Marginal Dose Research Articles

Arteriovenous Malformation (AVM) Treated with Robotic Radiosurgery: Impact of Beam Reduction in 12 Gy Normal Brain Volume and It’s Clinical Implication

Purpose: Dosimetric study to evaluate impact of “beam” reduction in AVM radiosurgery on normal brain dose parameters and it’s clinical implications. Materials and Methods: Five small volume AVMs (nidus volume 0.31 - 1.94 cc) planned for single fraction SRS with robotic radiosurgery system. Planning scans done with CT scan brain, CT & MR angiography, then nidus volume and organ at risk (OARs) were contoured. Planning was done with multiplan planning system. Plan evaluated as per Flickenger model parameters of 12 Gy nomal brain vol & marginal dose. 7.5 mm and 10 mm cons used, optimization done with seqential algorithm. 20 Gy was prescribed to isodose with appropriate nidus coverage (>98%). Total beams of five plans were 85 - 250, monitor unit 17,259 - 24,602 MU. 12 Gy normal brain volume is 0.9 - 7.6 cc. Then beam reduction is done by reducing beams with minimum MU in steps of 50, 100, 150, 200, 250 MU and after beam reduction, re-optimization done. Prescription isodose was changed to keep the nidus coverage > 98%. Impacts of beam reduction on 12 Gy normal brain vol and conformity/homogeniety index were analyzed. Results: Optimal plans of five patients with 20 Gy prescribed to 88% - 90% isodose, nidus coverage more than 98%. In dosimetric parameters, mean CI was 1.36 - 1.51, nCI 1.41 - 1.51, HI 1.1 - 1.4 and mean 12 Gy normal brain volume 0.17, 1.44, 5.3, 5.5 and 7.6cc respectively. After beam reduction of less than 50 MU contribution (in case#1), prescibing at suitable isodose (85%) beam reduces to 79 and 12 Gy volume marginally increases to 26.4 cc. Beam reduction of less than 100 MU reduces to 53 - 92 beamlets. Reduction of beams with less than 150 MU contribution did not significantly change the 12Gy normal brain volume. However, reduction of beamlets with more than 200 MU, 250 MU, 300 MU, 450 MU and 550 MU significantly affects the 12 Gy normal brain volume. Prescription-isodose modified from 83% to 50% to have >98% coverage. CI and HI increased from 1.36 - 1.51 to 2.51 - 2.63 and 1.1 - 1.4 to 1.52 - 1.54 respectively. There was exponential increase in 12 Gy volume with reduction of beams with higher proportion in larger nidus. Conclusions: In robotic radiosurgery system, beam reduction even after re-optimization impairs the conformity index and increase 12 Gy normal brain volume, hence long-term toxicity. Optimal beam numbers are required for optimal plan generation.

Stereotactic Radiosurgery for Intracranial Ependymomas: An International Multicenter Study.

Stereotactic radiosurgery (SRS) is a potentially important option for intracranial ependymoma patients. To analyze the outcomes of intracranial ependymoma patients who underwent SRS as a part of multimodality management. Seven centers participating in the International Gamma Knife Research Foundation identified 89 intracranial ependymoma patients who underwent SRS (113 tumors). The median patient age was 16.3 yr (2.9-80). All patients underwent previous surgical resection and radiation therapy (RT) of their ependymomas and 40 underwent previous chemotherapy. Grade 2 ependymomas were present in 42 patients (52 tumors) and grade 3 ependymomas in 48 patients (61 tumors). The median tumor volume was 2.2 cc (0.03-36.8) and the median margin dose was 15 Gy (9-24). Forty-seven (53%) patients were alive and 42 (47%) patients died at the last follow-up. The overall survival after SRS was 86% at 1 yr, 50% at 3 yr, and 44% at 5 yr. Smaller total tumor volume was associated with longer overall survival (P= .006). Twenty-two patients (grade 2: n= 9, grade 3: n= 13) developed additional recurrent ependymomas in the craniospinal axis. The progression-free survival after SRS was 71% at 1 yr, 56% at 3 yr, and 48% at 5 yr. Adult age, female sex, and smaller tumor volume indicated significantly better progression-free survival. Symptomatic adverse radiation effects were seen in 7 patients (8%). SRS provides another management option for residual or recurrent progressive intracranial ependymoma patients who have failed initial surgery and RT.

The Role of Leksell Radiosurgery in the Management of Craniopharyngiomas.

