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H. Peulen
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MINI 17 - WT EGFR, Angiogenesis and OMD (ID 131)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:R. Feld, R. Dziadziuszko
- Coordinates: 9/08/2015, 16:45 - 18:15, Mile High Ballroom 4a-4f
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MINI17.11 - Results of Radical Local Treatment of Non-Small Cell Lung Cancer Patients with One or Two Synchronous Metastases (ID 581)
17:45 - 17:50 | Author(s): H. Peulen
- Abstract
- Presentation
Background:
Stage IV non-small cell lung cancer (NSCLC) patients are considered incurable and mainly treated with palliative intent. The overall survival (OS) and disease free survival (DFS) of this patient group is considered as poor. The purpose of this study was to investigate the OS and DFS of NSCLC patients, diagnosed with synchronous oligometastatic disease treated with curative intent of the intrathoracic disease as well as the metastases.
Methods:
Patients treated between 2008 and 2014 were included in this retrospective cohort analysis. Main inclusion criteria were: synchronous presentation of NSCLC and oligometastatic disease at diagnosis, and multidisciplinary consent on a radical treatment of both the intrathoracic disease and the metastases. Besides systemic treatment. The intrathoracic disease was radically irradiated (> 55 Gy biological effective dose) or resected. Treatment of the metastases consisted of: radical/stereotactic radiotherapy, surgical resection or radiofrequency ablation (RFA).
Results:
A total of 56 patients, 31 men and 25 women, were included. The mean age was 61 years (range 36-79) and all were in good condition (WHO 0-1). Most patients had a solitary metastasis (brain (22), bone (17), adrenal gland (6), lymphe node (3), liver (2), soft tissue (1), pulmonary (1), thyroid gland (1) and breast (1)). Two patients had 2 metastases (liver and bone / pleural and bone). The intrathoracic tumor stage,ignoring M-status, was IA in 3 patients, IB in 2 patients, IIA in 8 patients, IIB in 4 patients, IIIA in 24 patients and IIIB in 15 patients. Fifty patients were treated with radiotherapy and 4 patients had a surgical intervention for the primary tumor; 2 patients only received systemical treatment for the intrathoracic disease. Fifty patients received chemotherapy (89%), of which 5 (10%) concurrent with the radiotherapy of the intrathoracic disease and 45 (90%) sequential. The metastases were treated with ablative/stereotactic radiotherapy (45), surgical intervention (2), only systemical treatment (5), combination of surgical intervention and radiotherapy (3) and RFA (1). The mean follow-up was 21 months (range 4-69). Forty-one (73%) patients developed recurrent disease of whom 29 (52%) died. Only 8 (20%) recurrences occurred within the irradiated area. Most recurrences where brain (13) and pulmonary metastases (11). For the whole group, the median DFS was 14 months (range 2-69, 95% CI 11-17) and the median OS was 32 months (range 4-69, 95% CI 16-48). The 1- and 2-year OS was 86% and 58%, respectively. The 1- and 2-year DFS was 66% and 30%, respectively.
Conclusion:
Radical local treatment of a highly selected group of NSCLC patients in good condition presenting with synchronous oligometastatic stage IV disease (maximum 2 metastases) resulted in excellent local control, and also in favorable long-term DFS and OS.
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MINI 33 - Radiotherapy and Complications (ID 164)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
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MINI33.03 - Heart Dose Is Associated with Shorter Overall Survival for Patients Treated with Chemo-Radiation for Locally Advanced NSCLC (ID 2755)
18:45 - 18:50 | Author(s): H. Peulen
- Abstract
Background:
Traditionally, sparing the heart in chemo-radiotherapy of locally advanced lung cancer has a low priority compared to the lungs and esophagus. Recently, however, the randomized phase III trial RTOG 0617 showed that the volume of the heart receiving a dose of at least 5Gy (V5) was associated with a lower overall survival (OS). The aim of the current study is to validate this in an independent database.
