Gamma Knife Stereotactic Radiosurgery Research Articles

Utility of 68Ga-DOTATATE PET-MRI for Gamma Knife® stereotactic radiosurgery treatment planning for meningioma.

To investigate the impact of adding 68Ga-DOTATATE PET/MRI to standard MRI for target volume delineation in Gamma Knife® stereotactic radiosurgery (GKSRS) for meningioma. Seventeen patients with 18 lesions undergoing GKSRS for WHO grade 1 meningioma were enrolled in a prospective study. All patients underwent pre-treatment 68Ga-DOTATATE PET/MRI examination in addition to standard procedures. Five clinicians independently contoured the gross tumour volume (GTV) based on standard MRI (GTVMRI) and PET/MRI (GTVPET/MRI) on separate occasions. Interobserver agreement was evaluated using Cohen's Kappa statistic (CKS), Dice similarity coefficient (DC), and Hausdorff distance (HD). Statistical analysis was performed with paired t-test and Wilcoxon signed rank test. The addition of PET/MRI significantly increased GTV contour volume (mean GTVPET/MRI 3.59 cm3 versus mean GTVMRI 3.18 cm3, P = .008). Using the treating clinician's pre-treatment GTVMRI as the reference, median CKS (87.2 vs 77.5, P = .006) and DC (87.2 vs 77.4, P = .006) were significantly lower, and median HD (25.2 vs 31.0, P = .001) was significantly higher with the addition of PET/MRI. No significant difference was observed in interobserver contouring reproducibility between GTVMRI and GTVPET/MRI. The addition of 68Ga-DOTATATE PET/MRI for target volume delineation in GKSRS for meningioma is associated with an increase in GTV volume and greater interobserver variation. PET/MRI did not affect interobserver contouring reproducibility. This study provides novel insights into the impact of 68Ga-DOTATATE PET/MRI on GTV delineation and interobserver agreement in meningioma GKSRS, highlighting its potential for improving GKSRS treatment accuracy.

The Role of Stereotactic Radiosurgery in Patients With Brain Metastases From Colorectal Cancers.

The role of stereotactic radiosurgery (SRS) in patients with brain metastases (BMs) from colorectal cancers (CRCs) has not been established. The authors present a single-institution experience of patients with CRC who underwent SRS with metastatic brain spread. We retrospectively analyzed 111 patients with metastatic CRC (64 female, 57.7%), with 449 BMs treated with Gamma Knife SRS between 2000 and 2022. The median age during SRS was 63 years (range: 28-86), and the median Karnofsky Performance Scale was 80 (range: 60-100). The primary sites were colon (85 patients, 76.6%) and rectal (26 patients, 23.4%). Three patients underwent hypofractionated SRS (3 sessions) with a median margin dose of 27 Gy (range: 27-30). All other patients underwent single-session SRS with a median margin dose of 18 Gy (range: 13-20). The median patient survival after SRS was 7 months (range: 1-174). Ninety-eight (88.3%) patients expired at last follow-up and 15 patients (15.3%) died related to progressive intracranial disease. A Karnofsky Performance Scale of <80 at SRS presentation ( P = .02, hazard ratio [HR]: 0.6, 95% CI: 0.4-0.9) and no previous surgical resection ( P < .01, HR: 0.4, 95% CI: 0.3-0.7) were associated with inferior overall survival using multivariate analysis. Seventeen patients (15.3%) had documented local tumor progression after SRS, at a median time of 7 months (range: 3-34) between SRS and progression. Twenty-six patients (23.4%) developed new BMs at a median of 5 months (range: 2-26) between SRS and new tumor detection. Less than three BMs at SRS presentation ( P = .02, HR: 2.6, 95% CI: 1.2-5.6) were associated with better distant tumor control on multivariate analysis. The incidence of adverse radiation effects was 5.4%. SRS effectively controls BMs from CRC with low risk of treatment-related toxicity. During follow-up, the development of additional metastases can be safely treated by repeat SRS.

