Session Stereotactic Radiosurgery Research Articles

Characterization of Pediatric Infratentorial Arteriovenous Malformations: A Retrospective, Multicenter Cohort Study.

Infratentorial arteriovenous malformations (AVMs) harbor different characteristics compared with supratentorial AVMs. This study aims to explore the unique characteristics of pediatric infratentorial AVMs and their response to single session stereotactic radiosurgery (SRS). The International Radiosurgery Research Foundation database of pediatric patients with AVM (age <18 years) who underwent SRS was retrospectively reviewed. Baseline demographics, AVM characteristics, outcomes, and complications post-SRS were compared between infratentorial and supratentorial pediatric AVMs. Unfavorable outcome was defined as the absence of AVM obliteration, post-SRS hemorrhage, or permanent radiation-induced changes at last follow-up. A total of 535 pediatric AVMs managed with SRS with a median follow-up of 67 months (IQR 29.0-130.6) were included, with 69 being infratentorial and 466 supratentorial. The infratentorial group had a higher proportion of deep location (58.4% vs 30.3%, P = <.001), deep venous drainage (79.8% vs 61.8%, P = .004), and prior embolization (26.1% vs 15.7%, P = .032). There was a higher proportion of hemorrhagic presentation in the infratentorial group (79.7% vs 71.3%, P = .146). There was no statistically significant difference in the odds of an unfavorable outcome (odds ratio [OR] = 1.36 [0.82-2.28]), AVM obliteration (OR = 0.85 [0.5-1.43]), post-SRS hemorrhage (OR = 0.83 [0.31-2.18]), or radiologic radiation-induced changes (OR = 1.08 [0.63-1.84]) between both cohorts. No statistically significant difference on the rates of outcomes of interest and complications were found in the adjusted model. Despite baseline differences between infratentorial and supratentorial pediatric AVMs, SRS outcomes, including AVM obliteration and post-SRS hemorrhage rates, were comparable amongst both groups. SRS appears to have a similar risk profile and therapeutic benefit to infratentorial pediatric AVMs as it does for those with a supratentorial location.

Phase I trial of dose escalation for preoperative stereotactic radiosurgery for patients with large brain metastases.

Single-session stereotactic radiosurgery (SRS) or surgical resection alone for brain metastases larger than 2 cm results in unsatisfactory local control. We conducted a phase I trial for brain metastases(>2 cm) to determine the safety of preoperative SRS at escalating doses. Radiosurgery dose was escalated at 3 Gy increments for 3 cohorts based on maximum tumor dimension starting at: 18 Gy for >2-3 cm, 15 Gy for >3-4 cm, and 12 Gy for >4-6 cm. Dose-limiting toxicity was defined as grade III or greater acute toxicity. A total of 35 patients/36 lesions were enrolled. For tumor size >2-3 cm, patients were enrolled up to the second dose level (21 Gy); for >3-4 cm and >4-6 cm cohorts the third dose level (21 and 18 Gy, respectively) was reached. There were 2 DLTs in the >3-4 cm arm at 21 Gy. The maximum tolerated dose of SRS for >2-3 cm was not reached; and was 18 Gy for both >3-4 cm arm and >4-6 cm arm. With a median follow-up of 64.0 months, the 6- and 12-month local control rates were 85.9% and 76.6%, respectively. One patient developed grade 3 radiation necrosis at 5 months. The 2-year rate of leptomeningeal disease (LMD) was 0%. Preoperative SRS with dose escalation followed by surgical resection for brain metastases greater than 2 cm in size demonstrates acceptable acute toxicity. The phase II portion of the trial will be conducted at the maximum tolerated SRS doses.

