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Stereotactic Body Radiotherapy (SBRT) in Patients Previously Treated with External Beam Radiation Therapy
I. J. Radiation Oncology d Biology d Physics
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2169
Volume 78, Number 3, Supplement, 2010
Tumor Volume Increase after Stereotactic Radiosurgery for Vestibular Schwannoma: Expected Radiographic Finding or Exception?
A. Carai, S. Green, B. Delman, S. R. Blacksburg, K. Maloney-Lutz, Y. Lo, R. Sheu, I. Germano Mount Sinai Medical Center, New York, NY Purpose/Objective(s): Stereotactic radiosurgery (SRS) has emerged as a valuable alternative to microsurgery in the treatment of vestibular schwannomas (VS). Tumor control rates have been reported between 74% and 99% at 12 months. Despite these encouraging results, transient VS tumor enlargement after SRS has been reported in different series, with an incidence varying from 3% to 74% and an onset varying from 3 to 12 months. The aim of the present study is to determine the tumor volume changes 3, 6, and 12 months after SRS for VS. Materials/Methods: In this retrospective study, we reviewed the MRIs of 25 VS tumors in 24 patients treated with single fraction Novalis SRS at our Institution at baseline and at 3, 6, and 12 months after SRS. The most common regimen consisted of 1250 cGy prescribed to the 85% isodose line. Tumor volumes were calculated independently by a neurosurgeon and a neuroradiologist on axial and coronal MRI sections on T1W contrast-enhanced images. Correlation with clinical symptoms at the same time points was performed. Paired Student’s t-test and one-way ANOVA were used for statistical analysis. Results: Mean tumor volume before SRS was 10.75 + 15.5 cc3 (range, 1.08-60.24 cc3). A significant increase in volume was seen 3 and 6 months after SRS, 39% and 72%, respectively (p \ 0.05). Volumes returned toward baseline values at 12 months. At 3 months, 16/22 (73%) VS tumors showed an increase in volume .10% (range, 14-144%) and 16/18 (89%) at 6 months (range, 19-185%). Increased heterogeneity in contrast enhancement with a ‘‘soap-bubble’’ appearance was seen in the majority of cases. Increase in tumor volume, however, did not correlate with changes in neurological symptoms. Conclusions: Our study demonstrates that transient volume enlargement 3-6 months after SRS for VS should be considered part of the normal response to SRS treatment and should not be mistaken for treatment failure. There are no neurological symptoms that correlate with this radiographic feature and volumes return toward baseline values at 12 months. Therefore, when assessing MRIs 3-6 months after SRS, caution should be applied when prescribing potentially unnecessary treatment. Author Disclosure: A. Carai, None; S. Green, None; B. Delman, None; S.R. Blacksburg, None; K. Maloney-Lutz, None; Y. Lo, None; R. Sheu, None; I. Germano, None.
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Cone-Beam CT 6 Degree-of-Freedom Image-Guidance for Intracranial Frameless Stereotactic RadioSurgery using 6D Robotic Couch
Z. Chang1, Z. Wang1, J. Ma2,1, Q. Wu1, J. Kirkpatrick1, F. Yin1 1
Duke University, Durham, NC, 2Fudan University Cancer Hospital, Shanghai, China
Purpose/Objective(s): Cone-beam CT (CBCT) 6 degree-of-freedom (6D) image guidance has been successfully demonstrated with hypofractionated spinal stereotactic radiotherapy. In this work, this technique is further developed to investigate localization accuracy for image-guided intracranial frameless stereotactic radiosurgery with a large patient volume based on our previous study. Materials/Methods: Phantom and patient studies were performed on a Novalis Tx system, equipped with a BrainLAB 6D robotic couch and Varian CBCT imaging system. In the phantom studies, CBCT was performed on a head phantom and then registered with planning CT, enabling 6D fusion. Matching results were used to test the accuracy of CBCT 6D fusion for correcting translational and rotational setup errors. For patient studies, 50 intracranial SRS cases were randomly selected. Patients were initially positioned with the BrainLAB frameless mask system with target-positioning-overlays (TAPO). Patients were then scanned with CBCT to refine the setup. The position of each patient was adjusted or verified based on CBCT 3D and 6D image fusion. Setup displacements between TAPO, CBCT 3D and 6D image fusion were quantitatively analyzed with the paired Student’s t-test. Statistical significance was defined as p \ 0.05. Results: Phantom experiments showed root-mean-square (RMS) discrepancies of 0.6 mm translationally and 0.5o rotationally between CBCT 6D fusion and the known displacements. In