Biologically effective dose correlates with linear tumor volume changes after upfront single-fraction stereotactic radiosurgery for vestibular schwannomas

AbstractVestibular schwannomas (VSs) are benign, slow-growing tumors. Management options include observation, surgery, and radiation. In this retrospective trial, we aimed at evaluating whether biologically effective dose (BED) plays a role in tumor volume changes after single-fraction first intention stereotactic radiosurgery (SRS) for VS. We compiled a single-institution experience (n = 159, Lausanne University Hospital, Switzerland). The indication for SRS was decided after multidisciplinary discussion. Only cases with minimum 3 years follow-up were included. The Koos grading, a reliable method for tumor classification was used. Radiosurgery was performed using Gamma Knife (GK) and a uniform marginal prescription dose of 12 Gy. Mean BED was 66.3 Gy (standard deviation 3.8, range 54.1–73.9). The mean follow-up period was 5.1 years (standard deviation 1.7, range 3–9.2). The primary outcome was changes in 3D volumes after SRS as function of BED and of integral dose received by the VS. Random-effect linear regression model showed that tumor volume significantly and linearly decreased over time with higher BED (p < 0.0001). Changes in tumor volume were also significantly associated with age, sex, number of isocenters, gradient index, and Koos grade. However, the effect of BED on tumor volume change was moderated by time after SRS and Koos grade. Lower integral doses received by the VSs were inversely correlated with BED in relationship with tumor volume changes (p < 0.0001). Six (3.4%) patients needed further intervention. For patients having uniformly received the same marginal dose prescription, higher BED linearly and significantly correlated with tumor volume changes after SRS for VSs. BED could represent a potential new treatment paradigm for patients with benign tumors, such as VSs, for attaining a desired radiobiological effect. This could further increase the efficacy and decrease the toxicity of SRS not only in benign tumors but also in other SRS indications.

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CyberKnife frameless single-fraction stereotactic radiosurgery for benign tumors of the spine

Neurosurgical FOCUS ◽

10.3171/foc.2003.14.5.17 ◽

2003 ◽

Vol 14 (5) ◽

pp. 1-5 ◽

Cited By ~ 59

Author(s):

Peter C. Gerszten ◽

Cihat Ozhasoglu ◽

Steven A. Burton ◽

William J. Vogel ◽

Barbara A. Atkins ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Tumor Volume ◽

Surgical Techniques ◽

Outpatient Setting ◽

Neurological Deficits ◽

Benign Tumors ◽

Minimal Risk ◽

Single Fraction ◽

Spinal Lesions

Object The role of stereotactic radiosurgery in the treatment of benign intracranial lesions is well established. Its role in the treatment of benign spinal lesions is more limited. Benign spinal lesions should be amenable to radiosurgical treatment similar to their intracranial counterparts. In this study the authors evaluated the effectiveness of the CyberKnife for benign spinal lesions involving a single-fraction radiosurgical technique. Methods The CyberKnife is a frameless radiosurgery system in which an orthogonal pair of x-ray cameras is coupled to a dynamically manipulated robot-mounted linear accelerator possessing six degrees of freedom, whereby the therapy beam is guided to the intended target without the use of frame-based fixation. Cervical spine lesions were located and tracked relative to skull osseous landmarks; lower spinal lesions were tracked relative to percutaneously placed fiducial bone markers. Fifteen patients underwent single-fraction radiosurgery (12 cervical, one thoracic, and two lumbar). Histological types included neurofibroma (five cases), paraganglioma (three cases), schwannoma (two cases), meningioma (two cases), spinal chordoma (two cases), and hemangioma (one case). Radiation dose plans were calculated based on computerized tomography scans acquired using 1.25-mm slices. Planning treatment volume was defined as the radiographic tumor volume with no margin. The tumor dose was maintained at 12 to 20 Gy to the 80% isodose line (mean 16 Gy). Tumor volume ranged from 0.3 to 29.3 ml (mean 6.4 ml). Spinal canal volume receiving more than 8 Gy ranged from 0.0 to 0.9 ml (mean 0.2 ml). All patients tolerated the procedure in an outpatient setting. No acute radiation-induced toxicity or new neurological deficits occurred during the follow-up period. Pain improved in all patients who were symptomatic prior to treatment. No tumor progression has been documented on follow-up imaging (mean 12 months). Conclusions Spinal stereotactic radiosurgery was found to be feasible, safe, and effective for the treatment of benign spinal lesions. Its major potential benefits are the relatively short treatment time in an outpatient setting and the minimal risk of side effects. This new technique offers an alternative therapeutic modality for the treatment of a variety of benign spinal neoplasms in cases in which surgery cannot be performed, in cases with previously irradiated sites, and in cases involving lesions not amenable to open surgical techniques or as an adjunct to surgery.