RADT-10. BRAINSTEM METASTASES TREATED WITH STEREOTACTIC RADIOSURGERY: MASKED VS. FRAMED IMMOBILIZATION

Abstract BACKGROUND Patients with brainstem metastases (BSM) have minimal surgical options due to high-risk anatomy. To review our efficacy treating BSM using Gamma Knife stereotactic radiosurgery (GK SRS), we compared results based on the utilization of mask-fixation (MF) or frame-fixation (FF). METHODS Data were retrospectively collected for 32 patients. Follow-up data for 49 lesions were analyzed for local control rate (LCR) and objective response rate (ORR). RESULTS Primary cancers included lung, breast, and melanoma; most lesions were pontine. MF was used in 18 patients. Average tumor volume was 0.99 cm3 (0.005 – 13.3 cm3). 39 lesions were treated with single fraction 16 Gy. 10 lesions were treated in 3-5 fractions with mean dose of 22.5 Gy. Mean follow-up was 14.2 months (1.2 - 48.2 months). 1-year LCR was 94.7%. ORR at last follow-up did not differ between MF vs. FF (p = .81). Average reduction of lesion volume at 6 and 12 months did not differ between MF vs. FF (64% vs 45%, p = .77; 70% vs 77%, p = .78). Failure occurred in a pontine colorectal cancer metastasis mask-immobilized for treatment with 14 Gy. CONCLUSIONS SRS for BSM achieved high LCR despite variability in tumor size and histology with no significant difference between MF vs. FF. Although trials have historically excluded patients with BSM, our data support SRS as a safe and efficacious treatment. This is the first study showing that MF provides equivalent, successful outcomes when compared to FF for patients with BSM.

METASTASES-01 OUTCOME OF BRAIN METASTASES TREATED WITH GAMMA KNIFE STEREOTACTIC RADIOSURGERY (GKSR): COHORT RETROSPECTIVE STUDY ON 205 CASES

Abstract BACKGROUND Brain metastases (BMs) are the most common expansive intracranial lesions in adults. Approximately 50% of patients diagnosed with new brain metastases have more than one brain metastasis at the time of diagnosis. OBJECTIVE We report our experience of brain metastases treated with GKSR and evaluate the outcome. METHODS Patients treated by Gamma Knife stereotactic radiosurgery (GKSR) in our institution between 2008 and 2021 for BM were recorded retrospectively. RESULTS A total of 205 patients (56.6% females) were included, with a median age of 59 (25-83) years old. Breast (n=85, 42.5%) and lung (n=76, 38%) were the common original locations for the primary tumors (Table 1). There were 103 patients (50.3%) with single BM and 102 patients (49.7%) with multiple BM⩾2. The median number of multiple BM treated was 4 (2-43). The overall mean survival time was 6.00(95% CI, 5.07-6.93) months for all BM. The median percentage of tumor control after radiosurgery treatment was 65% (20-99) over the median follow-up time of 6.00(3-84) months. In the overall population, the 1-year OS rate was 37.55%, the 2-year OS rate was 25.12%, and the 5-year OS was 18.51%. The mean survival time among patients with BM was higher in those with multiple BM than those with single BM ([10 (95%CI 6.67-13.33) months vs 5(4.21-5.70) months, P (0.03)]). Retreatment, tumor stability (control), and progression influence the overall survival of BM, whether single or multiple (P&amp;lt;0.001). CONCLUSION Stereotaxic Radiosurgery provides good results in terms of Overall survival and better Quality of Life for BM, whether single or multiple. Stability and retreatment influenced the overall survival of BM.

Delayed Imaging Changes 18 Months or Longer After Stereotactic Radiosurgery for Brain Metastases: Necrosis or Progression

Imaging changes after stereotactic radiosurgery (SRS) can occur for years after treatment, although the available data on the incidence of tumor progression and adverse radiation effects (ARE) are generally limited to the first 2 years after treatment. A single-institution retrospective review was conducted of patients who had >18 months of imaging follow-up available. Patients who had ≥1 metastatic brain lesions treated with Gamma Knife SRS were assessed for the time to radiographic progression. Those with progression ≥18 months after the initial treatment were included in the present study. The lesions that progressed were characterized as either ARE or tumor progression based on the tissue diagnosis or imaging characteristics over time. The cumulative incidence of delayed imaging radiographic progression was 35% at 5 years after the initial SRS. The cumulative incidence curves of the time to radiographic progression for lesions determined to be ARE and lesions determined to be tumor progression were not significantly different statistically. The cumulative incidence of delayed ARE and delayed tumor progression was 17% and 16% at 5 years, respectively. Multivariate analysis indicated that the number of metastatic brain lesions present at the initial SRS was the only factor associated with late radiographic progression. The timing of late radiographic progression does not differ between ARE and tumor progression. The number of metastatic brain lesions at the initial SRS is a risk factor for late radiographic progression.

Survival and Radiation Dose Differences Between Single Versus Multi-Session Gamma Knife Stereotactic Radiosurgery in Patients Treated for Multiple (≥10) Brain Metastases.

