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G.M.M. Videtic
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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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MINI18.11 - Does Motion Management Technique for Lung SBRT Influence Local Control? (ID 177)
17:45 - 17:50 | Author(s): G.M.M. Videtic
- Abstract
- Presentation
Background:
Abdominal compression (COMP) for motion management began with our lung stereotactic body radiotherapy (SBRT) practice. From 11/2009, breath hold technique by automatic breath control (ABC) device is selectively employed typically for fit oligometastatic patients (pts). We now compare local failure (LF) results for COMP versus ABC.
Methods:
Our IRB-approved SBRT registry was queried for pts. treated for either a primary lung cancer (PRIME) or an oligometastatic (OLIGO) diagnosis with a minimum 6 months follow up. SBRT was delivered by a stereotactic-specific LINAC platform with vacuum-bag based immobilization, and infrared-based X-ray positioning system+/- CBCT for image-guidance. With COMP, tumor excursion was limited to <1cm and the ITV was created one of two way dependent on treatment era: 1. Fused GTV excursion CTs from free breathing, fixed inhale and exhale travel or 2. by 4DCT, with PTV created from the MIP ITV after adding a 5mm margin. With ABC, 3 serial CT image sets confirmed target immobilization, with the PTV generated after 5 mm was added to the static GTV. SBRT was delivered either with dynamic arcs or step-and-shoot intensity–modulated beams. SBRT dose/fractionation schedules evolved over time and reflected treatment era, tumor location, clinician preference, and trial-based experience. LF was defined as progressive and increasing CT scan abnormalities confirmed by progressive and incremental increases in a lesion’s SUVs on serial PET imaging, with or without biopsy.
Results:
For the interval 10/2003 to 7/2014, 873 pts with 931 lesions were treated. Overall pt. characteristics were: 455 (52.1%) female; 83.9% Caucasian; median age 73 years (range 37-97); median KPS 80 (range 40-100); median BMI 26.2 (range 12.1-56.3). Overall tumor characteristics were: median tumor size 2.2 cm (range 0.7-10.0); median PET SUVmax 7.5 (range 0.8-59), per RTOG 0813 definitions 234 (25.4%) were central lesions, with no significant tumor differences between COMP and ABC cohorts. 830 (89.2%) lesions were PRIME, 101 (10.8%) were OLIGO. ABC was used significantly more for OLIGO vs. COMP (34.4% vs.8.3%, p<0.0001). Median follow-up and SBRT dose were 16.4 months (0-109.5) and 50 G/5 fractions respectively. Overall crude rate of LF was 9.9%. Use of ABC was not associated with increased LF compared to COMP: hazard ratio (HR)=1.043 [95% CI 0.48-2.29; p=0.92] Three-year actuarial rates of LF for ABC vs. COMP were 13.8% and 16.5%, respectively. After stratifying by OLIGO/PRIME, neither ABC nor COMP was significantly associated with LF. There is a suggestion that centrality may be associated with LF with ABC (HR =2.087, p=0.066)On univariate analysis, BMI, tumor size, PET SUVmax and central location were associated with failure, with size the most significant.
Conclusion:
Although form of motion control overall did not predict for LF in lung SBRT, LF for central tumors may be associated with ABC use.
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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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ORAL19.03 - NRG Oncology/RTOG 0813 Trial of Stereotactic Body Radiotherapy (SBRT) for Central Tumors - Adverse Events (ID 1458)
11:07 - 11:18 | Author(s): G.M.M. Videtic
- 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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ORAL19.07 - A Novel Nomogram for Predicting Distant Metastases after Lung Stereotactic Body Radiotherapy for Early Stage Lung Cancer (ID 1270)
11:50 - 12:01 | Author(s): G.M.M. Videtic
- Abstract
- Presentation
Background:
While stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer (NSCLC) results in excellent local control, distant metastases (DM) remain the most prevalent form of failure. In this analysis, we develop and internally validate a nomogram to predict DM following SBRT for NSCLC.