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Stereotactic radiosurgery for vestibular schwannomas: average 10-year follow-up results focusing on long-term hearing preservation

Journal of Neurosurgery ◽

10.3171/2016.7.gks161494 ◽

2016 ◽

Vol 125 (Supplement_1) ◽

pp. 64-72 ◽

Cited By ~ 34

Author(s):

Shinya Watanabe ◽

Masaaki Yamamoto ◽

Takuya Kawabe ◽

Takao Koiso ◽

Tetsuya Yamamoto ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Tumor Volume ◽

Hearing Preservation ◽

Interquartile Range ◽

Vestibular Schwannomas ◽

Long Term Results ◽

Tumor Control ◽

Univariable Analysis

OBJECTIVEThe aim of this study was to reappraise long-term treatment outcomes of stereotactic radiosurgery (SRS) for vestibular schwannomas (VSs). The authors used a database that included patients who underwent SRS with a unique dose-planning technique, i.e., partial tumor coverage designed to avoid excess irradiation of the facial and cochlear nerves, focusing on tumor control and hearing preservation. Clinical factors associated with post-SRS tumor control and long-term hearing preservation were also analyzed.METHODSThis institutional review board–approved, retrospective cohort study used the authors' prospectively accumulated database. Among 207 patients who underwent Gamma Knife SRS for VSs between 1990 and 2005, 183 (who were followed up for at least 36 post-SRS months) were studied. The median tumor volume was 2.0 cm3 (range 0.05–26.2 cm3). The median prescribed dose at the tumor periphery was 12.0 Gy (range 8.8–15.0 Gy; 12.0 Gy was used in 171 patients [93%]), whereas tumor portions facing the facial and cochlear nerves were irradiated with 10.0 Gy. As a result, 72%–99% of each tumor was irradiated with the prescribed dose. The mean cochlear doses ranged from 2.3 to 5.7 Gy (median 4.1 Gy).RESULTSThe median durations of imaging and audiometric follow-up were 114 months (interquartile range 73–144 months) and 59 months (interquartile range 33–109 months), respectively. Tumor shrinkage was documented in 110 (61%), no change in 48 (27%), and enlargement in the other 22 (12%) patients. A further procedure (FP) was required in 15 (8%) patients. Thus, the tumor growth control rate was 88% and the clinical control rate (i.e., no need for an FP) was 92%. The cumulative FP-free rates were 96%, 93%, and 87% at the 60th, 120th, and 180th post-SRS month, respectively. Six (3%) patients experienced facial pain, and 2 developed transient facial palsy. Serviceable hearing was defined as a pure tone audiogram result better than 50 dB. Among the 66 patients with serviceable hearing before SRS who were followed up, hearing acuity was preserved in 23 (35%). Actuarial serviceable hearing preservation rates were 49%, 24%, and 12% at the 60th, 120th, and 180th post-SRS month, respectively. On univariable analysis, only cystic-type tumor (HR 3.36, 95% CI 1.18–9.36; p = 0.02) was shown to have a significantly unfavorable association with FP. Multivariable analysis followed by univariable analysis revealed that higher age (≥ 65 years: HR 2.66, 95% CI 1.16–5.92; p = 0.02), larger tumor volume (≥ 8 cm3: HR 5.36, 95% CI 1.20–17.4; p = 0.03), and higher cochlear dose (mean cochlear dose > 4.2 Gy: HR 2.22, 95% CI 1.07–4.77; p = 0.03) were unfavorable factors for hearing preservation.CONCLUSIONSStereotactic radiosurgery achieved good long-term results in this series. Tumor control was acceptable, and there were few serious complications in patients with small- to medium-sized VSs. Unfortunately, hearing preservation was not satisfactory. However, the longer the observation period, the more important it becomes to compare post-SRS hearing decreases with the natural decline in untreated cases.