To explore whether treatment with multiple Gamma Knife sessions (mGK) resulted in different survival outcomes or cumulative radiation doses compared to single session Gamma Knife (sGK) in patients who have been treated for ≥10 brain metastases (BMs). Thirty-five patients with ≥10 BMs treated with Gamma Knife stereotactic radiosurgery (GK SRS) were identified and separated into sGK vs. mGK cohorts. Survival outcomes and dosimetry data were compared between the two groups. Recursive partitioning analysis (RPA) classes were used to further stratify patients. mGK patients survived longer from the first GK treatment (p<0.009). By RPA class, patients with class 1 had a prolonged survival from BM diagnosis than those in classes 2 and 3 (p=0.004). However, survival was not significantly different between the classes from the first GK treatment (p=0.089). Stratified by mGK vs. sGK and RPA classes, sGK patients in RPA class 1 had the longest survival from BM diagnosis but the worst survival from GK treatment. mGK patients in any RPA class had the best survival from the first GK treatment. For patients with RPA class 2+3, mGK was associated with longer survival from both BM diagnosis and first treatment. Statistical but not clinical differences between the mGK vs. sGK groups were observed in the max dose to the targets and cochlea, and the V40Gy whole brain dose. mGK may be beneficial if GK is initiated early at first BM diagnosis vs. sGK initiated late. Future research is required to confirm these findings and explore additional areas of interest, such as quality-of-life and economic considerations.

Role of Genetics and Surgical Interventions for the Management of Cerebral Cavernous Malformations (CMM).

Cerebral cavernous malformations (CCMs) are comprised of tissue matter within the brain possessing anomalous vascular architecture. In totality, the dilated appearance of the cavernomatakes on a mulberry-like shape contributed by the shape and relation to vascular and capillary elements. Analyzing its pathophysiology along with its molecular and genetic pathways plays a vital role in whether or not a patient receives GKRS, medical management, or Surgery, the most invasive of procedures. To avoid neurological trauma, microsurgical resection of cavernomas canbe guided by the novel clinical application of a 3D Slicer with Sina/MosoCam. When cavernomas present in deep lesions with poor accessibility, gamma knife stereotactic radiosurgery (GKSR) is recommended. For asymptomatic and non-multilobal lesions, medical and symptom management is deemed standard, such as antiepileptic therapy. The two-hit hypothesis serves to explain the mutations in three key genes that are most pertinent to the progression of cavernomas: CCM1/KRIT1, CCM2/Malcavernin, and CCM3/PDCD10. Various exon deletions and frameshift mutations can cause dysfunction in vascular structure through loss and gain of function mutations. MEKK3 and KLF2/4 are involved in a protein kinase signaling cycle that promotes abnormal angiogenesis and cavernoma formation. In terms of potential treatments, RhoKinase inhibitors have shown to decrease endothelial to mesenchymal transition and CCM lesion development in mice models. All in all, understanding the research behind the molecular genetics in CCMs can foster personalized medicine and potentially create new neurosurgical and medicative treatments.

Long-Term Outcomes of Non-Vestibular Cranial Nerve Schwannomas Treated with Fractionated Stereotactic Radiotherapy and Stereotactic Radiosurgery

Non-vestibular cranial nerve schwannomas (NVCNS) are rare tumors that account for approximately 10% of cranial nerve schwannomas. They are commonly treated with radiation therapy (XRT) due to their location often precluding safe resection. We examined the long-term outcomes of NVCNS treated with XRT as primary management and for post-operative salvage. We conducted a retrospective review of patients with NVCNS treated with fractionated stereotactic radiation therapy (FSRT) or Gamma Knife Stereotactic Radiosurgery (GK-SRS) from 1996 to 2018 at our institution. We examined patient demographics, cranial nerve (CN) involvement, CN function pre-/post-XRT, treatment volume (TV), toxicity, surgery pre-XRT, and local control. Kaplan-Meier analysis was performed for evaluation of local control. We identified 66 patients (38 female, 28 male) with NVCNS, a portion of whom had tumors involving more than one cranial nerve. Forty-six (69.7%) were treated with FSRT (median dose 50.4 Gy in 1.8 Gy/fraction; range 45-54 Gy), and 20 (30.3%) with GK-SRS (median dose 12 Gy; range 12-15 Gy). Median follow-up time was 92.5 months (5-306). Median Karnofsky Performance Status was 90 (70-100). Median age at start of XRT was 45 years old (15-92). Prior to XRT, 34.8% (23) of patients had surgical resection, with median time from surgery to XRT of 4.25 months (0.5-130 months). Median treatment volume was 4.72 cc (0.26-29). The cranial nerve most commonly involved was CN V (48.4%), followed by CN X (15.2%), CN VII (13.6%), CN VI (6.1%), CN XII (6.1%), CN III (6.1%), and CN IX (3%). Twenty-nine (43.9%) patients experienced grade 1 acute toxicity during treatment. Six (9%) patients experienced grade 1 chronic toxicity. No grade 2 or higher acute or chronic toxicity was observed. No significant difference in rates of acute or chronic toxicity was observed between patients treated with GK-SRS vs. FSRT. Post-XRT, 37 patients (56.1%) had improvement in CN function/symptom, 24 patients (36.3%) had stable function/symptoms, and 5 patients (7.6%) had worsening function/symptoms. Local control at one and five years was 100%. In-field recurrence was observed in one patient (1.5%), at 9 years post-XRT. For salvage this patient was treated with a second course of FSRT to the recurrent tumor. Our large institutional series with long term follow up showed excellent local control of NVCNS treated with FSRT or GK-SRS both for primary management and post-operative salvage. Treatment is well tolerated, with high rates of preservation or improvement of CN function, and minimal acute and chronic toxicity.