the retrospective patient studies, the RMS of the differences between the initial setup with TAPO and CBCT 6D image fusion was greater than 1.5 mm in all the three translational directions. The corresponding rotational discrepancy in RMS was 1.5 . If positioning was corrected using standard CBCT 3D fusion, the residual translational and rotational discrepancies in RMS were 0.9 mm and 1.2o, as compared with CBCT 6D fusion. More specifically, the translational differences in RMS were 0.5 mm along anterior-posterior direction, 0.5 mm along longitudinal direction, and 0.6 mm along lateral direction; the rotational differences in RMS were 0.58 in pitch, 0.97 in roll, and 0.29 in yaw. The difference in the lateral direction was, however, found to be statistically significant (p = 0.033). It implies that uncorrected rotational discrepancies may introduce translational errors. CBCT 6D image fusion was used to evaluate the setups of all 50 patients. CBCT guided 6D correction was applied to 12 of the 50 cases using the robotic couch. After the 6D correction, both translational and rotational discrepancies were effectively minimized. Conclusions: CBCT 6D image fusion provides an explicit method of verify patient positioning, and, when combined with a 6D couch, minimizes both translational and rotational setup errors. Author Disclosure: Z. Chang, None; Z. Wang, None; J. Ma, None; Q. Wu, None; J. Kirkpatrick, None; F. Yin, None.
2171
Stereotactic Body Radiotherapy (SBRT) in Patients Previously Treated with External Beam Radiation Therapy
A. Ghafoori, K. Allen, J. Nelson, R. Clough, F. Yin, Z. Wang, Z. Chang, C. Kelsey, J. Kirkpatrick Duke University Medical Center, Durham, NC Purpose/Objective(s): Stereotactic body radiotherapy (SBRT) is increasingly used for the definitive treatment of primary malignancies or for palliation of metastases. We wished to determine the efficacy of SBRT in the treatment of patients who had received prior external beam radiation therapy (EBRT) to the treated site.
Proceedings of the 52nd Annual ASTRO Meeting Materials/Methods: Records were reviewed for the 58 patients enrolled into a SBRT prospective observational database at Duke University Medical Center between 2008 and 2010. 68 lesions were treated with SBRT (25 spine, 26 lung, 5 liver, 12 other). Fiftytwo metastatic lesions were treated, while 16 lesions were treated with curative intent. The number of fractions ranged from 1 to 5 and dose per fraction ranged from 4.5 to 20, depending on the anatomic site treated. Overall survival (OS) and local control (LC) were estimated using the Kaplan-Meier method. Univariate regression analysis was used to evaluate the effect of patient- and treatment-related factors on these clinical endpoints. Toxicity was assessed by CTCAE v3.0. Results: The median age of the patients was 66 years. Median follow-up time was 6.8 months and median follow-up time with a radiological study to assess the treated lesion was 5.6 months. 5 patients reported a grade 1 acute treatment-related toxicity and 2 patients reported a grade 1 late treatment-related toxicity. No grade 2 or higher acute or late toxicities were observed. 89% of patients treated for a symptomatic lesion had improvement of their symptoms after SBRT. Actuarial rates of LC and OS at one year were 77% and 84%, respectively. The actuarial one-year radiologic local control of the treated site was 74%. On univariate analysis, the likelihood of local control for patients who had prior EBRT to the treated site at 1 year was 41% vs. 85% when SBRT was the sole local therapy (p = 0.01). Patients who had undergone prior EBRT were more likely to have SBRT with a lower total dose (median dose 22.5 Gy vs. 36 Gy, p = 0.04). Primary cancer histology (adenocarcinoma vs. other), site treated (liver, lung, spine, other) and goal of therapy (definitive vs. palliative) did not have a significant impact on the likelihood for local control. Conclusions: SBRT appears to be an effective, well-tolerated local therapy for metastatic lesions and localized cancers. These data suggest that treatment with upfront full-dose SBRT has a higher likelihood of achieving local control when compared with upfront EBRT followed by salvage SBRT at disease progression. Further investigation with larger patient cohorts is necessary to determine the factors leading to optimal local control after treatment with SBRT. These studies could lead to improved therapies for palliation of metastases and for durable control of oligometastatic disease. Author Disclosure: A. Ghafoori, None; K. Allen, None; J. Nelson, None; R. Clough, None; F. Yin, None; Z. Wang, None; Z. Chang, None; C. Kelsey, None; J. Kirkpatrick, None.
