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• W2044332607 abstract "Stereotactic body radiotherapy is an emerging treatment option for peripheral non-small cell lung cancer in medically inoperable patients. With high dose per fraction radiotherapy, late side effects are of possible concern. In our initial cohort of 42 patients treated with 54 to 60 Gy in three fractions, nine patients have rib fracture. The median dose to rib fracture sites was 46 to 50 Gy, depending on the method of dose calculation. We describe a typical case of poststereotactic radiotherapy rib fracture and present dosimetric analysis of patients with rib fracture. Stereotactic body radiotherapy is an emerging treatment option for peripheral non-small cell lung cancer in medically inoperable patients. With high dose per fraction radiotherapy, late side effects are of possible concern. In our initial cohort of 42 patients treated with 54 to 60 Gy in three fractions, nine patients have rib fracture. The median dose to rib fracture sites was 46 to 50 Gy, depending on the method of dose calculation. We describe a typical case of poststereotactic radiotherapy rib fracture and present dosimetric analysis of patients with rib fracture. An 85-year-old man presented with a peripheral nodule seen incidentally on chest radiograph ordered during work up of cardiac chest pain. Computed tomography (CT) imaging revealed a 2.3-cm right upper lobe, spiculated mass and multiple thoracic lymph nodes measuring up to 1.0 cm in maximum diameter. A CT-guided biopsy of the mass was consistent with non-small cell lung cancer (NSCLC). In addition, abdomen, brain, and bone imaging revealed no evidence of distant metastatic disease. Whole body fluorodeoxyglucose-positron emission tomography-CT imaging revealed abnormal metabolic activity in the primary mass (SUV 7.5) and equivocal fluorodeoxyglucose uptake in the mediastinal nodes. Because of cardiac comorbidity, mediastinoscopy was not performed, and his tumor, clinically stage Ia (cT1N0M0), was deemed inoperable because of his medical condition. He was referred for consideration of radiotherapy. He was eligible for stereotactic body radiation therapy (SBRT) and was treated on a research ethics board-approved protocol, with a dose of 60 Gray (Gy) in three fractions, prescribed to an 87% isodose line covering the planning target volume. Figure 1 shows the radiation isodose lines on a coronal slice reconstructed from the planning CT scan. Planning target volumes were constructed with patient-specific asymmetric margins using four-dimensional CT. Treatment was completed without complication. The patient remained well until 16 months postradiation therapy, when he developed pleuritic right-sided chest pain, which resolved with 1 month of over-the-counter analgesics. CT thorax showed ill margination of the outer cortex of the right fourth antero-lateral rib with associated chest wall thickening and adjacent increased lung parenchymal opacity (Figure 2). The radiologic differential diagnosis of these findings included rib osteonecrosis and progression of disease to involve the chest wall. During subsequent follow-up, a CT scan at 29 months postradiation therapy showed increased peripheral subpleural consolidation and adjacent rib fracture (Figure 3). All of the radiographic changes occurred in the region of high-radiation dose and, with control of primary mass, treatment-induced changes were favored over disease recurrence. Positron emission tomography scan was not performed. The patient’s radiographic changes were followed using interval-CT imaging. At last follow-up, he was clinically and radiologically disease free at 42 months posttreatment.FIGURE 3Progression to fracture (arrow) and further progression of parenchymal pulmonary fibrosis 29 months postradiation therapy (RT).View Large Image Figure ViewerDownload (PPT) Despite the increasing popularity of SBRT, experience with extremely hypofractionated, high-dose radiotherapy regimens and their posttreatment radiologic findings and clinical toxicity remains limited. At our institution, 42 medically inoperable patients with peripheral early-stage NSCLC were treated with 54 to 60 Gy in three fractions before December 2007 in a prospective phase II study. In a subsequent follow-up, nine of these patients had developed a total of 15 ipsilateral rib fractures, occurring at a median of 17 months follow-up. Two fractures were asymptomatic and detected radiologically. Chest wall pain was observed in 11 patients, seven of whom had fractures. Three patients developed chest wall pain that initially did not show imaging evidence of fracture but weeks to months later did evolve to include radiologically demonstrable fracture. All patients with fracture had tumors within 2 cm of the chest wall. Based on the radiotherapy treatment plans, the sites of rib fracture received a median radiation dose of 46.4 Gy (range, 16.5-74.2), calculated without tissue heterogeneity correction. The median standard deviation in this dose was 7.6 Gy, indicating steep radiation dose gradients at fracture sites. However, higher or lower doses