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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

OBJECTIVE

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.

Free access

Eric Lis, Atin Saha, Kyung K. Peck, Joan Zatcky, Michael J. Zelefsky, Yoshiya Yamada, Andrei I. Holodny, Mark H. Bilsky, and Sasan Karimi

OBJECTIVE

High-dose image-guided radiation therapy (HD IGRT) has been instrumental in mitigating some limitations of conventional RT. The recent emergence of dynamic contrast-enhanced (DCE) MRI to investigate tumor physiology can be used to verify the response of human tumors to HD IGRT. The purpose of this study was to evaluate the near-immediate effects of HD IGRT on spine metastases through the use of DCE MRI perfusion studies.

METHODS

Six patients with spine metastases from prostate, thyroid, and renal cell carcinoma who underwent HD IGRT were studied using DCE MRI prior to and 1 hour after HD IGRT. The DCE perfusion parameters plasma volume (Vp) and vascular permeability (Ktrans) were measured to assess the near-immediate and long-term tumor response. A Mann-Whitney U-test was performed to compare significant changes (at p ≤ 0.05) in perfusion parameters before and after RT.

RESULTS

The authors observed a precipitous drop in Vp within 1 hour of HD IGRT, with a mean decrease of 65.2%. A significant difference was found between Vp values for before and 1 hour after RT (p ≤ 0.05). No significant change was seen in Vp (p = 0.31) and Ktrans (p = 0.1) from 1 hour after RT to the first follow-up.

CONCLUSIONS

The data suggest that there is an immediate effect of HD IGRT on the vascularity of spine metastases, as demonstrated by a precipitous decrease in Vp. The DCE MRI studies can detect such changes within 1 hour after RT, and findings are concordant with existing animal models.