Outcomes of definitive or preoperative IMRT chemoradiation for ...

26 downloads 38 Views 429KB Size Report
IMRT was incorporated into esophageal cancer treatment at our center in 2006. Patients treated between 2006 and 2011 with either preoperative or definitive ...
J Radiat Oncol (2012) 1:347–354 DOI 10.1007/s13566-012-0048-5

ORIGINAL RESEARCH

Outcomes of definitive or preoperative IMRT chemoradiation for esophageal cancer Ravi Shridhar & Michael D. Chuong & Jill Weber & Jessica Freilich & Khaldoun Almhanna & Domenico Coppola & William Dinwoodie & Thomas J. Dilling & Daniel Fernandez & Richard C. Karl & Kenneth L. Meredith & Sarah E. Hoffe

Received: 26 April 2012 / Accepted: 5 June 2012 / Published online: 30 June 2012 # Springer-Verlag 2012

Abstract Objectives Intensity-modulated radiation therapy (IMRT) is evolving for the treatment of gastrointestinal cancers. The purpose of this study is to analyze our outcomes utilizing IMRT chemoradiation for esophageal cancer. Methods IMRT was incorporated into esophageal cancer treatment at our center in 2006. Patients treated between 2006 and 2011 with either preoperative or definitive IMRT chemoradiation to 50–60 Gy prescribed to the gross tumor volume and 45–50.4 Gy to the clinical target volume concurrently with chemotherapy were evaluated. IMRT techniques included multifield segmented step and shoot, compensatorbased, and volumetric arc therapy. Overall survival (OS) and disease-free survival (DFS) were analyzed by Kaplan–Meier and log-rank analysis. Multivariate analysis (MVA) for OS and DFS were performed with a Cox proportional hazard ratio model. Results We identified 108 patients with a median follow-up of 19 months. Median OS and DFS were 32 and 21.6 months, respectively. Fifty-eight (53.7 %) patients underwent surgical

R. Shridhar (*) : M. D. Chuong : J. Freilich : T. J. Dilling : D. Fernandez : S. E. Hoffe Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA e-mail: [email protected] J. Weber : K. Almhanna : W. Dinwoodie : R. C. Karl : K. L. Meredith Gastrointestinal Tumor Program, Moffitt Cancer Center, Tampa, FL, USA D. Coppola Department of Pathology, Moffitt Cancer Center, Tampa, FL, USA

resection. There was no difference in OS or DFS in patients who underwent surgery compared to patients treated definitively without surgery. Median weight loss was 5.5 %. Rates of hospital admissions, feeding tube placement, stent placement, dilation, and radiation pneumonitis were 15.7, 7.4 4.6, 12, and 1.9 %, respectively. Long-term radiation pneumonitis was observed in six (5.6 %) patients. MVA revealed that age, stage, and surgery were prognostic for DFS, while gender and histology were not. Gender, histology, and stage were prognostic of OS on MVA, while surgery and age were not. Conclusions IMRT chemoradiation for esophageal cancer is safe and effective when compared to published series of 2D or 3D conformal radiation therapy. This is the largest single institutional series with long-term follow-up, confirming that IMRT is a viable treatment option for the curative treatment of esophageal cancer. Keywords Intensity-modulated radiation therapy . Chemoradiation . Esophageal cancer . Survival . Toxicity . Surgery

Introduction In 2011, an estimated 17,000 cases of esophageal cancer will be diagnosed in the USA, with approximately 15,000 people dying from the disease [1]. Worldwide, an estimated 482,000 new esophageal cancer cases were diagnosed with approximately 407,000 deaths in 2008 [2]. Squamous cell carcinoma and adenocarcinoma account for >90 % of all esophageal cancer cases. While the incidence of squamous cell carcinoma has declined due to long-term reductions in smoking and alcohol consumption, the incidence of AC has

348

been rising due to increases in obesity and gastroesophageal reflux disease [2]. The management of esophageal or gastroesophageal junction (GEJ) cancers has shifted from surgery or radiation single modality approaches to trimodality with the addition of chemotherapy. RTOG 85-01 demonstrated a survival benefit with the addition of platinum-based chemotherapy to radiation over radiation alone for non-surgical esophageal cancer patients [3]. Several meta-analyses have also confirmed the survival benefit of trimodality therapy over surgery alone [4]. Intensity-modulated radiation therapy (IMRT) delivers highly conformal radiation therapy to tumor targets while sparing surrounding normal tissues from excessive doses of radiation. For the treatment of gastrointestinal malignancies, IMRT has been shown to reduce toxicity in anal [5], gastric [6], and pancreatic [7] cancers. There have been few reports on IMRT in esophageal cancer with small numbers of patients [8–11]. We present the largest series of esophageal cancer patients treated with IMRT with long-term follow-up.

Methods Patients An IRB-approved radiation oncology database was queried for patients treated preoperatively or definitively with IMRT chemoradiation for esophageal cancer (squamous cell carcinoma or adenocarcinoma). Staging included a computed tomography (CT) scan of the chest and abdomen, 18-fluorodeoxyglucose positron emission tomography, and endoscopic ultrasound (EUS) of the esophagus. Most patients had fiducials endoscopically placed at the time of EUS (Fernandez et al. [12]). Staging was performed according to the American Joint Committee on Cancer (AJCC) 7th edition staging guidelines. Radiation treatment planning CT-based planning was performed with the patients lying supine with arms up on a Vac-Lok immobilization device (Civco Medical Solutions). 4D CT simulation scans were obtained to assess tumor motion by respiration. IMRT motion management strategies included an MLC-based approach using abdominal compression or a solid compensator-based (Dot Decimal, Orlando, FL, USA) approach. Internal target volumes of gross disease were generated (internal gross tumor volume (GTV), IGTV). A clinical target volume (CTV) encompassing a 3–4-cm superior margin, 3–4-cm distal margin, and 3–5-mm radial margin was contoured. For upper thoracic tumors, bilateral supraclavicular lymphatics were included in the CTV. For distal esophageal and gastroesophageal cancers, celiac, paraaortic, gastrohepatic, splenic hilar, and portal lymphatics were included in the CTV. For patients with suspicious lymph nodes

J Radiat Oncol (2012) 1:347–354

identified in the gastrohepatic ligament, the field was extended to include superior mesenteric artery and vein as well as the portal confluence (portal vein, superior mesenteric vein, and splenic vein). Planning target volumes (PTVs) were created with margins individualized based on whether daily image guidance was used. Most patients were treated to a dose of 50.4 Gy in 1.8 Gy fractions; three patients underwent a sequential boost to the GTV to a total dose of 59.4 Gy. Thirtyseven patients underwent a simultaneous integrated IMRT boost, where a 3–5-mm margin around the GITV was treated to a dose of 50–60 Gy in 2 Gy fractions while the CTV was simultaneously treated with 1.7–1.8 Gy fractions to 45–54 Gy. IMRT techniques included volumetric arc therapy, solid state compensators, or a segmented multileaf collimator step and shoot technique delivered in five to nine fields. IMRT normal tissue constraints consisted of: lung (mean