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Rib Fracture Incidence after Stereotactic Body Radiotherapy for Non–small Cell Lung Cancer: Latency and Dose-response
I. J. Radiation Oncology d Biology d Physics
S456
2610
Volume 75, Number 3, Supplement, 2009
Rib Fracture Incidence after Stereotactic Body Radiotherapy for Non–small Cell Lung Cancer: Latency and Dose-response
C. W. Hodge, W. A. Tome, S. M. Bentzen, M. P. Mehta University of Wisconsin Hospitals & Clinics, Madison, WI Purpose/Objective(s): Late complications of SBRT include radiation related rib fractures; the dose response relationship for the incidence of this complication is unknown. Here, we estimate the incidence of late rib fracture as a function of maximum absorbed rib dose after stereotactic body radiotherapy (SBRT) for early stage lung cancer. Materials/Methods: Of 23 patients treated with image guided SBRT (60 Gy in 5 fractions of 12 Gy prescribed to the planning target volume (PTV)) between 2003 and 2006, 4 developed pathologic rib fracture proximate to the SBRT PTV. Planned maximum dose to the combined rib volume lying within the prescription isodose volume was estimated and a Cox proportional hazards model was fitted to the observed rib fracture data. Results: 23 patients were evaluated for rib fracture. 7 patients without rib fractures were excluded because of early death, leaving 16 evaluable patients, all with a minimum of 12 months follow-up. Median follow-up was 43 months (range, 15–60 months). The median time to rib fracture was 26.5 months (range, 15–34 months). The maximum rib dose ranged from 23.8–74.7 Gy (median 57.8 Gy) in 5 fractions. Application of a 2-tailed likelihood ratio test shows dose to be a borderline significant predictor of rib fracture (p = 0.06), with a D50 estimate of 68.9 Gy. The steepness of the dose-response curve was quantified by the g50 value, estimated at 2.2, and illustrated by a predicted incidence of rib fracture at 3.5 years of 54% and 11% at maximum doses of 70 Gy and 50 Gy, respectively. Conversion of these doses to a Normalized Total Dose (NTD) based upon 2 Gy fractions using linear-quadratic formalism yields NTDs of 238 Gy and 130 Gy, respectively. Conclusions: Maximum rib dose should be carefully considered in SBRT with appropriate risk counseling of patients whose maximum rib dose exceeds 50 Gy in 5 fractions, which is estimated to be associated with an 11% risk of rib fractures. It may, in the future, be feasible to incorporate the ribs as an organ at risk in IMRT planning to reduce the likelihood of fractures. Author Disclosure: C.W. Hodge, None; W.A. Tome, None; S.M. Bentzen, None; M.P. Mehta, None.
2611
Prognostic Factors for Lung Cancer Tumor Recurrence after Thoracic Radiotherapy Based on Sequential Post-treatment PET Scans
M. Werner-Wasik1, E. Pequignot1, T. Hyslop1, B. Shulli1, Y. Xiao1, M. Machtay1, A. Taylor1, W. Curran Jr2, R. Axelrod1 1
Thomas Jefferson University Hospital, Philadelphia, PA, 2Emory University, Atlanta, GA
Purpose/Objective(s): FDG-PET imaging (PET scan) is a useful tool for assessment of response to thoracic radiation therapy (RT) in patients with non–small cell lung cancer (NSCLC). Pattern of such response and prognostic factors were evaluated. Materials/Methods: Patients with Stages I–IV NSCLC who received 3D RT between 2004–2008 were eligible if they had pre-RT PET scan and at least one post-RT PET scan. All PET scans were analyzed using a semiautomatic contouring software (MimVista, Cleveland, OH). Primary tumors and involved lymph node areas (LNs) included in the RT field were contoured applying a ‘‘PET edge’’ as a threshold intensity value. The maximum Standardized Uptake Value (max SUV) and the Metabolic Tumor Volume (metabTV) were measured. Local Failure (LF) was defined as increase in maxSUV of any lesion encompassed in the RT field with accompanying tumor progression on chest CT. Factors prognostic for LF were investigated. Results: PET scan images of 50 patients with a total of 262 primary tumors and/or LNs were analyzed. Median age was 63 years (range, 38–88) and 33 (66%) were females. RT doses varied from 30–71 Gy. Post-RT PET scans were obtained at the median time of 2.9 months (first PET) and every 3–4 months thereafter. The following number of patients had post-RT PET scans: 50 (1 scan); 26 (2); 11 (3); 4 (4); 4 (5) and 3 (6). Median follow-up time was 15 months. Fourteen patients died, 8 suffered LF and 