Methods:
We queried our institutional registry of patients treated with lung SBRT over the past decade (2003-2014) and identified 729 patients with early stage NSCLC eligible for analysis. All patients were treated with definitive intent. Initial patient and tumor variables predicting the likelihood of developing distant metastases were identified from a multivariable Cox proportional hazard model. A nomogram was developed from the initial model using 16 candidate variables and was reduced to the find the best fitting parsimonious model. The nomogram was then internally validated using a 1000 bootstrap resampling process. Accuracy of the nomogram was measured using c-statistics.
Results:
The median follow up was 15.2 months. 157 patients (22%) developed DM at a median time of 10.3 (range 0.2-68.4) months. The median time to death after development of DM was 4.5 months. Sites of DM included lung (113/157 patients), bone (36/157 patients), liver (27/157 patients), brain (25/157 patients), adrenal (8/157 patients), and other (7/157 patients). Age at start of radiotherapy (p = 0.051), tumor size (p = 0.009), PET SUV (p = 0.026), and the presence of synchronous primaries (p = 0.048) were all predictive of DM on multivariable analysis. Using seven patient and tumor variables (Age, BMI, Charlson Comorbidity Index, Tumor Size, PET SUV, Medical Operability, and Presence of a synchronous primary NSCLC), our nomogram successfully predicted distant metastasis and has an internally validated c-statistic of 0.606 (95% CI: 0.563, 0.648). Internal validation with bootstrapping demonstrated persistent validity of the nomogram in predicting distant metastases. Figure 1
Conclusion:
This novel internally validated nomogram can predict the risk of distant metastases in early stage NSCLC treated with SBRT. External validation of this nomogram is warranted. This nomogram may help define subgroups for stratification in future clinical trials and identify patients who may benefit from adjuvant systemic therapies following lung SBRT.
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ORAL 20 - Chemoradiotherapy (ID 124)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:G. Blumenschein, J.Y. Chang
- Coordinates: 9/08/2015, 10:45 - 12:15, 201+203
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ORAL20.04 - Discussant for ORAL20.01, ORAL20.02, ORAL20.03 (ID 3288)
11:18 - 11:28 | Author(s): G.M.M. Videtic
- Abstract
- Presentation
Abstract not provided
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P1.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 212)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.03-017 - Radiation Dose-Related Lymphopenia as an Outcome Predictor in Stage III NSCLC Patients Treated with Chemoradiation (ID 2918)
09:30 - 09:30 | Author(s): G.M.M. Videtic
- Abstract
Background:
RTOG 0617 failed to show survival advantage from increased radiation dose in stage III concurrent chemo radiation-treated patients. While toxicity was not significantly different between standard and high dose radiation groups, local-regional control and survival were inferior in high dose, experimental arm. These findings have largely remained unexplained. There is increased evidence in literature suggesting survival disadvantage associated with lymphopenia in certain malignancies. We hypothesize radiation-induced lymphopenia may be dose-dependent and may carry a survival disadvantage.
Methods:
Stage III NSCLC patients treated with curative chemoradiation were retrospectively studied. Patients were categorized into those receiving standard dose and those receieiving high dose ( > 66Gy). Hematologic values including absolute lymphocyte count (ALC) was evaluated at diagnosis and at regular intervals during and after treatnent. Numerical variables were summarized using median (range) and compared between groups using non parametric Wilcoxon rank sum tests. Overall survival (OS) and other time to event endpoints were assessed using Kaplan-Meier (K-M) survival curves and compared between standard and high dose groups using log rank tests.