2172
Patterns of Tumor Recurrence following Concurrent Radiation and Temozolomide Treatment for Glioblastoma Multiforme
A. Ghose, R. Nordal, G. Lim, N. Wolfe, J. Easaw, S. Husain Tom Baker Cancer Centre, Calgary, AB, Canada Purpose/Objective(s): Historical series have shown that recurrences of glioblastoma multiforme (GBM) after surgery and radiation alone occur mainly within 2 cm of the primary tumor. Following radiotherapy alone, 3-25% of recurrences have been reported to occur outside of the high dose radiotherapy volume. Partial, and subsequently conformal, brain irradiation therefore became the standard approach vs. whole brain treatment. While temozolomide (tmz) has been shown to confer a modest survival benefit, the recurrence pattern after addition of tmz to postoperative radiotherapy has not been extensively studied. Specifically, if addition of tmz has altered the pattern of recurrence such that distant failures are now more common, radiation targets would have to be modified accordingly. Our purpose was to study GBM recurrence patterns after radiation and tmz by correlating the location of recurrence with dose delivered to the area of recurrence. We hypothesized that synergy of conformal radiotherapy with tmz at the primary site would alter the observed frequency of distant brain failure. Materials/Methods: We conducted a retrospective study of 10 eligible patients for whom adequate dosimetry and imaging records were available. All patients had surgically proven diagnosis of GBM. Patients received radiation and concurrent (+/- adjuvant) temozolomide. Radiation targets were identified with CT-MR fusion based planning. Phase 1 consisted of 46 Gy prescribed to the isocentre, with targets including enhancing tumor, surgical cavity and peri-tumoral edema + 2 cm margin to PTV. Phase 2 consisted of a 14 Gy boost to the residual tumor and surgical cavity + 2.5 cm to PTV. Plans were optimized such that the PTV was covered by the 95% isodose line. The first post-treatment MR documenting tumor progression was fused to the planning CT-scan acquired at simulation. Treatment isodose lines were overlaid onto this MR to delineate the location of recurrence relative to dose delivered. Results: One hundred percent of tumors recurred within the high dose radiation volume. All 10 patients had MR proven recurrences confined within the 54 Gy (90%) isodose volume. Of these, 6/10 patients had recurrences confined to within the 57 Gy (95%) isodose volume encompassing the boost PTV. Conclusions: In our experience, all tumors recurred within the high dose region receiving 54-60 Gy, concurrently with tmz. Addition of tmz did not alter the predominance of local failures previously seen with radiotherapy alone. Although tmz may act synergistically with radiation to temporarily control the primary tumor, the combination is not effective enough such that distant locations become more likely as the site of first recurrence. This result implies a continuing need for additional strategies to improve primary tumor control. Author Disclosure: A. Ghose, None; R. Nordal, None; G. Lim, None; N. Wolfe, None; J. Easaw, None; S. Husain, None.
2173
Survival in Patients Receiving Radiotherapy Plus Concomitant and Adjuvant Temozolomide (RCAT) for Glioblastoma (GBM)
S. J. Hargreaves, M. Williams, Z. Liu, V. Michalarea, D. Woolf, E. Wilson The Royal Free Hospital NHS Trust, London, United Kingdom Purpose/Objective(s): To examine overall survival and prognostic factors in patients with GBM diagnosed between February 2002 and December 2009 and who were treated with RCAT at The Royal Free Hospital, London. Chemoradiotherapy with concurrent and adjuvant temozolomide is currently the standard of care for GBM, based on the results of Phase 3 clinical trials. However, it is not clear whether the results found in the trial population are reproducible in routine clinical practice as there is little published data regarding this. Materials/Methods: We identified all patients with biopsy-proven GBM in whom there was an intention to offer RCAT between 2002 and 2009. We extracted data on age, gender, WHO performance status, length of symptoms, comorbidities, the presence of
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Volume 78, Number 3, Supplement, 2010
Tumor Volume Increase after Stereotactic Radiosurgery for Vestibular Schwannoma: Expected Radiographic Finding or Exception?