26, distant failure. Median values on pre-RT PET scans were as follows: maxSUV, 12.3 (1.9–31) in the primary tumor and 9.1 (2–24) in the LNs; total metabTV (tumor + LNs), 51.1 cc (1.5–491). The rate of reduction of the tumor maxSUV was 4.3% per month (log scale). The primary tumor median maxSUV declined 72% by the first post-RT PET; 76% by the 2nd PET and 77% by the 3rd PET in comparison to the pre-RT PET. A total of 19 (38%) patients achieved a metabolic CR (complete response, defined as maxSUV#2.5) at the median time of 10.6 months. Factors significantly associated in multivariate analysis with increasing risk of LF were: female gender, Stage IV, total metabTV (log scale) and initial maxSUV (HR of 4.78; 19.06; 30.77 and 1.24 with p values of 0.02; \0.001; \0.001 and 0.027, respectively). Risk of LF decreased for each unit decline in tumor maxSUV on first post-RT PET (HR 0.84; p value 0.038). Conclusions: LF after thoracic RT is not common during lifetime of patients with NSCLC receiving 3D thoracic RT and the rate of metabolic response based on PET scans is rapid. Females, patients with Stage IV NSCLC, larger total metabTV and higher maxSUV are more likely to fail locally. Fast decline in maxSUV on first post-RT PET is associated with significantly decreased risk of LF. Author Disclosure: M. Werner-Wasik, None; E. Pequignot, None; T. Hyslop, None; B. Shulli, None; Y. Xiao, None; M. Machtay, None; A. Taylor, None; W. Curran Jr, None; R. Axelrod, None.
2612
Clinical Results of Stereotactic Body Radiotherapy for Oligometastatic Lung Tumors
Y. Shioyama1, S. Nomoto1, S. Ohga1, T. Nonoshita1, K. Ohnishi1, K. Terashima1, K. Nakamura2, H. Hirata3, H. Honda1 1
Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Japan, Department of Radiology, Fukuoka University, Fukuoka City, Japan, 3School of Health Sciences, Kyushu University, Fukuoka City, Japan 2
Purpose/Objective(s): To evaluate the treatment outcomes of stereotactic body radiotherapy (SBRT) for oligometastatic lung tumors.
S456
2610
Volume 75, Number 3, Supplement, 2009
Rib Fracture Incidence after Stereotactic Body Radiotherapy for Non–small Cell Lung Cancer: Latency and Dose-response
C. W. Hodge, W. A. Tome, S. M. Bentzen, M. P. Mehta University of Wisconsin Hospitals & Clinics, Madison, WI Purpose/Objective(s): Late complications of SBRT include radiation related rib fractures; the dose response relationship for the incidence of this complication is unknown. Here, we estimate the incidence of late rib fracture as a function of maximum absorbed rib dose after stereotactic body radiotherapy (SBRT) for early stage lung cancer. Materials/Methods: Of 23 patients treated with image guided SBRT (60 Gy in 5 fractions of 12 Gy prescribed to the planning target volume (PTV)) between 2003 and 2006, 4 developed pathologic rib fracture proximate to the SBRT PTV. Planned maximum dose to the combined rib volume lying within the prescription isodose volume was estimated and a Cox proportional hazards model was fitted to the observed rib fracture data. Results: 23 patients were evaluated for rib fracture. 7 patients without rib fractures were excluded because of early death, leaving 16 evaluable patients, all with a minimum of 12 months follow-up. Median follow-up was 43 months (range, 15–60 months). The median time to rib fracture was 26.5 months (range, 15–34 months). The maximum rib dose ranged from 23.8–74.7 Gy (median 57.8 Gy) in 5 fractions. Application of a 2-tailed likelihood ratio test shows dose to be a borderline significant predictor of rib fracture (p = 0.06), with a D50 estimate of 68.9 Gy. The steepness of the dose-response curve was quantified by the g50 value, estimated at 2.2, and illustrated by a predicted incidence of rib fracture at 3.5 years of 54% and 11% at maximum doses of 70 Gy and 50 Gy, respectively. Conversion of these doses to a Normalized Total Dose (NTD) based upon 2 Gy fractions using linear-quadratic formalism yields NTDs of 238 Gy and 130 Gy, respectively. Conclusions: Maximum rib dose should be carefully considered in SBRT with appropriate risk counseling of patients whose maximum rib dose exceeds 50 Gy in 5 fractions, which is estimated to be associated with an 11% risk of rib fractures. It may, in the future, be feasible to incorporate the ribs as an organ at risk in IMRT planning to reduce the likelihood of fractures. Author Disclosure: C.W. Hodge, None; W.A. Tome, None; S.M. Bentzen, None; M.P. Mehta, None.