Clinical Outcomes and Patterns of Failure in Patients with High-Risk Atypical Meningioma Treated with Single Fraction vs. Hypofractionated Gamma Knife Radiosurgery

The recently completed RTOG 0539 supports fractionated radiation therapy for patients categorized as having intermediate (3 yr PFS 93.8%) or high-risk (3 yr LC 68.9%) meningiomas. Stereotactic radiosurgery (SRS) has not been widely established in the treatment of WHO grade 2 atypical meningiomas given concern that there is a greater risk of microscopic infiltration and therefore requires larger margins than safely achievable with SRS. We look to review a consecutive cohort of patients at our institution who have been diagnosed with atypical meningioma treated with either single fraction Gamma Knife SRS (GK-sfSRS) or hypofractionated Gamma Knife SRS (GK-hfSRS). We review both control rates and patterns of failure. Patients diagnosed with intermediate or high-risk WHO grade 2 meningioma per RTOG 0539 classification, without a history of prior radiation (RT) and treated with either GK-sfSRS or GK-hfSRS between 2014 to 2021 at our institution, were included. Patient charts were reviewed, and follow-up data were analyzed for local control (LC) and failure patterns. Local failure was defined as tumor recurrence within the prescription isodose line, marginal was ≤5 mm outside the prescription isodose line, and distant was >5 mm outside of the prescription isodose line Primary outcome was LC, and secondary outcomes were overall survival (OS) and progression free survival (PFS). We identified 47 pathologically confirmed WHO grade 2 meningiomas in 27 patients. 33 lesions were treated with GK-sfSRS and 14 lesions with GK-hfSRS. 6 lesions were intermediate risk, and 41 were high-risk per RTOG 0539. With a median follow up of 36 months (range 2-86 mo), the 3yr LC was 82.7%, PFS was 83.1%, and OS was 96.3%. A total of 4 patients with 8 lesions failed treatment - all with high-risk disease. All failures were local (4) or marginal (4). The 4 local failures were all from a single patient with 4 distinct meningiomas that were treated with GK-sfSRS without surgical resection. The 4 marginal failures were all in patients treated with GK-sfSRS. There were no failures in patients treated with GK-hfSRS. Our institutional data for patients with atypical meningiomas treated with radiosurgical techniques compare favorably to the patients treated with EBRT in RTOG 0539, though longer follow-up is needed to confirm these findings. Outside of one patient, no patients developed recurrence within the prescription volume. There were 4 tumors with marginal failures, suggesting that additional dural margins than what were prescribed may be meaningful. At our institution, we are increasingly moving to hypofractionated radiosurgery with 5 mm of dural margin when using radiosurgical techniques for high-risk atypical meningioma. However, longer term follow-up is needed to validate the use of radiosurgical techniques in atypical meningioma.

Frameless Linear Accelerator (LINAC) Based Radiosurgery (SRS) vs. Framed Gamma Knife SRS for Idiopathic Trigeminal Neuralgia (TN)

Stereotactic radiosurgery (SRS) is an effective treatment for idiopathic trigeminal neuralgia (TN). Conventional treatment is done through frame-based solution due to small target and high radiation dose. More recently, LINAC based frameless SRS technique has been established as a patient friendly alternative. Herein we compared our single institution experience of LINAC based frameless SRS vs frame-based gamma knife SRS for TN. The hypothesis is LINAC based frameless SRS can provide equivalent dosimetric and clinical outcome as compared frame-based gamma knife treatment. Patients with idiopathic TN who received SRS treatment (LINAC based frameless treatment or Gamma knife framed treatment) at our institution from 2015-2022 were included. A minimum follow up of 1 year was required. Patient data was extracted from electronic medical records and radiation treatment planning system. Pain intensity was evaluated utilizing a modified 0-4 Barrow Neurological Institute (BNI) pain intensity score, and then dichotomized where BNI score 0-2 represented response to treatment and BNI score 3-4 represented no response. Statistical analysis was conducted with a linear regression model accounting for race, gender, prior pain, pain distribution including laterality and branch involvement, medication regimen at time of treatment, previous radiation treatment, and prior procedures. Response was then compared between both modalities overall and within each sub-group with chi-square testing and linear regression. A total of 81 patients were identified, 14 patients were excluded due to lack of adequate follow-up, leaving 67 for analysis. 12 (17.9%) were male and, 55 (82.1%) were female. All patients were managed with medication prior to SRS treatment. 5 (7.5%) had rhizotomy and 13 (19.4) had microvascular decompression, and 8 (11.9%) had previous gamma-knife radiosurgery prior to SRS treatment at our institution. Of the 67 patients, 23 (34.3%) received frame-based gamma knife SRS, 44(65.7%) received frameless LINAC treatment. 58 (86.6%) radiation naïve patients received 90 Gy in 1 fraction, while out of the 9 who had previously had intracranial radiation treatment 7 (10.4%) received 70 Gy and 2 (3%) received 80 Gy all prescribed to 100% isodose line. All patients were treated with 4 mm cone. There was no significant difference in brainstem dose between these two techniques. Between LINAC-based or Gamma Knife modalities rate of pain control (77.3 % vs 82.6 %, respectively, p = 0.61) as well as toxicity in facial numbness (31.8% vs 21.7%, respectively, p = 0.38) showed no statistical difference. There was no statistically significant signal (p > 0.05) detected within the subgroups analyzed. The linear regression model also showed no significant difference. LINAC based frameless SRS provides comparable dosimetry and pain control for TN as compared to frame-based gamma knife treatment. It is a patient friendly solution for patients with TN.