A. Carai, S. Green, B. Delman, S. R. Blacksburg, K. Maloney-Lutz, Y. Lo, R. Sheu, I. Germano Mount Sinai Medical Center, New York, NY Purpose/Objective(s): Stereotactic radiosurgery (SRS) has emerged as a valuable alternative to microsurgery in the treatment of vestibular schwannomas (VS). Tumor control rates have been reported between 74% and 99% at 12 months. Despite these encouraging results, transient VS tumor enlargement after SRS has been reported in different series, with an incidence varying from 3% to 74% and an onset varying from 3 to 12 months. The aim of the present study is to determine the tumor volume changes 3, 6, and 12 months after SRS for VS. Materials/Methods: In this retrospective study, we reviewed the MRIs of 25 VS tumors in 24 patients treated with single fraction Novalis SRS at our Institution at baseline and at 3, 6, and 12 months after SRS. The most common regimen consisted of 1250 cGy prescribed to the 85% isodose line. Tumor volumes were calculated independently by a neurosurgeon and a neuroradiologist on axial and coronal MRI sections on T1W contrast-enhanced images. Correlation with clinical symptoms at the same time points was performed. Paired Student’s t-test and one-way ANOVA were used for statistical analysis. Results: Mean tumor volume before SRS was 10.75 + 15.5 cc3 (range, 1.08-60.24 cc3). A significant increase in volume was seen 3 and 6 months after SRS, 39% and 72%, respectively (p \ 0.05). Volumes returned toward baseline values at 12 months. At 3 months, 16/22 (73%) VS tumors showed an increase in volume .10% (range, 14-144%) and 16/18 (89%) at 6 months (range, 19-185%). Increased heterogeneity in contrast enhancement with a ‘‘soap-bubble’’ appearance was seen in the majority of cases. Increase in tumor volume, however, did not correlate with changes in neurological symptoms. Conclusions: Our study demonstrates that transient volume enlargement 3-6 months after SRS for VS should be considered part of the normal response to SRS treatment and should not be mistaken for treatment failure. There are no neurological symptoms that correlate with this radiographic feature and volumes return toward baseline values at 12 months. Therefore, when assessing MRIs 3-6 months after SRS, caution should be applied when prescribing potentially unnecessary treatment. Author Disclosure: A. Carai, None; S. Green, None; B. Delman, None; S.R. Blacksburg, None; K. Maloney-Lutz, None; Y. Lo, None; R. Sheu, None; I. Germano, None.
2170
Cone-Beam CT 6 Degree-of-Freedom Image-Guidance for Intracranial Frameless Stereotactic RadioSurgery using 6D Robotic Couch
Z. Chang1, Z. Wang1, J. Ma2,1, Q. Wu1, J. Kirkpatrick1, F. Yin1 1
Duke University, Durham, NC, 2Fudan University Cancer Hospital, Shanghai, China
Purpose/Objective(s): Cone-beam CT (CBCT) 6 degree-of-freedom (6D) image guidance has been successfully demonstrated with hypofractionated spinal stereotactic radiotherapy. In this work, this technique is further developed to investigate localization accuracy for image-guided intracranial frameless stereotactic radiosurgery with a large patient volume based on our previous study. Materials/Methods: Phantom and patient studies were performed on a Novalis Tx system, equipped with a BrainLAB 6D robotic couch and Varian CBCT imaging system. In the phantom studies, CBCT was performed on a head phantom and then registered with planning CT, enabling 6D fusion. Matching results were used to test the accuracy of CBCT 6D fusion for correcting translational and rotational setup errors. For patient studies, 50 intracranial SRS cases were randomly selected. Patients were initially positioned with the BrainLAB frameless mask system with target-positioning-overlays (TAPO). Patients were then scanned with CBCT to refine the setup. The position of each patient was adjusted or verified based on CBCT 3D and 6D image fusion. Setup displacements between TAPO, CBCT 3D and 6D image fusion were quantitatively analyzed with the paired Student’s t-test. Statistical significance was defined as p \ 0.05. Results: Phantom experiments showed root-mean-square (RMS) discrepancies of 0.6 mm translationally and 0.5o rotationally between CBCT 6D fusion and the known displacements. In the retrospective patient studies, the RMS of the differences between the initial setup with TAPO and CBCT 6D image fusion was greater than 1.5 mm in all the three translational directions. The corresponding rotational discrepancy in