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Toxicity Data For Hypofractionated Radiosurgery Using the Linear Quadratic Model to Constrain Normal Organ Tolerance Doses
I. J. Radiation Oncology d Biology d Physics
S140
298
Volume 78, Number 3, Supplement, 2010
Analysis of Factors Predicting for Pain Resolution after Gamma Knife Radiosurgery for Medically Refractory Trigeminal Neuralgia
J. L. Cartier, I. S. Grills, P. Chen, H. Ye, A. Maitz, L. L. Kestin, D. J. Krauss, R. Olson, J. Fontanesi, D. R. Pieper William Beaumont Hospital, Royal Oak, MI Purpose/Objective(s): To evaluate the clinical outcomes of patients undergoing Gamma Knife (GK) stereotactic radiosurgery as a non-surgical treatment for trigeminal neuralgia (TGN). Materials/Methods: Ninety-five patients underwent GK for TGN between 12/2006-6/2009 at William Beaumont Hospital. Eighty had follow-up $6 weeks and were the subject of this report. Median patient age was 68y (30-92); 58 female, 22 male. 74% of patients had typical trigeminal pain, 11% atypical features and 11% multiple sclerosis. Thirty patients (38%) had undergone prior surgical procedures and 37 (46%) had preexisting sensory complaints. The median dose delivered was 40 Gy (range: 35-45 Gy) to the 50% isodose line (80 Gy max) using either a single (85%) or two (6%) isocenters with a 4 mm collimator, or two isocenters with a 4 and 8 mm collimator (9%). Patients were seen #2 weeks post-GK, then every 3-6 months in addition to periodic mail surveys and telephone interviews. Pain was evaluated using the Barrow Neurological Institute Pain Intensity Scale. Multiple patient and GK factors were analyzed for association with pain relief. Mean follow-up duration was 15.6 months. Results: Ninety-one percent of patients (n = 73) reported at least partial pain resolution: 45% (n = 36) complete pain relief, 46% (n = 37) partial relief. Median time to pain resolution was 23d. Seventeen patients (23%) who had partial to complete resolution had pain recurrence (median: 6.2 months). The pain recurrence rate was higher in MS patients than non-MS (44% vs. 20%) and in those who experienced partial rather than complete relief. The 1, 2 and 3-year rates of freedom from pain recurrence for patients achieving partial relief after GK were 73%, 55% and 37% compared to 78%, 78%, and 78% for patients achieving complete relief after GK (p = 0.097). Sixteen (20%) patients reported new post-treatment sensory complaints; no other complications were noted. We identified that the greater the treated nerve length, the greater the probability of achieving a BNI of I-II (p = 0.021) and of pain resolution (p = 0.037). The cut-point length for partial/complete relief was a treated length of 0.51cm. Number of isocenters, treatment volume and thickness, dose distribution, and distance from the root entry zone to the GK isocenter were examined but not significant for relief. Conclusions: In this study, GK radiosurgery for trigeminal neuralgia was associated with complete or partial pain resolution in 91% of patients. Longer treated nerve length (cutpoint: 0.51cm) was associated with better pain resolution. Although 23% of patients had pain recurrence, the initial success and recurrence rates appeared similar to those reported after percutaneous treatment approaches with minimal post-treatment neurological complaints. Author Disclosure: J.L. Cartier, None; I.S. Grills, None; P. Chen, None; H. Ye, None; A. Maitz, None; L.L. Kestin, None; D.J. Krauss, None; R. Olson, None; J. Fontanesi, None; D.R. Pieper, None.
