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Prognostic Factors in Patients With Brain Metastases at Initial Non-Small Cell Lung Cancer Diagnosis
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Volume 87 Number 2S Supplement 2013 evaluated according to MacDonald’s criteria. LC failure was defined as a 25% increase in maximum tumor area. The cumulative incidence of LC failure was calculated by accounting for death as competing risks. The Fine and Gray hazard model was used to adjust baseline imbalances. The OS rate was calculated by the Kaplan-Meier method. Toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Results: OS rates were 52% and 31% at 6 and 12 months, respectively. Median survival time was 6 months. LC rates of total 102 BMs were 84% and 78% at 6 and 12 months, respectively. LC rates of 61 large BMs were 77% and 69% at 6 and 12 months, respectively. Upon first evaluation at 1-3 months after FSRT, LC failure and neurological worsening were observed in 11 of 54 patients. Seizure (Grade 2) and perifocal edema were observed in a breast cancer patient at 4 months after FSRT (30 Gy/3 fr). Grade 3 or higher toxicities were not observed. Conclusions: The highest dose levels of 26.4-30 Gy/3 fr and 31-35 Gy/5 fr appeared to be tolerable and effective against large BMs. These doses may be used in FSRT for large BMs. Author Disclosure: T. Murai: None. H. Ogino: None. Y. Manabe: None. T. Okumura: None. Y. Matsushita: None. Y. Tsuji: None. M. Iwabuchi: None. Y. Shibamoto: None.
2180 Prognostic Factors in Patients With Brain Metastases at Initial Non-Small Cell Lung Cancer Diagnosis C.E. Rutter, B.R. Mancini, J.B. Yu, V.L. Chiang, and R.S. Bindra; Yale New Haven Hospital, New Haven, CT Purpose/Objective(s): Patients with brain metastases at the time of initial diagnosis of non-small cell lung cancer (NSCLC) are an intriguing population, as their systemic disease is naı¨ve to cytotoxic or targeted agents. Thus, prognostic factors in this population are poorly defined; this study aims to address this uncertainty. Materials/Methods: A prospectively-maintained database of patients receiving stereotactic radiosurgery (SRS) was queried to identify patients with brain metastases discovered at the time of initial NSCLC diagnosis, who ultimately received some form of systemic therapy. Factors including demographics, Karnofsky performance status (KPS), extent of intracranial and extracranial disease, and length of delay to initiation of systemic therapy were recorded. Tumor mutations were determined via sequencing (EGFR and KRas) or FISH (Alk rearrangement). Univariate and multivariate Cox proportional hazards analyses were utilized to determine the impact of these factors on overall survival. Results: Sixty-five patients undergoing SRS between June 2006 and November 2012 were identified. Median age was 60 years (range, 29-81 years), 33 (51%) were male, and median KPS was 90 (range, 60-100). Patients had a median of one extracranial metastatic site (range, 0-3) and 1.5 brain metastases (range, 1-15). Chemotherapy or targeted agents were started within a median of 46 days of diagnosis (range, 8-127). EGFR, KRas, and Alk mutations were identified in 11, 5, and 3 patients, respectively (16.9%, 7.7%, and 4.6%). Sex and KPS did not impact survival in this cohort. Length of delay until institution of systemic therapy also did not impact survival. Age less than 60 was associated with a decreased risk of death in univariate analysis (HR 0.40, p Z 0.0026). Presence of a tyrosine kinase mutation was also associated with a reduced risk of death (p Z 0.0075), particularly among EGFR-mutated patients (HR 0.26, p Z 0.006). In multivariate analyses, both age less than 60 (HR 0.42, p Z 0.009) and presence of an EGFR mutation (HR 0.25, p Z 0.005) were associated with significant reductions in the risk of death. Conclusions: The prognosis of patients with brain metastases at the time of systemic cancer diagnosis can be quite varied. While it is intuitive to presume that a prolonged delay to the initiation of systemic therapy would negatively impact survival, this effect was not observed in this cohort. Patients with NSCLC driven by a tyrosine kinase mutation, particularly of EGFR, had improved survival compared to patients with wild type tumors.
Author Disclosure: C.E. Rutter: None. B.R. Mancini: None. J.B. Yu: None. V.L. Chiang: None. R.S. Bindra: None.