than planned may actually have been delivered to the rib fracture sites as a result of our practice of image guiding the radiation treatment to the tumor itself (as opposed to neighboring soft tissue or bony structures) and variation in patient positions among fractions. Two patients with asymptomatic fractures received maximum doses of 47.5 and 29.1 Gy (corrected for tissue heterogeneity, Pinnacle ADAC v 7.6c, Philips Radiation Oncology Systems, Milpitas, CA) to the fracture site. Six patients with symptomatic fracture had transient pain or pain that was manageable with the medications received at a maximum of 33.0, 39.4, 49.8, 52.7, 56.1, and 67.7 Gy to the fracture site(s). One patient who developed a fracture with chronic, neuropathic pain incompletely relieved by medications received 76.4 Gy to the fracture site. With the tissue inhomogeneity corrections, the median dose delivered to sites of fracture (including each fractured rib in patients who experienced multiple rib fractures) was 50.1 Gy (range, 17.1-76.4). Our experience suggests that rib fracture, pulmonary or chest wall fibrosis, and chest wall pain can be observed after SBRT for peripheral NSCLC and may occur commonly in patients with tumors adjacent to the chest wall. The pathogenesis of the different forms of chest wall pain is uncertain. Of note, chronic chest wall pain is observed in approximately 30% of lung cancer patients treated using thoracotomy 4 to 5 years after resection.1Karmaker MK Ho AM Postthoracotomy pain syndrome.Thorac Surg Clin. 2004; 14: 345-352Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar As patient follow-up matures, information relevant to predicting the likelihood of longer-term chest wall side effects will become available from our population of patients as well as those treated at other institutions and with other hypofractionated regimens. Nguyen et al.2Nguyen NP Garland L Welsh J Hamilton R Cohen D Vinh-Hung V Can stereotactic fractionated radiation therapy become the standard of care for early stage non-small cell lung carcinoma?.Cancer Treat Rev. 2008; 34: 719-727Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar recently reviewed the complications of SBRT and included crude rates from seven studies that observed a total of 16 fractures, with fracture rates varying from 1.5 to 5%. However, in studies large enough to examine subgroups of patients who received high doses to rib or chest wall, fracture rates are considerably higher. Dunlap et al.3Dunlap NE Biedermann GB Yang W et al.Chest wall volume receiving more than 30 Gy predicts risk of severe pain and/or rib fracture following lung SBRT.Int J Radiat Oncol Biol Phys. 2008; 72: S36Abstract Full Text Full Text PDF Google Scholar reported a steep dose-response relationship between dose to volume of chest wall and fracture rate, with fracture rates as high as 63% for patients with more than 120 mL of chest wall receiving above 30 Gy. Pettersson et al.4Pettersson N Nyman J Johansson KA Radiation induced rib fractures after stereotactic body radiation therapy of non-small cell lung cancer: A dose- and volume-response analysis.Radiother Oncol. 2009; 91: 360-368Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar found a fracture rate of 37% for patients when a volume of chest wall greater than 2 mL received in excess of 40 Gy. Dose prescription has been variable in SBRT studies, and length of follow-up is generally short. Because hypofractionated radiation can be associated with complications occurring more than 2 years after treatment, the true fracture rate within our population and the rate from other centers are uncertain but will certainly be higher than the crude rates quoted from studies with short follow-up. Kaplan-Meier fracture-free proportion for our study population is shown in Figure 4. Based on these observations, our current practice is to consider reducing the total dose to tumor and maximum dose to chest wall; increasing the number of noncoplanar beams; increasing the number of fractions for stereotactic treatment of peripheral lesions where chest wall and/or rib is/are within the high-dose region, recognizing that there is uncertainty in both the complication risk and the control probability with SBRT. The informed patient consent process in our ongoing phase II study of stereotactic lung radiotherapy includes a discussion of the potential for fibrosis, chest wall pain, and fracture. Chest Wall Pain and Rib Fracture after Stereotactic Radiotherapy for Peripheral Non-small Cell Lung Cancer: ErratumJournal of Thoracic OncologyVol. 5Issue 5PreviewIn the article that appeared on page 1035 of the August 2009 issue, an author's name was misspelled. The author's name should have appeared as Thomas G. Purdie, PhD. This error has been noted in the online version of the article, which is available at www.jto.org . Full-Text PDF Open Archive" @default.
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• W2044332607 title "Chest Wall Pain and Rib Fracture after Stereotactic Radiotherapy for Peripheral Non-small Cell Lung Cancer" @default.
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