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Background - Circulating tumor cells (CTCs) are the liquid phase of a solid tumor. An advanced CTC phenotyping and genotyping procedure could allow a superior understanding of tumor heterogeneity aimed at improving personalized treatment selection. However, these investigations are hampered by the difficulty to catch and analyze CTCs. EML4-ALK chromosomal rearrangement is a fundamental marker of sensitivity in metastatic non-small cell lung cancer (mNSCLC), but conventional tissue-based ALK scrutiny is not always possible. A CTC-based ALK evaluation may be an easy and not invasive method for identifying rearrangements and hence patients eligible for specific treatments. Methods - Analyses were performed via the Gilupi CellCollector CANCER01 (DC01), a device that allows the in vivo isolation of CTCs from a high volume of peripheral blood. The DC01 is a CE-approved functionalized 16 cm long medical wire that includes a functionalized 2 cm long gold-coated tip covalently coupled with antibodies against EpCAM. The DC01 can be inserted through a standard venous cannula into the cubital vein of cancer patients for 30 minutes where it captures CTCs directly from the bloodstream of cancer patients. CTC presence was investigated in 18 mNSCLC patients and CTC-ALK-chromosomal status was studied by an innovative method, the 3D-immuno-FISH, that combined immuno-fluorescence and FISH approaches on a 3D structure (the DC01). Two DC01 per patients were utilized. After removal, on one wire, CTCs were identified and counted by nuclei, EpCAM and cytokeratins staining. On the second wire, CTCs were recognized by EpCAM staining and analyzed for ALK alterations by FISH. Formalin-fixed paraffin-embedded primary tumor tissues from the same patients were analyzed for comparison. Immortalized cell lines attached to DC01 devices were exploited as positive controls. Results - Using the DC01 it was feasible to isolate and detect CTCs. Among the 18 enrolled patients, 7 presented tumor-tissue ALK-translocation, whereas 11 were wild type. Overall, 61.1% patients were CTC positive (median CTC number, 3.0 per patient). Amid those that owned ALK-translocation, 28.6% were CTC-positive, whereas 81.8 % patient without ALK-translocation were CTC positive. ALK rearrangements were detectable directly on cells attached to the wires. However, the 3D-immuno-FISH analysis in patients was hampered by the low median number of detected CTCs. Conclusions - The detection of ALK-chromosomal rearrangements with the 3D-immuno-FISH analysis in cells recovered by DC01 was feasible. This method is valid for tracking positive CTC patients, but the few cells retrieved per patients still limit CTC full exploitation. Although further studies are needed to validate our data and to improve DC01 capture efficiency, our results pave the way to CTC-based chromosomal rearrangement identification and therapy personalization. Citation Format: Giulia Gallerani, Angelo Delmonte, Claudia Cocchi, Martine Bocchini, Filippo Piccinini, Marco Angelo Burgio, Carla Casadei, Andrea Rocca, Francesco Fabbri. Feasibility investigation of EML4-ALK rearrangements in mNSCLC CTCs using a new in vivo procedure [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5196.

Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, disrupts PD-1-mediated signaling and may restore antitumor immunity.In this randomized, open-label, international phase 3 study, we assigned patients with nonsquamous non-small-cell lung cancer (NSCLC) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival.Overall survival was longer with nivolumab than with docetaxel. The median overall survival was 12.2 months (95% confidence interval [CI], 9.7 to 15.0) among 292 patients in the nivolumab group and 9.4 months (95% CI, 8.1 to 10.7) among 290 patients in the docetaxel group (hazard ratio for death, 0.73; 96% CI, 0.59 to 0.89; P=0.002). At 1 year, the overall survival rate was 51% (95% CI, 45 to 56) with nivolumab versus 39% (95% CI, 33 to 45) with docetaxel. With additional follow-up, the overall survival rate at 18 months was 39% (95% CI, 34 to 45) with nivolumab versus 23% (95% CI, 19 to 28) with docetaxel. The response rate was 19% with nivolumab versus 12% with docetaxel (P=0.02). Although progression-free survival did not favor nivolumab over docetaxel (median, 2.3 months and 4.2 months, respectively), the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel (19% and 8%, respectively). Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression (≥1%, ≥5%, and ≥10%) of the PD-1 ligand. Treatment-related adverse events of grade 3 or 4 were reported in 10% of the patients in the nivolumab group, as compared with 54% of those in the docetaxel group.Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy, overall survival was longer with nivolumab than with docetaxel. (Funded by Bristol-Myers Squibb; CheckMate 057 ClinicalTrials.gov number, NCT01673867.).