Methods:
Patients treated with IMRT (24x2.75Gy with daily low-dose cisplatin) at our hospital between 2006 and 2014 were retrospectively selected. For the heart both mean dose and Vx denoting the volume receiving x Gy or more (x in range 5-50Gy with 5Gy increments) were calculated. Associations of these parameters with OS were evaluated using univariate and multivariate proportional hazards analysis. In multivariate analysis we separately paired the total GTV (primary tumor plus involved lymph nodes) to Vx and mean dose.
Results:
375 pts were available for analysis. Median follow up was 16 months and median OS was 26 months. Using univariate proportional hazard modeling mean dose and all Vx for x<40Gy were significantly associated (p<0.05) with OS. For V5, which was most significant in the analyzed set, the hazard ratio (HR) was 1.008. When pts are split at the median V5 = 37.0%, the median OS was 29 ± 2.5 months versus 19 ± 2.4 months for pts below and above the median respectively (p=0.03, Log Rank). Similarly, the figure illustrates significant separation in Kaplan-Meier plots of OS with the pts divided in V5 quartiles. In the multivariate analysis the correlation between GTV (median volume 109 cc) and mean dose or Vx was less than 0.15, indicating that a higher heart dose is not the effect of larger tumor volumes and hence a worse survival due to more advanced decease. Both GTV (p<0.001, HR=1.001) and V5 (p=.003, HR=1.007) were significant in multivariate analysis as was the case with GTV (p<0.001, HR=1.001) and mean dose (p=0.033, HR=1.018).
Conclusion:
For pts treated with chemoradiation the dose received by the heart is strongly associated with overall survival. Our results are in accordance with the results of RTOG 0617 [1] for the V5 with similar HR despite the different fractionation scheme and chemo regimen. This indicates that cardial toxicity might be more important in lung cancer patients treated with chemoradiation than previously anticipated. Consequently, better sparing of the heart potentially improves outcome. [1] Bradley et.al. J Clin Oncol 31, 15 pp. 7501
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ORAL 19 - Radiation for Localized Lung Cancer (ID 126)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 2
- Moderators:D. De Ruysscher, M. Hiraoka
- Coordinates: 9/08/2015, 10:45 - 12:15, 102+104+106
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ORAL19.02 - Higher Risk of Failure and Death after Stereotactic Lung Radiotherapy for T2 Lung Cancer (ID 2945)
10:56 - 11:07 | Author(s): H. Peulen
- Abstract
- Presentation
Background:
Limited data are available on the use of SBRT for tumors larger than 3cm. We analyzed results from a collaborative database to compare clinical outcomes for patients with tumors > 3cm to those with smaller tumors (<3cm).
Methods:
1192 patients with 1288 T1-T3N0M0 tumors underwent cone-beam CT image-guided lung SBRT between 10/2004-12/2014. The median prescription dose was 50 Gy in 3 fractions (range 24-64 Gy in 1-10) to the PTV. Patient, tumor and treatment factors and clinical outcomes were extracted from the database. Local recurrence (LR), regional recurrence (RR), distant metastasis (DM), overall (OS) and cause-specific survival (CSS) were calculated from SBRT completion using the Kaplan-Meier method. Univariate analyses were performed using the Cox proportional hazards model. Student’s unpaired t-test and Pearson chi-square/Fisher’s Exact test were used to compare continuous and categorical variables between groups, respectively.