Pentoxifylline and Vitamin E Can Restrict Radiation Necrosis via Vascular Pathways, Experimental Study in an Animal Model

Radiation necrosis (RN) is a long-term side effect of Gamma Knife stereotactic radiosurgery that may require surgical intervention. Pentoxifylline and vitamin E have previously been shown to be effective in the treatment of RN in the published literature, but there are no data on the prophylactic use of these molecules or, more importantly, whether prophylaxis is required. The iatrogenic RN model included 50 Sprague-Dawley rats of both sexes. There were 7 treatment subgroups established. Gamma-Plan 8.32 was used to plan after magnetic resonance scans were performed in a specially designed frame. The injection doses used in the treatment groups were vitamin E (30mg/kg/day in a single dose) and pentoxifylline (50mg/kg/day in 2 doses). Control magnetic resonance scans were performed at the end of a 16-week treatment, and the subjects were decapitated for pathological evaluations. The intensity of hypoxia - inducible factor 1α immunoreactivity is statistically significantly lower in the therapeutic vitamin E, prophylactic pentoxifylline and vitamin E, and therapeutic pentoxifylline and vitamin E groups than in the other groups. Similarly, the intensity of vascular endothelial growth factor immunoreactivity was reduced in the therapeutic vitamin E and prophylactic pentoxifylline and vitamin E treatment modality groups.When compared with other groups, the therapeutic pentoxifylline group had significantly fewer vascular endothelial growth factor-immunoreactive cells in the perinecrotic area, with an accompanying decreased contrast enhancement pattern. Both vitamin E and pentoxifylline are effective for the treatment and/or restriction of RN, either alone or in combination. The use of these molecules as a preventive measure did not outperform the therapeutic treatment.

Preradiosurgical Embolization of Arteriovenous Malformations Reduces Target Volume – The Main Determinant for Complete Obliteration

Embolization and stereotactic radiosurgery (SRS) have increasingly been used to treat complex arteriovenous malformations (AVMs). We studied outcomes of AVM patients treated through a multidisciplinary approach, examined the effect of embolization on SRS success, and analyzed predictors of treatment failure. We retrospectively reviewed a prospectively maintained database of patients with AVMs treated with Gamma Knife (Leksell) SRS over an 11-year period. Patients with incomplete medical records and follow-up <2years were excluded. Demographics, clinical presentation, previous rupture history, angiographic nidus size, Spetzler-Martin (S-M) grade, adjunctive endovascular embolization and microsurgical resection, radiologic evidence of obliteration and hemorrhage, and clinical outcomes (modified Rankin Scale [mRS] scores) were recorded. Radiosurgery-related details including nidus volume and number of sessions and radiosurgery-, embolization-, and resection-associated complications were also recorded. Eighty-three patients (mean age, 41.0 ± 21.3years) were included. Mean reduction in AVM nidus target volume with endovascular embolization was 66.0 ± 19.7%. S-M grade reduction was achieved in 51.6% cases. Total obliteration after SRS was achieved in 56 AVMs (67.5%) after 2years, and in 38 (86.4%) after 4years. Two (2.4%) patients had rehemorrhage after SRS. Overall complication rate was 3.6%. Median angiographic follow-up was 55.5months. Favorable outcomes (mRS=0-2) were seen in 77.1%. SRS target volume was an independent predictor of treatment failure regardless of pre-SRS embolization. High AVM obliteration rates were achieved with judicious use of radiosurgery alone or with embolization. Embolization reduced target nidus volume by an average of 66%. SRS target volume was an independent predictor of treatment failure.

