and multivariate Cox model for prognostic factors was developed.

      Results:
      Pts’ characteristics are shown in Table 1. Most pts received chemotherapy (91%): 85% platinum doublet and 56% ≥4 cycles. 57 of 90 pts (63%) received thoracic radical therapy (TRT): surgical resection (16%), SBRT (3.5%), concurrent chemoradiotherapy (CRT; 70%) and sequential CRT (10.5%). Median OS for all patients was 17.4m (95% CI 9.6 – 25.2). In the multivariate Cox analysis of OS, T extension, histology, smoking history and TRT were independent prognostic factors. As TRT was a highly favourable prognostic factor (HR=0.39, 95% CI 0.20 - 0.80), we looked at the characteristic of pts according to whether they received TRT. Pts treated with TRT had significantly lower number of metastases and metastatic organs involved. 70 of 90 pts (78%) received local therapy (LT) in the metastatic sites: surgery (10%), radiotherapy (61%) or both (29%). Interestingly, pts treated with TRT and LT had significantly longer median OS (32.8; 95% CI 10.8 – 54.9) as compared with other pts (9.3; 95% CI 4.3 – 14.2; p=0.006). Figure 1



      Conclusion:
      In this retrospective cohort of SOM-NSCLC pts, TRT combined with LT provided a remarkable median OS of 33 months. These data support radical treatment of the primary tumor including definitive chemoradiation in the setting of SOM-NSCLC.

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    P2.05 - Poster Session with Presenters Present (ID 463)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Radiotherapy
    • Presentations: 3
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      P2.05-018 - Re-Irradiation Using SBRT: A Good Option as a Salvage Treatment in Pulmonary Lesions (ID 5936)

      14:30 - 15:45  |  Author(s): R. Ramos

      • Abstract
      • Slides

      Background:
      Isolated intrathoracic relapse is common across distinct tumors and especially in lung cancer. Patients who received previous radiotherapy treatment (PRT) are not suitable for salvage surgery and chemotherapy provides poor local control. This study aimed to assess the toxicity and outcome of SBRT re-irradiation (reRT) in patients with solid tumors who developed an intrathoracic relapse.

      Methods:
      35p treated with PRT who received salvage SBRT were identified in our database and their medical records were retrospectively reviewed. All patients underwent complete pulmonary function tests (cPFTs) (including DLCO, FEV1 and FVC) and PET-CT scan was performed before and after receiving lung reRT. Treatment planning was based on image fusion with the previous treatment plan and calculating the cumulative total nominal dose. Survival estimations were performed using Kaplan-Meier and differences between PFTs prior and post-reRT were analyzed using Student T-Test. Early toxicity was defined when it occurred up to 6 months.

      Results:
      Median age: 68 (r53-81); 29p (83%) were male The previous treatments SBRT in 17p (49%), 3D-RT 4p (11%) and CT+RT 14p (40%) Mean RT dose 60,4Gy (r34-74). Primary tumors: lung 24 (69%), colorectal 9 (25%), oesophagus 2 (6%). For lung cancer p, the stage distribution was: IA 8 (23%), IB 2 (6%), IIA 2 (5.7%), IIB 1 (3%), IIIA 5 (4%), IIIb 4 (11%), IV 2 (6%). For other primaries, 8p (23%) were non metastatic at diagnosis and developed oligoprogressive disease in thorax which was treated with SBRT and 3 (8.5%) were oligometastatic. The location of reRT site: same lobe 17 (48%), ipsilateral different lobe 7 (20%), contralateral lobes 11 (32%). Median delivered dose of salvage SBRT was 50Gy (50-60) in 10 fractions (r3-10). Median accumulated dose in the lung was 81Gy (r60.10Gy-176Gy). With a median follow-up of 10m local control rate was 74% (IC95%; 0.59-0.9) and 1-year OS was 84% (IC 95%;0.67-1). The metabolic complete response rate was 23%. No differences in the baseline and post re-irradiation PFTs were observed: FEV1, FVC and DLCO difference and CI95% were 2.41 (-1.79-6.62); 65 (-125-257) and 12.5 (-95 - 121). Asthenia GII in 12p (31%) was the most frequent acute toxicity, no long-term toxicities were detected.

      Conclusion:
      Salvage SBRT for treating isolated intrathoracic relapses achieved an outstanding local control and overall survival in selected p . This treatment did not impair post-reirradiation PFT and long-term toxicities were not observed.

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      P2.05-035 - Interim Analysis of the Phase II Trial Dose Risk Adapted FFF Using SBRT in Stage I NSCLC and Lung Metastases (NCT01823003) (ID 4368)

      14:30 - 15:45  |  Author(s): R. Ramos

      • Abstract
      • Slides

      Background:
      This study is a phase II, prospective, pilot feasibility study designed to evaluate the safety of SBRT in selected patients with stage I NSCLC or metastatic lung cancer lesions using an ablative dose-adapted scheme with Free Flattening Filters (FFF) beams. An interim analysis was planned after enrollment of the first 27 patients. We present our results of this interim analysis.