Results of a Phase I Trial of Dose Escalation for Preoperative Stereotactic Radiosurgery for Patients with Large Brain Metastases

Single session stereotactic radiosurgery (SRS) alone for brain metastases larger than 2 cm in diameter results in unsatisfactory local control. Surgical resection alone also produces unreliable local control and perioperative radiation is required. We conducted a prospective phase I trial (NCT01891318) for brain metastases greater than 2 cm to determine the safety of preoperative SRS at escalating doses followed by surgical resection. Radiosurgery dose started at RTOG 9005 dose levels for the 3 cohorts based on maximum tumor diameter of the index lesion: 18 Gy for >2-3 cm, 15 Gy for >3-4 cm, and 12 Gy >4-6 cm. Concurrent SRS alone to other smaller lesions was allowed using standard RTOG dose. Dose limiting toxicity (DLT) was defined as grade 3 or greater acute toxicity within 3 to 4 months after SRS. Patients underwent surgical resection within 2 weeks and were followed with imaging and neurological evaluations every 3 months. A total of 35 patients were enrolled into the trial (see Table 1 below). The median age was 63, and median interval between SRS and surgery was 2 days. The most common histology was non-small cell lung cancer (57.1%), followed by breast cancer (14.3%). For tumor size >2-3 cm, patients were enrolled up to the 2nd dose level (21 Gy); for >3-4 cm and >4-6 cm cohorts the 3rd dose level (21 Gy and 18 Gy, respectively) was reached. There was a total of 3 DLTs: 2 in the >3-4 cm cohort and 1 in the >4-6 cm cohort (Table 1). The maximum tolerable dose (MTD) was 18 Gy (2nd dose level) for >3-4 cm, and 18 Gy (3rd dose level) for >4-6 cm. With a median follow-up of 64 months, the 6- and 12-month local control rates were 88.8% and 79.1%, respectively. The 6- and 12-month distant brain control was 63.1% and 55.3%, respectively. Overall survival at 6 and 12 months was 82.9% and 59.0%. The rate of leptomeningeal disease (LMD) at 2 years was 0%. Preoperative SRS with dose escalation followed by surgical resection for brain metastases greater than 2 cm in size results in local control comparable to postoperative SRS or whole-brain radiation therapy and demonstrates acceptable acute toxicity. The Phase II portion of the trial will be conducted at the maximum tolerated SRS doses.

CTNI-40. PHASE I TRIAL OF SULFASALAZINE COMBINED WITH STEREOTACTIC RADIOSURGERY FOR RECURRENT GLIOBLASTOMA: STUDY PROTOCOL FOR NCT04205357

Abstract Glioblastoma (GBM) is one of the most aggressive, radioresistant types of cancer with a dismal prognosis. Sulfasalazine (SAS) has shown tumor selective radiosensitizing properties in preclinical studies. The antioxidant glutathione (GSH) produced at high levels in glioma cells normally protects against radiation injury by scavenging reactive oxygen species produced during radiation therapy (RT). SAS blocks cysteine uptake through the xCT-channel, a rate-limiting step for GSH production. We have previously shown slowing of tumor growth and prolonged survival when SAS was combined with stereotactic radiosurgery (SRS) in vivo compared to either treatment alone. Our hypothesis is that SAS potentiates the efficacy of SRS for recurrent GBM with a low risk of adverse events (AE). The primary end-point is to establish the recommended dose for efficacy testing in phase II/III trials. This phase 1 dose-escalation trial utilizes a standard 3 + 3 design with 3-6 patients per cohort. Patients will be treated with oral SAS (1.5, 3.0, 4.5 or 6.0 g/day) 3 days prior to single session SRS. The SAS-dose will be escalated depending on the absence/presence of toxicity in the previous cohort of treated patients. If more than 1 of 3-6 patients ( ≥ 33 %) is experiencing grade 3 or higher toxicity levels, the study will be terminated. The dose below will be the recommended dose. Toxicity is graded using the Common Toxicity Criteria for Adverse Events (CTCAE) v5.0 recorded the first 30 days. Secondary end-points are assessments of 1) intratumoral GSH production (GSH-spectroscopy), 2) late AE utilizing 11C-MET-MRI-PET 3) changes in KPS/quality of life (FACT-Br), 4) need for steroidal treatment, 5) progression free and overall survival. Novel treatment modalities are urgently needed. This trial will establish the recommended dose for SAS repurposed as a radiosensitizer for a future phase 2/3 trial and may ultimately lead to improvement of current GBM treatment.

