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Evangelia Katsoulakis, Ilya Laufer, Mark Bilsky, Narasimhan P. Agaram, Michael Lovelock, and Yoshiya Yamada


Spine radiosurgery is increasingly being used to treat spinal metastases. As patients are living longer because of the increasing efficacy of systemic agents, appropriate follow-up and posttreatment management for these patients is critical. Tumor progression after spine radiosurgery is rare; however, vertebral compression fractures are recognized as a more common posttreatment effect. The use of radiographic imaging alone posttreatment may makeit difficult to distinguish tumor progression from postradiation changes such as fibrosis. This is the largest series from a prospective database in which the authors examine histopathology of samples obtained from patients who underwent surgical intervention for presumed tumor progression or mechanical pain secondary to compression fracture. The majority of patients had tumor ablation and resulting fibrosis rather than tumor progression. The aim of this study was to evaluate tumor histopathology and characteristics of patients who underwent pathological sampling because of radiographic tumor progression, fibrosis, or collapsed vertebrae after receiving high-dose single-fraction stereotactic radiosurgery.


Between January 2005 and January 2014, a total of 582 patients were treated with linear accelerator–based single-fraction (18–24 Gy) stereotactic radiosurgery. The authors retrospectively identified 30 patients (5.1%) who underwent surgical intervention for 32 lesions with vertebral cement augmentation for either mechanical pain or instability secondary to vertebral compression fracture (n = 17) or instrumentation (n = 15) for radiographic tumor progression. Radiation and surgical treatment, histopathology, and long-term outcomes were reviewed. Survival and time to recurrence were calculated using the Kaplan-Meier method.


The mean age at the time of radiosurgery was 59 years (range 36–80 years). The initial pathological diagnoses were obtained for all patients and primarily included radioresistant tumor types, including renal cell carcinoma in 7 (22%), melanoma in 6 (19%), lung carcinoma in 4 (12%), and sarcoma in 3 (9%). The median time to surgical intervention was 24.7 months (range 1.6–50.8 months). The median follow-up and overall survival for all patients were 42.5 months and 41 months (overall survival range 7–86 months), respectively. The majority of assessed lesions showed no evidence of tumor on pathological review (25 of 32, 78%), while a minority of lesions revealed residual tumor (7 of 32, 22%). The median survival for patients after tumor recurrence was 5 months (range 2–70 months).


High-dose single-fraction radiosurgery is tumor ablative in the majority of instances. In a minority of cases, tumor persists and salvage treatments should be considered.

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Evangelia Katsoulakis, Nadeem Riaz, Brett Cox, James Mechalakos, Joan Zatcky, Mark Bilsky, and Yoshiya Yamada


The objective of this study was to investigate the feasibility and safety of delivering a third course of radiation to patients with multiply recurrent metastatic disease to the spine.


Between 2009 and 2011, 10 patients received a third course of radiation to spinal metastases at Memorial Sloan–Kettering Cancer Center using image-guided intensity-modulated radiation therapy (IMRT). Patient and tumor characteristics, dosimetry details, and outcomes were obtained using retrospective chart review. Spinal imaging was performed prior to treatment and at regular follow-up intervals. The cumulative biologically effective dose (BED) to the spinal cord and cauda equina was calculated and was normalized to 2 Gy equivalents (Gy2/2). Toxicity and local control were assessed.


The median time between the first and second courses of radiation was 18.5 months and the median time between the second and third courses was 11.5 months. The median follow-up from the third course of radiation was 12 months and the median overall survival was 13 months. Pain or neurological symptoms were improved in 80% of patients. The median spinal cord maximum dose normalized BED (nBED) for the whole cohort was 70.73 Gy2/2 (range 51.9–101.7 Gy2/2). The median dose to 5% of the spinal cord D05 nBED for the entire cohort was 59.4 Gy2/2. Acute toxicity was most commonly fatigue and dermatitis, with 1 patient experiencing Grade 3 fatigue and 1 patient Grade 3 dermatitis. Late toxicity was limited to 2 cases of Grade 1 dysphagia. There was 1 case of Grade 1 neuropathy and 1 case of Grade 2 neuropathy. The crude rate of local control was 80% with 1 in-field failure and 1 marginal failure.


In this cohort of patients, a third course of IMRT to the spine was well tolerated with no significant late toxicities. Used as salvage therapy for select patients, a third course of radiation is a safe and effective treatment strategy.

Free access

Yoshiya Yamada, Evangelia Katsoulakis, Ilya Laufer, Michael Lovelock, Ori Barzilai, Lily A. McLaughlin, Zhigang Zhang, Adam M. Schmitt, Daniel S. Higginson, Eric Lis, Michael J. Zelefsky, James Mechalakos, and Mark H. Bilsky


An analysis of factors contributing to durable radiographic control of spinal metastases was undertaken, drawing from a large single-institution database in an attempt to elucidate indications and dose requirements for successful treatment.


All patients treated at a single institution with stereotactic radiosurgery (SRS) of the spine as first-line therapy were assessed for local progression of the treated site, defined as radiographic enlargement of the treated tumor and/or biopsy-proven evidence of active tumor cells. All patients were followed with CT, PET, or MR imaging every 3–6 months until death. Treatment decisions were made by a multidisciplinary team of radiation oncologists, neurosurgeons, and neuroradiologists. Target volumes were defined according to the international consensus guidelines and were reviewed in a multidisciplinary conference. Image-guided techniques and intensity modulation were used for every case. The tumor's histological type, gross tumor volume (GTV), dose that covers 95% of the GTV (GTV D95), percentage of GTV covered by 95% of the prescribed dose (GTV V95), planning target volume (PTV), dose that covers 95% of the PTV (PTV D95), and percentage of PTV covered by 95% of the prescribed dose (PTV V95) were analyzed for significance in relation to local control, based on time to local progression.


A total of 811 lesions were treated in 657 patients between 2003 and 2015 at a single institution. The mean follow-up and overall survival for the entire cohort was 26.9 months (range 2–141 months). A total of 28 lesions progressed and the mean time to failure was 26 months (range 9.7–57 months). The median prescribed dose was 2400 cGy (range 1600–2600 cGy). Both GTV D95 and PTV D95 were highly significantly associated with local failure in univariate analysis, but GTV and PTV and histological type did not reach statistical significance. The median GTV D95 for the cohort equal to or above the GTV D95 1830 cGy cut point (high dose) was 2356 cGy, and it was 1709 cGy for the cohort of patients who received less than 1830 cGy (low dose). In terms of PTV D95, the median dose for those equal to or above the cut point of 1740 cGy (high dose) was 2233 cGy, versus 1644 cGy for those lesions below the PTV D95 cut point of 1740 cGy (low dose).


High-dose single-session SRS provides durable long-term control, regardless of the histological findings or tumor size. In this analysis, the only significant factors predictive of local control were related to the actual dose of radiation given. Although the target volumes were well treated with the intended dose, those lesions irradiated to higher doses (median GTV D95 2356 cGy, minimum 1830 cGy) had a significantly higher probability of durable local control than those treated with lower doses (median PTV D95 2232 cGy, minimum of 1740 cGy) (p < 0.001). Patients in the high-dose cohort had a 2% cumulative rate of local failure. Histological findings were not associated with local failure, suggesting that radioresistant histological types benefit in particular from radiosurgery. For patients with a favorable prognosis, a higher dose of SRS is important for long-term outcomes.