Background: Small-cell lung cancer (SCLC) is known to express antigens of both the neural crest and epithelium, and to secrete polypeptide hormones and enzymes. Anecdotal reports correlate lung cancer with marked hyperamylasemia, and a review of the literature reveals only one case of metastatic SCLC linked to high paraneoplastic lipase production. Case presentation: We present the case of a patient with metastatic SCLC who showed both lipase and pancreatic isoamylase elevation in the absence of acute pancreatitis. Chemotherapy resulted in a rapid reduction in serum lipase and in pancreatic isoamylase which was correlated with the radiological response of the tumor to therapy. Lipase and pancreatic isoamylase expression in tumor cells from the lung biopsy was confirmed by immunohistochemical staining. Conclusions: This is a very rare case of paraneoplastic syndrome linked to metastatic SCLC. The enzymes secreted could be used as markers of response to treatment until clonal selection mechanisms and intratumor heterogeneity induce changes in biochemical characteristics and consequently in tumor behavior.

Objectives Anaplastic lymphoma kinase ( ALK )-positive non-small cell lung cancer (NSCLC) is sensitive to treatment with an ALK-tyrosine kinase inhibitor (-TKI). However, the benefit of sequential treatment with a 2nd ALK-TKI in patients who fail a 1st ALK-TKI has been poorly addressed. Materials and methods We collected the data of 69 advanced ALK -positive NSCLCs who were treated with one or more ALK-TKIs at three Italian institutions. The clinical outcome of treatment with an ALK-TKI and the patterns of treatment upon failing a 1st ALK-TKI were recorded. Results Objective response rate (ORR) and median progression-free survival (PFS) on a 1st ALK-TKI (mostly crizotinib) were 60.9% and 12 months, respectively. Of the 50 patients who progressed on a 1st ALK-TKI, 22 were further treated with a 2nd ALK-TKI (either ceritinib or alectinib), for whom an ORR of 86.4% and median PFS of 7 months, respectively, were reported. Conversely, 13 patients underwent rapid clinical/radiographic disease progression leading to death shortly after discontinuation of the 1st ALK-TKI, 7 patients were managed with a 1st ALK-TKI beyond progression, and 8 patients transitioned to other systemic treatments (mostly chemotherapy). Post-progression survival (PPS) significantly favored the 22 patients who were sequentially treated with a 2nd ALK-TKI over those who transitioned to other systemic treatments ( P =0.03), but not versus those who were treated with a 1st ALK-TKI beyond progression ( P =0.89). Conclusion Sequential treatment with a 2nd ALK-TKI is effective in patients who fail a 1st ALK-TKI. Continuous ALK-inhibition upon failing a 1st ALK-TKI may be associated with improved clinical outcome.

