Tumor Necrosis and Cavitation after Stereotactic Body Radiation Therapy

Abstract

Two asymptomatic, elderly patients with a distant history of smoking presented with solitary lung masses on screening chest radiographs ordered by their primary care physicians. One was an 87-year-old man with a 3.7-cm left upper lobe mass and the other a 72-year-old woman with a 2.6-cm right upper lobe mass. Both had a significant history of cardiovascular disease, peripheral vascular disease, and type II diabetes mellitus. Because of clinical suspicion for a primary lung malignancy, positron emission tomography/ computed tomography (CT) scans were ordered and demonstrated increased hypermetabolic activity within the lung masses, but not within the mediastinum or outside the thorax. CT-guided biopsies revealed poorly differentiated, nonkeratinizing squamous cell carcinoma in both patients. Per standard guidelines, the patients were referred to a thoracic surgeon; however, both were deemed high-risk surgical candidates. 1 Therefore, both patients were referred for definitive radiotherapy of their stage I lung cancers. Using CT-based radiotherapy planning, both patients were treated with stereotactic body radiation therapy (SBRT) using three doses of 18 Gy delivered within 1 week and at least 72 hours between each fraction (Figures 1A, B). Per our standard practice, on each day of treatment, we performed cone beam CT scans on the treatment machine to ensure proper positioning before the delivery of each radiotherapy dose. In these two patients, the cone beam CT scans performed before the first and second radiation doses did not identify any tumor changes. However, the cone beam CT scan before the third radiation dose demonstrated a large, central cavitation within the tumors of both patients (Figures 2A, B). These findings represented a rapid and significant change from the second treatment cone beam CT that was just 3 days prior. A review of the literature and experienced practitioners (personal communications) failed to reveal any similar cases of rapid tumor cavitation during or after SBRT. The phenomenon of central tumor cavitation in nonsmall cell lung cancer has been observed in patients receiving the antivascular endothelial growth factor antibody, bevacizumab. In two randomized trials, central tumor cavitation with associated pulmonary hemorrhage was observed in patients receiving bevacizumab, carboplatin, and paclitaxel, but not in those receiving just carboplatin and paclitaxel. 2,3 A subsequent pooled matched analysis from these studies found that pretreatment tumor cavitation was the only significant factor predictive of pulmonary hemorrhage in the setting of bevacizumab. 4 This pretreatment cavitation could actually reflect already compromised vasculature. We speculate that SBRT-mediated damage acted similar to the antivascular effects of bevacizumab. 5 Both patients presented here had significant atherosclerotic disease in the setting of type II diabetes mellitus. SBRT may have been the tipping point for occluding the already compromised vasculature that lead to nutrient depletion and subsequent rapid central necrosis and cavitation. This is merely a hypothesis-generating observation; however, it should be followed carefully because central cavitation has been a harbinger for severe and lethal toxicity in patients with non-small cell lung cancer treated with systemic antivascular therapy. 2