Long‐term experience of one‐day stereotactic irradiation in patients with uveal melanoma

AbstractPurposeUveal melanoma (iris, ciliary body, choroid) is the most frequent intraocular malignant tumor in adults. One day session stereotactic radiosurgery (SRS) with 35.0 Gy is one of current treatment options. Radiation complications can lead to visual acuity reduction or secondary enucleation of the eye globe. Radiation‐induced optic neuropathy (RION) is a severe ocular complication developing in high‐risk patients with uveal melanoma after SRS.MethodsLong‐term analysis of 210 patients with intraocular uveal melanoma treated by SRS at linear accelerator LINAC in Slovakia by ‘One‐day session’ method: we analyzed association between the secondary enucleation and the presence of secondary glaucoma as well as the radiation‐induced optic neuropathy after SRS.ResultsThe median tumor volume at baseline was 0.3cm3 with range from 0.1 to 2.7 cm3. The therapeutic dose was 35.0Gy by 99% of DVH (dose volume histogram). Average overall survival after stereotactic irradiation was 1st year after SRS 95%, 2nd year 81%, in 5 years 80%.Secondary enucleation was necessary 17% patients due to secondary glaucoma. The presence of RION was significantly associated with a higher dose on the optic nerve (p = 0.0122 in invariable and 0.0039 in multivariable analysis, respectively). Importantly, the overall survival of patients who underwent secondary enucleation was not different from the survival of patients without enucleation (p = 0.691).ConclusionsSurvival rates at 5‐year interval and percentage of secondary enucleation due to complications after one‐day session linear accelerator irradiation are comparable to those achieved with other irradiation techniques (brachytherapy, proton beam irradiation).

Clinical Outcomes of Non-Small Cell Lung Cancer Brain Metastases Treated With Stereotactic Radiosurgery and Immune Checkpoint Inhibitors, EGFR Tyrosine Kinase Inhibitors, Chemotherapy and Immune Checkpoint Inhibitors, or Chemotherapy Alone

Immune checkpoint inhibitors (ICI) and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) have shown responses in the management of non-small cell lung cancer (NSCLC) brain metastases (BM). However, optimizing control with stereotactic radiosurgery (SRS) and various systemic therapies in the management of NSCLC BM remains an area of investigation. We evaluated clinical outcomes in NSCLC BM treated with SRS and ICI, EGFR-TKI, ICI and chemotherapy, compared to conventional chemotherapy.A total of 174 NSCLC BM patients, treated between 2015 and 2019, to a total of 660 intact (non-operative) BM over 239 single-fraction SRS sessions within 3 months of receiving ICI (n = 58; 33%), EGFR-TKI (n = 30; 17%), chemotherapy and ICI (n = 22; 13%) or standard chemotherapy (n = 64; 37%) were identified. Time-to-event analysis was conducted with the Kaplan-Meier method, and outcomes included distant intracranial control (DIC), local control (LC), and overall survival (OS) from SRS. Cox proportional hazards model was utilized for multivariate analysis (MVA) to identify correlations of clinical variables with outcomes.Median follow-up from BM diagnosis was 8.9 months (0.26-126.5 months) and 7.3 months from SRS (2.5-17.6 months). No significant differences in age (P = 0.55), gender (P = 0.49), treated gross tumor volume (P = 0.31), presence of systemic metastasis (P = 0.1), SRS dose (P = 0.61), or KPS (0.35) were noted between treatment groups. The 12-month DIC was 35%, 53%, 41%, and 20% (P = 0.02) for ICI, EGFR-TKI, ICI and chemotherapy, and chemotherapy alone groups, respectively. No differences were noted in LC (P = 0.1) and OS (P = 0.5) between treatment groups. Upon MVA, factors found to be significant for improved DIC included treatment with EGFR-TKI therapy compared to conventional chemotherapy (HR 0.4; 95% CI 0.25-0.76; P = 0.04) and treatment with SRS before systemic therapy (HR 0.6; 95% CI 0.3-0.9; P = 0.03). Factors found to be significant for improved LC on MVA included treatment with SRS before (HR 0.4; 95% CI 0.2-0.9; P = 0.03) or concurrent (HR 0.3; 95% CI 0.1-0.6; P = 0.003) compared to following receipt of systemic therapy. Rates of radiation necrosis (RN) did not differ between treatment groups and were 6% (n = 12), 5% (n = 12), 3% (n = 3), 3% (n = 3), for ICI, EGFR-TKI, ICI and chemotherapy, and chemotherapy alone groups, respectively, P = 0.43. In addition, no differences were noted in RN between timing of SRS and receipt of systemic therapy, (P = 0.81).In our analysis of NSCLC BM patients treated with single session SRS alongside systemic therapy, we found significant differences in DIC based on receipt of systemic therapy. In addition, treatment with SRS before or concurrent with systemic therapy improved control rates. No differences in RN were noted between treatment groups or by timing of SRS and systemic therapy. Prospective evaluation of the potential synergistic effect between systemic therapy and SRS in NSCLC BM management is warranted.A.E. Dohm: None. J. Tang: None. M.N. Mills: None. B.A. Perez: Research Grant; BMS.T.J. Robinson: None. B. Creelan: Research Grant; NGenomics Laboratories, Adaptive Biotechnologies Corp. Consultant; Xilio Inc, E.R. Squibb LLC, F. Hoffmann-La Roche AG, AstraZeneca plc, AbbVie, KSQ Therapeutics Inc, GlaxoSmithKline plc, Gilead Sciences Inc, Celgene corp. Speaker's Bureau; AstraZeneca plc, ARIAD Pharmaceuticals, Hoffmann-La Roche AG.J. Gray: None. A.B. Etame: None. M. Vogelbaum: Honoraria; Celgene, Tocagen. Stock Options; Infuseon Therapeutics. Royalty; Infuseon Therapeutics. P. Forsyth: Research Grant; Pfizer, Celgene. Advisory Board; Novocure, BTG, Inovio, AbbVie, Ziopharm, Tocagen, Pfizer. H.M. Yu: Honoraria; UpToDate. Speaker's Bureau; BrainLab. Advisory Board; Novocure, AbbVie. D.E. Oliver: None. K.A. Ahmed: Research Grant; Bristol-Myers Squibb, Genentech.

