Title: Postoperative Pulmonary Complications after Neoadjuvant Chemoradiotherapy with IMRT for Esophageal Cancer
Abstract: Intensity-modulated radiation therapy (IMRT) for esophageal cancer improves target dose conformality at the expense of potentially exposing more normal tissue to low-dose radiation. Increased lung volume exposed to low-dose radiation during 3-D conformal RT has been suggested to increase the risk of postoperative pulmonary complications (PPC). The potential impact of neoadjuvant chemoradiation (CRT) using IMRT on the incidence of PPC is not well-established. Between 5/07 and 4/09, 20 patients completed a course of CRT with IMRT prior to definitive surgery at Memorial Sloan-Kettering Cancer Center. Fifteen patients (75%) had adenocarcinoma and 5 (25%) had squamous cell carcinoma. Primary tumor locations included GE junction (n = 8), distal esophagus (n = 10), and mid-esophagus (n = 2). Four patients had stage II disease and 16 had stage III-IVA disease. Patients received 5040 cGy to the tumor and draining lymph nodes in 28 fractions. Eight patients (40%) were treated with respiratory motion management. Most patients were treated using a five-field arrangement and 6MV photons. Eighteen of 20 patients (90%) received induction chemotherapy (mostly platinum-based) prior to CRT. All received concurrent chemotherapy, mostly platinum-based. Nine of 20 patients (45%) had normal pulmonary function tests prior to surgery, with the remainder exhibiting mild obstructive airways disease and/or low diffusing capacity. Median interval between completion of IMRT and surgery was 12 weeks. Surgical resection was performed by Ivor-Lewis (n = 16) or McKeown (n = 2) esophagectomy, left thoracoabdominal esophagectomy (n = 1), or total gastrectomy with distal esophagectomy (n = 1). Lung DVH parameters and the incidence of PPC were retrospectively reviewed. PPC was defined as pneumonia or respiratory insufficiency within 30 days after surgery. The mean PTV size was 750 cc (range: 428-1480 cc). The mean lung dose was 1108 cGy (range: 260-1901 cGy). The median lung V10, V15, and V20 was 40%, 30%, and 19% respectively. All but 4 patients had a lung V20 of less than 20%, and none had V20 greater than 35%. Four patients (20%) developed anastomotic leaks. Two patients (10%) experienced PPC. One patient had mucus plugging with infectious pneumonia and recovered; the second developed hypoxia related to aspiration pneumonia and expired 15 weeks after surgery. This patient had the highest lung V20 (35%) in the cohort. The median hospital stay after surgery was 14 days. Neoadjuvant chemoradiotherapy for esophageal cancer using IMRT does not appear to be associated with elevated risk of PPCs when lung volumes receiving low-dose irradiation are kept within appropriate limits.