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RADI-40. STEREOTACTIC RADIOSURGERY FOR BRAINSTEM METASTASES: AN ANALYSIS OF SINGLE FRACTION AND MULTI FRACTION TECHNIQUES

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz014.131 ◽

2019 ◽

Vol 1 (Supplement_1) ◽

pp. i29-i29

Author(s):

Elana Nack ◽

Varun Iyengar ◽

Esther Yu ◽

Thomas DiPetrillo ◽

Timothy Kinsella ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Tumor Volume ◽

Small Sample Size ◽

Small Sample ◽

Single Institution ◽

Single Fraction ◽

Whole Brain Radiation ◽

Kaplan Meier ◽

Brain Radiation

Abstract PURPOSE: Utilization of stereotactic radiosurgery (SRS) for brainstem metastases (BSM) is increasing. Multi-fraction SRS (MF-SRS) is a potential means of obtaining therapeutic gain while limiting toxicity. However, most available data assesses only single-fraction SRS (SF-SRS). This study aims to evaluate the efficacy and safety of SF-SRS and MF-SRS for BSM. METHODS: Data was retrospectively collected for patients with BSM treated with SRS between 2003–2018 at a single institution. Kaplan-Meier method was used to evaluate overall survival (OS) and local control (LC). Independent t-test was used for correlations between groups. RESULTS: 29 patients (31 lesions) were identified; 13 patients (15 lesions) underwent SF-SRS and 16 patients (16 lesions) underwent MF-SRS. Median follow-up was 6.8 months (1–80.8 months). Post-SRS MRI was available for 78% of patients. Median dose was 16Gy (12–18 Gy) for SF-SRS and 24 Gy (18–30 Gy) for MF-SRS. MF-SRS was delivered in a median of 3 fractions (3–5). There was a trend toward larger mean tumor volume with MF-SRS (1.297 vs 0.302mL, p=0.055). OS was 64.8% at 6 months and 49.3% at 12 months. LC was 90.9% at 6 months and 69.9% at 12 months. LC was similar between SF-SRS and MF-SRS at 6 months (100% vs 79.5%, p=0.143) and 12 months (50.0% vs 79.5%, p=0.812). Among the 4 patients who experienced local recurrence, 3 received salvage whole brain radiation and median OS was 8.1 months after LF. Distant CNS failures occurred in 40.3% of patients at 6 months and 72.4% at 12 months. Tumor volume >0.5 mL was associated with worse LC at 6 months (64.3% vs 100%, p=0.022). One patient developed symptomatic radiation necrosis (1/29 lesions, 3.4%) after MF-SRS. CONCLUSION: SRS is a safe and effective treatment for small BSM. Outcomes were not different between SF-SRS and MF-SRS but analysis is limited by small sample size.

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Tumor shrinkage of vestibular schwannomas after Gamma Knife surgery: results after more than 5 years of follow-up

Journal of Neurosurgery ◽

10.3171/2010.8.gks10960 ◽

2010 ◽

Vol 113 (Special_Supplement) ◽

pp. 122-127 ◽

Cited By ~ 19

Author(s):

Osamu Nagano ◽

Toru Serizawa ◽

Yoshinori Higuchi ◽

Shinji Matsuda ◽

Makoto R.T. Sato ◽

...

Keyword(s):