Enucleation after Stereotactic Radiosurgery in Patients with Uveal Melanoma.

In the past enucleation was the treatment of choice for all the patients with uveal melanoma. Nowadays, we prefer glope-sparing treatment modalities, except for large tumors, tumors with extrascleral extension and painful blind eyes. Most of the patients perform radiotherapy or local resection techniques. In Slovak Republic, the only one possibility is astereotactic radiotherapy on alinear accelerator LINAC. Nevertheless, enucleation after radiotherapy is necessary for some patients. The causes are postradiation complications, mainly neovascular glaucoma, tumor recurrence, tumor progression or patient´sdecision. The retrospective non-randomised study of 168 eyes of the patients with choroidal or ciliary body melanoma, who performed one-day session stereotactic radiosurgery at the linear accelerator LINAC during period 2007-2016. The data about postradiation complications were analysed based on the medical records of the patients and the data about enucleated eyes based on the histopathological findings. The occurence of enucleation after radiotherapy in our cohort was 17 % (28 patients), with median time period after radiotherapy 21,5 months. The most common cause was neovascular glaucoma (82 %), then tumor progression (14 %) and patient´sdecision (4 %). The most common histopathological finding was spindle-cell melanoma. Others authors describe similar enucleation rate and causes. The histopathological findings indentified more viable melanoma cells in eyes enucleated for tumor progression in comparison with enucleation for other causes. Enucleation may be more difficult and the occurence of postoperative complications can be higher in the eyes after radiotherapy rather than primary enucleation. The management of the patients with uveal melanoma is difficult, and requires the cooperation of ophthalmologist, oncologist, radiation physicist and pathologist. Even if we make effort to preserve the eye, enucleation after radiotherapy is necessary in some patients.

Image-Guided Multisession Radiosurgery of Skull Base Meningiomas.