Results:
Mean follow-up time was 2.1y (0.02-10.12y) and similar for both groups. 295 tumors were > 3cm (T2) and 993 < 3cm (T1) (mean size 3.98 v 1.91cm (0.5-9.6cm), p<0.001). There were no statistically significant differences between groups for gender, pulmonary function (median FEV1 1.7 L (56-60% predicted); DLCO 10 ml/min/mmHg (50-51% predicted), medical inoperability (89%), PET (94%) or any invasive mediastinal staging (6%). T1 patients were slightly younger (73.5y T1 v 76.0y T2, p<0.01) and had mildly better ECOG (80% 0-1 T1 v 71% 0-1 T2, p=0.001). T2 tumors were more often biopsied (74% T2 v 63% T1, p<0.001), less often non-squamous (74% v 83%, p=0.002), had higher SUVmax (10.3 T2 v 6.4 T1, p<0.001), more often central (0236) (19% T2 v 11% T1, p=0.001) and treated to a median prescription dose of 53.8Gy T2 v 52.2Gy T1, p<0.001. 3% received chemotherapy (T1 2.6% v T2 4.4%, p=0.11). Although LR was similar between groups, large tumors had a higher risk of RR, DM and death (Table 1). On univariate analysis, LR was predicted by multiple BED parameters (p<0.001), baseline SUVmax (p=0.003) and squamous histology (p=0.012); RR was higher for lower lobe tumors (p=0.008); DM (p=0.006) was higher while OS and CSS lower for central tumors (p=0.03, 0.01).Clinical Outcome Tumor < 3 cm Tumor > 3 cm p-value Local recurrence 3y 7% 11% 0.13 5y 11% 13% Regional Recurrence 3y 9% 13% 0.006 5y 11% 24% Distant Metastasis 3y 11% 16% <0.001 5y 16% 18% Cause-Specific Survival 3y 88% 73% <0.001 5y 81% 66% Overall Survival 3y 61% 45% <0.001 5y 42% 28%
Conclusion:
Large tumors had a higher risk of RR, DM and death after SBRT. These data have implications for consideration and study of pre-SBRT invasive nodal staging and/or systemic therapy in this population. OS and CSS were lower for central tumors warranting further analysis.
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ORAL19.06 - Tumor Location Is Associated with Recurrence Pattern and Survival after SBRT in Early Stage NSCLC Patients (ID 2623)
11:39 - 11:50 | Author(s): H. Peulen
- Abstract
Background:
For NSCLC patients treated with SBRT, we investigated if tumor location is associated with recurrence pattern and overall survival.
Methods:
From 2006-2013 1129 patients with early stage NSCLC were treated with cone beam CT guided SBRT (median 54 Gy in 3 fractions, range 23-64 Gy in 1-10 fractions) in 5 different institutes. 719 patients were analyzed after exclusion of patients with (meta)synchronous tumors (n=185), incomplete scanning data or incomplete follow-up (n=225). An average anatomy was constructed based on 109 patients of the 5 institutes using deformable image registration[1]. Subsequently, all patients were registered to this average anatomy and the corresponding dose distribution was deformed accordingly. Tumor location was defined as a 3D Gaussian distribution (standard deviation 2 cm) at the center of the high dose region. These Gaussian distributions were added to a total and per voxel a mean and standard deviation was determined. Totals were obtained for 5 different groups: local recurrence, regional recurrence, distant metastasis, all recurrent disease combined, deceased as well as their complements. By comparing 2 complimentary groups using Welch’s t-test, locations that were significantly associated (p<0.01) with recurrent disease or with overall survival were identified. Recurrent disease rates and overall survival were calculated using the Kaplan-Meier method.
Results:
With a median follow-up of 19 months, local recurrence occurred in 5% of patients, regional recurrence in 5% and distant metastasis in 9%. 74% of patients were alive and 18% was lost to follow-up. Tumors located medially in the left upper lobe were significantly associated with controlled disease (local, regional, distant and all combined). Figure 1A displays as heatmap: disease control (green), recurrent disease (purple), and the region where the two groups differ significantly (yellow). Tumors located peripherally in the left lower lobe were significantly associated with regional recurrences. Tumors located medially/centrally in the right upper lobe were significantly associated with distant metastases and all recurrent disease combined (local, regional and distant together). Tumors located medially/centrally in the right upper lobe were significantly associated with a decreased overall survival (Figure 1B). Figure 1
Conclusion:
In this group of 719 NSCLC patients treated with SBRT, an average anatomy was utilized to analyze associations of tumor location with treatment outcome. Several regions were identified that were significantly associated with disease recurrence and overall survival. Further investigations in the underlying mechanisms of these associations are warrented. 1.ADMIRE Research 2015, Elekta AB, Stockholm, Sweden