Management of craniopharyngiomas remains challenging due to the tumor's often intimate relationship with the optic apparatus, the hypothalamus, and the pituitary gland. Often multimodal management is needed to achieve the best treatment outcome: tumor control coupled with endocrine, visual, and neurocognitive preservation. Many surgeons favor initial subtotal resection followed by adjunctive therapy to improve quality of life in a tumor with potentially long-term survival even if coupled with a need for periodic new interventions. During the patient's subsequent follow-up, solid or cystic tumor recurrence or progression often require additional management options. Leksell stereotactic radiosurgery (SRS) is a valuable adjuvant strategy that enhances long-term outcomes in patients with residual or recurrent craniopharyngiomas. Tumor control rates of 70-90% have been reported using 11- to 13-Gy tumor margin doses delivered using the Gamma Knife. Smaller tumors are associated with better radiosurgery outcomes. SRS is an effective management for residual or recurrent solid craniopharyngiomas with a favorable benefit-to-risk profile.

Gamma Knife Radiosurgery of Arteriovenous Malformations: Long-Term Outcomes and Late Effects.

Gamma Knife radiosurgery (GKRS) of cerebral arteriovenous malformations (AVM) is an accepted treatment option that has been performed for more than 40 years. The goal of AVM GKRS is nidus obliteration to eliminate the risk of intracranial hemorrhage while minimizing the risk of short- and long-term adverse radiation effects (ARE). Nidus obliteration typically occurs between 1 and 5 years after GKRS. The most important factor associated with nidus obliteration is the prescribed radiation dose. The chance of obliteration ranges from 60 to 70% for margin doses of 15-16 Gy to 90% or more for margin doses of 20-25 Gy. Neurologic decline after GKRS can occur from either hemorrhage or ARE. Numerous studies have shown that the risk of AVM bleeding is either unchanged or decreased following GKRS. Advances in neuroimaging and dose-planning software have reduced the incidence of early ARE to <4%. Volume-staged procedures can be safely performed for large-volume AVM that were previously considered too large for GKRS. Late ARE (generally cyst formation) are common in patients who develop early MRI imaging changes (areas of high T2 signal) after GKRS, but most cases can be managed with either observation or resection of the thrombosed AVM.

Treatment of Cavernous Sinus Hemangiomas with Gamma Knife Radiosurgery as a Primary and Sole Therapy.

To evaluate the effectiveness of Gamma Knife radiosurgery (GKRS) as the primary and only therapy for the treatment of cavernous sinus hemangiomas (CSH) and to report the tumor volume dynamics, course of symptoms, and complications after stereotactic radiosurgery. A total of 10 CSH patients were treated with GKRS using a median margin dose of 14.2Gy (range 13-16Gy). The median follow-up period was 42 months (range 12-85 months). Tumor volumes were calculated from magnetic resonance images before treatment and compared with those after treatment. Prior to the treatment, all patients complained of headache and retro-orbital pain, and six patients complained of diplopia due to abducens nerve paralysis. Within six months of treatment, all patients declared some improvement in headache and retro-orbital pain, and abducens nerve paralysis recovered fully in all six patients. At the first-year follow-up, at least 74% decrease in tumor volume was noted with average tumor volume reduction of 90.2% in all treated patients. Tumors less than 6 cm3 in volume nearly disappeared at 24 months. No tumor progression, re-growth, or radiation-induced adverse effects were noted in our patients. Characteristic radiological features that enable identification of CSH avert the need for an open biopsy for diagnosis. Under suitable circumstances, GKRS may be considered as the primary and only therapy for CSH. GKRS has favorable outcomes in the treatment of CSH, demonstrating good tumor shrinkage, symptom recovery, and low incidence of side effects.

Gamma Knife radiosurgery for intravestibular and intracochlear schwannomas.

