philosophies among the various physicians staffing the radiation oncology department during the time of this study. The dose per fraction varied between 1.5 and 2.5 Gy (median 1.95 Gy). The three most common fractionation schemes were 40 Gy in 20 fractions, 45 Gy in 25 fractions, and 50 Gy in 25 fractions. The linear quadratic formula was used to calculate the 1.8-Gy per fraction normalized total dose equivalent (NTD 1.8 ) for treatment of late responding tissue, assuming an α/β ratio of 2.5. 5 Radiation was administered by linear accelerator (LINAC) in 75 patients, cobalt
Patrick Breen, John C. Flickinger, Douglas Kondziolka, and Augusto J. Martinez
John C. Flickinger, Douglas Kondziolka, Ajay Niranjan, and L. Dade Lunsford
results. Int J Radiat Oncol Biol Phys 36: 141–145, 1996 See the Letter to the Editor and the Response in this issue in Neurosurgical Forum, pp 141–142. This paper was presented in part at the 41st Annual Meeting of the American Society for Therapeutic Radiology and Oncology, November 1, 1999.
Ajay Niranjan, Hideyuki Kano, Aditya Iyer, Douglas Kondziolka, John C. Flickinger, and L. Dade Lunsford
, 14 , 23 , 24 , 27 , 29 , 32 , 34 , 39 others have found no added benefit. 4 , 9 , 16 , 37 , 38 A single prospective randomized trial by the Radiation Therapy Oncology Group (RTOG 93–05) 42 found no improvement in overall survival (OS) when various forms of linear accelerator–and Gamma Knife–based SRS were given prior to conventional fractionated RT. 15 That study was not designed to evaluate the potential role of SRS at the time of GBM progression in patients who had received standard of care initial management. The present retrospective report evaluates
Gillian Harrison, Hideyuki Kano, L. Dade Lunsford, John C. Flickinger, and Douglas Kondziolka
The reported tumor control rates for meningiomas after stereotactic radiosurgery (SRS) are high; however, early imaging assessment of tumor volumes may not accurately predict the eventual tumor response. The objective in this study was to quantitatively evaluate the volumetric responses of meningiomas after SRS and to determine whether early volume responses are predictive of longer-term tumor control.
The authors performed a retrospective review of 252 patients (median age 56 years, range 14–87 years) who underwent Gamma Knife radiosurgery between 2002 and 2010. All patients had evaluable pre- and postoperative T1-weighted contrast-enhanced MRIs. The median baseline tumor volume was 3.5 cm3 (range 0.2–33.8 cm3) and the median follow-up was 19.5 months (range 0.1–104.6 months). Follow-up tumor volumes were compared with baseline volumes. Tumor volume percent change and the tumor volume rate of change were compared at 3-month intervals. Eventual tumor responses were classified as progressed for > 15% volume change, regressed for ≤ 15% change, and stable for ± 15% of baseline volume at time of last follow-up. Volumetric data were compared with the final tumor status by using univariable and multivariable logistic regression.
Tumor volume regression (median decrease of −40.2%) was demonstrated in 168 (67%) patients, tumor stabilization (median change of −2.7%) in 67 (26%) patients, and delayed tumor progression (median increase of 104%) in 17 (7%) patients (p < 0.001). Tumors that eventually regressed had an average volume reduction of −18.2% at 3 months. Tumors that eventually progressed all demonstrated volume increase by 6 months. Transient progression was observed in 15 tumors before eventual decrease, and transient regression was noted in 6 tumors before eventual volume increase.
The volume response of meningiomas after SRS is dynamic, and early imaging estimations of the tumor volume may not correlate with the final tumor response. However, tumors that ultimately regressed tended to respond in the first 3 months, whereas tumors that ultimately progressed showed progression within 6 months.
Georgios Zenonos, Douglas Kondziolka, John C. Flickinger, Paul Gardner, and L. Dade Lunsford
Microsurgical management of foramen magnum meningiomas (FMMs) can be associated with significant morbidity and mortality. Stereotactic radiosurgery may be an efficient and safe alternative treatment modality for such tumors. The object of this study was to increase the documented experience with Gamma Knife surgery (GKS) for FMMs and to delineate its role in an overall management paradigm.
The authors report on their experience with 24 patients harboring FMMs managed with GKS. Twelve patients had primary symptomatic tumors, 5 had asymptomatic but enlarging primary tumors, and 7 had recurrent or residual tumors after a prior surgery.
Follow-up clinical and imaging data were available in 21 patients at a median follow-up of 47 months (range 3–128 months). Ten patients had measurable tumor regression, which was defined as an overall volume reduction > 25%. Eleven patients had no further tumor growth. Two patients died as a result of advanced comorbidities before follow-up imaging. One patient was living 8 years after GKS but had no clinical evaluation. Ten of 17 symptomatic patients with at least 6 months of follow-up had symptom improvement, and 7 remained clinically stable. Smaller tumors were more likely to regress. No patient suffered an adverse radiation effect after radiosurgery.
Gamma Knife surgery was a safe management strategy for small, minimally symptomatic, or growing FMMs as well as for residual tumors following conservative microsurgical removal.