      Methods:
      Medically inoperable patients or medically operable patients who refuse surgery with a life expectancy >12 months with lung lesions were candidates. All patients will be treated using FFF beams and the following schedule:

      Topographical Criteria
      Dose Distance to Chest Wall Size Distance to main Bronchus Patients
      A. 34Gy single fr. >1cm < 2cm >2cm 5p (18.5%)
      C. 50Gy (12 x 5 fr.s)Peripheral <1cm <5cm >2cm 13p (48%)
      D. 60Gy (7.5Gy x 8fr.)Central >1cm <5cm <2cm 9p (33.3%)
      Physical examination, toxicity and clinical response will been performed every three months for the first year and 6 months thereafter. Follow up will include Thoracic CT, pulmonary function, quality of life survey and blood test.

      Results:
      After median of follow up of 33 months (r 10-45) we analyzed 27p, with median age of 74y (r 83-58), 21 males (78%). Main reasons for inoperability were: 7 (26%) poor respiratory function, 10 (37%) with multiple comorbidities and 6 (22%) who refused surgery. Location was RUL 9 (33%), RLL 6 (22%), LUL 7 (26%), LLL 4 (15%). Lung primaries in 19p (70%) and the main histologies were Squamous Carcinoma (7, 26%) and Adenocarcinoma (7, 26%). T1a (9 , 33%), T1b (7, 26%),T2a (5, 18%) and T3 (2, 7%). Maximum grade of acute toxicity was GIII 1p(asthenia), and for chronic toxicity was GII (asthenia) 4p (15%). Local Control at 30 months was 84% (three local failures, two from metastasis) and overall survival was 100% at this time.

      Conclusion:
      FFF beams using dose risk adapted schedule seem to be a safe approach with a good response profile. Further analysis with the entire cohort of the trial is needed in order to confirm these early results.

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      P2.05-036 - Single Fraction of SBRT for Pulmonary Lesions (ID 4100)

      14:30 - 15:45  |  Author(s): R. Ramos

      • Abstract
      • Slides

      Background:
      Nowadays pulmonary oligometastatic disease it´s a common situation. SBRT for these patients is a feasible therapeutic choice. We present our experience using single fraction of 34Gy in solitary lesions in Lung. The main aim of this report is to show that single fraction of 34 Gy in lung lesions is feasible, without toxicity and good response profile.

      Methods:
      11 patients with 11 metastatic pulmonary lesions were prospectively treated with single dose of 34Gy. Inclusion criteria were: lesion size smaller than 2 cm, distance from the chest wall and main bronchus tree higher than 2 cm , in metastatic lesions primary tumour should be under control in PET scan. Patients were treated using True Beam machine (VARIAN). In 6 cases treatments were delivered without flattening filter beams. Median Age 68.7y (r51-82), Gender distribution 3 women and 8 men, Histology: 4 cases (36.4%) were metastasic lesions from rectum, 2cases (18.2%) were metastasic lesions from Colon), 3 (27.3%) were primary lesions from lung, 1 (9.1%) was metastasic lesions from sigma and another 1 (9.1%) was from lachrimal gland. All patients underwent 4DCT for contouring. Inmobilization was done by thermoplastic mask (Lorca Marin.S.A). Location: 4 cases (36.4%) were on the Right superior lobe (RSL), 3(27.3%) were on Left Superior Lobe (LSL), 2(18.2%) were on Medial Lobe (ML), 1(9.1%) was on the Lingula and another 1 (9.1%) on Left Inferior Lobe (LIL). Pulmonary function impact was annalyzed using pulmonary function tests performed before and after treatment .

      Results:
      After 45 months of follow up (r 8-45) no toxicity higher than grade 2 was detected. Dosimetric characteristics: mean volume of GTV 1.46cc (r 0.6-4.1), mean volume of PTV 10.85 (r7.1-22.2), D Max oesophagus 4.84 (r 2.7-8.3), D max Heart 8.63 (r0.22-30.07), D max trachea 6.09 Gy (r 0.3-11.1), Dmax skin 10.98(r7.0-14.4). Local control and distant control at 20 months were 77% and 54% respectively. Overall survival was 72% at this time . We detected a significant DLCO impairment of 18% r(2.82-35.13) p=0,027.

      Conclusion:
      To sum up, even this is a preliminary study with a small sample size, this fractionation scheme of SBRT is fast and well tolerated. However, we have detected an impairment of DLCO, so further study with bigger sample size is needed in order to stablish the magnitude of this impairment.

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