Schwannomas of the VIIIth cranial nerve are benign tumours, with vast majority occurring in vestibular division. Rarely, they can also arise from distal branches of cochlear, superior or inferior vestibular. We review our experience with Gamma Knife radiosurgery (GKR), as first intention treatment for intracochlear (ICS) and intravestibular (IVS) schwannomas. A total number of five patients were analysed, treated over 8years, between June 2010 and September 2018, with Leksell Gamma Knife Perfexion or Icon (Elekta Instruments, AB, Sweden). The marginal dose prescribed was 12Gy at a mean prescription isodose line of 61.4% (range 50-70). Clinical evaluation included auditory and facial function. The mean age was 49.9 (range 34-63). The mean follow-up period was 52.8months (range 12-84). The mean target volume (TV) was 0.087ml (range 0.014-0.281). The mean maximal dose received by the cochlea was 11.2Gy (range 2.6-20.3). The mean marginal dose received by the vestibule (e.g. utricula) was 14.2Gy (range 3.8-17.5). No patient experienced an acute or subacute clinical adverse radiation effect after GKR. Four cases had overall symptom stability. In one patient (1/5), the vertigo, which was the main clinical complain, disappeared 1year after GKR. However, it reappeared 3years later, with same pretherapeutic characteristics and is currently fluctuating. One patient experienced hearing decrease after GKR, during the first 12months. This case received 11.2Gy to the cochlea. Follow-up MRI course showed a decrease in size in four patients, and stability in one. Gamma Knife radiosurgery is a valuable first intention treatment for ICS or IVS, in selected cases. Special attention should be paid for the dose delivered to the cochlea and the vestibular apparatus. Acute and subacute clinical effects are exceptional, while tumour control was achieved in all cases in our small series.

Defining Long-Term Clinical Outcomes and Risks of Stereotactic Radiosurgery for Brainstem Cavernous Malformations

We evaluated clinical outcomes in patients with symptomatic brainstem cavernous malformations (CMs) treated by stereotactic radiosurgery (SRS). Between 1988 and 2016, Gamma Knife SRS was performed in 76 evaluable patients with solitary symptomatic brainstem CMs. Forty-nine (66%) were intrinsic (not reaching a pial or ependymal surface). Most patients (91%) had experienced 2 or more hemorrhages associated with new neurologic deficits. Fourteen patients (18%) underwent resection before radiosurgery. The median CM volume was 0.66 cm3 (range, 0.05-6.8), and the median margin dose was 15.0 Gy. After SRS, 15 patients (20%) had an imaging confirmed new hemorrhage at a median follow-up of 48 months. The hemorrhage-free survival after SRS for brainstem CMs was 92% at 1 year, 87% at 3 years, and 85% at 5 years. The annual hemorrhage rate was 31% before and 4% after SRS. In univariate analysis, CM volume, previous surgical resection, and increased number of hemorrhages before SRS were significantly associated with a higher rate of hemorrhage after SRS. In multivariate analysis, only number of previous hemorrhages was significant (P<0.0005; hazard ratio, 1.51, 95% confidence interval, 1.23-1.85). Symptomatic adverse radiation effects developed in 7 patients (9%). The rate of symptom deterioration related to hemorrhage or symptomatic adverse radiation effects was 10% at 1 year, 18% at 3 years, and 20% at 5 years. Patients with an increased rate of hemorrhage before SRS had an increased risk of repeat hemorrhage and symptom deterioration rate after SRS. Intrinsic CM location did not significantly affect rates of symptom deterioration or rebleeding.

Seizures After Stereotactic Radiosurgery for Benign Supratentorial Meningiomas: An Uncontrollable Type of Seizure?

We investigated seizure outcomes of patients with supratentorial meningiomas (ST-MNGs) treated with stereotactic radiosurgery (SRS). One hundred and thirty-three patients with a total of 144 ST-MNGs, who were treated with SRS between 2009 and 2016, were included in this study. The mean age was 59.0 ± 11.9 years (range, 13-87 years). The mean follow-up duration was 49.8 ± 24.5 months (range, 9-96 months). The median tumor volume was 2.60 cm3 (range, 0.06-32.40 cm3), and the median marginal dose was 14.0 Gy (range, 11.0-20.0 Gy). Postradiosurgery peritumoral edema (PRPTE) was developed in 43 lesions (29.9%). New seizure attacks developed in 16 patients (12.0%) after SRS (first seizure attack in 14 [87.5%]; seizure aggravation in 2 [12.5%]). In 15 patients with new seizure attacks (93.8%), PRPTE was proved on magnetic resonance imaging. The mean interval between SRS and new seizure attack was 6.6 ± 7.1 (range, 0.23-28.8) months. Simple partial seizure was the most common type of seizure (n= 9 [56.3%]). Five patients (31.3%) were seizure-free with antiepileptic drug (AED) medication (3 [18.8%] withdrew AEDs during the follow-up period); however, the remaining 11 patients (68.7%) did not achieve seizure-free outcomes even with AED medication. Moreover, seizures became intractable in 8 patients (50.0%). From multivariate analysis, the significant predictors of post-SRS seizure attack werePRPTE (odds ratio, 53.99; 95% confidence interval, 5.214-559.1; P= 0.001) and brain-tumor contact-surface index (odds ratio, 2.466; 95% confidence interval, 1.183-5.138; P= 0.016). The clinical outcomes of seizures after SRS for ST-MNGs fall short of our expectation, and seizures seem to be uncontrollable and even intractable.