Peter C. Gerszten, Josef Novotny Jr., Mubina Quader, Valerie C. Dewald, and John C. Flickinger
59 : 1288 – 1294 , 2004 6 Chang S , Hancock S , Gibbs IC , Adler JR Jr , Spinal cord arteriovenous malformation radiosurgery . Gerszten PC , Ryu S : Spine Radiosurgery New York , Thieme , 2009 . 123 – 127 7 Chang SD , Adler JR Jr : Current status and optimal use of radiosurgery . Oncology (Williston Park) 15 : 209 – 221 , 2001 8 Colombo F , Pozza F , Chierego G , Casentini L , De Luca G , Francescon P : Linear accelerator radiosurgery of cerebral arteriovenous malformations: an update . Neurosurgery
Nathan T. Zwagerman, Michael M. McDowell, Ronald L. Hamilton, Edward A. Monaco III, John C. Flickinger, and Peter C. Gerszten
Increased survival time after diagnosis of neoplastic disease has resulted in a gradual increase in spine tumor incidence. Radiosurgery is frequently a viable alternative to operative management in a population with severe medical comorbidities. The authors sought to assess the histopathological consequences of radiosurgery in the subset of patients progressing to operative intervention.
Eighteen patients who underwent radiosurgery for spine tumors between 2008 and 2014 subsequently progressed to surgical treatment. A histopathological examination of these cases was performed. Indications for surgery included symptomatic compression fractures, radiographic instability, and symptoms of cord or cauda equina compression. Biopsy samples were obtained from the tumor within the radiosurgical zone in all cases and were permanently fixated. Viable tumor samples were stained for Ki 67.
Fifteen patients had metastatic lesions and 3 patients had neurofibromas. The mean patient age was 57 years. The operative indication was symptomatic compression in 10 cases (67%). The most frequent metastatic lesions were breast cancer (4 cases), renal cell carcinoma (3), prostate cancer (2), and endometrial cancer (2). In 9 (60%) of the 15 metastatic cases, histological examination of the lesions showed minimal evidence of inflammation. Viable tumor at the margins of the radiosurgery was seen in 9 (60%) of the metastatic cases. Necrosis in the tumor bed was frequent, as was fibrotic bone marrow. Vascular ectasia was seen in 2 of 15 metastatic cases, but sclerosis with ectasia was frequent. No evidence of malignant conversion was seen in the periphery of the lesions in the 3 neurofibroma cases. In 1 case of neurofibroma, the lesion demonstrated some small areas of remnant tumor in the radiosurgical target zone.
This case series demonstrates important histopathological characteristics of spinal lesions treated by SRS. Regions with the highest exposure to radiation appear to be densely necrotic and show little evidence of tumor growth, whereas peripheral regions distant from the radiation dosage are more likely to demonstrate viable tumor in malignant and benign neoplasms. Physiological tissue appears to be similarly affected. With additional investigation, a more homogenized field of hypofractionated radiation exposure may allow for tumor obliteration with relative preservation of critical anatomical structures.
Neal Luther, Douglas Kondziolka, Hideyuki Kano, Seyed H. Mousavi, John C. Flickinger, and L. Dade Lunsford
The authors sought to better define the clinical response of patients who underwent stereotactic radiosurgery (SRS) for brain metastases located in the region of the motor cortex.
A retrospective analysis was performed in 2026 patients with brain metastasis who underwent SRS with the Gamma Knife between 2002 and 2012, and multiple factors that affect motor function before and after SRS were evaluated. Ninety-four patients with tumors ≥ 1.5 cm in diameter located in or adjacent to the motor strip were identified, including 2 patients with bilateral motor strip metastases.
Motor function improved after SRS in 30 (31%) of 96 cases, remained stable in 48 (50%), and worsened over time in 18 (19%) instances. Forty-seven patients had no motor weakness prior to radiosurgery; 10 (22%) developed new Grade 3/5–4/5 weakness. Thirty (68%) of 44 patients with ≥ 3/5 pre-SRS weakness improved, 6 (14%) remained stable, and 8 (18%) worsened. Three of 5 patients with < 3/5 pre-SRS motor function improved. Motor deficits prior to SRS did not correlate with a worse outcome; however, worse outcomes were associated with larger tumor volumes. The median tumor volume in patients whose function improved or remained stable was 5.3 cm3, but it was 9.2 cm3 in patients who worsened (p < 0.05). Tumor volumes > 9 cm3 were associated with a higher risk of worsening motor function. Adverse radiation effects occurred in 5 patients.
Most intact patients with brain metastases in or adjacent to motor cortex maintained neurological function after SRS, and most patients with symptomatic motor weakness remained stable or improved. Larger tumor volumes were associated with less satisfactory outcomes.
Ronny Kalash, Scott M. Glaser, John C. Flickinger, Steven Burton, Dwight E. Heron, Peter C. Gerszten, Johnathan A. Engh, Nduka M. Amankulor, and John A. Vargo
. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Vargo. Statistical analysis: Vargo, Kalash, Glaser, Flickinger. Study supervision: Vargo. Supplemental Information Previous Presentations These data were presented at the Annual Meeting of the Radiosurgery Society, Las Vegas, NV, November 3, 2017. Current Affiliations Dr. Glaser: Department of Radiation Oncology, City of Hope Hospital, Duarte, CA. Dr. Vargo: Department of Radiation Oncology, West
Hideyuki Kano, Alejandro Morales-Restrepo, Aditya Iyer, Gregory M. Weiner, Seyed H. Mousavi, John M. Kirkwood, Ahmad A. Tarhini, John C. Flickinger, and L. Dade Lunsford
melanoma . Melanoma Res 16 : 51 – 57 , 2006 10.1097/01.cmr.0000198451.26827.b2 16432456 4 Doss LL , Memula N : The radioresponsiveness of melanoma . Int J Radiat Oncol Biol Phys 8 : 1131 – 1134 , 1982 7118615 10.1016/0360-3016(82)90060-8 5 Gaspar L , Scott C , Rotman M , Asbell S , Phillips T , Wasserman T , : Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials . Int J Radiat Oncol Biol Phys 37 : 745 – 751 , 1997 10.1016/S0360-3016(96)00619-0 9128946 6