Gamma Knife ◽

Volume Expansion ◽

Tumor Volume ◽

Gamma Knife Surgery ◽

Vestibular Schwannomas ◽

Mr Images ◽

Volume Changes ◽

Cardiovascular Center ◽

The Mean

Object The authors prospectively analyzed volume changes in vestibular schwannomas (VSs) after Gamma Knife surgery (GKS). Methods Among 104 VSs treated by GKS at the Chiba Cardiovascular Center between 1998 and 2004, 87 consecutively treated unilateral VSs observed on follow-up MR imaging for at least 5 years were analyzed. These lesions were harbored by 31 men and 56 women, with a mean age of 58.6 years (range 29–80 years). The Gd-enhanced volume of each lesion was measured serially every 3 months during the 1st year and every 6 months thereafter using GammaPlan or SurgiPlan. The frequency and degree of volume shrinkage were documented and possible prognostic factors were analyzed. Results The mean tumor volume at GKS was 2.5 cm3 (range 0.1–13.2 cm3). The lesions were irradiated by directing a mean dose of 12.0 Gy (range 10.5–13.0 Gy) to the tumor margin, which was located at the mean 52.2% isodose line (range 50%–67% isodose line). The mean follow-up period was 7.5 years (range 5.0–11.1 years). Peak tumor volume expansion was most frequently observed at 8.6 months after GKS and averaged 58% (range 0%–613%). Five years after GKS, the mean reduction in tumor volume was 31%, and 9 tumors still remained larger than their initial volumes. Tumors that homogeneously enhanced on MR images displayed less shrinkage than other tumors. Conclusions Most VSs exhibit shrinkage 5 years after GKS. The mean volume reduction in this series was 31%. These results indicate that careful serial follow-up is necessary for patients who harbor tumors that display homogeneous enhancement on MR images and patients whose tumors continue to expand in size after GKS.

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STEREOTACTIC RADIOSURGERY FOR VESTIBULAR SCHWANNOMAS IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 2

Neurosurgery ◽

10.1227/01.neu.0000255340.26027.53 ◽

2007 ◽

Vol 60 (3) ◽

pp. 460-470 ◽

Cited By ~ 102

Author(s):

David Mathieu ◽

Douglas Kondziolka ◽

John C. Flickinger ◽

Ajay Niranjan ◽

Richard Williamson ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Tumor Volume ◽

Gamma Knife Radiosurgery ◽

Neurofibromatosis Type ◽

Hearing Preservation ◽

Neurofibromatosis Type 2 ◽

Vestibular Schwannomas ◽

Factors Affecting

Abstract OBJECTIVE Vestibular schwannomas present significant management challenges in patients with neurofibromatosis Type 2 (NF2). We evaluated the results of gamma knife radiosurgery for the management of these tumors, focusing on tumor response, hearing preservation, and other factors affecting outcomes. METHODS Stereotactic radiosurgery was performed to manage 74 schwannomas in 62 patients. Ipsilateral serviceable hearing was present in 35% of tumors before the procedure. The mean tumor volume was 5.7 cm3. The mean margin and maximum dose used were 14 and 27.5 Gy, respectively. Cox regression analyses were performed to identify factors affecting outcomes. RESULTS The median follow-up period was 53 months, and two patients were lost to follow-up. Actuarial local control rates at were 85, 81, and 81% at 5, 10, and 15 years, respectively. Tumor volume was significant as a predictor of local control. Since 1992, using current radiosurgery techniques (magnetic resonance imaging scan targeting and reduced margin dose to 14 Gy or less), the actuarial serviceable hearing preservation rate is 73% at 1 year, 59% at 2 years, and 48% at 5 years after radiosurgery. Facial neuropathy occurred in 8% of tumors, trigeminal neuropathy occurred in 4%, and vestibular dysfunction occurred in 4%. Radiation dose and tumor volume were predictive of development of new deficits. No radiosurgery-associated secondary tumors or atypical or malignant changes were noted. CONCLUSION Stereotactic radiosurgery is a safe and effective management modality for neurofibromatosis Type 2 vestibular schwannomas. Although results do not seem to be as good as for patients with sporadic unilateral tumors, gamma knife radiosurgery results seem favorable and indicate that radiosurgery should be strongly considered for primary tumor management in selected patients.

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CyberKnife frameless single-fraction stereotactic radiosurgery for tumors of the sacrum

Neurosurgical FOCUS ◽

10.3171/foc.2003.15.2.7 ◽

2003 ◽

Vol 15 (2) ◽

pp. 1-5 ◽

Cited By ~ 40

Author(s):

Peter C. Gerszten ◽

Cihat Ozhasoglu ◽

Steven A. Burton ◽

William C. Welch ◽

William J. Vogel ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Tumor Volume ◽