RMS was 1.5 . If positioning was corrected using standard CBCT 3D fusion, the residual translational and rotational discrepancies in RMS were 0.9 mm and 1.2o, as compared with CBCT 6D fusion. More specifically, the translational differences in RMS were 0.5 mm along anterior-posterior direction, 0.5 mm along longitudinal direction, and 0.6 mm along lateral direction; the rotational differences in RMS were 0.58 in pitch, 0.97 in roll, and 0.29 in yaw. The difference in the lateral direction was, however, found to be statistically significant (p = 0.033). It implies that uncorrected rotational discrepancies may introduce translational errors. CBCT 6D image fusion was used to evaluate the setups of all 50 patients. CBCT guided 6D correction was applied to 12 of the 50 cases using the robotic couch. After the 6D correction, both translational and rotational discrepancies were effectively minimized. Conclusions: CBCT 6D image fusion provides an explicit method of verify patient positioning, and, when combined with a 6D couch, minimizes both translational and rotational setup errors. Author Disclosure: Z. Chang, None; Z. Wang, None; J. Ma, None; Q. Wu, None; J. Kirkpatrick, None; F. Yin, None.
2171
Stereotactic Body Radiotherapy (SBRT) in Patients Previously Treated with External Beam Radiation Therapy
A. Ghafoori, K. Allen, J. Nelson, R. Clough, F. Yin, Z. Wang, Z. Chang, C. Kelsey, J. Kirkpatrick Duke University Medical Center, Durham, NC Purpose/Objective(s): Stereotactic body radiotherapy (SBRT) is increasingly used for the definitive treatment of primary malignancies or for palliation of metastases. We wished to determine the efficacy of SBRT in the treatment of patients who had received prior external beam radiation therapy (EBRT) to the treated site.
Proceedings of the 52nd Annual ASTRO Meeting Materials/Methods: Records were reviewed for the 58 patients enrolled into a SBRT prospective observational database at Duke University Medical Center between 2008 and 2010. 68 lesions were treated with SBRT (25 spine, 26 lung, 5 liver, 12 other). Fiftytwo metastatic lesions were treated, while 16 lesions were treated with curative intent. The number of fractions ranged from 1 to 5 and dose per fraction ranged from 4.5 to 20, depending on the anatomic site treated. Overall survival (OS) and local control (LC) were estimated using the Kaplan-Meier method. Univariate regression analysis was used to evaluate the effect of patient- and treatment-related factors on these clinical endpoints. Toxicity was assessed by CTCAE v3.0. Results: The median age of the patients was 66 years. Median follow-up time was 6.8 months and median follow-up time with a radiological study to assess the treated lesion was 5.6 months. 5 patients reported a grade 1 acute treatment-related toxicity and 2 patients reported a grade 1 late treatment-related toxicity. No grade 2 or higher acute or late toxicities were observed. 89% of patients treated for a symptomatic lesion had improvement of their symptoms after SBRT. Actuarial rates of LC and OS at one year were 77% and 84%, respectively. The actuarial one-year radiologic local control of the treated site was 74%. On univariate analysis, the likelihood of local control for patients who had prior EBRT to the treated site at 1 year was 41% vs. 85% when SBRT was the sole local therapy (p = 0.01). Patients who had undergone prior EBRT were more likely to have SBRT with a lower total dose (median dose 22.5 Gy vs. 36 Gy, p = 0.04). Primary cancer histology (adenocarcinoma vs. other), site treated (liver, lung, spine, other) and goal of therapy (definitive vs. palliative) did not have a significant impact on the likelihood for local control. Conclusions: SBRT appears to be an effective, well-tolerated local therapy for metastatic lesions and localized cancers. These data suggest that treatment with upfront full-dose SBRT has a higher likelihood of achieving local control when compared with upfront EBRT followed by salvage SBRT at disease progression. Further investigation with larger patient cohorts is necessary to determine the factors leading to optimal local control after treatment with SBRT. These studies could lead to improved therapies for palliation of metastases and for durable control of oligometastatic disease. Author Disclosure: A. Ghafoori, None; K. Allen, None; J. Nelson, None; R. Clough, None; F. Yin, None; Z. Wang, None; Z. Chang, None; C. Kelsey, None; J. Kirkpatrick, None.
