Incidence and Risk Factors for Chest Wall Toxicity After Risk-Adapted Stereotactic Radiotherapy for Early-Stage Lung Cancer

Introduction: High local control rates are reported after stereotactic ablative body radiotherapy (SABR) in stage I non-small cell lung cancer. Toxicity is uncommon, but few reports on long-term follow-up are available. We studied the incidence of chest wall pain (CWP) and rib fractures in patients with long-term follow-up. Methods: Between 2003 and 2009, 500 patients (530 tumors) underwent SABR using risk-adapted fractionation schemes, consisting of three fractions of 20 Gy, five fractions of 12 Gy, or eight fractions of 7.5 Gy. Toxicity data were collected in a prospective database and scored using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Chest wall volumes receiving doses of 30, 40, 45, and 50 Gy (V30 Gy-V50 Gy) and maximum dose in 2 cm3 of chest wall (D2 ml) were determined for patients with CWP or rib fractures (n = 57). Results: With a median follow-up of 33 months, the 3-year overall survival and local control rates were 53.1% and 90.4%, respectively. CWP developed in 11.4% of patients and was severe (grade 3) in 2.0%. Rib fractures were observed in eight patients (1.6%), accompanied by CWP in seven of these patients. On multivariate analysis, patients with CWP had larger treatment volumes and shorter tumor-chest wall distances, whereas patients with rib fractures had larger tumor diameters and treatment volumes. Grade 3 CWP and rib fractures were associated with larger volumes of chest wall receiving doses of 30 to 50 Gy and rib fractures specifically with a higher maximum dose in the chest wall. Conclusions: Severe (grade 3) chest wall toxicity is uncommon after risk-adapted SABR and manifests in 2% or fewer of patients.

[1]  H. Groen,et al.  Traditional versus up-front [18F] fluorodeoxyglucose-positron emission tomography staging of non-small-cell lung cancer: a Dutch cooperative randomized study. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  Jan Nyman,et al.  Outcome in a prospective phase II trial of medically inoperable stage I non-small-cell lung cancer patients treated with stereotactic body radiotherapy. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  E. Smit,et al.  Outcomes of risk-adapted fractionated stereotactic radiotherapy for stage I non-small-cell lung cancer. , 2008, International journal of radiation oncology, biology, physics.

[4]  C. Reddy,et al.  Prediction of chest wall toxicity from lung stereotactic body radiotherapy (SBRT). , 2009, International journal of radiation oncology, biology, physics.

[5]  Andrea Bezjak,et al.  Stereotactic body radiation therapy for inoperable early stage lung cancer. , 2010, JAMA.

[6]  Jan Nyman,et al.  Radiation-induced rib fractures after hypofractionated stereotactic body radiation therapy of non-small cell lung cancer: a dose- and volume-response analysis. , 2009, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[7]  Joe Y. Chang,et al.  Obesity increases the risk of chest wall pain from thoracic stereotactic body radiation therapy. , 2011, International journal of radiation oncology, biology, physics.

[8]  S. Senan,et al.  Treatment of large stage I-II lung tumors using stereotactic body radiotherapy (SBRT): planning considerations and early toxicity. , 2010, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[9]  H. Kehlet,et al.  Consequences of persistent pain after lung cancer surgery: a nationwide questionnaire study , 2011, Acta anaesthesiologica Scandinavica.

[10]  S. Senan,et al.  Stage I nonsmall cell lung cancer in patients aged > or =75 years: outcomes after stereotactic radiotherapy. , 2010, Cancer.

[11]  A. Bezjak,et al.  Chest wall pain and rib fracture after stereotactic radiotherapy for peripheral non-small cell lung cancer. , 2009, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[12]  Peter A S Johnstone,et al.  Chest wall toxicity after stereotactic body radiotherapy for malignant lesions of the lung and liver. , 2011, International journal of radiation oncology, biology, physics.

[13]  H. Withers,et al.  Stereotactic radiotherapy for stage I non-small-cell lung cancer—the triumph of technology over biology? , 2007, Nature Clinical Practice Oncology.

[14]  Benjamin Movsas,et al.  Consideration of dose limits for organs at risk of thoracic radiotherapy: atlas for lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus. , 2011, International journal of radiation oncology, biology, physics.

[15]  Suresh Senan,et al.  Stereotactic radiotherapy for peripheral lung tumors: a comparison of volumetric modulated arc therapy with 3 other delivery techniques. , 2010, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[16]  A. Ho,et al.  Postthoracotomy pain syndrome. , 2004, Thoracic surgery clinics.

[17]  O. Hoekstra,et al.  Clinical prediction model to characterize pulmonary nodules: validation and added value of 18F-fluorodeoxyglucose positron emission tomography. , 2005, Chest.

[18]  J. Fowler The linear-quadratic formula and progress in fractionated radiotherapy. , 1989, The British journal of radiology.

[19]  H. Kehlet,et al.  Persistent postsurgical pain: risk factors and prevention , 2006, The Lancet.

[20]  A. Bosch,et al.  Institutional report - Thoracic oncologic Complete video-assisted thoracoscopic surgery lobectomy and its learning curve. A single center study introducing the technique in The Netherlands , 2010 .

[21]  Ke Sheng,et al.  Chest wall volume receiving >30 Gy predicts risk of severe pain and/or rib fracture after lung stereotactic body radiotherapy. , 2010, International journal of radiation oncology, biology, physics.

[22]  Hiroki Shirato,et al.  Stereotactic body radiotherapy (SBRT) for operable stage I non-small-cell lung cancer: can SBRT be comparable to surgery? , 2011, International journal of radiation oncology, biology, physics.

[23]  Jose Belderbos,et al.  Impact of introducing stereotactic lung radiotherapy for elderly patients with stage I non-small-cell lung cancer: a population-based time-trend analysis. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  M. Boers,et al.  Effectiveness of positron emission tomography in the preoperative assessment of patients with suspected non-small-cell lung cancer: the PLUS multicentre randomised trial , 2002, The Lancet.

[25]  J. Duffy,et al.  Surgical aspects of chronic post-thoracotomy pain. , 2000, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[26]  Russ Hamilton,et al.  Can stereotactic fractionated radiation therapy become the standard of care for early stage non-small cell lung carcinoma. , 2008, Cancer treatment reviews.