Cauda Equina ◽

Surgical Techniques ◽

Outpatient Setting ◽

Neurological Deficits ◽

Therapeutic Modality ◽

Radiation Toxicity ◽

Single Fraction

Object The role of stereotactic radiosurgery for the treatment of intracranial lesions is well established. The experience with radiosurgery for the treatment of spinal and sacral lesions is more limited. Sacral lesions should be amenable to radiosurgical treatment similar to that used for their intracranial counterparts. The authors evaluated a single-fraction radiosurgical technique performed using the CyberKnife Real-Time Image-Guided Radiosurgery System for the treatment of the sacral lesion. Methods The CyberKnife is a frameless radiosurgery system based on the coupling of an orthogonal pair of x-ray cameras to a dynamically manipulated robot-mounted linear accelerator possessing six degrees of freedom, which guides the therapy beam to the intended target without the need for frame-based fixation. All sacral lesions were located and tracked for radiation delivery relative to fiducial bone markers placed percutaneously. Eighteen patients were treated with single-fraction radiosurgery. Tumor histology included one benign and 17 malignant tumors. Dose plans were calculated based on computerized tomography scans acquired using 1.25-mm slices. Planning treatment volume was defined as the radiographically documented tumor volume with no margin. Tumor dose was maintained at 12 to 20 Gy to the 80% isodose line (mean 15 Gy). Tumor volume ranged from 23.6 to 187.4 ml (mean 90 ml). The volume of the cauda equina receiving greater than 8 Gy ranged from 0 to 1 ml (mean 0.1 ml). All patients underwent the procedure in an outpatient setting. No acute radiation toxicity or new neurological deficits occurred during the mean follow-up period of 6 months. Pain improved in all 13 patients who were symptomatic prior to treatment. No tumor progression has been documented on follow-up imaging. Conclusions Stereotactic radiosurgery was found to be feasible, safe, and effective for the treatment of both benign and malignant sacral lesions. The major potential benefits of radiosurgical ablation of sacral lesions are relatively short treatment time in an outpatient setting and minimal or no side effects. This new technique offers a new and important therapeutic modality for the primary treatment of a variety of sacral tumors or for lesions not amenable to open surgical techniques.

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Long-Term Outcome Following Stereotactic Radiosurgery for Glomus Jugulare Tumors: A Single Institution Experience of 20 Years

Neurosurgery ◽

10.1093/neuros/nyx566 ◽

2017 ◽

Vol 83 (5) ◽

pp. 1007-1014 ◽

Cited By ~ 7

Author(s):

Mayur Sharma ◽

Antonio Meola ◽

Sushma Bellamkonda ◽

Xuefei Jia ◽

Joshua Montgomery ◽

...

Keyword(s):

Hearing Loss ◽

Stereotactic Radiosurgery ◽

Tumor Volume ◽

Benign Tumors ◽

Tumor Diameter ◽

Long Term Outcome ◽

Lower Cranial Nerve ◽

Glomus Jugulare

Abstract BACKGROUND Glomus jugulare tumors (GJTs) are rare benign tumors, which pose significant treatment challenges due to proximity to critical structures. OBJECTIVE To evaluate the long-term clinical and radiological outcome in patients undergoing stereotactic radiosurgery (SRS) for GJTs through retrospective study. METHODS Forty-two patients with 43 GJTs were treated using Gamma Knife radiosurgery (GKRS; Elekta AB, Stockholm, Sweden) at our institute from 1997 to 2016. Clinical, imaging, and radiosurgery data were collected from an institutional review board approved database. RESULTS Most patients were females (n = 35, 83.3%) and median age was 61 yr (range 23-88 yr). Median tumor volume and diameter were 5 cc and 3 cm, respectively, with a median follow-up of 62.3 mo (3.4-218.6 mo). Overall, 20 patients (47.6%) improved clinically and 14 (33.3%) remained unchanged at last follow-up. New onset or worsening of hearing loss was noted in 6 patients (17.2%) after SRS. The median prescription dose to the tumor margin was 15 Gy (12-18 Gy). Median reduction in tumor volume and maximum tumor diameter at last follow-up was 33.3% and 11.54%, respectively. The 5-yr and 10-yr tumor control rates were 87% ± 6% and 69% ± 13%, respectively. There was no correlation between maximum or mean dose to the internal acoustic canal and post-GK hearing loss (P > .05). CONCLUSION SRS is safe and effective in patients with GJTs and results in durable, long-term control. SRS has lower morbidity than that associated with surgical resection, particularly lower cranial nerve dysfunction, and can be a first-line management option in these patients.