LMAP-03 OUTCOME OF BRAIN METASTASES TREATED WITH GAMMA KNIFE STEREOTACTIC RADIOSURGERY (GKSR): COHORT RETROSPECTIVE STUDY ON 205 CASES

Abstract BACKGROUND Brain metastases (BMs) are the most common expansive intracranial lesions in adults. Approximately 50% of patients diagnosed with new brain metastases have more than one brain metastasis at the time of diagnosis. OBJECTIVE We report our experience of brain metastases treated with GKSR and evaluate the outcome. METHODS Patients treated by Gamma Knife stereotactic radiosurgery (GKSR) in our institution between 2008 and 2021 for BM were recorded retrospectively. RESULTS A total of 205 patients (56.6% females) were included, with a median age of 59 (25-83) years old. Breast (n=85, 42.5%) and lung (n=76, 38%) were the common original locations for the primary tumors (Table 1). There were 103 patients (50.3%) with single BM and 102 patients (49.7%) with multiple BM⩾2. The median number of multiple BM treated was 4 (2-43). The overall mean survival time was 6.00(95% CI, 5.07-6.93) months for all BM. The median percentage of tumor control after radiosurgery treatment was 65% (20-99) over the median follow-up time of 6.00(3-84) months. In the overall population, the 1-year OS rate was 37.55%, the 2-year OS rate was 25.12%, and the 5-year OS was 18.51%. The mean survival time among patients with BM was higher in those with multiple BM than those with single BM ([10 (95%CI 6.67-13.33) months vs 5(4.21-5.70) months, P (0.03)]). Retreatment, tumor stability (control), and progression influence the overall survival of BM, whether single or multiple (P&amp;lt;0.001). CONCLUSION Stereotaxic Radiosurgery provides good results in terms of Overall survival and better Quality of Life for BM, whether single or multiple. Stability and retreatment influenced the overall survival of BM.

LMAP-22 STEREOTACTIC RADIOSURGERY FOR PATIENTS WITH BRAIN METASTASES FROM GASTROESOPHAGEAL PRIMARY CANCERS

Abstract BACKGROUND Patients with brain metastases from gastroesophageal primary cancers have poor prognoses, and current management remains unclear. The authors present the largest single-institution experience of utilizing stereotactic radiosurgery (SRS) to treat patients with brain metastases from primary gastroesophageal cancers. METHODS A retrospective review of 71 patients (64 male, 90.14%) treated with Gamma Knife SRS from 2000 to 2022 for gastroesophageal primary cancers was conducted. Overall, 243 brain metastases were treated, and the median number of metastases per patient was 2 (range:1-21). The primary sites were esophagus (59 patients, 83.10%), gastric (7 patients, 9.86%), and gastroesophageal junction (5 patients, 7.04%). The median age at SRS was 66 years (range: 26-85), and the median KPS was 80 (range: 50-100). The median cumulative tumor volume was 6.7 cc (range: 0.27-104.76), and the median margin dose was 18 Gy (range: 11-20). RESULTS The median overall survival after SRS was 7 months (range: 1-64). At the last follow-up, 54 (76.06%) patients were deceased, and 8 (14.81%) patients died due to intracranial metastases. Four patients (5.63%) experienced local tumor progression at a median time of 8 months (range: 2-13) after SRS. On univariate analysis, &amp;gt; 2 brain metastases at SRS presentation (p=0.02, HR: 10.76, 95% CI: 1.48-78.40) was found to be the only significant predictor of local tumor progression. Ten patients (14.08%) experienced new tumor development at a median time of 4 months (range: 0-14) after SRS. On multivariate analysis, both the absence of concurrent systemic therapy (p=0.01, HR: 6.58, 95% CI: 1.55-27.0) and ≤ 2 tumors at SRS presentation (p&amp;lt;0.01, HR: 1.21, CI: 1.08-1.36) were found to be significant predictors of distant tumor control. The incidence of transient adverse radiation effects was 8.45%. CONCLUSIONS SRS can safely and effectively be used to treat primary gastroesophageal cancer brain metastases while allowing patients to focus on primary disease management.