Volume-staged Gamma Knife radiosurgery for orbital venous malformations.

OBJECTIVEThis article is a preliminary evaluation of the efficacy of volume-staged Gamma Knife radiosurgery (GKRS) in the treatment of patients with orbital venous malformations (OVMs).METHODSTwenty patients with moderate to large OVMs were treated with volume-staged GKRS between March 2005 and October 2015. The series included 8 male and 12 female patients with an average age of 22.5 years (range 9-45 years). The diagnoses were confirmed intraoperatively and at pathological examination in 14 cases and presumed in accordance with clinical and imaging findings in 6 cases. The median OVM volume was 12.2 cm3 (range 7.1-34.6 cm3). The median interval between stages was 10 months (range 6-12 months). The tumor margin dose for each stage ranged from 11.0 to 13.5 Gy. The median duration of follow-up was 45.5 months (range 18-98 months).RESULTSPeriodically scheduled MRI studies demonstrated evidence of a significant reduction of the original OVM volume in all cases. Visual acuity (VA) was preserved in 18 cases (90%). Five patients (25%) experienced vision improvement of varying degrees, and 13 (65%) experienced long-term preservation of VA at their pre-GKRS level. Deterioration in VA was observed in only 2 cases (10%). MRI demonstrated OVM regression after treatment in all cases, and all patients were found to have reduction of exophthalmos after volume-staged GKRS. Follow-up MRI revealed recurrence in only 1 case (5%). Three patients (15%) developed transient conjunctival edema.CONCLUSIONSThis retrospective investigation indicates that volume-staged GKRS provides an effective management option in selected patients with OVMs, providing excellent visual outcomes. The study adds substantial support for volume-staged GKRS as a major treatment for OVMs.

Radiology and radiation therapy

A closed-loop radiation therapy process is adaptive radiation treatment where the treatment process can be modified using a systematic feedback of measurements. Adaptive radiation therapy has the intention to improve radiation treatment by systematically monitoring treatment variations and incorporating them to re-optimize the treatment plan early on during the course of treatment. By this process, field margin and treatment dose can be consistently customized to each respective patient to achieve a safe dose escalation.

Gamma Knife Radiosurgery for Metastatic Brain Tumors from Cancer of Unknown Primary

We retrospectively analyzed treatment efficacy and identified prognostic factors impacting tumor control and survival in patients with brain metastases from cancer of unknown primary (CUP) treated with gamma knife radiosurgery (GKRS). We retrospectively reviewed the medical records of 87 patients with 520 tumors who underwent GKRS for brain metastases from CUP. The median overall survival time after initial GKRS was 6 months. The 6- and 12-month overall survival rates were 79.3% and 14.9%, respectively. Older age (P=0.002), lower Karnofsky Performance Status Index score (P= 0.026), extracranial metastases (P= 0.013), and multiple brain metastases (P= 0.007) were significantly correlated with shorter survival periods. The 6- and 12-month neurologic death rates were 25.3% and 32.2%, respectively. The 6- and 12-month neurologic deterioration rates were 24.1% and 27.6%, respectively. The 6- and 12-month distant brain control failure rates were 21.8% and 24.1%, respectively. The median tumor volume was 1.7 cm3. The median marginal prescription dose was 18 Gy. The 6- and 12-month tumor recurrence rates were 5.1% and 15.7%, respectively. Larger tumor volume (P < 0.0001) and lower prescription dose (P= 0.001) were significantly correlated with local tumor control failure. Seven patients had symptomatic radiation injury. The 6- and 12-month GKRS-related complication rates were both 6.9%. Our findings suggest that GKRS is a relatively effective and safe treatment for control of tumor progression in patients with brain metastases from CUP. Overall and neurologic survivals were short, but we recommend GKRS treatment to prevent early neurologic dysfunction and death in patients with CUP.

