Predictors of High-grade Esophagitis After Definitive Three-dimensional Conformal Therapy, Intensity-modulated Radiation Therapy, or Proton Beam Therapy for Non-small cell Lung Cancer

Abstract

Introduction We analyzed the ability of various patient- and treatment-related factors to predict radiation-induced esophagitis (RE) in patients with non-small cell lung cancer (NSCLC) treated with three-dimensional (3D) conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or proton beam therapy (PBT). Methods and Materials Patients were treated for NSCLC with 3D-CRT, IMRT, or PBT at MD Anderson from 2000 to 2008 and had full dose-volume histogram (DVH) data available. The endpoint was severe (grade ≥3) RE. The Lyman-Kutcher-Burman (LKB) model was used to analyze RE as a function of the fractional esophageal DVH, with clinical variables included as dose-modifying factors. Results Overall, 652 patients were included: 405 treated with 3D-CRT, 139 with IMRT, and 108 with PBT; corresponding rates of grade ≥3 RE were 8%, 28%, and 6%, with a median time to onset of 42 days (range 11–93 days). A fit of the fractional-DVH LKB model demonstrated that the volume parameter n was significantly different (p=0.046) than 1, indicating that high doses to small volumes are more predictive than mean esophageal dose. The model fit was better for 3D-CRT and PBT than for IMRT. Including receipt of concurrent chemotherapy as a dose-modifying factor significantly improved the LKB model (p=0.005), and the model was further improved by including a variable representing treatment with >30 fractions. Examining individual types of chemotherapy agents revealed a trend toward receipt of concurrent taxanes and increased risk of RE (p=0.105). Conclusions The fractional dose (dose rate) and number of fractions (total dose) distinctly affect the risk of severe RE estimated using the LKB model, and concurrent chemotherapy improves the model fit. This risk of severe RE is underestimated by this model in patients receiving IMRT.

Multivariable normal-tissue complication modeling of acute esophageal toxicity in advanced stage non-small cell lung cancer patients treated with intensity-modulated (chemo-)radiotherapy

“…This issue has been addressed in a study reported by Gomez et al [29], showing Grade P3 AET in 28% of patients treated with IMRT (N = 139) vs 8% (p < 0.05) of patients treated with 3D-CRT (N = 405). However, another study reported the contrary with equal risks of AET after IMRT or 3D-CRT [30].…”

Effect of Platinum-Based Chemoradiotherapy on Cellular Proliferation in Bone Marrow and Spleen, Estimated by 18F-FLT PET/CT in Patients with Locally Advanced Non–Small Cell Lung Cancer

“…In NSCLC during radical chemo-RT, however, oesophagitis and pneumonitis are usually the most significant acute side effects after completion of therapy (24)(25)(26).…”

A Contralateral Esophagus-Sparing Technique to Limit Severe Esophagitis Associated With Concurrent High-Dose Radiation and Chemotherapy in Patients With Thoracic Malignancies

“…On long-term follow-up, the development of AE was associated with late esophageal stricture in 15 patients (9%). In another report, IMRT was associated with 28% grade 3 AE (11). Similarly, Kwint et al (12) assessed the AE outcomes in 139 patients with inoperable NSCLC treated with IMRT and concomitant chemotherapy.…”