Simple SummaryStereotactic radiosurgery has changed the landscape of treatment for skull base meningiomas. Lesions encasing or compressing radiosensitive structures are considered not suitable for single session stereotactic radiosurgery because of the high risk of side effects. Multisession stereotactic radiosurgery can reduce these risks, allowing for normal tissue repair between fractions, while delivering a high dose per fraction. The aim of this study is to validate the role of multi-session stereotactic radiosurgery in the treatment of skull base meningiomas, through a retrospective analysis of 156 patients affected by skull base meningioma, treated at the University of Messina between 2008 and 2018. Our study suggests that multisession stereotactic radiosurgery represents a safe and effective profile in the treatment of skull base meningioma, providing a satisfactory local control and a low toxicity rate, together with patient comfort from a frameless procedure.Background: The efficacy of single-session stereotactic radiosurgery (sSRS) for the treatment of intracranial meningioma is widely recognized. However, sSRS is not always feasible in cases of large tumors and those lying close to critically radiation-sensitive structures. When surgery is not recommended, multi-session stereotactic radiosurgery (mSRS) can be applied. Even so, the efficacy and best treatment schedule of mSRS are not yet established. The aim of this study is to validate the role of mSRS in the treatment of skull base meningiomas. Methods: A retrospective analysis of patients with skull base meningiomas treated with mSRS (two to five fractions) at the University of Messina, Italy, from 2008 to 2018, was conducted. Results: 156 patients met the inclusion criteria. The median follow-up period was 36.2 ± 29.3 months. Progression-free survival at 2-, 5-, and 10- years was 95%, 90%, and 80.8%, respectively. There were no new visual or motor deficits, nor cranial nerves impairments, excluding trigeminal neuralgia, which was reported by 5.7% of patients. One patient reported carotid occlusion and one developed brain edema. Conclusion: Multisession radiosurgery is an effective approach for skull base meningiomas. The long-term control is comparable to that obtained with conventionally-fractionated radiotherapy, while the toxicity rate is very limited.

Stereotactic radiosurgery combined with targeted/ immunotherapy in patients with melanoma brain metastasis

BackgroundThere is limited data on the use of targeted or immunotherapy (TT/IT) in combination with single fraction stereotactic radiosurgery (SRS) in patients with melanoma brain metastasis (MBM). Therefore, we analyzed the outcome and toxicity of SRS alone compared to SRS in combination with TT/IT.MethodsPatients with MBM treated with single session SRS at our department between 2014 and 2017 with a minimum follow-up of 3 months after first SRS were included. The primary endpoint of this study was local control (LC). Secondary endpoints were distant intracranial control, radiation necrosis-free survival (RNFS), and overall survival (OS). The local/ distant intracranial control rates, RNFS and OS were analyzed using the Kaplan-Meier method. The log-rank test was used to test differences between groups. Cox proportional hazard model was performed for univariate continuous variables and multivariate analyses.ResultsTwenty-eight patients (17 male and 11 female) with 52 SRS-lesions were included. The median follow-up was 19 months (range 14–24 months) after first SRS. Thirty-six lesions (69.2%) were treated with TT/IT simultaneously (4 weeks before and 4 weeks after SRS), while 16 lesions (30.8%) were treated with SRS alone or with sequential TT/IT. The 1-year local control rate was 100 and 83.3% for SRS with TT/IT and SRS alone (p = 0.023), respectively. The estimated 1-year RNFS was 90.0 and 82.1% for SRS in combination with TT/IT and SRS alone (p = 0.935). The distant intracranial control rate after 1 year was 47.7 and 50% for SRS in combination with TT/IT and SRS alone (p = 0.933). On univariate analysis, the diagnosis-specific Graded Prognostic Assessment including the BRAF status (Melanoma-molGPA) was associated with a significantly improved LC. Neither gender nor SRS-PTV margin had a prognostic impact on LC. V10 and V12 were significantly associated with RNFS (p < 0.001 and p = 0.004).ConclusionSRS with simultaneous TT/IT significantly improved LC with no significant difference in radiation necrosis rate. The therapy combination appears to be effective and safe. However, prospective studies on SRS with simultaneous TT/IT are necessary and ongoing.Trial registrationThe institutional review board approved this analysis on 10th of February 2015 and all patients signed informed consent (UE nr. 128–14).

Prospective Phase I Dose Escalation Study for Neoadjuvant Radiosurgery for Large Brain Metastases