LMAP-19 THE ROLE OF STEREOTACTIC RADIOSURGERY IN PATIENTS WITH BRAIN METASTASES FROM COLORECTAL CANCERS

Abstract BACKGROUND AND OBJECTIVES The role of stereotactic radiosurgery (SRS) for patients with brain metastases from colorectal cancers (CRC) has not been established. The authors present a single-institution experience of CRC patients who underwent SRS with metastatic brain spread. METHODS We retrospectively analyzed 112 metastatic CRC patients (64 female, 57.14%) with 450 brain metastases that were treated with Gamma Knife SRS between 2000-2022. The median age at SRS was 63 years (range: 28-86) and the median Karnofsky Performance Score (KPS) was 80 (range: 60-100). The primary sites were colon (86 patients, 76.79%) and rectal (26 patients, 21%). Three patients underwent hypo-fractionated SRS (3 sessions) with a median margin dose of 27 Gy (range: 27- 30). All other patients underwent single-session SRS with a median margin dose of 18 Gy (range: 11-20). RESULTS The median patient survival after SRS was 7 months (range: 1-174). Ninety-eight (87.5%) patients expired at last follow up and 15 patients (15.31%) died related to progressive intracranial disease. KPS &amp;lt; 80 at SRS presentation (p=0.03, HR: 0.63, 95% CI: 0.41-0.96) was associated with inferior overall survival using multivariate analysis. Seventeen patients (15.18%) had documented local tumor progression after SRS, at a median time of 7 months (range: 3-34) between SRS and progression. Twenty-six patients (23.21%) developed new brain metastases at a median of 5 months (range: 2-26) between SRS and new tumor detection. KPS ≥ 80 (p=0.05, HR: 0.96, 95% CI: 0.93-0.99), and &amp;lt; 3 brain metastases at SRS presentation (p&amp;lt;0.01, HR: 3.62, 95% CI: 1.53-8.56) were associated with better distant tumor control on multivariate analysis. The incidence of adverse radiation effects was 5.36%. CONCLUSIONS SRS effectively controls brain metastases from CRC with a low risk of treatment-related toxicity, allowing patients to focus on primary disease management. During follow-up, the development of progressive or additional metastases can be safely treated by repeat SRS.

Evaluation of inverse treatment planning for gamma knife radiosurgery using fMRI brain activation maps as organs at risk.

Stereotactic radiosurgery (SRS) can be an effective primary or adjuvant treatment option for intracranial tumors. However, it carries risks of various radiation toxicities, which can lead to functional deficits for the patients. Current inverse planning algorithms for SRS provide an efficient way for sparing organs at risk (OARs) by setting maximum radiation dose constraints in the treatment planningprocess. We propose using activation maps from functional MRI (fMRI) to map the eloquent regions of the brain and define functional OARs (fOARs) for Gamma Knife SRS treatment planning. We implemented a pipeline for analyzing patient fMRI data, generating fOARs from the resulting activation maps, and loading them onto the GammaPlan treatment planning software. We used the Lightning inverse planner to generate multiple treatment plans from open MRI data of five subjects, and evaluated the effects of incorporating the proposed fOARs. The Lightning optimizer designs treatment plans with high conformity to the specified parameters. Setting maximum dose constraints on fOARs successfully limits the radiation dose incident on them, but can have a negative impact on treatment plan quality metrics. By masking out fOAR voxels surrounding the tumor target it is possible to achieve high quality treatment plans while controlling the radiation dose on fOARs. The proposed method can effectively reduce the radiation dose incident on the eloquent brain areas during Gamma Knife SRS of braintumors.

Comparison of preoperative versus postoperative treatment dosimetry plans of single-fraction stereotactic radiosurgery for surgically resected brain metastases.

Stereotactic radiosurgery (SRS) for operative brain metastasis (BrM) is usually administered 1 to 6 weeks after resection. Preoperative versus postoperative timing of SRS delivery related to surgery remains a critical question, as a pattern of failure is the development of leptomeningeal disease (LMD) in as many as 35% of patients who undergo postoperative SRS or the occurrence of radiation necrosis. As they await level I clinical data from ongoing trials, the authors aimed to bridge the gap by comparing postoperative with simulated preoperative single-fraction SRS dosimetry plans for patients with surgically resected BrM. The authors queried their institutional database to retrospectively identify patients who underwent postoperative Gamma Knife SRS (GKSRS) after resection of BrM between January 2014 and January 2021. Exclusion criteria were prior radiation delivered to the lesion, age < 18 years, and prior diagnosis of LMD. Once identified, a simulated preoperative SRS plan was designed to treat the unresected BrM and compared with the standard postoperative treatment delivered to the resection cavity per Radiation Therapy Oncology Group (RTOG) 90-05 guidelines. Numerous comparisons between preoperative and postoperative GKSRS treatment parameters were then made using paired statistical analyses. The authors' cohort included 45 patients with a median age of 59 years who were treated with GKSRS after resection of a BrM. Primary cancer origins included colorectal cancer (27%), non-small cell lung cancer (22%), breast cancer (11%), melanoma (11%), and others (29%). The mean tumor and cavity volumes were 15.06 cm3 and 12.61 cm3, respectively. In a paired comparison, there was no significant difference in the planned treatment volumes between the two groups. When the authors compared the volume of surrounding brain that received 12 Gy or more (V12Gy), an important predictor of radiation necrosis, 64% of patient plans in the postoperative SRS group (29/45, p = 0.008) recorded greater V12 volumes. Preoperative plans were more conformal (p < 0.001) and exhibited sharper dose drop-off at the lesion margins (p = 0.0018) when compared with postoperative plans. Comparison of simulated preoperative and delivered postoperative SRS plans administered to the BrM or resection cavity suggested that preoperative SRS allows for more highly conformal lesional coverage and sharper dose drop-off compared with postoperative plans. Furthermore, V12Gy was lower in the presurgical GKSRS plans, which may account for the decreased incidence of radiation necrosis seen in prior retrospective studies.

