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I. Grills
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MINI 18 - Radiation Topics in Localized NSCLC (ID 139)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
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MINI18.06 - Validation of High Risk Features on CT for Detection of Local Recurrence After SBRT for Stage I NSCLC (ID 2138)
17:15 - 17:20 | Author(s): I. Grills
- Abstract
- Presentation
Background:
Fibrotic changes after SBRT for stage I NSCLC are difficult to distinguish from local recurrences (LR), hampering proper selection for salvage therapy. Huang et al. (1) defined CT high risk features (HRF) for detection of LR. This study attempts to validate these HRFs in an independent patient cohort.
Methods:
From a multicenter combined database of patients treated with SBRT for stage I NSCLC between 2006 and 2012, 53 LR were detected of which 14 were biopsy proven. The biopsy proven LR (N=14) were matched 1:2 to patients without LR (n=28) based on: 1) dose 2) PTV 3) follow up time 4) central/peripheral location 5) lung lobe. Of the resulting 42 patients 18 were male and 24 female with a median age of 73 years (range 56-89years). Median tumor size, PTV and dose were 2.3 cm (range 1.0-4.9cm), 49cc (range 9-166cc), 48 Gy (range 48-60Gy) in 4 fractions (range 3-8) respectively. Most tumors were peripheral (76%) and located in the upper lobes (55%). Median follow up (FU) was 36 months (range 14-78months) and median time to LR was 18 months (range 12-45months). For all patients, planning CT scans and at least two follow up scans were available. Two blinded observers scored eight HRFs for each scan. Sensitivity and specificity in predicting LR were assessed and compared using Fisher’s exact test. Analysis for best fit was done using AUC.
Results:
Results of sensitivity and specificity are shown in Table 1. The best performing HRF was cranio-caudal growth: sensitivity 86%, specificity 82%. The odds of LR increased on average by 2.6 (95%CI1.5-4.3) for each additional HRF detected, while the AUC was 0.86. The presence of ≥ 3 HRFs resulted in the best cut-off with sensitivity 79% and specificity 86%. Loss of linear margin and bulging margin were scored identical and therefore only the latter was included in the model. The two best combinations of HRFs were: 1) bulging margin & cranio-caudal growth, with a sensitivity of 93% and specificity of 82% or 2) bulging margin & enlarging opacity after 12 months, with a sensitivity of 86% and specificity of 89%. Table 1CT high risk factor for local recurrence Sensitivity (%) Specificity (%) p-value Any HRF 93 64 .001 enlarging opacity (≥5mm and ≥20%) 86 68 .003 sequential enlarging opacity 57 89 .002 enlarging opacity after 12 months 71 89 <.001 bulging margin 64 100 <.001 loss of linear margin 64 100 <.001 loss of air bronchograms 7 100 0.33 cranio-caudal growth (≥5mm and ≥20%) 86 82 <.001 new pleural effusion 14 93 0.59
Conclusion:
In this matched group of biopsy proven LR and controls, cranio-caudal growth was the best individual predictor of LR after SBRT. Combining HRF bulging margin with either cranio-caudal growth or enlarging opacity after 12 months resulted in higher sensitivities and specificities than number of HRFs. 1)Huang et al. Radiotherapy&Oncology 2013
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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: 3
- 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): I. Grills
- 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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ORAL19.03 - NRG Oncology/RTOG 0813 Trial of Stereotactic Body Radiotherapy (SBRT) for Central Tumors - Adverse Events (ID 1458)
11:07 - 11:18 | Author(s): I. Grills
- Abstract
- Presentation
Background:
The safety of SBRT for medically inoperable patients with centrally located early stage non-small cell lung cancer (NSCLC) was evaluated in this phase I/II multicenter RTOG study that completed accrual in Sept 2013. This is the first report of adverse events (AE) observed on the study.
Methods:
Eligible patients were medically inoperable with biopsy proven, PET staged T1-2N0M0 NSCLC, ≤ 5 cm in size, centrally located tumors (within or touching the zone of the proximal bronchial tree or adjacent to mediastinal or pericardial pleura). Patients were successively accrued onto dose-escalating 5 fraction SBRT schedules delivered over 1.5-2 weeks, starting with 10 Gy per fraction (fr), then 10.5Gy/fr, 11 Gy/fr, 11.5 Gy/fr and 12 Gy /fr. Toxicity was graded using CTCAE v4.0; any potential dose-limiting toxicity within the initial 365 days post SBRT could have led to dose reduction for subsequent patients accrued, using TITE-CRM (time-to-event continual reassessment method) statistical design.
Results:
120 patients (100 evaluable) from 43 centers were accrued between 2/2009 and 9/2013. 12 were excluded as they did not receive protocol treatment (6 of these on the 12Gy/fr cohort) and another 8 did not meet eligibility criteria. Cohort sizes were 8 (10Gy/fr), 8 (10.5Gy/fr), 18 (11Gy/fr), 43 (11.5Gy/fr), and 43 pts (12Gy/fr). Median age was 72 (range 52- 89) years, 57% were female, 45% had squamous cell carcinoma, 39% had adenocarcinoma, 65% had T1 tumors. Median follow up was 26.6 months. Most adverse events were grade (G) 1 or 2. 5/8 pts in lowest SBRT dose cohort (10 Gy/fr) experienced G2 toxicity, none had G>3. Of 7 pts in 10.5 Gy/fr, 1 had G2 and 1 had G5 toxicity. Of 14 pts in 11 Gy/fr cohort, 4 had G2 and 1 had G3. Of 38 pts in 11.5Gy/fr cohort, 11 had G2, 4 had G3 and 2 had G5. Of 33 pts in 12Gy/fr, 4 had G2, 5 had G3, 1 G4 and 1Gr 5 as the worst overall toxicity definitely, probably or possibly related to SBRT. All Gr 5 toxicities were due to hemoptysis, occuring at a mean of 13 mo post SBRT (range 5.5-14mo). G2+ GI toxicity only occurred in the 11.5Gy/fr (1/38) and 12.0Gy/fr (2/33) cohorts. G2+ pulmonary toxicity occurred in 4/8 10.0Gy/fr, 0/8 10.5Gy/fr, 5/14 11.0Gy/fr, 15/38 11.5Gy/fr, and 10/33 12.0Gy/fr pts.
Conclusion:
This phase I/II trial of SBRT provides data to inform patients of the potential toxicities with a 5 fraction SBRT schedule for centrally located NSCLC. Although SBRT was well tolerated, 4/100 pts (4%) had fatal hemoptysis potentially attributable to SBRT. Determination of the optimal SBRT dose needs to await analysis of tumor locations, DVH data and efficacy data. This project was supported by grants U10CA21661, U10CA180868, U10CA180822 and U10CA37422 from the National Cancer Institute (NCI).
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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): I. Grills
- 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
