1
Outcomes of first three years of frame-less stereotactic radiosurgery in controlling brain metastases Amandeep Taggar, Joanna Mackenzie, Harold Lau, Gerald Lim, Robert Nordal, Rao Khan, Karen Breitman, Alana Hudson, David Spencer, Jon-Paul Voroney Background and Objective Brain metastasis is an important cause of morbidity and mortality in cancer patients (1). Corticosteroids can improve symptoms by decreasing peritumoral edema, but do not improve survival. Although, whole brain radiotherapy (WBRT) plus corticosteroids are standard of care for patients with multiple brain metastasis, the addition of WBRT has not been shown to improve survival (1-3). Patchell et.al. found that in patients with solitary metastatic lesions and good performance status, surgical resection along with WBRT improved local control rate and overall survival compared with WBRT alone (4). Over the last decade, surgery is reserved for symptomatic patients and stereotactic radiosurgery (SRS) has become standard for patients with less than four lesions. The precise targeting of SRS, however, demands a rigid, stereotactic head frame (5). This is not only invasive and uncomfortable, but also requires coordination of multiple disciplines to deliver treatment in reasonable time. With development of technology and evolution of linear accelerators that use image guidance for patient alignment and lesion localization, frame-less techniques provide an attractive alternative to the rigid head frame. Frame-less SRS has significant advantages for patient comfort, ability to use fractionated regimens, flexibility in scheduling treatments and improvement in workflow. Table 1: Patient, disease and treatment characteristics. We report radiotherapy outcomes for patients with brain metastasis treated with frame-less SRS at the Alberta Radiosurgery Centre, Tom Baker Cancer Centre, Alberta Health Services Results Median follow-up of all patients was 12.6 months from time of diagnosis of brain metastasis.. References (1) Patil et al. Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases. Cochrane Database Syst Rev 2012 Sep 12;9 (2) Langley et al. Interim data from the Medical Research Council QUARTZ Trial: does whole brain radiotherapy affect the survival and quality of life of patients with brain metastases from non-small cell lung cancer? Clin Oncol (R Coll Radiol) 2013 Mar;25(3):e23-30. (3) Tsao et al. Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases. Cochrane Database Syst Rev 2012 Apr 18;4:CD003869. (4) Patchell et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 1990 Feb 22;322(8):494-500. (5) LEKSELL L. The stereotaxic method and radiosurgery of the brain. Acta Chir Scand 1951 Dec 13;102(4):316-319. (6) Breneman et al. frame-less image-guided intracranial stereotactic radiosurgery: clinical outcomes for brain metastases. Int J Radiat Oncol Biol Phys 2009 Jul 1;74(3):702-706. (7) Chen et al. Control of brain metastases using frame-less image-guided radiosurgery. Neurosurg Focus 2009 Dec;27(6):E6. (8) Liepa et al. Initial experience with using frame-less image-guided radiosurgery for the treatment of brain metastases. Exp Oncol 2012 Jul;34(2):125-128. (9) Minniti et al. frame-less linac-based stereotactic radiosurgery (SRS) for brain metastases: analysis of patient repositioning using a mask fixation system and clinical outcomes. Radiat Oncol 2011 Nov 16;6:158-717X-6-158. (10) Pan et al. frame-less, real-time, surface imaging-guided radiosurgery: clinical outcomes for brain metastases. Neurosurgery 2012 Oct;71(4):844-851. (11) Kamath et al. Initial clinical experience with frame-less radiosurgery for patients with intracranial metastases. International Journal of Radiation Oncology*Biology*Physics 2005 4/1;61(5):1467-1472. (12) Nath et al. Optically-guided frame-less linac-based radiosurgery for brain metastases: clinical experience. J Neurooncol 2010 Mar;97(1):67-72. Materials and methods • Patients were accrued on a prospective protocol. Data on first 130 frame-less sessions was collected prospectively and retrospectively, and analyzed. Patients were selected after multidisciplinary review and were eligible with 1-4 brain metastases with the largest lesion measuring 3.5 cm or less. • Table 1. lists patient, disease and treatment factors. • GTV was outlined using the diagnostic MRI which was fused with the planning CT scan on the Brainlab TM system. A GTV to PTV margin was 1 mm. • Treatment was delivered using the frame-less technique similar to Minniti et al (9). Figure 1 illustrates the clamshell head mask and TaPoS box used for immobilization and localization. • Verification of setup was obtained with the ExacTrac TM image guidance system and treatment delivered with tolerance of 0.6 mm • Analysis used SPSS 22 statistical software. Kaplan-Meier curves were generated to obtain overall survival and medians were compared using log-rank chi-squared method Total number of patients 120 Total number of SRS sessions 130 Total number of lesions treated 237 Age, years Median Range 59.6 26.3 – 80.7 Gender Male Female No. of patients 52 68 KPS 100 90 80 70 <70 No. of patients 7 44 38 26 5 Lesions per patient Median Range 1 1-4 Histology Lung Breast Melanoma Renal cell GI GU Other No. of patients 53 21 20 10 7 5 4 Treatment SRS alone WBRT + SRS Chemo post SRS No. of patients 46 74 58 SRS Radiation dose, Gy Median Range WBRT dose, Gy Mean (fractions) Range 1800 1200 – 2400 28 (9) 20 – 37.5 (5 – 15) Local failure 24/234 (10.2%) Mean time to local failure (months) 6.6 (95% CI 5.5 – 7.7) Regional failure rate 45/120 (37.5%) Mean time to regional progression 4.6 (95% CI 3.4 – 5.7) Radiation Necrosis 10/237 (4.2%) Figure 2. Overall survival of all patients treated with frame-less SRS. Median survival 17.9 months (95% CI 14.2 – 21.6). Actuarial survival rates at 6, 12 and 24 months were 83 +/- 3%, 63 +/- 5% and 39 +/- 5% respectively. Figure 3. Overall survival of patients treated with WBRT plus SRS versus SRS alone. Median survival 19.2 (95% CI 13.2 – 25.2) versus 9.3 months (95% CI 5.7 – 13.0), p-value 0.012. Table 2. Local control, regional failure and radionecrosis rates in all patients treated with frame-less SRS for metastatic brain lesions Study No. of patients (lesions) Median survival, months 1year survival, % 6month local control, % Breneman et. al. (6) 53 (158) 44 90 Chen et. al. (7) 54 (108) 8.6 88 Liepa et. al. (8) 16 (28) 10 89 Minniti et. al. (9) 102 15.5 58 91 Pan et. al. (10) 44 (115) 7.7 90 Kamath et. al. (11) 64 8.7 88 Nath et. al. (12) 65 (204) 40 76 Present Study 120 (241) 17.9 63 90 Figure 1: Clamshell thermoplastic aquaplast mask and TaPoS box used for immobilization and localization during frame-less SRS. Table 3. Comparative results of published frame-less SRS series. Our series had similar local control but improved median and 1-year actuarial survival. Conclusion Our results validate that frame-less SRS is an effective way to treat intracranial lesions. Clinical outcomes are comparable to rigid frame-based stereotactic SRS. These results are from a select group of brain metastases patients with 1-4 lesions and good performance status. The low rate of radionecrosis seen in our patient population indicates that a small margin around the lesion to compensate for the frame-less technique is an acceptable compromise for the advantages it offers. Discussion