Gamma Knife radiosurgery for glomus tumors: Long-term results in a series of 30 patients.

Glomus tumors are rare and benign hypervascular tumors. Surgery represented the mainstay of their treatment, even if it has been associated with high morbidity and mortality rates. Recently, the treatment shifted to a multimodal approach and Gamma Knife radiosurgery represents one of the treatment options. Authors retrospectively analyzed the clinical and radiological outcome of a series of patients who underwent Gamma Knife radiosurgery for glomus tumors. Thirty patients underwent Gamma Knife radiosurgery. Mean tumor volume was 7.69 cc (range 0.36-24.6). Mean tumor margin dose was 16 Gy (range 13-18). Median follow-up was of 91 months (mean 90; range 11-172). Overall clinical control rate was 100%; overall volumetric tumor control rate was 96.6%. Patients' and tumors' characteristics, treatment data, and outcome have been analyzed. Gamma Knife radiosurgery represents a safe and effective treatment for glomus tumors. Longer follow-up and larger cohort studies are needed to definitively outline the role of Gamma Knife radiosurgery for glomus tumors.

A practical approach to estimating optic disc dose and macula dose without treatment planning in ocular brachytherapy using 125I COMS plaques

BackgroundIt has been reported that proximity of the tumor to the optic disc and macula, and radiation dose to the critical structures are substantial risk factors for vision loss following plaque brachytherapy. However, there is little dosimetry data published on this. In this study, therefore, the relationship between distance from tumor margin and radiation dose to the optic disc and macula in ocular brachytherapy using 125I Collaborative Ocular Melanoma Study (COMS) plaques was comprehensively investigated. From the information, this study aimed to allow for estimation of optic disc dose and macula dose without treatment planning.MethodsAn in-house brachytherapy dose calculation program utilizing the American Association of Physicists in Medicine Task Group-43 U1 formalism with a line source approximation in a homogenous water phantom was developed and validated against three commercial treatment planning systems (TPS). Then optic disc dose and macula dose were calculated as a function of distance from tumor margin for various tumor basal dimensions for seven COMS plaques (from 10 mm to 22 mm in 2 mm increments) loaded with commercially available 125I seeds models (IAI-125A, 2301 and I25.S16). A prescribed dose of 85 Gy for an irradiation time of 168 h was normalized to a central-axis depth of 5 mm. Dose conversion factors for each seed model were obtained by taking ratios of total reference air kerma per seed at various prescription depths (from 1 mm to 10 mm in 1 mm intervals) to that at 5 mm.ResultsThe in-house program demonstrated relatively similar accuracy to commercial TPS. Optic disc dose and macula dose decreased as distance from tumor margin and tumor basal dimension increased. Dose conversion factors increased with increasing prescription depth. There existed dose variations (<8%) among three 125I seed models. Optic disc dose and macula dose for each COMS plaque and for each seed model are presented in a figure format. Dose conversion factors for each seed model are presented in a tabular format.ConclusionsThe data provided in this study would enable clinicians in any clinic using 125I COMS plaques to estimate optic disc dose and macula dose without dose calculations.

Radiosurgery and fractionated radiotherapy for cavernous sinus meningioma: a systematic review and meta-analysis.