Tyrosine kinase inhibitors (TKIs) are very efficacious in non-small-cell lung cancer (NSCLC) patients harboring activating Epidermal Growth Factor Receptor (EGFR) mutations. However, about 10% of EGFR wild type (wt) patients respond to TKI, with unknown molecular mechanisms of sensitivity. We considered a case series of 34 EGFR wt NSCLC patients responsive to erlotinib after at least one line of therapy. Responsive patients were matched with an equal number of non-responsive EGFR wt patients. A panel of 26 genes, for a total of 214 somatic mutations, was analyzed by MassARRAY® System (Sequenom, San Diego, CA, USA). A 15% KRAS mutation was observed in both groups, with a prevalence of G12C in non-responders (80% vs. 40% in responders). NOTCH1, p53 and EGFR-resistance-related mutations were found more frequently in non-responders, whereas EGFR-sensitizing mutations and alterations in genes involved in proliferation pathways were more frequent in responders. In conclusion, our findings indicate that p53, NOTCH1 and exon 20 EGFR mutations seem to be related to TKI resistance. KRAS mutations do not appear to influence the TKI response, although G12C mutation is more frequent in non-responders. Finally, the use of highly sensitive methodologies could lead to the identification of under-represented EGFR mutations potentially associated with TKI sensitivity.

9002 Background: The role of platinum in first line treatment of elderly patients with advanced NSCLC is still debated. We tested its efficacy in two parallel phase 3 trials. Methods: Advanced NSCLC patients, > 70 years, ECOG performance status 0-1, were eligible. In MILES-3 (started in 2011) patients with any tumor histology were randomly assigned 1:1 to cisplatin/gemcitabine (C 60 mg/m² d1, G 1000mg/m² dd1,8) or gemcitabine (G 1200 mg/m² dd1,8). In MILES-4 (started in 2013 with a factorial design) patients with non-squamous histology were randomly assigned 1:1:1:1 to CG, G, cisplatin/pemetrexed (C 60 mg/m² d1, P 500 mg/m² d1) or pemetrexed (P 500 mg/m² d1). Six cycles were planned. In each trial, to have 80% power in detecting a HR of death 0.75 (corresponding to 3-month prolongation of median survival), with 0.05 two-tailed α, 382 events were required. The two trials were closed prematurely because of slow accrual but a joint analysis allowed to properly perform the final analysis, according to IDMC advice. Analysis was based on intention-to treat and adjusted by possible confounding factors. Results: From Mar 2011 to Aug 2016, 531 patients (MILES-3: 299, MILES-4: 232) were assigned to cisplatin-doublet (n = 263) or single-agent chemotherapy (n = 268). Median age was 75, 79% were male, 70% had non-squamous histology. Median number of cycles was 4 and 3 with and without cisplatin, respectively. With a median follow-up of 2 years, 384 deaths and 448 progression-free survival (PFS) events were reported. With and without cisplatin, median OS was 9.6 vs 7.5 months (HR 0.86, 95% CI: 0.70-1.04, p = 0.14); median PFS was 4.6 vs 3.0 months (HR 0.76, 95% CI: 0.63-0.92, p = 0.005); response rate was 15.5% vs 8.5% (p = 0.02). Significantly more severe hematologic toxicity and fatigue were reported with cisplatin. Conclusions: Although improving PFS and response rate, addition of cisplatin to single-agent chemotherapy does not significantly prolong overall survival of elderly patients with advanced NSCLC. QOL data will be reported separately. Partially supported by AIFA (grant FARM8KAJZK) and Eli Lilly. Clinical trial information: NCT01405586 and NCT01656551.

Chemo-radiotherapy is standard treatment of stage IIIA-N2 bulky or IIIB non-small cell lung cancer (NSCLC). Surgical resection of residual disease in downstaged patients may improve overall survival. In this setting, restaging disease is still a challenge. 18F-FDG PET/CT represents the gold standard although accuracy results are disappointing. Endoscopic bronchial/ esophageal ultrasound (EBUS/EUS)-guided fine needle aspiration (FNA) may confirm lymph node (LN) involvement. We analyzed 16 patients with stage IIIA-N2 bulky or IIIB NSCLC treated with chemo-radiotherapy. At restaging, all patients performed EBUS/EUS with FNA and PET/CT scan and results were compared. Patients underwent PET/CT scan 43 days (range: 24-89) and EBUS/EUS 42 days (range: 14-71) after therapy. Overall, 7 EBUS and 9 EUS procedures were performed: no complications resulting from the procedure occurred. In 6 patients EBUS/EUS did not reveal any suspicious lesions; in 2 the exam showed enlarged mediastinal LN that were biopsied, but with no evidence of tumor cells; in 2 the sample was not considered diagnostic; 6 had persistent mediastinal LN involvement. PET/CT scan showed 4 cases of complete metabolic response, 9 partial metabolic response, 2 stable metabolic disease and one progressive metabolic disease. Notably, all 7 patients with .80% decrease in SUV with respect to basal value showed a pathological complete response or negative EBUS/EUS. EBUS/EUS could be used to complement PET/CT scanning to verify mediastinal LN clearance. Further prospective trials are warranted to confirm the utility of EBUS/EUS together with PET/CT in restaging locally advanced NSCLC.

