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Jeffrey Bradley
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MA01 - Early Stage Lung Cancer: Questions and Controversies (ID 894)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 10:30 - 12:00, Room 202 BD
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MA01.03 - An Externally Validated Nomogram for Predicting Distant Metastasis After SBRT for Early Stage Non-Small Cell Lung Cancer (ID 11182)
10:40 - 10:45 | Author(s): Jeffrey Bradley
- Abstract
- Presentation
Background
SBRT is a standard option for patients with early stage NSCLC who are medically inoperable. While SBRT is associated with excellent local control, distant metastases (DM) represent the primary pattern of failure. Adjuvant systemic therapy has not traditionally been used in this patient population due to medical comorbidities. With the advent of immunotherapy that may be better tolerated, there has been a renewed interest in identifying patients that may derive benefit. We developed and internally validated a nomogram to predict the likelihood of DM after SBRT for early stage NSCLC which was then externally validated.
a9ded1e5ce5d75814730bb4caaf49419 Method
Our lung SBRT registry was queried for patients with early stage NSCLC treated with definitive intent from 2003-2017 and 1002 patients were identified for analysis to develop the model. A dataset from an external institution was used to similarly identify patients and 737 were used for the validation cohort. Random Survival Forest was used to assess importance, interactivity, and overall predictive ability with respect to DM for 14 variables. A Fine-Gray competing-risks regression model was formulated where apparent interactions were examined with likelihood-ratio tests. Backward variable selection was implemented to reduce to a parsimonious model. The concordance probability (C-index) of the model was internally validated with 10-fold cross validation.
4c3880bb027f159e801041b1021e88e8 Result
The median overall survival was 1.71 years internally and 1.92 years externally. Median follow-up was 18.3 months and 21.1 months. 1-year incidence of DM was 16% and 12.1% in the internal and external cohorts, respectively. Random Forest analysis suggested that tumor size and PET SUV are the most important predictors of distant failure. The 1-year cumulative incidence (CI) of DM was 18.5% for PET SUV ≥4.1 vs 8.4% for <4.1. 1-year CI for tumor size >3 cm was 26% vs 12.6% for ≤3 cm. The median time to DM was 0.86 years internally and 1.1 years externally. The final nomogram included tumor size, histology, PET SUV, age, KPS, and active smoking status, and had a cross-validated C-index of 0.62. The nomogram provides predictive value for probability of DM at 1-year between 10 and 70%.
8eea62084ca7e541d918e823422bd82e Conclusion
This novel nomogram with external validation can be used to predict the 1-yr DM risk after SBRT for patients with early-stage NSCLC, accounting for the competing risk of death. This nomogram may help define patient subsets for stratification in future clinical trials to help identify who may benefit from adjuvant systemic therapy after SBRT to reduce the incidence of DM and disease-related death.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MA05 - Improving Outcomes in Locoregional NSCLC II (ID 901)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 13:30 - 15:00, Room 105
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MA05.09 - PFS and Cardiac-Toxicity-Adjusted-PFS As Predictors of OS in Locally Advanced NSCLC Treated with Concurrent Chemoradiation (ID 12391)
14:30 - 14:35 | Author(s): Jeffrey Bradley
- Abstract
- Presentation
Background
Overall survival (OS) is the gold standard for LA-NSCLC with chemoradiation (CCRT), while the complex relationships among RT dosimetry, systemic therapies, cardiopulmonary toxicity, progression (PD) and OS are also of increasing scientific and clinical interest.
a9ded1e5ce5d75814730bb4caaf49419 Method
NRG Oncology RTOG 0617 (NCT00533949) was a randomized phase 3 trial comparing standard (SD, 60 Gy) versus high-dose (HD, 74 Gy) CCRT +/- cetuximab from 11/07-06/11. This secondary analysis includes 469 patients (pts) given ≥50 Gy. A PFS event was defined as the first occurrence of local, regional, distant PD or death w/o documented PD. A CTA-PFS event was the first occurrence of grade 2+ treatment-related cardiac toxicity event or a PFS event. Landmark analyses at 6mo and 12mo were used to minimize the immortal time bias. Cox model with PD or CT/PD as a time-dependent covariate was used to evaluate their predictive roles. Median f/u time for surviving pts was 5.1 years.