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Stereotactic radiosurgery as the primary management for patients with Koos grade IV vestibular schwannomas

Journal of Neurosurgery ◽

10.3171/2020.8.jns201832 ◽

2021 ◽

pp. 1-9

Author(s):

Akiyoshi Ogino ◽

L. Dade Lunsford ◽

Hao Long ◽

Stephen Johnson ◽

Andrew Faramand ◽

...

Keyword(s):

Stereotactic Radiosurgery ◽

Tumor Volume ◽

Hearing Preservation ◽

Vestibular Schwannomas ◽

Tumor Control ◽

Tumor Diameter ◽

Single Session ◽

Lower Margin ◽

Long Term Outcome

OBJECTIVEWhile extensive long-term outcome studies support the role of stereotactic radiosurgery (SRS) for smaller-volume vestibular schwannomas (VSs), its role in the management for larger-volume tumors remains controversial.METHODSBetween 1987 and 2017, the authors performed single-session SRS on 170 patients with previously untreated Koos grade IV VSs (volumes ranged from 5 to 20 cm3). The median tumor volume was 7.4 cm3. The median maximum extracanalicular tumor diameter was 27.5 mm. All tumors compressed the middle cerebellar peduncle and distorted the fourth ventricle. Ninety-three patients were male, 77 were female, and the median age was 61 years. Sixty-two patients had serviceable hearing (Gardner-Robertson [GR] grades I and II). The median margin dose was 12.5 Gy.RESULTSAt a median follow-up of 5.1 years, the progression-free survival rates of VSs treated with a margin dose ≥ 12.0 Gy were 98.4% at 3 years, 95.3% at 5 years, and 90.7% at 10 years. In contrast, the tumor control rate after delivery of a margin dose < 12.0 Gy was 76.9% at 3, 5, and 10 years. The hearing preservation rates in patients with serviceable hearing at the time of SRS were 58.1% at 3 years, 50.3% at 5 years, and 35.9% at 7 years. Younger age (< 60 years, p = 0.036) and initial GR grade I (p = 0.006) were associated with improved serviceable hearing preservation rate. Seven patients (4%) developed facial neuropathy during the follow-up interval. A smaller tumor volume (< 10 cm3, p = 0.002) and a lower margin dose (≤ 13.0 Gy, p < 0.001) were associated with preservation of facial nerve function. The probability of delayed facial neuropathy when the margin dose was ≤ 13.0 Gy was 1.1% at 10 years. Nine patients (5%) required a ventriculoperitoneal shunt because of delayed symptomatic hydrocephalus. Fifteen patients (9%) developed detectable trigeminal neuropathy. Delayed resection was performed in 4% of patients.CONCLUSIONSEven for larger-volume VSs, single-session SRS prevented the need for delayed resection in almost 90% at 10 years. For patients with minimal symptoms of tumor mass effect, SRS should be considered an effective alternative to surgery in most patients, especially those with advanced age or medical comorbidities.

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The Impact of Insulin-Like Growth Factor Index and Biologically Effective Dose on Outcomes After Stereotactic Radiosurgery for Acromegaly: Cohort Study

Neurosurgery ◽

10.1093/neuros/nyaa054 ◽

2020 ◽

Vol 87 (3) ◽

pp. 538-546 ◽

Cited By ~ 7

Author(s):

Christopher S Graffeo ◽

Diane Donegan ◽

Dana Erickson ◽

Paul D Brown ◽

Avital Perry ◽

...

Keyword(s):