Background: Systemic capillary leak syndrome is a rare disease with a high mortality rate. This syndrome is characterised by generalised edema, hypotension, hemoconcentration, and hypoproteinemia. The cause is the sudden onset of capillary hyperpermeability with extravasations of plasma from the intravascular to the extravascular compartment. We present the case of a patient who experienced two episodes of systemic capillary leak syndrome and pulmonary hypertension; the first after gemcitabine in an adjuvant setting and the second three years later after treatment with nab-paclitaxel for metastatic disease.Case presentation: A 65-year-old patient underwent a pancreatectomy in January 2010 for ductal carcinoma (pT3 N0 M0, stage IIa), followed by adjuvant chemotherapy. Seven days after the last cycle, she developed dyspnea associated with orthopnea and cough. A transthoracic cardiac ecocolordoppler was performed, with evidence of pulmonary hypertension (58 mmHg). Blood tests showed an increase in creatinine, pro-BNP and D-Dimer. She began high-dose diuretic therapy combined with cortisone. After a month, the patient was eupneic and the anasarca had resolved. We decided gradually to reduce the steroid and diuretic therapy. After ten days of the reduction, the patient began to re-present the same symptoms after treatment with gemcitabine. Corticosteroid therapy was restored with rapid clinical benefit and decreased pro-BNP after a week of treatment. After two years, the disease returned. As a first line treatment, it was decided to use nab-paclitaxel 100 mg/m2 weekly. After two doses, followed by approximately 14 days of treatment, the patient developed acute respiratory distress syndrome. The clinical suspicion was a relapse of capillary leak syndrome and treatment with a high-dose diuretic (furosemide 250 mg daily) was started combined with cortisone (40 mg methylprednisolone). The patient showed a progressive clinical benefit.Conclusions: In patients treated with gemcitabine and nab-paclitaxel who experience a sudden onset of diffuse edema with respiratory distress, capillary leak syndrome should be suspected. Immediate treatment with corticosteroids may be life-saving. © 2013 Casadei Gardini et al.; licensee BioMed Central Ltd.

This multicenter analysis evaluated patient outcome and clinical pathologic features of thymic epithelial tumors after complete surgical resection and adjuvant treatment. Histologic classification and clinical staging were performed according to WHO classification and Masaoka staging system, respectively. We analyzed 62 patients, 20 (32 %) of whom had myasthenia at diagnosis. Clinical and pathologic staging was as follows: 31 (50 %) and 30 (48 %) patients had stage I disease, 19 (30 %) and 22 (35 %) stage II, 5 (8 %) and 3 (6 %) stage III, 2 (4 %) and 2 (3 %) stage IVa, and 5 (8 %) and 5 (8 %) stage IVb, respectively. Histologic examination revealed 11 (19%) type A tumors, 19 (30%) type AB tumors, 7 (12 %) type B1 tumors, 11 (17 %) type B2 tumors, 11 (17 %) type B3 tumors, and 3 (5 %) type C tumors. Adjuvant therapies comprised chemotherapy in 3 (5 %) patients and radiotherapy in 16 (26 %) patients. Median follow-up was 71 months (range 1–145). DFS and OS at 48, 60, and 72 months were 89 and 89 %, 86 and 97 %, and 95% and 92%, respectively. Myasthenia at the onset of disease (P = 0.18 for DFS; P = 0.97) and tumor size >5 cm (P = 0.94 for DFS; P = 0.56) were not prognostic factors. TETs are rare and indolent tumors. Complete surgical resection followed by adjuvant therapies, such as chemotherapy and/or radiotherapy, in patients at risk of recurrence show very good DFS and OS results, even in cases with radically resected pleural-pulmonary metastases.