2181 Clinical Outcomes of Single Isocenter Frameless Radiosurgery for Multiple Brain Metastases S. Lau, X. Zhao, E. Knipprath, D.R. Simpson, C.C. Chen, and K.T. Murphy; University of California San Diego, La Jolla, CA Purpose/Objective(s): Radiosurgery is well accepted in the treatment of patients with intracranial metastases, but the role of frameless radiosurgery is unknown. Here, we describe our clinical experience with a novel single isocenter technique for frameless intensity modulated stereotactic radiosurgery (IMRS) to treat multiple intracranial metastases. Materials/Methods: After obtaining institutional review board approval, a review of radiation oncology records was performed. Between 2006 and 2012, 100 consecutive patients received optically guided frameless IMRS using a single centrally located isocenter for multiple intracranial metastases at a single center. Patients had a median of 4 intracranial metastases (range, 2-18). A total of 465 intracranial metastases were treated in a median of 1 fraction (range, 1-5) to a median dose of 20 Gy (range, 15-50 Gy). Clinical examination occurred every 2-4 months and included magnetic resonance imaging (MRI) to assess intracranial progression. Regional failure was defined as intracranial failure outside of the treatment volume. Local control, regional control, and overall survival were estimated by the Kaplan-Meier method. Toxicity was graded according to the Radiation Therapy Oncology Group scale. Results: Median follow-up for all patients was 4.3 months (range, 0.2-58.3 months), with 83 patients (83.0%) followed until their death. For the remaining 17 patients alive at the time of analysis, median follow-up was 9.2 months (range, 2.2-58.3 months). Actuarial 6- and 12-month overall survival was 49.5% (95% Confidence Interval [CI], 40.5-60.6%) and 34.1% (95% CI, 25.7-45.2%), respectively. Actuarial 6- and 12-month local control was 89% (95% CI, 83-95%) and 84% (95% CI, 77-91%), respectively. Regional failure was observed in 39 patients (39.0%). 25 patients (25.0%) received salvage therapy. Grade 3 or greater treatmentrelated toxicity was observed in 5 patients (5.0%) and included intracranial hemorrhage, seizure, and radionecrosis. Median total treatment time was 17.2 minutes (range, 2.8-55.3 minutes). Conclusions: Frameless, single isocenter IMRS for the simultaneous treatment of multiple intracranial metastases can produce clinical outcomes comparable to those of conventional frame-based radiosurgery techniques with the advantages of a noninvasive approach and shortened treatment time. Author Disclosure: S. Lau: None. X. Zhao: None. E. Knipprath: None. D.R. Simpson: None. C.C. Chen: None. K.T. Murphy: F. Honoraria; x.
2182 WITHDRAWN
2183 Local Control, Patterns of Failure, and Vertebral Compression Fracture After Spine Stereotactic Radiation Therapy for Metastatic Renal Cell Cancer I. Thibault,1 A. Al-Omair,1,2 G. Masucci,2 L. Masson-Cote´,2 F. Lochray,1 G. Bjarnason,3 A. Yee,3 R. Korol,1 L. Cheng,2 and A. Sahgal1,2; 1 Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, 2Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada, 3Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
Volume 87 Number 2S Supplement 2013 evaluated according to MacDonald’s criteria. LC failure was defined as a 25% increase in maximum tumor area. The cumulative incidence of LC failure was calculated by accounting for death as competing risks. The Fine and Gray hazard model was used to adjust baseline imbalances. The OS rate was calculated by the Kaplan-Meier method. Toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Results: OS rates were 52% and 31% at 6 and 12 months, respectively. Median survival time was 6 months. LC rates of total 102 BMs were 84% and 78% at 6 and 12 months, respectively. LC rates of 61 large BMs were 77% and 69% at 6 and 12 months, respectively. Upon first evaluation at 1-3 months after FSRT, LC failure and neurological worsening were observed in 11 of 54 patients. Seizure (Grade 2) and perifocal edema were observed in a breast cancer patient at 4 months after FSRT (30 Gy/3 fr). Grade 3 or higher toxicities were not observed. Conclusions: The highest dose levels of 26.4-30 Gy/3 fr and 31-35 Gy/5 fr appeared to be tolerable and effective against large BMs. These doses may be used in FSRT for large BMs. Author Disclosure: T. Murai: None. H. Ogino: None. Y. Manabe: None. T. Okumura: None. Y. Matsushita: None. Y. Tsuji: None. M. Iwabuchi: None. Y. Shibamoto: None.
