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L.B. Marks
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OA24 - Radiotherapy of Lung Cancer: Recent Developments (ID 411)
- Event: WCLC 2016
- Type: Oral Session
- Track: Radiotherapy
- Presentations: 1
- Moderators:K. Dieckmann, S. Rieken
- Coordinates: 12/07/2016, 14:20 - 15:50, Stolz 1
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OA24.03 - Cardiac Toxicity after Radiation for Stage III NSCLC: Pooled Analysis of Dose-Escalation Trials Delivering 70-90 Gy (ID 4322)
14:40 - 14:50 | Author(s): L.B. Marks
- Abstract
- Presentation
Background:
Radiation (RT) associated cardiac injury in patients with lung cancer is of unclear significance. RTOG 0617 demonstrated reduced overall survival (OS) with dose-escalated RT for Stage III NSCLC, with higher heart doses predicting for worse OS. We assessed the impact of heart doses on toxicity and survival for patients enrolled on several prospective RT dose-escalation trials.
Methods:
From 1996-2009, 133 patients with Stage III NSCLC (ECOG PS 0-1) were treated on six prospective trials using induction/concurrent chemotherapy and dose-escalated conformal RT to 70-90 Gy. Broad clinical outcomes (e.g. OS) were prospectively assessed. RT plans were reviewed, cardiac structures were defined, and dose/volume metrics were computed. Patient records were retrospectively reviewed for post-RT symptomatic cardiac events (symptomatic pericardial effusion, acute coronary syndrome, and pericarditis). Baseline cardiac risk was calculated using the World Health Organization / International Society of Hypertension (WHO/ISH) score. A competing risks model accounting for the risk of death was used for statistical analysis.
Results:
112 patients were included in the final analysis. Median f/u was 19 mo. (75 mo. for the 39 patients without documented progression). Median OS and PFS were 22 and 12 mo. Median prescribed RT dose was 74 Gy. 15 patients (13%) had symptomatic cardiac events (6 pericardial effusion, 5 myocardial infarction, 2 unstable angina, 2 pericarditis) at median 26 mo. post-RT (range, 7-68). On univariate analysis, Heart mean dose (p=0.001), Heart V5Gy (p<0.001), and Heart V30Gy (p=0.002) were associated with symptomatic cardiac events, whereas baseline WHO/ISH score (p=0.204) and coronary artery disease (p=0.109) were not. Heart doses were higher in patients with vs without events (mean 22Gy vs 11Gy, V5Gy 60% vs 35%, V30Gy 35% vs 14%). On multivariate pair analysis accounting for baseline risk, heart doses remained significant predictors of cardiac events (e.g. Heart mean dose, p=0.001, HR 1.05 / 1Gy). 2-year competing risk-adjusted rate of symptomatic cardiac events was 11.1% vs 1.5% for Heart mean dose ≥15Gy vs <15Gy (p=0.003, HR 6.7). 34 patients (30%) had asymptomatic pericardial effusions. There was no association between heart doses and OS.
Conclusion:
Clinically significant symptomatic cardiac events following high-dose thoracic RT for Stage III NSCLC occurred in 13% of patients at a median 2 years post-RT, with the rate appearing to be heart dose dependent. RT-associated cardiac toxicity in the definitive treatment of Stage III NSCLC may occur earlier than historically understood, and heart doses should be minimized. Supported in part by NIH grant CA69579.
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P1.03 - Poster Session with Presenters Present (ID 455)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.03-070 - The Impact of Advances in Systemic Staging on the Rate of Metachronous and Synchronous Metastases in Patients Lung Cancer (ID 4335)
14:30 - 14:30 | Author(s): L.B. Marks
- Abstract
Background:
To quantify the impact of advances in systemic staging (i.e. from CT-based to PET-based over the last ≈ 20 years) on the rate of distant metastases detected at their time of initial diagnosis (synchronous) and sometime after initial diagnosis (metachronous) in patients with lung cancer.
Methods:
The Surveillance, Epidemiology, and End Results (SEER) data base, representing 10 % of the US population was used to analyze lung cancers from 1988-2008. (a) The fraction of patients with overt synchronous metastases at diagnosis was noted. (b) Among patients without overt metastasis at diagnosis, their 5-year mortality rate was taken as an estimate of their rate of metachronous metastasis (as most deaths were due to distant metastases). (c) The overall rate of metastases (synchronous + metachronous) amongst all patients was computed. (d) The fraction of all metastases detectable at initial diagnosis (synchronous / [synchronous + metachronous]) was computed. Rates were computed for patient cohorts diagnosed in different time intervals from 1988-2008, to reflect the use of different systemic staging methods over the 20-year interval.
Results:
(a) The rate of synchronous metastatic disease slowly increased from ≈ 53% in the earlier years to ≈ 55% in 2008. (b) Among patients without overt metastasis at diagnosis, the rate of metachronous metastatic disease slowly decreased from ≈ 73% in the earlier years to ≈ 62% in 2008. (c) If one assumes that most of the metachronous metastatic lesions were present (but covert) at the time of the initial diagnosis of the primary disease, then one can estimate that ≈ 83-87% of patients have micro/macro metastatic disease at presentation (this rate is basically unchanged over time, but small changes over time may reflect the impact of systemic chemotherapy). (d) Among all patients with metastatic disease, ≈ 60.4% of metastatic lesions were detectable clinically or with CT at the time of diagnosis in the pre-PET era, vs. ≈ 66.6% of these lesions being detectable clinically or with CT and/or PET in the PET era.
Conclusion:
The addition of PET appears to have a small but measurable impact on the rates of synchronous and metachronous metastasis, resulting in stage migration from metachronous to synchronous (i.e. from covert to overt) metastases at the time of diagnosis. The addition of PET to the pre-treatment evaluation increases the ability to detect metastatic disease by ≈ 6% (from 60.4 to 66.6%).