9052Background: Patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations are usually responsive to tyrosine kinase inhibitors (TKIs). However, ab...

e20513Background: Epidermal growth factor receptor (EGFR) mutations are associated with response to tyrosine kinase inhibitors (TKIs). However, different EGFR mutations appear to have different pre...

e19149 Background: the association of venous thromboembolic events (VTE) and lung cancer has a high prevalence. Limited data are available in the adenocarcinoma subtype population especially in rel...

LBA109 Background: Options for advanced non-SQ NSCLC patients (pts) who progress after platinum-based doublet chemotherapy (PT-DC) are limited, with minimal improvement in overall survival (OS). We report results from a randomized, global phase III study of NIVO, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, vs DOC in pts with advanced non-SQ NSCLC after failure of PT-DC and tyrosine kinase inhibitor, if eligible. Methods: Pts were randomized to NIVO 3 mg/kg Q2W (n=292) or DOC 75 mg/m2 Q3W (n=290) until progression or discontinuation due to toxicity/other reasons. Primary objective was OS; Secondary objectives were investigator-assessed objective response rate (ORR; per RECIST v1.1), progression-free survival (PFS), efficacy by PD-L1 expression, quality of life, and safety. Results: NIVO demonstrated superior OS (HR=0.73; 96% CI: 0.59, 0.89; P=0.00155) and improved ORR (19.2% vs 12.4%; P=0.0235). HR for PFS was 0.92 (95% CI: 0.77, 1.11; P=0.393). PD-L1 expression was associated with benefit from NIVO (Table). In PD-L1+ pts, NIVO showed improved efficacy across all endpoints at predefined 1%, 5%, and 10% cut- points. Grade 3–5 drug-related AEs occurred in 10.5% (30/287) of NIVO and 53.7% (144/268) of DOC pts. No deaths were related to NIVO vs 1 DOC-related death. After discontinuation, 42.1% of NIVO and 49.7% of DOC pts received subsequent systemic therapy. Conclusions: NIVO demonstrated superior OS vs DOC in pts with advanced non-SQ NSCLC after failure of PT-DC. The safety profile of NIVO 3 mg/kg Q2W was favorable vs DOC. NIVO demonstrated survival benefit across histologies in two randomized phase III trials. Clinical trial information: NCT01673867. [Table: see text]

Purpose thymic epithelial tumors (TETs) are a rare neoplasms. Due to their rarity, large-scale prospective trials are lacking. The present retrospective multicenter analysis aimed to evaluate clinical outcome and clinical-pathological features of TETs after complete surgical resection and adjuvant treatments (Adj) such as chemotherapy (CHT) or radiotherapy (RT). Patients and methods Patients who underwent a complete surgical resections for TETs between 2000 and 2007 were reviewed. WHO histological classification criteria and Masaoka staging system were used. Adj were: anthracycline- and platin-based CHT, RT on irradiation fields covering the primary tumor bed. Overall survival (OS) was calculated from the date of diagnosis until patient death or last follow-up visit. Disease free-survival (DFS) was defined as the interval between surgery and date of first documentation of recurrence. OS, DFS and 95% Confidence Interval (95% CI) were estimated by Kaplan-Meier method. Results 62 patients were analyzed: 30 patients (48%) male and 32 (52%) female. Median age was 60 years (range: 33 - 86). At the beginning of their cancer history 20 (32%) patients had myasthenia. Clinical staging showed: 31 (50%) stage I disease, 19 (30%) stage II, 5 (8%) stage III, 2 (4%) stage IVa, 5 (8%) stage IVb. Histologies were: 11 (19%) A tumor type, 18 (29%) AB type, 7 (12%) B1 type, 11 (17%) B2 type, 11 (17%) B3 type and 3 (6%) C type. Pathological staging were: 30 (48%) stage I, 22 (35%) stage II, 3 (6%) stage III, 2 (3%) stage IVa, 5 (8%) stage IVb. 3 (5%) patients received Adj-CHT and 16 (26%) Adj-RT. Median follow-up was 71 months (range 1-145), DFS and OS are the following: % DFS (95% CI) % OS (95% CI) Events 48 mo 60 o0 72 mo Events 48 mo 60 mo 72 mo 9 89 (80-97) 89 (80-97) 86 (76-96) 7 97 (92-100) 95 (88-100) 92 (85-100) mo, months. Conclusions TETs are rare and indolent tumors. Surgery offers good results which can be further improved by Adj such as CHT and/or RT. Supported by GIPO. Disclosure All authors have declared no conflicts of interest.