Radiosurgery (RS) and fractionated radiotherapy (FRT) are part of the therapeutic armamentarium for the management of cavernous sinus meningiomas. We propose a systematic review of the local tumor control and clinical outcomes after monofractionated radiosurgical treatment, including gamma knife radiosurgery (GKRS) and linear accelerator (Linac RS), or fractionated radiotherapy. The current review and meta-analysis adhered to the PRISMA guidelines. We performed a search in PubMed, Embase, and Medline based on the following mesh terms, used alone or in diverse combinations, in both title and abstract: "cavernous sinus," "meningioma," "radiosurgery," "gamma knife," "linac," "cyberknife," and "radiotherapy". We screened 425 studies. We selected 36 studies, matching all selection criteria: 24 for GK, 5 for Linac, and 7 for FRT. Were included 2817 patients (GKRS, n = 2047, LinacRS, n = 350, FRT, n = 420). Half of patients benefited from upfront RS or FRT; the other half benefited from adjuvant RS or FRT (combined approach or tumor recurrence). The mean gross target volume (GTV) was smaller for RS as compared to FRT (p = 0.07). The median marginal doses were 13.9Gy (range, 11 to 28) for GKRS and 14Gy (range, 12.8 to 17.7) for LinacRS. For FRT, patients received a mean dose of 51.2Gy (25.5 fractions, 1.85Gy each). The mean overall follow-up values were 48months (range, 15 to 89) for GKRS, 69months (range, 46 to 87) for Linac, and 59.5months (range, 33 to 83) for FRT. PFS at 5years for GKRS, LinacRS, and FRT were respectively 93.6%, 95.6%, and 97.4% (p = 0.32, the Kruskal-Wallis). Monofractionated treatments (GKRS and LinacRS) induced more tumor volume regression than FRT (p = 0.001). Tumor recurrence or progression ranged between 3 and 5.8%, without statistically significant differences between modalities (p > 0.05). Trigeminal symptoms improved in approximately 54%, and III-IV-VI cranial nerves (CN) palsies improved in approximately 45%. After GKRS, visual acuity improved in 21% (not enough data available for other modalities). De novo deficits occurred in 5 to 7.5%. Adverse radiation effects appeared in 4.6 to 9.3% (all techniques pooled). RS achieved a twice-higher rate of tumor volume regression than FRT. GKRS series reported an improvement in visual acuity in 21% of the cases. GKRS, Linac, and FRT provided similar clinical post therapeutic outcomes for the trigeminal and oculomotor CN.

Long-Term Outcomes After Gamma Knife Radiosurgery for Benign Meningioma: A Single Institution's Experience With 424 Patients

Gamma knife radiosurgery (GKRS) is recognized as an important treatment modality for meningioma. To analyze the long-term outcomes in meningioma patients treated with GKRS to determine the risk factors related to treatment failure and peritumoral edema (PTE) development. Between 1998 and 2010, 770 consecutive patients were treated with GKRS for intracranial meningioma. After the exclusion of patients with follow-up periods of less than 5 yr and those with neurofibromatosis, multiple meningiomas, nonbenign meningioma, or radiotherapy, a total of 424 patients were enrolled in this study. The median follow-up duration was 92 mo. The median tumor volume was 4.35 cm3, and the median marginal dose was 14 Gy. The overall local tumor control rate was 84%. The actuarial tumor control rates were 91.7% and 78.9% at 5 and 10 yr, respectively. The tumor control rate of a radiologically diagnosed tumor was higher than that of a grade I tumor (82% vs 70.1% at 10 yr, P = .001). In multivariate analysis, factors associated with tumor progression were female sex (hazard ratio: 0.5, P = .025) and a previous history of craniotomy (hazard ratio: 1.9, P = .009). Symptomatic PTE was identified in 36 (8.5%) patients, and the factor associated with poor PTE was the presence of PTE before GKRS (odds ratio: 4.6, P < .001). Permanent complication rate was 4%. GKRS appears to be an effective treatment modality for meningioma with long-term follow-up. However, the identification of delayed tumor progression in our study suggests that extended follow-up data should be collected after GKRS.

Radiosurgery as primary management for acromegaly.

Transsphenoidal surgery (TSS) remains the recommended primary treatment for acromegaly. Long-term outcome data are not available for patients treated with gamma knife radiosurgery (STRS) as a primary treatment. Retrospective cohort study. notes review, laboratory results, general physician notes, patient questionnaire and death certification. Twenty acromegaly patients underwent primary STRS at the National Centre for Radiosurgery, Sheffield, UK, between 1985 and 2015. Biochemical control (GH/IGF1), hypopituitarism, morbidity and mortality were all recorded. At 20years of follow-up, control was seen in all on acromegaly-specific medication (n=12) and 75% of those off medication (3/4). Time for 50% to achieve control on medication was 3years, and 7.4years off medication. Median marginal radiation dose was 27.5Gy, and median follow-up was 166.5months. 53% of patients developed new hypopituitarism at a median follow-up of 146months, and the development of first onset of hypopituitarism occurred as late as 20years after treatment. With MRI planning, no other complications were noted. Three patients underwent subsequent TSS due to poor biochemical control. During follow-up, 7 patients died at a median age of 65years. There were no STRS-related deaths. This is the longest follow-up of patients who have undergone primary STRS for acromegaly. It shows low morbidity, but significant latency to biochemical control and new-onset hypopituitarism. This mandates very long-term follow-up for these patients. STRS has shown good long-term efficacy providing initial control can be afforded by optimal medical management. While TSS remains best practice, STRS offers an alternative for those in whom surgery is not an option.