Toxicity and outcomes of melanoma brain metastases treated with stereotactic radiosurgery: the risk of subsequent symptomatic intralesional hemorrhage exceeds that of radiation necrosis.

We aimed to assess the outcomes and patterns of toxicity in patients with melanoma brain metastases (MBM) treated with stereotactic radiosurgery (SRS) with or without immunotherapy (IO). From a prospective registry, we reviewed MBM patients treated with single fraction Gamma Knife SRS between 2008 and 2021 at our center. We recorded all systemic therapies (chemotherapy, targeted therapy, or immunotherapy) administered before, during, or after SRS. Patients with prior brain surgery were excluded. We captured adverse events following SRS, including intralesional hemorrhage (IH), radiation necrosis (RN) and local failure (LF), as well as extracranial disease status. Distant brain failure (DBF), extracranial progression-free survival (PFS) and overall survival (OS) were determined using a cumulative Incidence function and the Kaplan-Meier method. Our analysis included 165 patients with 570 SRS-treated MBM. Median OS for patients who received IO was 1.41 years versus 0.79 years in patients who did not (p = 0.04). Ipilimumab monotherapy was the most frequent IO regimen (30%). In the absence of IO, the cumulative incidence of symptomatic (grade 2 +) RN was 3% at 24 months and remained unchanged with respect to the type or timing of IO. The incidence of post-SRS g2 + IH in patients who did not receive systemic therapy was 19% at 1- and 2 years compared to 7% at 1- and 2 years among patients who did (HR: 0.33, 95% CI 0.11-0.98; p = 0.046). Overall, neither timing nor type of IO correlated to rates of DBF, OS, or LF. Among patients treated with IO, the median time to extracranial PFS was 5.4 months (95% IC 3.2 - 9.1). The risk of g2 + IH exceeds that of g2 + RN in MBM patients undergoing SRS, with or without IO. IH should be considered a critical adverse event following MBM treatments.

Stereotactic radiosurgery for patients with brain metastases from gastroesophageal cancers.

The prognosis of patients with brain metastases from gastroesophageal (GE) cancers remains unclear despite recent advances in systemic therapies. The authors present a large single-institution experience in the use of stereotactic radiosurgery (SRS). A retrospective review of 71 GE cancer patients (64 male, 90.14%) who underwent Gamma Knife SRS was conducted. Overall, 243 brain metastases were treated and the median number of metastases per patient was 2 (range:1-21). The median age at SRS was 66 years (range: 26-85) and the median treatment day KPS was 80 (range: 50-100). The median cumulative tumor volume was 6.7cc (range: 0.27-104.76) and the median single-session margin dose was 18Gy (range: 12-20). The median overall survival after SRS was 7 months (range: 1-64). At last follow up, 54 (76.06%) patients were deceased, 8 of whom (14.81%) expired secondary to their intracranial metastases. Four patients (5.63%) experienced local tumor progression at a median time of 8 months (range: 2-13) after SRS. Ten patients (14%) experienced new remote tumor development at a median time of 4 months (range: 0-14) after SRS. Whole-brain radiation therapy (2 patients, 20%) and repeat SRS (8 patients, 80%) were used for newly developed tumors. The incidence of transient adverse radiation effects was 8.45%. In this study, the 12-month local tumor control rate was 90%. Incidences of adverse radiation effect rates were rare. The median overall survival of 7 months indicates the poor prognosis of patients with brain spread of their GE cancer.

Occipital bone and tumor-induced osteomalacia: a rare tumor site for an uncommon paraneoplastic syndrome

IntroductionTumor-induced osteomalacia (TIO) is an uncommon paraneoplastic syndrome due to the overproduction of fibroblast growth factor 23 (FGF23). It is predominantly caused by mesenchymal tumors and cured upon their complete removal. Non-surgical treatment is an alternative option but limited to specific clinical conditions.MethodsWe report a challenging case of TIO caused by a tumor involving the occipital bone. We also performed a literature review of TIO caused by tumors localized at this site, focusing on clinical findings, treatment, and outcomes.ResultsThe patient, a 62-year-old male, presented with a long-lasting history of progressive weakness. Biochemical evaluation revealed severe hypophosphatemia due to low renal tubular reabsorption of phosphate with raised intact FGF23 values. A 68 Ga-DOTATATE PET/TC imaging showed a suspicious lesion located in the left occipital bone that MRI and selective venous catheterization confirmed to be the cause of TIO. Stereotactic gamma knife radiosurgery was carried out, but unfortunately, the patient died of acute respiratory failure.To date, only seven additional cases of TIO have been associated to tumors located in the occipital bone. Furthermore, the tumor involved the left side of the occipital bone in all these patients.ConclusionThe occipital region is a difficult area to access so a multidisciplinary approach for their treatment is required. If anatomical differences could be the basis for the predilection of the left side of the occipital bone, it remains to be clarified.