Single session stereotactic radiosurgery (SRS) alone for brain metastases larger than 2cm in maximal dimension results in local control of only 50%. Surgical resection followed by SRS to the resection cavity can result in leptomeningeal failure (LMD). Neoadjuvant SRS followed by resection has been investigated as a dose de-escalation approach with good local control and without LMD. The purpose of this Phase I trial is to determine the maximum tolerated radiosurgery dose (MTD) for neoadjuvant radiosurgery for brain metastases larger than 2cm in maximal dimension. Radiosurgery dose was escalated at 3 Gy increments from currently accepted RTOG dosing; and cohorts of 2-6 patients were treated at each dose. Initially 2 patients were treated at a particular dose and followed for 4 months. If no dose-limiting toxicities (DLT) were observed the dose was escalated and a new cohort of 4 patients were treated. Patients underwent surgical resection of brain metastases within 2 weeks of SRS and were followed with brain MRIs and neurologic evaluations every 3 months. A total of 27 patients have enrolled on the trial. Median and mean follow up are 9.2 and 15.2 months, respectively. For tumor size >2.0 - 3.0 cm, 2 patients completed treatment at 18 Gy and 3 patients at 21Gy. For tumor size >3.0 - 4.0 cm, 4 patients were treated at 15 Gy and 9 patients were treated at 18 Gy and 1 patient at 21 Gy. For tumor size > 4.0 - 5.0 cm, 1 patient was treated at 12 Gy and 7 patients at 15 Gy. No DLT have occurred. MTD has not yet been met. Twenty-six patients were evaluable for acute toxicity. Twenty-two patients (85%) had no adverse events related to protocol treatment. Three patients had grade I fatigue or headaches and 1 patient had grade II fatigue possibly related to treatment. No patients have experienced radiation necrosis. 13 patients have died at time of analysis. The 6 and 12 month local control was 94.7% and 94.7%, respectively. Six and 12 month distant brain control was 71.7% and 49.6% respectively. Overall survival at 6 and 12 months was 81.5% and 54.9%, respectively. One patient developed LMD 5 months following SRS. Only one patient has received whole brain radiotherapy. There are low rates of toxicity for neoadjuvant SRS with dose escalation followed by surgical resection for brain metastases greater than 2 cm in size. MTD has not yet been reached. Early results demonstrate excellent local control with low risk of LMD.

RADIATION MACULOPATHY AFTER ONE-DAY SESSION STEREOTACTIC RADIOSURGERY IN PATIENTS WITH CILIARY BODY AND CHOROIDAL MELANOMA.

Nowadays radiotherapy is thestandard treatment care for patients with uveal melanoma. In Slovakia the only one option is aone-day session stereotactic radiosurgery atlinear accelerator LINAC. Irradiation of surrounding tissues of the eye and orbit causes radiation complications. One of the most serious and vision-threatening is theradiation retinopathy, which divides into maculopathy and peripheric retinopathy. The clinical signs include microanerysms, teleangiectases, hard exsudates, cotton wool spots and macular edema, neovascularisation, and vitreous hemorrhage. Radiation macular edema can be classified by optical coherence tomography into cystoid or noncystoid edema. On fluorescein angiography macular edema is divided into non-ischemic and ischemic, while the latter means usually irreversible loss of the visual acuity. This paper is focused on risk factors of radiation retinopathy although it strongly influences functional result of radiotherapy and preservation of the visual acuity. By means of bivariate and multivariate analysis to determine the association of radiation dose and other variables with the development of radiation maculopathy. The retrospective analysis of 168 patients with ciliary body or choroidal melanoma who performed one-day session stereotactic radiosurgery on alinear accelerator LINAC in aperiod 2007-2016. The prevalence of theradiation maculopathy was 29% with the median time from the irradiation to maculopathy 16 months. Median radiation dose on the macula was 37 Gy. Variables statistically significantly associated with the maculopathy were: radiation dose (p=0.0016), postequatorial location of the tumor (p=0.0271) and better visual acuity before treatment (p=0.0007). The tumor touch of the macula was strongly associated with the visual acuity in the bivariate analysis (p=0.0006), thus it could be omitted from the final model. The radiation dose on amacula is thekey determinant for radiation-induced maculopathy, according to other authors and our study approvingly. Other variables were related to proximity of the tumor to the macula, so the radiation dose on the macula was higher indirectly. Better visual acuity before treatment as arisk factor for maculopathy can be aconsequence of: a) earlier diagnostics of tumor with proximity to the posterior pole, b) lower enucleation rate; frequency of the enucleation was 1.6 higher in patients without maculopathy. Naturally, on enucleated eyes maculopathy was not diagnosed. Five patients underwent intravitreal application of the bevacizumab as atreatment of the radiation maculopathy, without improvement of the visual acuity. Radiation complications can be vision and eye threatening. Radiation maculopathy is aconsequence of higher radiation dose on the macula. The treatment modalities of radiation maculopathy are rather ineffective.