299
Toxicity Data For Hypofractionated Radiosurgery Using the Linear Quadratic Model to Constrain Normal Organ Tolerance Doses
J. Choe1, W. Chen1, C. Woods1, B. Wessels2, Y. Zheng3, J. Brindle2, Y. Zhang2, C. Kunos1, J. Lyons1, D. Einstein2,4 University Hospitals Case Medical Center, Cleveland, OH, 2Case Western Reserve University School of Medicine, Cleveland, OH, 3Case Western Reserve University, Cleveland, OH, 4Wright State University School of Medicine, Dayton, OH 1
Purpose/Objective(s): Normal tissue tolerance doses for organs have been well described for conventionally fractionated radiation. Tolerance doses for large fraction sizes are still controversial. Prior radiation also contributes to the difficulty in defining dose constraints. Here, we report toxicity data of a large series of patients treated with hypofractionated radiosurgery using the linear quadratic (LQ) model to derive normal organ constraints. Materials/Methods: We retrospectively reviewed 259 consecutive patients treated with Cyberknife radiosurgery at our institution between 2007 and 2010. Dose constraints were defined by the LQ model using appropriate alpha-beta ratios. For patients who received prior radiation, a bioequivalent dose was subtracted from the dose constraint. Toxicities were scored according to NCI CTCAE. Toxicities were classified as acute if they occurred within 90 days or as late toxicity after 90 days. Results: Out of 259 patients, 208 had available follow-up data. Median follow-up was 206 days (range, 7 - 784 days). 60 patients (28.8%) received prior radiation that altered dose constraints during planning. 21 patients (10.1%) received multiple courses of radiosurgery. Target sites were: brain (10), spine (25), H&N (17), thoracic (43), abdomen (57), prostate (34), other pelvic sites (15), and musculoskeletal (7). Maximum acute treatment toxicities occurred in the following numbers: grade 1 in 62 (29.8%), grade 2 in 30 (14.4%), grade 3 in 4 (1.9%), and no grade 4-5 toxicities. The grade 3 toxicities were: cranial nerve palsy (n = 1) after pituitary adenoma treatment, pneumonitis (n = 1) after NSCLC treatment, and nausea (n = 2) after periaortic lymph node and HCC treatments, respectively. Late toxicity was assessable in 162 patients. The maximum late treatment toxicities occurred in the following numbers: grade 1 in 21 (13.0%), grade 2 in 22 (13.6%), grade 3 in 4 (2.5%), and no grade 4-5 toxicities. The grade 3 toxicities were: vaginal stricture after treatment to the pelvis, leg weakness/incontinence after treatment to the cauda equina, myelitis after treatment of a spinal cord lesion, and cerebral edema/ataxia after treatment of meningioma. Some toxicities may have been due to disease progression. Conclusions: Using the LQ model to derive dose constraints for normal structures yielded an acceptable toxicity profile across a variety of targets treated with hypofractionated radiosurgery. The rate of severe toxicity (grade $ 3) was low and compares favorably with standard fractionated radiation, although late toxicity will likely increase with longer follow-up. In our data series, the LQ model appears to be a safe and effective method of determining dose constraints for normal structures while accounting for previous radiation doses. Author Disclosure: J. Choe, None; W. Chen, None; C. Woods, None; B. Wessels, None; Y. Zheng, None; J. Brindle, None; Y. Zhang, None; C. Kunos, None; J. Lyons, None; D. Einstein, None.
S140
298
Volume 78, Number 3, Supplement, 2010
Analysis of Factors Predicting for Pain Resolution after Gamma Knife Radiosurgery for Medically Refractory Trigeminal Neuralgia
J. L. Cartier, I. S. Grills, P. Chen, H. Ye, A. Maitz, L. L. Kestin, D. J. Krauss, R. Olson, J. Fontanesi, D. R. Pieper William Beaumont Hospital, Royal Oak, MI Purpose/Objective(s): To evaluate the clinical outcomes of patients undergoing Gamma Knife (GK) stereotactic radiosurgery as a non-surgical treatment for trigeminal neuralgia (TGN). Materials/Methods: Ninety-five patients underwent GK for TGN between 12/2006-6/2009 at William Beaumont Hospital. Eighty had follow-up $6 weeks and were the subject of this report. Median patient age was 68y (30-92); 58 female, 22 male. 74% of patients had typical trigeminal pain, 11% atypical features and 11% multiple sclerosis. Thirty patients (38%) had undergone prior surgical procedures and 37 (46%) had preexisting sensory complaints. The median dose delivered was 40 Gy (range: 35-45 Gy) to the 50% isodose line (80 Gy max) using either a single (85%) or two (6%) isocenters with a 4 mm collimator, or two isocenters with a 4 and 8 mm collimator (9%). Patients were seen #2 weeks post-GK, then every 3-6 months in addition to periodic mail surveys and telephone interviews. Pain was evaluated using the Barrow Neurological Institute Pain Intensity Scale. Multiple patient and GK factors were analyzed for association with pain relief. Mean follow-up duration was 15.6 months. Results: Ninety-one percent of patients (n = 73) reported at least partial pain resolution: 45% (n = 36) complete pain relief, 46% (n = 37) partial relief. Median time to pain resolution was 23d. Seventeen patients (23%) who had partial to complete resolution had pain recurrence (median: 6.2 months). The pain recurrence rate was higher in MS patients than non-MS (44% vs. 20%) and in those who experienced partial rather than complete relief. The 1, 2 and 3-year rates of freedom from pain recurrence for patients achieving partial relief after GK were 73%, 55% and 37% compared to 78%, 78%, and 78% for patients achieving complete relief after GK (p = 0.097). Sixteen (20%) patients reported new post-treatment sensory complaints; no other complications were noted. We identified that the greater the treated nerve length, the greater the probability of achieving a BNI of I-II (p = 0.021) and of pain resolution (p = 0.037). The cut-point length for partial/complete relief was a treated length of 0.51cm. Number of isocenters, treatment volume and thickness, dose distribution, and distance from the root entry zone to the GK isocenter were examined but not significant for relief. Conclusions: In this study, GK radiosurgery for trigeminal neuralgia was associated with complete or partial pain resolution in 91% of patients. Longer treated nerve length (cutpoint: 0.51cm) was associated with better pain resolution. Although 23% of patients had pain recurrence, the initial success and recurrence rates appeared similar to those reported after percutaneous treatment approaches with minimal post-treatment neurological complaints. Author Disclosure: J.L. Cartier, None; I.S. Grills, None; P. Chen, None; H. Ye, None; A. Maitz, None; L.L. Kestin, None; D.J. Krauss, None; R. Olson, None; J. Fontanesi, None; D.R. Pieper, None.