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Aim: In the TORCH trial, molecularly unselected pts with advanced NSCLC were randomized to erlotinib (E) or cisplatin + gemcitabine (CG) as first line within planned treatment sequences. Several biomarkers were studied with exploratory aim. Here we report cMET and PTEN data. Methods: cMET and PTEN immunohistochemistry (IHC) was performed using standard method and SP44 (Ventana) and 138G6 (Cell Signaling) antibodies, respectively. H-score (intensity x % stained tumor cells) was used to classify cMET IHC ( Results: PTEN was positive in 118 pts (80%). PTEN showed no significant interaction with treatment and did not vary between EGFR mut+ and wildtype (wt). cMET was high in 92 pts (59%). As for PFS, HR (E vs CG) was 1.22 (95% CI 0.71-2.07) in cMET low and 2.81 (95% CI 1.79 – 4.41) in cMET high (interaction p = 0.013); in the E arm, HR for cMET low vs cMET high pts was 0.45 (95% CI 0.27-0.74). Response rate (RR) to E/CG was 21%/17% in cMET low vs 0%/24% in cMET high (interaction p = 0.005). The RR difference within the E arm was statistically significant (p = 0.002). cMET was high in 76% (16/21) of EGFR mut+ pts and 58% (76/132) of EGFR wildtype (wt) pts (p = 0.11). Among EGFR wt pts, PFS HR (E vs CG) was 1.65 (95% CI 0.95-2.89) in cMET low and 3.25 (95% CI 1.95 – 5.42) in cMET high (interaction p = 0.07). In the E arm, HR for cMET low vs cMET high was 0.49 (95% CI 0.29-0.83). RR to E/CG was 14%/19% in cMET low vs 0%/21% in cMET high (interaction 0.07). The RR difference within the E arm was statistically significant (p = 0.03). Numbers were too small to test interaction in EGFR mut+ pts. Conclusions: In pts unselected for EGFR mutation and in those with EGFR wt, the relative effect on PFS of E vs CG is less worse among low cMET cases. Objective responses to first line E were only reported among low cMET cases, even if EGFR wt. Disclosure: M. Tsao: received honoraria on this subject matter from: Roche, AstraZeneca, and received a research grant from Roche; M. Di Maio: acted as consultant or advisory role for Eli Lilly and received honoraria from Eli Lilly and Roche; A. Rossi, P. Maione and C. Gridelli: acted as consultant for Eli Lilli, Roche and received honoraria from Eli Lilli, Roche; C.A. Butts: acted as consultant for Roche and received honoraria from Roche; R. Feld: acted as consultant for Roche, received honoraria from Roche and received a research grant from Roche; F. Perrone: received honoraria from Roche and received a research funding from Roche. All other authors have declared no conflicts of interest.

e19086 Background: Tyrosine kinase inhibitors (TKIs) are the first choice of treatment in a subset of patients with non- small cell lung cancer (NSCLC) harboring specific epidermal growth factor re...

Purpose/Objective(s): To analyze retrospectively 47 cases of malignant pleural mesothelioma (MPM) treated during the period 2008-2012 using helical tomotherapy (HT) either to confirm the role of adjuvant radiation therapy after extra-pleural pneumonectomy (EPP) or to define the role of radiation therapy after pleurectomy/decortication (P/D) or medical/surgical biopsy (B). Materials/Methods: In the Radiotherapy Department of our institute (IRCCS IRST), 47 consecutive patients with MPM (I-IV stage) were treated by HT. Thirty-six patients had previously received chemotherapy (platins and pemetrexed), 9 had undergone adjuvant radiation therapy after EPP and 38 had received definitive radiation therapy after P/D or B. Two different radiation therapy strategies and schedules were planned: (1) Adjuvant treatment after EPP: conventional fractionation schedule and 50 Gy/25 daily fractions to the hemithorax. (2) Definitive treatment after P/D or B: accelerated hypofractionation schedule and 25 Gy/5 daily fractions dose prescription at the reference isodose (60%-70% isodose) with an increasing dose of up to 37.5-40 Gy inside the gross tumor mass/masses) to the PTV (pleura) whilst maintaining the dose to the organs at risk (BED 2 Gy) below conventional fractionation values. Feasibility and toxicity were evaluated. Results: We obtained satisfactory dose distributions while also sparing organs at risk in both treatment schedules: (1) at least 95% of the dose prescription was delivered to 95% of the target volume. The median dose to the target was 51.39 Gy (range, 50.5-52.2 Gy) for conventional fractionation and 29 Gy (range, 26.7-30 Gy) for the hypofractionated schedule; (2) at least 5 Gy covered less than 5% of the controlateral lung volume with an average dose lower than 4 Gy in both treatment schedules; and (3) one-third intact lung volume of the homolateral pleural tumor received 10 Gy/5 daily fractions with the accelerated hypofractionation schedule. We closely adhered to normal tissue constraints relative to the IMRT treatment in order to compare DVHs. Conclusions: Our results indicate the usefulness/efficacy of helical tomotherapy for patients who have already undergone extrapleural/pneumonectomy and also for those submitted to P/D or biopsy using an accelerated hypofractionated schedule. No heavy functional injuries were recorded for either treatment schedule. A study is ongoing to treat patients with accelerated hypofractionated radiation therapy after P/D using tomotherapy. Author Disclosure: E. Parisi: None. A. Romeo: None. G. Ghigi: None. M. Burgio: None. E. Neri: None. M. Taurchini: None. M. Romagnoli: None. A. Sarnelli: None. C. Arienti: None. R. Polico: None.

e18052 Background: Non Small Cell Lung Cancer (NSCLC) accounts for almost 80% of all lung malignancies, and 40% of these patients go on to develop brain metastases (BM). Furthermore, there are no g...

e19591 Background: Chronic cancer pain (CCP) is present in 50% of cancer patients at any stage of disease and in 70% of those in an advanced setting. Preliminary results have shown the effectivenes...