2180 Prognostic Factors in Patients With Brain Metastases at Initial Non-Small Cell Lung Cancer Diagnosis C.E. Rutter, B.R. Mancini, J.B. Yu, V.L. Chiang, and R.S. Bindra; Yale New Haven Hospital, New Haven, CT Purpose/Objective(s): Patients with brain metastases at the time of initial diagnosis of non-small cell lung cancer (NSCLC) are an intriguing population, as their systemic disease is naı¨ve to cytotoxic or targeted agents. Thus, prognostic factors in this population are poorly defined; this study aims to address this uncertainty. Materials/Methods: A prospectively-maintained database of patients receiving stereotactic radiosurgery (SRS) was queried to identify patients with brain metastases discovered at the time of initial NSCLC diagnosis, who ultimately received some form of systemic therapy. Factors including demographics, Karnofsky performance status (KPS), extent of intracranial and extracranial disease, and length of delay to initiation of systemic therapy were recorded. Tumor mutations were determined via sequencing (EGFR and KRas) or FISH (Alk rearrangement). Univariate and multivariate Cox proportional hazards analyses were utilized to determine the impact of these factors on overall survival. Results: Sixty-five patients undergoing SRS between June 2006 and November 2012 were identified. Median age was 60 years (range, 29-81 years), 33 (51%) were male, and median KPS was 90 (range, 60-100). Patients had a median of one extracranial metastatic site (range, 0-3) and 1.5 brain metastases (range, 1-15). Chemotherapy or targeted agents were started within a median of 46 days of diagnosis (range, 8-127). EGFR, KRas, and Alk mutations were identified in 11, 5, and 3 patients, respectively (16.9%, 7.7%, and 4.6%). Sex and KPS did not impact survival in this cohort. Length of delay until institution of systemic therapy also did not impact survival. Age less than 60 was associated with a decreased risk of death in univariate analysis (HR 0.40, p Z 0.0026). Presence of a tyrosine kinase mutation was also associated with a reduced risk of death (p Z 0.0075), particularly among EGFR-mutated patients (HR 0.26, p Z 0.006). In multivariate analyses, both age less than 60 (HR 0.42, p Z 0.009) and presence of an EGFR mutation (HR 0.25, p Z 0.005) were associated with significant reductions in the risk of death. Conclusions: The prognosis of patients with brain metastases at the time of systemic cancer diagnosis can be quite varied. While it is intuitive to presume that a prolonged delay to the initiation of systemic therapy would negatively impact survival, this effect was not observed in this cohort. Patients with NSCLC driven by a tyrosine kinase mutation, particularly of EGFR, had improved survival compared to patients with wild type tumors.
Author Disclosure: C.E. Rutter: None. B.R. Mancini: None. J.B. Yu: None. V.L. Chiang: None. R.S. Bindra: None.
2181 Clinical Outcomes of Single Isocenter Frameless Radiosurgery for Multiple Brain Metastases S. Lau, X. Zhao, E. Knipprath, D.R. Simpson, C.C. Chen, and K.T. Murphy; University of California San Diego, La Jolla, CA Purpose/Objective(s): Radiosurgery is well accepted in the treatment of patients with intracranial metastases, but the role of frameless radiosurgery is unknown. Here, we describe our clinical experience with a novel single isocenter technique for frameless intensity modulated stereotactic radiosurgery (IMRS) to treat multiple intracranial metastases. Materials/Methods: After obtaining institutional review board approval, a review of radiation oncology records was performed. Between 2006 and 2012, 100 consecutive patients received optically guided frameless IMRS using a single centrally located isocenter for multiple intracranial metastases at a single center. Patients had a median of 4 intracranial metastases (range, 2-18). A total of 465 intracranial metastases were treated in a median of 1 fraction (range, 1-5) to a median dose of 20 Gy (range, 15-50 Gy). Clinical examination occurred every 2-4 months and included magnetic resonance imaging (MRI) to assess intracranial progression. Regional failure was defined as intracranial failure outside of the treatment volume. Local control, regional control, and overall survival were estimated by the Kaplan-Meier method. Toxicity was graded according to the Radiation Therapy Oncology Group scale. Results: Median follow-up for all patients was 4.3 months (range, 0.2-58.3 months), with 83 patients (83.0%) followed until their death. For the remaining 17 patients alive at the time of analysis, median follow-up was 9.2 months (range, 2.2-58.3 months). Actuarial 6- and 12-month overall survival was 49.5% (95% Confidence Interval [CI], 40.5-60.6%) and 34.1% (95% CI, 25.7-45.2%), respectively. Actuarial 6- and 12-month local control was 89% (95% CI, 83-95%) and 84% (95% CI, 77-91%), respectively. Regional failure was observed in 39 patients (39.0%). 25 patients (25.0%) received salvage therapy. Grade 3 or greater treatmentrelated toxicity was observed in 5 patients (5.0%) and included intracranial hemorrhage, seizure, and radionecrosis. Median total treatment time was 17.2 minutes (range, 2.8-55.3 minutes). Conclusions: Frameless, single isocenter IMRS for the simultaneous treatment of multiple intracranial metastases can produce clinical outcomes comparable to those of conventional frame-based radiosurgery techniques with the advantages of a noninvasive approach and shortened treatment time. Author Disclosure: S. Lau: None. X. Zhao: None. E. Knipprath: None. D.R. Simpson: None. C.C. Chen: None. K.T. Murphy: F. Honoraria; x.
2182 WITHDRAWN
2183 Local Control, Patterns of Failure, and Vertebral Compression Fracture After Spine Stereotactic Radiation Therapy for Metastatic Renal Cell Cancer I. Thibault,1 A. Al-Omair,1,2 G. Masucci,2 L. Masson-Cote´,2 F. Lochray,1 G. Bjarnason,3 A. Yee,3 R. Korol,1 L. Cheng,2 and A. Sahgal1,2; 1 Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, 2Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada, 3Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada