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S. Aso
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MA06 - Locally Advanced NSCLC: Risk Groups, Biological Factors and Treatment Choices (ID 379)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:P. Van Houtte, M. Zemanová
- Coordinates: 12/05/2016, 16:00 - 17:30, Strauss 2
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MA06.07 - Impact of Type 2 Diabetes Mellitus and Its Metabolic Control on Prognosis of Unresectable Non-Small Cell Lung Cancer Patients (ID 4314)
16:42 - 16:48 | Author(s): S. Aso
- Abstract
- Presentation
Background:
Type 2 Diabetes Mellitus (T2DM) has been associated with an increased risk of relapse and mortality in several cancer locations, but the prognostic value of T2DM or its metabolic control (MC) in patients (pts) with stage III non-small cell lung cancer (NSCLC) have not been studied yet. The purpose of this study is to evaluate the influence of T2DM and its MC on the prognosis of pts with NSCLC treated with concurrent chemoradiotherapy (cCT-RT).
Methods:
170 pts with NSCLC stage III treated with cCT-RT at the Catalan Institute of Oncology from 2010-2014 were retrospectively reviewed. The overall survival (OS) and progression free survival (PFS) were calculated using Kaplan-Meier method and multivariate Cox model was adjusted by: age, histology, stage, ECOG PS and smoking history.
Results:
Patient characteristics: median age 64y (37-87), male 87%; ECOG≤1 92%; smoking history: current 49%, former 46%, never 5%; histology: adenocarcinoma 34%, squamous 43%, NOS 23%. Platinum doublet CT: Cisplatin 64%, Carboplatin 36%. RT between 60-70 Gys: 94%. At a median follow-up of 38 months (m), 108 patients relapsed (63%), mPFS; 13m (95% CI 10-16) and mOS: 28m (95% CI 22-34). 54 pts (32%) had been diagnosed with T2DM before NSCLC diagnosis. In the overall population mean baseline glycemia was 6.75 mmol/L (3-17). OS and PFS were significantly shorter in patients with T2DM (mOS 17m vs 31m, p=0,005; mPFS 10m vs 16m; p =0,003). T2DM pts were classified into 3 groups of MC based on glycated hemoglobin (HbAc1) before treatment: good MC (HbAc1 <7%), n=26pts; moderate MC (HbAc1 between 7.1-8.5%), n=18pts and poor MC (HbAc1 >8.6%), n=10pts. Poor MC was significantly associated with shorter mOS (11m) as compared with moderate MC (20m) and good MC (28m; p=0.029). T2DM pts treated with insulin had shorter mOS (8m vs 20m; p=0.002) and mPFS (7m vs 12m; p=0.002) than non-insulin treated pts. However there were no differences based on whether pts were taking metformin or not. T2DM was not associated with higher risk of treatment toxicity (pneumonitis or esophagitis). In the multivariate analysis, baseline glycemia and T2DM were both independent prognostic factors for OS (HR 1.2; IC95%1.17-1.3 and HR 1.51; IC95% 1.02 -2.27, respectively).
Conclusion:
Our data suggest that T2DM and poor MC is associated with worse prognosis in pts with stage III NSCLC treated with cCT-RT. Optimal control of T2DM and prevention of hyperglicaemia might benefit those pts, and further studies are warranted.
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P1.04 - Poster Session with Presenters Present (ID 456)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Pulmonology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.04-002 - Positive Airway Pressure-Enhanced CT to Improve Virtual Bronchoscopic Navigation (ID 4869)
14:30 - 14:30 | Author(s): S. Aso
- Abstract
Background:
A main weakness of virtual bronchoscopic navigation (VBN) is unsuccessful segmentation of distal branches approaching peripheral pulmonary nodules (PPN). CT scan acquisition protocol is pivotal for segmentation covering the utmost periphery. We hypothesize that application of continuous positive airway pressure (CPAP) during CT acquisition could improve visualization and segmentation of peripheral bronchi. The purpose of the present pilot study is to compare quality of segmentations under 4 CT acquisition modes: inspiration (INSP), expiration (EXP) and both with CPAP (INSP-CPAP and EXP-CPAP).
Methods:
In 10 patients 320-detector row CT scans with slice thickness of 0.5 mm were performed in the 4 modes. In first 5 patients a pressure ranging 6-10 cmH~2~O was applied for 3 min immediately before CT acquisition (CPAP6-10). In following 5 a pressure of 10 cmH~2~O was applied, followed by 3 min of expiratory maneuvers and non-CPAP acquisitions (CPAP10). Segmentations were obtained and measurements manually calculated with a VBN system (LungPoint, Broncus Technologies, Inc., Mountain View, CA, USA). Comparisons for the inspiratory and expiratory models were made upon main airways area (proximal trachea, distal trachea and main bronchi) and distance of the path to the nodule (DIST-PN). Also, 2 random bronchi per lobe were selected and the number of bifurcations (BIF) and distance (DIST) from carina to the very end of the selected bronchi were manually counted and median calculated. Statistical analyses with R-3.2.3.
Results:
See table 1.Figure 1
Conclusion:
A tendency towards enlargement and improved segmentation of airways is seen with the use of CPAP in both levels of pressure. However, the power of this pilot study is limited and larger studies might be encouraged. Funded by La MaratóTV3-20133510, FIS PI09/90917, DPI2015-65286-R, 2014-SGR-1470, PROD-2014-00065, FUCAP and SEPAR.
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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
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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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 - 14:30 | Author(s): S. Aso
- Abstract
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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P2.02 - Poster Session with Presenters Present (ID 462)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.02-010 - Prognosis Impact of Oligoprogression Following Definitive Chemo-Radiotherapy in Stage III Non-Small Cell Lung Cancer (ID 4456)
14:30 - 14:30 | Author(s): S. Aso
- Abstract
Background:
The influence of recurrence pattern on outcome in stage III NSCLC following definitive chemo-radiotherapy (CRT) has been scarcely addressed in the literature. Our aim was to analyze the relevance of oligoprogression (OP) in this clinical setting.
Methods:
Patients (pts) with stage III NSCLC who underwent concurrent CRT from 2010 to 2014 at the Catalan Institute of Oncology were retrospectively reviewed (n=170). Recurrence pattern at first progression was recorded. OP was defined as a single metastatic organ with up to 3 lesions. Overall Survival (OS) and Progression-Free Survival (PFS) were plotted using Kaplan Meier method, and multivariate Cox proportional hazards model was developed.
Results:
Median age 64 (37-87); male 87%; ECOG-PS≤1 92%; histology: adenocarcinoma 34%, squamous 43%, NOS+large cell 23%; cN0-1 21%, cN2 60%, cN3 19%. Platinum doublet: cisplatin 62%, carboplatin 38%. RT between 60-70 Gy (2Gy/fr): 94%. At a median follow-up of 38 months (m), 108 of 170 pts relapsed (63%) and 66% died. mPFS was 13m (95% CI 10-16), mOS was 28m (95% CI 22-34). Twenty-five of pts who relapsed (23%) developed OP. Sites involved: visceral 17, brain 4, lymph nodes 3, bone 1. Treatments delivered: local therapy with curative intent 9; palliative intention 12; no treatment 4 (table 1). Among pts who relapsed, mOS was longer in those with OP (32m) compared to pts without OP (18m, p=0.007). Pts with OP who received treatment, mOS according to curative or palliative intention was 53m versus 32m (p=0.1), respectively. In the multivariate Cox analysis of post-progression OS, OP remained a favourable prognostic factor (HR=0.36, 95% CI 0.17-0.74) independently of age, PS, stage, histology, smoking history, and platinum doublet.
Conclusion:
OP was associated with substantial better prognosis in this cohort of pts treated with concurrent CRT. Local ablative therapies in the context of OP yielded promising results in terms of survival and warrants further investigation.
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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
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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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 - 14:30 | Author(s): S. Aso
- Abstract
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
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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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 - 14:30 | Author(s): S. Aso
- Abstract
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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P2.05-036 - Single Fraction of SBRT for Pulmonary Lesions (ID 4100)
14:30 - 14:30 | Author(s): S. Aso
- Abstract
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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P2.05-054 - Radiation Pneumonitis; Early Diagnosis and Protein Expression Profile in NSCLC Patients (ID 5375)
14:30 - 14:30 | Author(s): S. Aso
- Abstract
Background:
Radiotherapy (RT) alone or in combination with chemotherapy (CT) are essential in treatment of non small cell lung cancer (NSCLC). A limitation for those therapies is the radiosensitivity of the lung. The aim of this study was to evaluate the incidence of radiation pneumonitis as well to identify potential markers for its early detection and to determine changes in the BAL protein expression.
Methods:
Fourteen NSCLC patients diagnosed at Multidisciplinary Lung Cancer Unit treated with chemotherapy-radiotherapy (CT-RT) or RT alone were enrolled in this prospective study. The collected variables were anthropometric values, lung function, tumor features and RT dosimetric data. A fiberopticbronchoscopy for bronchoalveolar lavage (BAL) was performed in both lungs before RT and at the third week of treatment. Radiation pneumonitis was scored according to the “Common Terminology Criteria for Adverse Events v4.0”. One patient with grade 1 pneumonitis and one patient with grade 3 pneumonitis were selected to perform the protein analysis using “Human Cytokine Array Panel A” (R&D Systems). The normality was determined with the Kolmogorov-Smirnov test. Student’s t-test was used when variables had a normal distribution. Differences were considered statistically significant when p values were < 0.05.
Results:
All patients develop radiation pneumonitis, 35.75% of patients developed grade 1 pneumonitis, 20% grade 2, 35.75% grade 3 and 6.66% grade 5. Four patients developed pneumonitis in the lung without tumour. The decrease in lung diffusion capacity for carbon monoxide (DLCO) was the most sensitive parameter for determining the existence of early lung damage (p=0.04). Development of radiation pneumonitis was not associated with baseline lung function neither RT dosimetric data. The BAL protein expression profile was different between the two patients before RT. Expression of PAI-1, IL-1ra, MIF, and CXCL-1 in patient with pneumonitis grade 1 were increased only in the lung with tumor however these proteins were also increased in patient with pneumonitis grade 3 but in both lungs. It was significant that in the 2 cases, RT induced similar changes in BAL protein expression in both lungs.
Conclusion:
In this prospective study, the incidence of radiation pneumonitis was greater than previously reported in the literature. The DLCO decline was the most sensitive parameter for its early detection. The risk to develop radiation pneumonitis appeared to be independent of dosimetric parameters and might be related with the baseline inflammatory state. According to BAL protein expression analysis, RT produced comparable molecular changes in both lungs. Funded by SEPAR and IDIBELL.