Results:
182 patients with stage III NSCLC were identified. 77 % male, 52% adenocarcinoma, and 41% squamous cell carcinoma. 155 patients received SD RT and 27 received HD RT. Pre-treatment ALC were not different between Standard and High dose groups [ 1730 /ul vs. 2065/ul (p=0.4955) ]. The High dose group showed lower Nadir ALC ( 279/ul vs 324/ul and shorter time to Nadir ( 29 d vs 35 d) than the Standar group ( two sided p’s =0.11and 0.06, and one sided p’s=0.05, 0.03 respectively). The K–M survival curves showed that Standard dose group has better OS than the High dose group (31.3 m vs 11.4 m , p<0.001). For patients whose Nadir ALC >600 (about 80% percentile level of Nadir ALC), median survival was 37.8 month as compared to 18.2 month among those Nadir ALC≤600 (p=0.192).
Conclusion:
Our study showed sutrvival among patients treated with higher dose radiation was significantly worse. Although baseline absulte lymphocyte counts were not different between the two groups, patient treated with high dose radiation reached their nadir counts more quickly and also developed a lower absolute lymphocyte count compared to patients treated with standard dose. Regardless of treatment group, there was a trend towards a worse survival among patients who developed lower lymphocyte counts subsequent to traetment.
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P2.07 - Poster Session/ Small Cell Lung Cancer (ID 222)
- Event: WCLC 2015
- Type: Poster
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.07-013 - Medically Inoperable Early Stage Small Cell Lung Cancer: Patterns of Failure after SBRT (ID 176)
09:30 - 09:30 | Author(s): G.M.M. Videtic
- Abstract
Background:
To report on the patterns of failure for medically inoperable early stage small cell lung cancer (SCLC) when stereotactic body radiotherapy (SBRT) manages the primary lung tumor.
Methods:
We queried our institutional IRB-approved SBRT registry for the period 2004-2014 for any early stage SCLC patients with a minimum of 6 months follow up. All patients had biopsy proven disease and were deemed medically inoperable after multi-disciplinary review. Routine staging consisted of PET/CT and MRI brain scans only. The treatment model consisted of SBRT to the primary followed by adjuvant platinum-based chemotherapy (CHT) and then prophylactic cranial irradiation (PCI). SBRT was delivered employing a stereotactic-specific LINAC with vacuum-bag based immobilization, and infrared-based X-ray positioning system+/- CBCT for image-guidance.
Results:
Of 747 definitively treated cancers over 10 years , 16 (2%) were SCLCs meeting study criteria. Patient characteristics revealed: median KPS was 80 (range 50-90), median age was 69 years (range 45-87), 50% of patients were female, median BMI was 28.2 (range 17.4-41.2). Tumor characteristics revealed: median tumor size was 3.25cm (range1.4-7.2 ), 4 (25%) tumors were “central” (per RTOG 0813 criteria), median PET-SUVmax was 10.3 (range 2.8-21.1). Median time to SBRT from diagnosis was 2.1 months (range 0.6-6.7). SBRT schedules were: 60 Gy/3 fractions in 25%, 50 Gy/5 fractions in 68.75%, 30 Gy/1 fraction in 6.25% of cases. Mean follow up was 15 months. Fifteen (94%) received at least 2 cycles CHT, of which 2 (12.5%) received CHT before SBRT. Nine patients (56%) received PCI and of the 7 (44%) that did not, 1 developed brain metastases prior, 1 refused, and 5 died of non-cancer issues before PCI . There was no grade 3 or higher toxicity; rate of grade 2 or less toxicity was 12.5%. Seven patients (43.75%) were alive at analysis and of the 9 deaths, 2 (22%)were cancer, 5 were non-cancer (56%), 2 unknown cause(22%). Local control was 100% with 13 patients (81.25%) without any failure. Crude rates of failure were one (6.3%) distant and regional nodal and two (12.5%) distant. Median survival was 39 months. Three-year actuarial overall and progression-free survivals were 50.5% and 76%, respectively.
Conclusion:
SBRT for stage I medically inoperable SCLC yields excellent local control. The absence of regional nodal failure lends support to PET for mediastinal staging. The primary pattern of failure is distant.