e17546 Background: Thymic epithelial tumors (TETs) consist of a series of neoplasm arising from the anterior mediastinum. Due to its rarity, large-scale prospective trials have been lacking. This retrospective multicenter analysis aimed to evaluate clinical outcome and clinico-pathological features of TETs after surgery resection and adjuvant treatments as chemotherapy and/or radiotherapy. Methods: All medical records about TETs surgically resected between 2000 and 2007 and eventually treated with adjuvant therapies (chemotherapy and/or radiotherapy) were reported. Surgical procedures included complete removal of thymic, mediastinal fat tissue and any suspicious lesions. Histological classification has been made in according to WHO criteria and Masaoka staging system was adopted. Adjuvant chemotherapy was represented by anthracycline and platin-based regimen whereas adjuvant radiotherapy was delivered on irradiation field covered primary tumor bed. Overall survival was calculated from the date of diagnosis until patient death or last follow-up visit. Disease free-survival was defined the interval from operation until date of recurrence. Results: Overall 32 patients were analyzed of whom 12 (37%) male and 20 (63%) female. Median age was 61 years (range: 33 - 86). At the beginning of their oncologic history 14 (42%) patients had miastenia. Overall at clinical staging there were 19 (60%) stage I, 4 (12%) stage II, 4 (12%) stage III, and 5 (16%) stage IVb at radiological staging. The histological exam reported: 5 (16%) A tumor type, 11 (34%) AB type, 3 (10%) B1 type, 3 (10%) B2 type, 8 (24%) B3 type, 2 (6%) C type. At pathological staging there were: 18 (56%) stage I, 7 (22%) stage II, 2 (6%) stage III and 5 (16%) stage IVb. Post-surgical therapies were represented by chemotherapy in 2 (6%) patients and radiotherapy in 13 (41%) patients. Disease relapse was recorded in 1 (3%) patient after 27 months from diagnosis. Overall survival rate at 78 months is 86% (CI: 66-100). Conclusions: TETs are rare and indolent cancer. Surgery offers the good perspectives eventually improved with adjuvant therapies like chemotherapy and/or radiotherapy. Supported by GIPO.

(50% drop, 75% drop, @ 3 cutoffs) was the same in the 2 dose groups. Median survival was 50 months for the entire cohort, with a 2& 5year survival of 88%, 65%. DE-RT pts have not yet achieved median survival. The 2-year DFS was 70% (37 mo median DFS). None of the factors including RT dose, T down staging, MNC, different cut off points for SUV drop were significant for outcomes on DFS, OS. At last follow-up, 17 pts (46%) were free of disease and 14 alive (38%). Conclusions: RT dose escalation resulted in improvement in MNC and correlated with the PET response in our series. Long-term follow-up and larger pt numbers are needed for the DE-RT pts to prove the concept. PET response can be utilized as predictor of outcomes in operable NSCLC pts. Author Disclosure: A. Turaka: None. S. Hasan: None. T. Li: None. R. Mehra: None. W.J. Scott: None. J.Q. Yu: None.

e18561 Background: Response and duration to initial chemotherapy are important factors used to classify SCLC patients into two groups. The first group comprises sensitive disease that responds to initial chemotherapy and relapses after more than 3 months and for which disease control could be obtained by re-challenging with first-line chemotherapy. The second group comprises refractory disease that progresses at the end or within 3 months of finishing first-line chemotherapy and for whom second-line chemotherapy represents the gold-standard. Methods: We reviewed clinical data from 4 Oncology Departments on sensitive SCLC treated with a first-line chemotherapy re-challenge in order to evaluate its activity and efficacy. Results: Of 211 SCLC patients diagnosed from January 2007 to December 2011, 25 (12%; 20 males, 5 females) had sensitive disease of whom 13 (52%) limited disease (LD) and 12 (48%) extended disease (ED). Median interval between the last day of chemotherapy and the onset of disease progression was 205 days (95% CI 169 – 279; range: 90 – 665). Chemotherapy consisted of etoposide + carboplatin in 15 (60%) patients or cisplatin in 10 (40%). On average 3-4 (range: 1-6) chemotherapy courses were administered, producing 8 (32%) partial responses, 3 (12%) stable disease, 10 (40%) progressive disease and 4 (16%) non evaluable disease. Further-line chemotherapy, mainly topotecan, was administered in 13 (52%) patients. Median overall survival produced by all treatments was 19.6 months (95% CI 16.5 – 27.6). Conclusions: In our experience, sensitive SCLC treated with first-line platinum/etoposide re-challenge produced interesting results in terms of activity and efficacy. Prospective randomized trials are warranted to investigate whether this strategy produces better results than standard second-line chemotherapy.

7600 Background: Rechallenge might be used as rescue therapy in progressing platinum-sensitiveSmall Cell Lung Cancer (SCLC). This international multicenter retrospective analysis evaluates the clin...