4c3880bb027f159e801041b1021e88e8 Result
As previously reported, pts treated with HD had significantly lower OS rates (HR=1.28, 95%CI: 1.04-1.58, p=0.018) and CTA-PFS rates (HR=1.24, 95%CI: 1.02-1.51, p=0.035), and marginally lower PFS rates (HR=1.21, 95%CI: 0.99-1.47, p=0.06) than pts treated with SD. Median survival time (MST) among pts having PD within 6mo versus not were 13.4mo (95%CI: 10.0-19.0mo) and 30.7mo (95%CI: 28.0-37.0mo) (p<0.001). MST for pts having PD within 12mo versus not were 20.6mo (95%CI: 18.8-25.0mo) and 60mo (95%CI: 47.6-74.5mo)(p<0.001). Results are similar when using CTA-PFS with 6mo or 12mo cutoff (p<0.001). RT dose was no longer significantly associated with OS (p=0.08 or p=0.15) when PD or CT/PD was included in multivariable analysis (p<0.001), suggesting OS differences in HD/SD may be partially captured by PFS or CTA-PFS.
8eea62084ca7e541d918e823422bd82e Conclusion
Long-term survival results from RTOG 0617 suggest that PFS (or CTA-PFS) status at 6mo or 12mo predicts long-term OS, and may potentially be considered as a surrogate endpoint of OS in clinical trials. Pts who were progression-free at 12mo had a MST of 5 years. Further validation on external datasets and in the modern era of immunotherapy are needed.
Funding: This project was supported by grants NCORP (UG1CA189867), NRG Operations (U10CA180868), NRG SDMC (U10CA180822), IROC (U24CA180803), and CTEP from the National Cancer Institute (NCI).
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MS30 - Modern Day RT in LA NSCLC: Where Is the Evidence? (ID 808)
- Event: WCLC 2018
- Type: Mini Symposium
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 13:30 - 15:00, Room 202 BD
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MS30.03 - What Evidence Is Available to Support RT Treatment Intensification in LA NSCLC? (ID 11532)
14:05 - 14:20 | Presenting Author(s): Jeffrey Bradley
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P3.17 - Treatment of Locoregional Disease - NSCLC (Not CME Accredited Session) (ID 983)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.17-02 - Increasing Radiation Dose to Central Structures is Associated with Worse Survival Following Thoracic Proton Reirradiation (ID 12763)
12:00 - 13:30 | Author(s): Jeffrey Bradley
- Abstract
Background
Background: Historically, thoracic reirradiation has been associated with high rates of toxicity from cumulative doses delivered to organs at risk (OARs). Conformal treatment in the form of proton therapy (PT) offers the opportunity to deliver definitive doses of radiotherapy with limited dose to surrounding OARs. We performed dosimetric analyses of patients undergoing thoracic re-irradiation with PT to identify parameters associated survival outcomes.
a9ded1e5ce5d75814730bb4caaf49419 Method
Methods: We identified patients with complete clinical and dosimetric information who received thoracic re-irradiation with PT on an IRB-approved prospective patient registry. Prior radiation courses were fused with PT plans to create composite plans, which were recalculated to an equivalent dose of 200 cGy per fraction (EQD2) using an α/β of 3. Toxicity was retrospectively assessed using CTCAE v4.0. Toxicity, disease control, and survival were estimated with the Kaplan-Meier method. The Cox proportional hazards model was used to estimate hazard ratios for univariate analysis (UVA), and significant dosimetric parameters were further assessed using cutpoint analysis. Patients were dichotomized based on these cutpoints, and survival differences were assessed using the log-rank test.
4c3880bb027f159e801041b1021e88e8 Result
Results: A total of 25 patients were included with a median age of 64 years (range 26-89). The majority of patients had non-small cell lung cancer (84%). Median PT re-irradiation dose was 6000 CGE (range 4000-6250) in 30 fractions (range 5-30 fractions). At a median follow-up of 17.5 months (range 1-34), one-year rates of local control, distant control, and overall survival, were 70.9%, 55.6%, and 71.2% respectively. No grade 4/5 toxicities were observed, and there were 5 late grade 3 events (2 non-malignant pleural effusions, 2 episodes of hemoptysis, 1 one esophageal stricture) with an estimated rate of 21% at 1 year. UVA revealed worse survival in patients with increasing maximum dose to the esophagus, carina, heart, pulmonary artery, and spinal cord, and increasing mean dose to the esophagus (p<0.05 for each). Patients who received a cumulative point max dose of ≥ 7500 cGy to the esophagus, ≥11620 cGy to the heart, ≥ 12000 cGy to the pulmonary artery, or ≥ 3250 mean dose to the esophagus had significantly worse survival than those who did not (all p<0.05).
8eea62084ca7e541d918e823422bd82e Conclusion
Conclusion: PT re-irradiation is a viable treatment option for patients with thoracic recurrences and offers excellent outcomes with limited toxicity. In this study, we identified dosimetric parameters associated with worse survival that can be used in treatment planning for recurrent disease.
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