2611
Prognostic Factors for Lung Cancer Tumor Recurrence after Thoracic Radiotherapy Based on Sequential Post-treatment PET Scans
M. Werner-Wasik1, E. Pequignot1, T. Hyslop1, B. Shulli1, Y. Xiao1, M. Machtay1, A. Taylor1, W. Curran Jr2, R. Axelrod1 1
Thomas Jefferson University Hospital, Philadelphia, PA, 2Emory University, Atlanta, GA
Purpose/Objective(s): FDG-PET imaging (PET scan) is a useful tool for assessment of response to thoracic radiation therapy (RT) in patients with non–small cell lung cancer (NSCLC). Pattern of such response and prognostic factors were evaluated. Materials/Methods: Patients with Stages I–IV NSCLC who received 3D RT between 2004–2008 were eligible if they had pre-RT PET scan and at least one post-RT PET scan. All PET scans were analyzed using a semiautomatic contouring software (MimVista, Cleveland, OH). Primary tumors and involved lymph node areas (LNs) included in the RT field were contoured applying a ‘‘PET edge’’ as a threshold intensity value. The maximum Standardized Uptake Value (max SUV) and the Metabolic Tumor Volume (metabTV) were measured. Local Failure (LF) was defined as increase in maxSUV of any lesion encompassed in the RT field with accompanying tumor progression on chest CT. Factors prognostic for LF were investigated. Results: PET scan images of 50 patients with a total of 262 primary tumors and/or LNs were analyzed. Median age was 63 years (range, 38–88) and 33 (66%) were females. RT doses varied from 30–71 Gy. Post-RT PET scans were obtained at the median time of 2.9 months (first PET) and every 3–4 months thereafter. The following number of patients had post-RT PET scans: 50 (1 scan); 26 (2); 11 (3); 4 (4); 4 (5) and 3 (6). Median follow-up time was 15 months. Fourteen patients died, 8 suffered LF and 26, distant failure. Median values on pre-RT PET scans were as follows: maxSUV, 12.3 (1.9–31) in the primary tumor and 9.1 (2–24) in the LNs; total metabTV (tumor + LNs), 51.1 cc (1.5–491). The rate of reduction of the tumor maxSUV was 4.3% per month (log scale). The primary tumor median maxSUV declined 72% by the first post-RT PET; 76% by the 2nd PET and 77% by the 3rd PET in comparison to the pre-RT PET. A total of 19 (38%) patients achieved a metabolic CR (complete response, defined as maxSUV#2.5) at the median time of 10.6 months. Factors significantly associated in multivariate analysis with increasing risk of LF were: female gender, Stage IV, total metabTV (log scale) and initial maxSUV (HR of 4.78; 19.06; 30.77 and 1.24 with p values of 0.02; \0.001; \0.001 and 0.027, respectively). Risk of LF decreased for each unit decline in tumor maxSUV on first post-RT PET (HR 0.84; p value 0.038). Conclusions: LF after thoracic RT is not common during lifetime of patients with NSCLC receiving 3D thoracic RT and the rate of metabolic response based on PET scans is rapid. Females, patients with Stage IV NSCLC, larger total metabTV and higher maxSUV are more likely to fail locally. Fast decline in maxSUV on first post-RT PET is associated with significantly decreased risk of LF. Author Disclosure: M. Werner-Wasik, None; E. Pequignot, None; T. Hyslop, None; B. Shulli, None; Y. Xiao, None; M. Machtay, None; A. Taylor, None; W. Curran Jr, None; R. Axelrod, None.
2612
Clinical Results of Stereotactic Body Radiotherapy for Oligometastatic Lung Tumors
Y. Shioyama1, S. Nomoto1, S. Ohga1, T. Nonoshita1, K. Ohnishi1, K. Terashima1, K. Nakamura2, H. Hirata3, H. Honda1 1
Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Japan, Department of Radiology, Fukuoka University, Fukuoka City, Japan, 3School of Health Sciences, Kyushu University, Fukuoka City, Japan 2
Purpose/Objective(s): To evaluate the treatment outcomes of stereotactic body radiotherapy (SBRT) for oligometastatic lung tumors.