Stereotactic Radiosurgery for Hemorrhagic Brain Metastases from Malignant Melanoma

Stereotactic radiosurgery is a common treatment modality among patients with brain metastases, particularly from malignant melanoma. In this study, we investigate the difference in local control, toxicity, and survival among patients with hemorrhagic and solid melanoma brain metastases. We collected demographic, treatment, local control, toxicity and survival data for 134 patients with a total of 936 intracranial melanoma metastases who underwent Gamma Knife stereotactic radiosurgery between 1998 and 2015 at the University of Virginia Medical Center. Pre-radiosurgical diagnostic imaging was reviewed for evidence of hemorrhage (melanin containing or clearly hemorrhagic). The population consisted of 92 men and 42 women with a mean age of 61.7 years (range 21.2–84.9) at the time of radiosurgery. Overall survival of patients with brain metastases from malignant melanoma was 42%, 31%, 12% at 12, 24 and 72 months from date of first stereotactic radiosurgery. At 6 months, 43% of the patients with hemorrhagic metastases had local tumor control compared to 83% of solid melanoma metastases (log rank p < 0.001). No significant difference in toxicity was noted between the two groups. Factors that were significantly associated with time to local tumor progression on multivariate analysis include prior WBRT (HR 1.62, p = 0.003), prior chemotherapy (HR 0.69, p = 0.011), margin dose (HR 0.88, p < 0.001) and radiographic features of melanin deposition (HR 3.73, p < 0.001), or clear hemorrhage (HR 2.20, p < 0.001). Our findings demonstrate that hemorrhagic intracranial melanoma metastases are associated with inferior local tumor control when treated with SRS, as compared to solid tumors. These results highlight the importance of early radiosurgery among patients with melanoma brain metastases before hemorrhage occurs. Among patients with hemorrhagic metastases at diagnosis, neurosurgical resection should be considered in appropriate patients.

Endocrine Remission after Pituitary Stereotactic Radiosurgery: Differences in Rates of Response for Matched Cohorts of Cushing’s Disease and Acromegaly Patients

To compare and describe the time to endocrine remission and new hypopituitarism among patients with growth hormone (GH) and adrenocorticotropic hormone (ACTH) secreting pituitary adenomas after radiosurgery after controlling for several known prognostic factors. An institutional review board approved, institutional retrospective analysis of patients with GH- and ACTH-secreting pituitary adenomas was performed, with matching based on patient gender, age at radiosurgery, time interval between the last resection and radiosurgery, use of previous radiotherapy, whole sella treatment, suprasellar extension, cavernous sinus invasion, and margin dose. Endocrine remission was defined, off of suppressive medications, as a normal serum IGF-1 (GH-secreting) or a normal 24-hour urine free-cortisol (ACTH-secreting). Endocrine remission and the incidence of new hypopituitarism after single fraction radiosurgery were described and compared between groups. Two-hundred and forty-two (242) patients were evaluated, 121 with GH-secreting tumors and 121 with ACTH-secreting tumors. A total of 75% of patients had cavernous sinus invasion and 10% had suprasellar extension at the time of radiosurgery. The median radiosurgical marginal dose was 25 Gy to the 50% isodose line between each group. After multivariable adjustment, factors associated with increased time to endocrine remission included patient age (HR 1.016, p = 0.023), cavernous sinus invasion (HR 1.793, p = 0.004), and patients with acromegaly (HR 2.912, p < 0.001). The incidence of a new hypopituitarism developing after SRS was 29% and did not appreciably differ by adenoma subtype (p = 0.180). After radiosurgery, patients with ACTH-secreting tumors achieve endocrine remission sooner than those with GH-secreting tumors. These results provide insight into the relative tumor biology and post-radiosurgical disease course that will serve to further improve clinical outcomes and patient management in the future.