299
Toxicity Data For Hypofractionated Radiosurgery Using the Linear Quadratic Model to Constrain Normal Organ Tolerance Doses
J. Choe1, W. Chen1, C. Woods1, B. Wessels2, Y. Zheng3, J. Brindle2, Y. Zhang2, C. Kunos1, J. Lyons1, D. Einstein2,4 University Hospitals Case Medical Center, Cleveland, OH, 2Case Western Reserve University School of Medicine, Cleveland, OH, 3Case Western Reserve University, Cleveland, OH, 4Wright State University School of Medicine, Dayton, OH 1
Purpose/Objective(s): Normal tissue tolerance doses for organs have been well described for conventionally fractionated radiation. Tolerance doses for large fraction sizes are still controversial. Prior radiation also contributes to the difficulty in defining dose constraints. Here, we report toxicity data of a large series of patients treated with hypofractionated radiosurgery using the linear quadratic (LQ) model to derive normal organ constraints. Materials/Methods: We retrospectively reviewed 259 consecutive patients treated with Cyberknife radiosurgery at our institution between 2007 and 2010. Dose constraints were defined by the LQ model using appropriate alpha-beta ratios. For patients who received prior radiation, a bioequivalent dose was subtracted from the dose constraint. Toxicities were scored according to NCI CTCAE. Toxicities were classified as acute if they occurred within 90 days or as late toxicity after 90 days. Results: Out of 259 patients, 208 had available follow-up data. Median follow-up was 206 days (range, 7 - 784 days). 60 patients (28.8%) received prior radiation that altered dose constraints during planning. 21 patients (10.1%) received multiple courses of radiosurgery. Target sites were: brain (10), spine (25), H&N (17), thoracic (43), abdomen (57), prostate (34), other pelvic sites (15), and musculoskeletal (7). Maximum acute treatment toxicities occurred in the following numbers: grade 1 in 62 (29.8%), grade 2 in 30 (14.4%), grade 3 in 4 (1.9%), and no grade 4-5 toxicities. The grade 3 toxicities were: cranial nerve palsy (n = 1) after pituitary adenoma treatment, pneumonitis (n = 1) after NSCLC treatment, and nausea (n = 2) after periaortic lymph node and HCC treatments, respectively. Late toxicity was assessable in 162 patients. The maximum late treatment toxicities occurred in the following numbers: grade 1 in 21 (13.0%), grade 2 in 22 (13.6%), grade 3 in 4 (2.5%), and no grade 4-5 toxicities. The grade 3 toxicities were: vaginal stricture after treatment to the pelvis, leg weakness/incontinence after treatment to the cauda equina, myelitis after treatment of a spinal cord lesion, and cerebral edema/ataxia after treatment of meningioma. Some toxicities may have been due to disease progression. Conclusions: Using the LQ model to derive dose constraints for normal structures yielded an acceptable toxicity profile across a variety of targets treated with hypofractionated radiosurgery. The rate of severe toxicity (grade $ 3) was low and compares favorably with standard fractionated radiation, although late toxicity will likely increase with longer follow-up. In our data series, the LQ model appears to be a safe and effective method of determining dose constraints for normal structures while accounting for previous radiation doses. Author Disclosure: J. Choe, None; W. Chen, None; C. Woods, None; B. Wessels, None; Y. Zheng, None; J. Brindle, None; Y. Zhang, None; C. Kunos, None; J. Lyons, None; D. Einstein, None.