Cohort Study ◽

Growth Factor ◽

Effective Dose ◽

Stereotactic Radiosurgery ◽

Univariate Analysis ◽

Biologically Effective Dose ◽

Insulin Like Growth Factor ◽

Biochemical Remission ◽

The Impact

Abstract BACKGROUND Stereotactic radiosurgery (SRS) is a safe and effective treatment for acromegaly. OBJECTIVE To improve understanding of clinical and dosimetric factors predicting biochemical remission. METHODS A single-institution cohort study of nonsyndromic, radiation-naïve patients with growth hormone-producing pituitary adenomas (GHA) having single-fraction SRS between 1990 and 2017. Exclusions were treatment with pituitary suppressive medications at the time of SRS, or <24 mo of follow-up. The primary outcome was biochemical remission—defined as normalization of insulin-like growth factor-1 index (IGF-1i) off suppression. Biochemical remission was assessed using Cox proportional hazards. Prior studies reporting IGF-1i were assessed via systematic literature review and meta-analysis using random-effect modeling. RESULTS A total of 102 patients met study criteria. Of these, 46 patients (45%) were female. The median age was 49 yr (interquartile range [IQR] = 37-59), and the median follow-up was 63 mo (IQR = 29-100). The median pre-SRS IGF-1i was 1.66 (IQR = 1.37-3.22). The median margin dose was 25 Gy (IQR = 21-25); the median estimated biologically effective dose (BED) was 169.49 Gy (IQR = 124.95-196.00). Biochemical remission was achieved in 58 patients (57%), whereas 22 patients (22%) had medication-controlled disease. Pre-SRS IGF-1i ≥ 2.25 was the strongest predictor of treatment failure, with an unadjusted hazard ratio (HR) of 0.51 (95% CI = 0.26-0.91, P = .02). Number of isocenters, margin dose, and BED predicted remission on univariate analysis, but after adjusting for sex and baseline IGF-1i, only BED remained significant—and was independently associated with outcome in continuous (HR = 1.01, 95% CI = 1.00-1.01, P = .02) and binary models (HR = 2.27, 95% CI = 1.39-5.22, P = .002). A total of 24 patients (29%) developed new post-SRS hypopituitarism. Pooled HR for biochemical remission given subthreshold IGF-1i was 2.25 (95% CI = 1.33-3.16, P < .0001). CONCLUSION IGF-1i is a reliable predictor of biochemical remission after SRS. BED appears to predict biochemical outcome more reliably than radiation dose, but confirmatory study is needed.

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Single-fraction versus multifraction spinal stereotactic radiosurgery for spinal metastases from renal cell carcinoma: secondary analysis of Phase I/II trials

Journal of Neurosurgery Spine ◽

10.3171/2015.8.spine15844 ◽

2016 ◽

Vol 24 (5) ◽

pp. 829-836 ◽

Cited By ~ 39

Author(s):

Amol J. Ghia ◽

Eric L. Chang ◽

Andrew J. Bishop ◽

Hubert Y. Pan ◽

Nicholas S. Boehling ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Stereotactic Radiosurgery ◽

Renal Cell ◽

Tumor Volume ◽

Secondary Analysis ◽

Spinal Metastases ◽

Survival Duration ◽

Single Fraction ◽

Entire Cohort

OBJECTIVE The objective of this study was to compare fractionation schemes and outcomes of patients with renal cell carcinoma (RCC) treated in institutional prospective spinal stereotactic radiosurgery (SSRS) trials who did not previously undergo radiation treatment at the site of the SSRS. METHODS Patients enrolled in 2 separate institutional prospective protocols and treated with SSRS between 2002 and 2011 were included. A secondary analysis was performed on patients with previously nonirradiated RCC spinal metastases treated with either single-fraction (SF) or multifraction (MF) SSRS. RESULTS SSRS was performed in 47 spinal sites on 43 patients. The median age of the patients was 62 years (range 38–75 years). The most common histological subtype was clear cell (n = 30). Fifteen sites underwent surgery prior to the SSRS, with laminectomy the most common procedure performed (n = 10). All SF SSRS was delivered to a dose of 24 Gy (n = 21) while MF regiments were either 27 Gy in 3 fractions (n = 20) or 30 Gy in 5 fractions (n = 6). The median overall survival duration for the entire cohort was 22.8 months. The median local control (LC) for the entire cohort was 80.6 months with 1-year and 2-year actuarial LC rates of 82% and 68%, respectively. Single-fraction SSRS correlated with improved 1- and 2-year actuarial LC relative to MF SSRS (95% vs 71% and 86% vs 55%, respectively; p = 0.009). On competing risk analysis, SF SSRS showed superior LC to MF SSRS (subhazard ratio [SHR] 6.57, p = 0.014). On multivariate analysis for LC with tumor volume (p = 0.272), number of treated levels (p = 0.819), gross tumor volume (GTV) coverage (p = 0.225), and GTV minimum point dose (p = 0.97) as covariates, MF SSRS remained inferior to SF SSRS (SHR 5.26, p = 0.033) CONCLUSIONS SSRS offers durable LC for spinal metastases from RCC. Single-fraction SSRS is associated with improved LC over MF SSRS for previously nonirradiated RCC spinal metastases.

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