Evaluation of Target Volume Determination for Single Session Stereotactic Radiosurgery (SRS) of Brain Metastases

Evaluation of Target Volume Determination for Single Session Stereotactic Radiosurgery (SRS) of Brain Metastases

Fractionated Stereotactic Radiosurgery for Brain Metastases Using the Novalis Tx® System.

ObjectiveTo evaluate the efficacy of fractionated stereotactic radiosurgery (FSRS) performed using the Novalis Tx® system (BrainLAB AG, Feldkirchen, Germany; Varian Medical Systems, Palo Alto, CA, USA) for brain metastases.MethodsBetween March 2013 and July 2016, 23 brain metastases patients were admitted at a single institute. Twenty-nine lesions too large for single session stereotactic radiosurgery or located in the vicinity of eloquent structures were treated by FSRS. Based on the results obtained, we reviewed the efficacy and toxicity of FSRS for the treatment of brain metastases.ResultsThe most common lesion origin was lung (55%) followed by breast (21%). Median overall survival was 10.0 months (95% confidence interval [CI], 4.9–15.0), and median progression-free survival was 10.0 months (95% CI, 2.1–13.9). Overall survival rates at 1 and 2 years were 58.6% and 36.0%, respectively. Local recurrence and neurological complications affecting morbidity each occurred in two cases. ConclusionFSRS using the Novalis-Tx® system would appear to be an effective, safe noninvasive treatment modality for large and eloquently situated brain metastases. Further investigation is required on a larger number of patients.

Clinical experience of stereotactic radiosurgery at a linear accelerator for intraocular melanoma.

Long-term results with linear accelerator LINAC-based stereotactic radiosurgery for intraocular uveal malignant melanoma were assessed. A retrospective study was carried out of patients with uveal melanoma after a 1-day session stereotactic radiosurgery at LINAC in Slovakia. In the period 2001-2015, a group of 150 patients with uveal melanoma (139 choroidal melanoma, 11 ciliary body melanoma) was treated. The median tumor volume at baseline was 0.5 cm (with range from 0.2 to 1.6 cm). Tumors ranged in size from 2.4 to 20.8 mm in basal diameter and from 2.0 to 18.3 mm in thickness. The therapeutic dose was 35.0 Gy by 99% of dose volume histogram. Older age at treatment was correlated with the largest basal tumor diameter, tumor thickness, and TNM stage. The survival after stereotactic irradiation was 96% in 1 year, 93% in 2 years, 84% in 5 years, 80% in 7 years, and 53% in 11 years. In 20 (13.3%) patients, secondary enucleation was necessary because of complications (secondary glaucoma). Enucleation-free interval ranged from 1 to 6 years. The median age at death was lower (65.7 years) for patients who died from metastatic disease than for those who died from any other cause (75.0 years). Survival rates at 5-year intervals and the need for secondary enucleation because of complications after linear accelerator irradiation are comparable to other techniques.

Single-Session Gamma Knife Stereotactic Radiosurgery for Contralateral Vestibular Schwannoma and Trigeminal Neuralgia

Introduction: Gamma Knife stereotactic radiosurgery (SRS) is a well-established treatment modality for both vestibular schwannoma (VS) and trigeminal neuralgia (TN). In rare cases, VS patients present with TN symptoms attributable to mass effect at the trigeminal root entry zone, which typically improves following tumor treatment. We report a patient with contralateral TN and VS, both treated via single session SRS.

Successful Treatment of Metastatic Relapse of Medulloblastoma in Childhood With Single Session Stereotactic Radiosurgery

Stereotactic radiosurgery (SRS) is an increasingly used treatment modality in adults, but its use and effectiveness in pediatric brain tumors is still uncertain. We describe 3 patients with metastatic relapse of medulloblastoma, who were treated with SRS, and achieved prolonged, progression-free survival. Tolerability of the treatment was excellent with no adverse effects reported. This work adds to the growing evidence that SRS may have an important role to play in the treatment of pediatric brain tumors.

