Incidence and Predictors of Pericardial Effusion After Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

Abstract

Purpose Findings from RTOG 0617 suggested that collateral radiation to the heart may contribute to early death in patients receiving chemoradiation therapy for non-small cell lung cancer (NSCLC); however, reports of cardiac toxicity after thoracic radiation therapy (RT) remain limited. Because pericardial disease is the most common cardiac complication of thoracic RT, we investigated the incidence of and risk factors for pericardial effusion (PCE) in patients enrolled in a phase II, prospective randomized study of intensity modulated RT (IMRT) versus proton therapy for locally advanced NSCLC. Methods and Materials From July 2009 through April 2014, 201 patients were prospectively treated with proton beam therapy or IMRT to 60-74 Gy with concurrent chemotherapy. The primary endpoint (grade ≥2 PCE) was diagnosed upon review of follow-up images. Clinical characteristics and cardiac dose-volume parameters associated with PCE were identified via Cox proportional hazards modeling and recursive partitioning analysis of null Martingale residuals. Reproducibility was evaluated in a separate retrospective cohort of 301 patients. Results Cumulative incidence rates of PCE among patients in the trial were 31.4% at 1 year and 45.4% at 2 years, with median time to PCE of 8.9 months. Several cardiac dose-volume parameters (e.g., V20–V65) predicted PCE, but heart V35 (HV35) was the most strongly associated, with cut-off volume of 10%. On multivariable analysis, HV35 >10% independently predicted PCE (hazard ratio [HR] 2.14, p=0.002), a finding that maintained reproducibility in the retrospective validation cohort. Other factors associated with PCE included receipt of adjuvant chemotherapy (HR 2.82, p<0.001) and prior cardiac disease (HR 1.68, p=0.020). Conclusions PCE was common after RT for NSCLC, occurring in nearly half of patients even after moderate radiation doses to the heart. Adjuvant chemotherapy may increase the risk of PCE, and HV35 >10% may identify patients at risk for development of this cardiac toxicity.

Cardiac radiation dose distribution, cardiac events and mortality in early-stage lung cancer treated with stereotactic body radiation therapy (SBRT)

“…Time to death (months) However, the present study provides more detailed analysis on cardiac dose and patient outcomes after SBRT in early-stage lung cancer. Interestingly, in our cohort no pericardial effusions were observed, which is commonly observed after radiotherapy for locally advanced lung cancer (14).…”

“…Recently, interest in cardiac toxicity in lung cancer patients has increased (10). Several studies showed that radiation dose to the heart in stage III lung cancer patients was associated with the development of cardiac events (7,(11)(12)(13)(14)(15) and overall survival (12,14,15). Importantly, RTOG 0617 showed that the heart volume receiving ≥5 and 30 Gy predicted overall survival.…”

Dosimetric Predictors of Symptomatic Cardiac Events After Conventional-Dose Chemoradiation Therapy for Inoperable NSCLC

“…Whereas asymptomatic pericardial effusions occur in up to 40.3% of patients after RT, symptomatic pericardial effusions occur only in 0.7% to 6.3%. 4,14,41 Nevertheless, prior work found associations between cardiac doses and mostly asymptomatic pericardial or pleural effusions. 41,42 A few actionable steps may potentially limit cardiotoxicity after RT for inoperable NSCLC.…”

“…4,14,41 Nevertheless, prior work found associations between cardiac doses and mostly asymptomatic pericardial or pleural effusions. 41,42 A few actionable steps may potentially limit cardiotoxicity after RT for inoperable NSCLC. First, on the basis of a high cardiac event rate among patients receiving mean WH dose 20 Gy (4-year rate, 48.6% in this study and 41% in Wang et al 3 ), a reasonable constraint for routine planning might be to keep mean WH dose <20 Gy, below the current recommendation of 26 Gy by the NCCN.…”

Heart dose linked with cardiac events and overall survival in lung cancer radiotherapy

“…In addition, some studies focused on the specific cardiac events. Ning et al [ 40 ] investigated the potential risk factors for pericardial effusion which is the most common complication in radiotherapy and they found that HV35 >10% (cutoff volume is 10%), adjuvant chemotherapy, and previous cardiac disease were predictors of pericardial effusion. Wang et al [ 17 ] also discussed 3 types of cardiac events including pericardial events, ischemic events, and arrhythmic events, respectively.…”