2172
Patterns of Tumor Recurrence following Concurrent Radiation and Temozolomide Treatment for Glioblastoma Multiforme
A. Ghose, R. Nordal, G. Lim, N. Wolfe, J. Easaw, S. Husain Tom Baker Cancer Centre, Calgary, AB, Canada Purpose/Objective(s): Historical series have shown that recurrences of glioblastoma multiforme (GBM) after surgery and radiation alone occur mainly within 2 cm of the primary tumor. Following radiotherapy alone, 3-25% of recurrences have been reported to occur outside of the high dose radiotherapy volume. Partial, and subsequently conformal, brain irradiation therefore became the standard approach vs. whole brain treatment. While temozolomide (tmz) has been shown to confer a modest survival benefit, the recurrence pattern after addition of tmz to postoperative radiotherapy has not been extensively studied. Specifically, if addition of tmz has altered the pattern of recurrence such that distant failures are now more common, radiation targets would have to be modified accordingly. Our purpose was to study GBM recurrence patterns after radiation and tmz by correlating the location of recurrence with dose delivered to the area of recurrence. We hypothesized that synergy of conformal radiotherapy with tmz at the primary site would alter the observed frequency of distant brain failure. Materials/Methods: We conducted a retrospective study of 10 eligible patients for whom adequate dosimetry and imaging records were available. All patients had surgically proven diagnosis of GBM. Patients received radiation and concurrent (+/- adjuvant) temozolomide. Radiation targets were identified with CT-MR fusion based planning. Phase 1 consisted of 46 Gy prescribed to the isocentre, with targets including enhancing tumor, surgical cavity and peri-tumoral edema + 2 cm margin to PTV. Phase 2 consisted of a 14 Gy boost to the residual tumor and surgical cavity + 2.5 cm to PTV. Plans were optimized such that the PTV was covered by the 95% isodose line. The first post-treatment MR documenting tumor progression was fused to the planning CT-scan acquired at simulation. Treatment isodose lines were overlaid onto this MR to delineate the location of recurrence relative to dose delivered. Results: One hundred percent of tumors recurred within the high dose radiation volume. All 10 patients had MR proven recurrences confined within the 54 Gy (90%) isodose volume. Of these, 6/10 patients had recurrences confined to within the 57 Gy (95%) isodose volume encompassing the boost PTV. Conclusions: In our experience, all tumors recurred within the high dose region receiving 54-60 Gy, concurrently with tmz. Addition of tmz did not alter the predominance of local failures previously seen with radiotherapy alone. Although tmz may act synergistically with radiation to temporarily control the primary tumor, the combination is not effective enough such that distant locations become more likely as the site of first recurrence. This result implies a continuing need for additional strategies to improve primary tumor control. Author Disclosure: A. Ghose, None; R. Nordal, None; G. Lim, None; N. Wolfe, None; J. Easaw, None; S. Husain, None.
2173
Survival in Patients Receiving Radiotherapy Plus Concomitant and Adjuvant Temozolomide (RCAT) for Glioblastoma (GBM)
S. J. Hargreaves, M. Williams, Z. Liu, V. Michalarea, D. Woolf, E. Wilson The Royal Free Hospital NHS Trust, London, United Kingdom Purpose/Objective(s): To examine overall survival and prognostic factors in patients with GBM diagnosed between February 2002 and December 2009 and who were treated with RCAT at The Royal Free Hospital, London. Chemoradiotherapy with concurrent and adjuvant temozolomide is currently the standard of care for GBM, based on the results of Phase 3 clinical trials. However, it is not clear whether the results found in the trial population are reproducible in routine clinical practice as there is little published data regarding this. Materials/Methods: We identified all patients with biopsy-proven GBM in whom there was an intention to offer RCAT between 2002 and 2009. We extracted data on age, gender, WHO performance status, length of symptoms, comorbidities, the presence of
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