Geometric Variation in Gastrointestinal Organs-At-Risk in MR-Guided Online Treatment Adaptation

MR-guided RT has enabled online treatment adaptation by evaluating dose to anatomy defined on pre-treatment MRI. Adaptation is especially compelling for treating GI cancers where MRI allows OARs to be reliably delineated. This study characterizes daily anatomical variation observed during adaptive treatments and identifies geometric measures that correlate with the decision of whether or not to adapt treatment. These quantities for characterizing clinically meaningful anatomy changes will be useful for better understanding potential for margin reduction and dose escalation while preserving OAR sparing. Pre-treatment imaging was acquired for 56 patients treated for GI cancers. All patients were treated via SBRT in five fractions. Adaptation was performed depending on dose calculated to anatomy on a given day. OARs were retrospectively re-contoured by a radiation oncologist to within a 2 cm expansion superior and inferior to the GTV. Per OAR volume (a) variation was summarized for the cohort. Shape-based quantities including surface area (b), volume-to-surface area ratio (c), compactness (d), sphericity (e), disproportion (f) and maximum diameter (g) were calculated for all fractions. Metrics describing GTV-to-OAR proximity – including centroid-to-centroid distance (h), Hausdorff distance (i) and solid angle subtended by the OAR to the GTV centroid (j) – were also computed. Each fraction was labeled as either 1) not being adapted, or being adapted due to 2) an OAR constraint being exceeded or 3) PTV coverage being improved. Analysis of variance (ANOVA) was performed to identify significant associations between calculated metrics and labels. Median (inter-quartile range, IQR) GTV volume for the cohort was 25 (49) cc. Duodenum (DU), stomach (ST), small bowel (SB) and large bowel (LB) were contoured whenever sufficiently close to the GTV. Median volumes for OARs were measured to be 37 (27), 188 (172), 142 (209), and 261 (317) cc for DU, ST, SB and LB respectively. Largest-to-smallest variation in OAR volume per treatment course was observed to be ST, LB, SB, and then DU. Heeding notation in Methods, significant (p < 0.05) associations were measured for ST (i), DU (d), SB (a, b, c, d, h, i) and LB (h, i, j). MR-guided radiotherapy provides fruitful imaging data for assessing inter-fractional variation in OARs. Intuitive associations between various geometric quantities (volume and OAR-to-GTV proximity) and the decision of whether to adapt a treatment were confirmed to be statistically significant especially for small and large bowel. Substantial variation in OAR volume and overlap was calculated across the cohort. While this data was derived from an MR-IGRT system, these metrics constitute an initial step toward understanding GI variation over a treatment course and enabling OAR margins to be determined for achieving dosimetrically robust plans across platforms.

Stereotactic Radiosurgery as a Component of Treatment for Brain Metastases in Small Cell Lung Cancer Patients

Small cell lung cancer (SCLC) aggressively metastasizes to the brain with a poor prognosis. Whole brain radiation therapy (WBRT) is the current standard of care based on historical treatment paradigms. Stereotactic radiosurgery (SRS) is known to preserve quality of life and increase intracranial local control compared to WBRT alone for non-SCLC and other non-lung histologies. Here we report outcomes and failure patterns for SRS used as upfront or salvage therapy for SCLC. The charts of 44 patients with brain metastases from SCLC who underwent SRS as either primary or salvage therapy at a single institution from 2001-2017 were retrospectively reviewed as part of an institutional review board approved study. Demographic data, use of prior prophylactic cranial irradiation (PCI) or WBRT, type of first failure (local vs. elsewhere brain), and dates of treatment failure and death were recorded. Kaplan-Meier survival analysis was used to estimate overall survival (OS) and neurologic progression-free survival (nPFS) from SRS date. Median patient age at was 63.5 years (range = 34 – 86). 5 patients (11%) had prior PCI, 24 (55%) had prior WBRT and 10 (23%) had both prior to salvage SRS. 5 patients (11%) had SRS as upfront treatment. Median number of treated lesions was 3 (range = 1-12). Median SRS tumor volume was 0.173 cubic centimeters (range = 0.007 – 22.99). Median marginal dose was 18 Gy (range = 8-21) to the 50% isodose line. First brain failure post-SRS was elsewhere in 25 patients (57%), local in 4 patients (9%), and the remainder of patients (34%) were controlled at last follow up. Median OS was 7.6 months (95% CI: 6.1-9.1) for all patients. Median nPFS was 3.7 months (95% CI: 2.5-4.9) for all patients and 9.2 months (95% CI: 4.2-14.2) for upfront SRS patients. SRS effectively salvaged or primarily treated SCLC brain metastases with a median overall survival similar to those with newly diagnosed brain metastases from other histologies. Future analysis of this dataset will study prognostic factors for PCI or WBRT failure. Prospective studies evaluating upfront SRS for SCLC are warranted.