One-Day Session LINAC–Based Stereotactic Radiosurgery of Posterior Uveal Melanoma

LINAC-based stereotactic radiosurgery (SRS) of posterior uveal melanoma is a conservative method to treat uveal melanoma. This was a retrospective clinic-based study of patients with posterior uveal melanoma in stage T2/T3 who underwent 1-day session SRS at LINAC accelerator or SRS plus combined methods from 2001 to 2008. Thirty-nine patients with posterior uveal melanoma were treated with SRS (age 25-80 years, median 54 years). Median tumor volume at baseline was 0.6 cm3 (range 0.2-1.3 cm3). The therapeutic dose (TD) was 35.0 Gy, median of maximal dose applied was 49.0 Gy (range 37.0-60.0 Gy). Patient data were analyzed in groups: group 1, single SRS irradiation; group 2, SRS with subsequent endoresection or cyclectomy or additional transpupillary thermotherapy (TTT) or brachytherapy by Ru106 plaques; group 3a, enucleation after single SRS; group 3b, enucleation after SRS and endoresection/cyclectomy or TTT or brachytherapy Ru106. In patients with visual acuity of 20/40 or better, the median rate of best-corrected visual acuity (BCVA) decline was higher than that of the total and significantly higher than the rate of decline in the complementary group of patients with BCVA less than 20/40 (p=0.0077; Mann-Whitney U test). One-step LINAC-based SRS with a single dose 35.0 Gy is a method to treat middle-stage posterior uveal melanoma and to preserve the eye globe or as the first step of combined methods: irradiation before endoresection or cyclectomy.

Safety and feasibility of image-guided robotic radiosurgery for patients with limited bone metastases of prostate cancer

ObjectiveTo determine the safety and feasibility after image-guided single fraction robotic stereotactic radiosurgery (SRS) in patients with bone metastases of prostate cancer. Materials and methodsForty patients with 64 bone metastases of prostate cancer were prospectively enrolled in a single center study and underwent 54 consecutive outpatient single session SRS procedures during a 4-year period. F-18 choline PET/CT in addition to standard CT imaging was done prior to SRS in all patients. Nineteen patients were under anti-androgen therapy, 8 patients had undergone chemotherapy before SRS. Overall survival and freedom from local tumor recurrence was analyzed with the Kaplan-Meier method. ResultsMean follow-up was 14 months (3–48 months). Seventy-five percent of patients had a single bone metastasis. The median tumor volume was 13 cc. The mean prescribed tumor dose was 20.2 Gy (16.5–22 Gy). Eight patients had died at the time point of the data analysis. The actuarial 6-months, 12-months, and 24-months local tumor control rate was 95.5% (95% CI: 83.0–98.8) as measured by MRI and PET CT imaging. The median initial PSA before SRS was 5.4 ng/dl (CI: 1.4–8.2) and dropped to 2.7 ng/dl (CI: 0.14–10) after 3 months. One case of progressive neurological deficits was documented. ConclusionsThis first report on single session, image-guided robotic SRS documents a safe, feasible, and patient-friendly treatment option in selected patients with bone metastases of prostate cancer.

Single session stereotactic radiosurgery boost to the post-operative site in lieu of whole brain radiation in metastatic brain disease

Whole brain radiation (WBXRT) reduces the incidence of local and distant recurrence following resection of metastatic brain disease but does not prolong life and may entail neurocognitive decline. We employed a novel treatment modality of providing a single-session stereotactic radiosurgery (SRS) boost to the surgical resection site to achieve local control without the risk of cognitive effects. We reviewed all patients at our institution that were treated with SRS to the post-operative bed following resection of a metastatic brain deposit. There were 32 patients identified (16 F) and median age was 60 years. One lesion was resected in all patients of whom 21 were solitary (eight with two lesions, three with three). Median survival was 16.4 months with a 14 month median follow-up. Factors which improved survival were solitary tumor, age <65 and RPA 1, although none achieved statistical significance. In the Cox multivariate analysis only smaller post-operative treatment volume correlated with survival (P = .04). There were two local recurrences (6.25%) to the surgical site and four patients required SRS for new lesions. Nine patients ultimately required salvage WBXRT (3/21 solitary v. 6/11 multiple lesions, P = .03 chi(2)), two for local recurrence post resection and seven for diffuse new disease. The use of SRS to the surgical site results in local recurrence rates comparable to WBXRT and is associated with excellent survival. Over 70% of patients managed this way were spared WBXRT. The presence of multiple lesions on presentation is predictive of the need for subsequent salvage WBXRT.