Postoperative SRS Research Articles

Patterns of failure after radiosurgery for WHO grade 1 or imaging defined meningiomas: Long-term outcomes and implications for management

BackgroundWe analyzed long-term control and patterns of failure in patients with World Health Organization Grade 1 meningiomas treated with definitive or postoperative stereotactic radiosurgery at the authors’ affiliated institution. Methods96 patients were treated between 2004 and 2019 with definitive (n = 57) or postoperative (n = 39) stereotactic radiosurgery. Of the postoperative patients, 17 were treated adjuvantly following subtotal resection and 22 were treated as salvage at time of progression. Patients were treated to the gross tumor alone without margin or coverage of the dural tail to a median dose of 15 Gy. Median follow up was 7.4 years (inter-quartile range 4.8–11.3). Local control, marginal control, regional control, and progression-free survival were analyzed. ResultsLocal control at 5 and 10 years was 97 % and 95 %. PFS at 5 and 10 years was 94 % and 90 % with no failures reported after 6 years. Definitive and postoperative local control were similar at 5 (95 % [82–99 %] vs. 100 %) and 10 years (92 % [82–99 %] vs. 100 %). Patients treated with postoperative SRS did not have an increased marginal failure rate (p = 0.83) and only 2/39 (5 %) experienced recurrence elsewhere in the cavity. ConclusionsStereotactic radiosurgery targeting the gross tumor alone provides excellent local control and progression free survival in patients treated definitively and postoperatively. As in the definitive setting, patients treated postoperatively can be treated to gross tumor alone without need for additional margin or dural tail coverage.

NCOG-01. BASELINE PATIENT-REPORTED OUTCOMES IN AN ONGOING PHASE III TRIAL OF PRE-OPERATIVE SRS VERSUS POST-OPERATIVE SRS FOR BRAIN METASTASES

Abstract In ongoing phase III randomized trial (NCT03741673) evaluating risk of LMD in patients with brain metastasis, patients are stratified by tumor size, location, and histology, and randomized to pre- versus post-operative SRS. Exploratory endpoints include patient reported outcomes (PROs) assessing symptoms (MDASI-BT) and health status (EQ-5D-5L). Characteristics of patients (N=40) with pre-treatment baseline include: mean (SD): age 59.3(11.4) years; 2.6(2.2) mets; 15.2(10.3) cc brain met volume; median KPS: 90 (range: 70-100). On the MDASI-BT, 22.5%, 47.5%, 27.5%, 12.5%, and 80% reported no symptoms on the Cognitive, Neurologic, Affective, Constitutional, and Gastrointestinal Factors, respectively. The median factor score was <1 on all factors. Neurologic (r=-.35, p=.03) and Constitutional Factors (r=-0.34, p=.03) correlated with KPS. There was no correlation between MDASI-BT Factors and number/volume of metastases. On the EQ-5D-5L, patients reported no problems with Mobility (45%), Self-Care (72.5%), Usual Activities (62.5%), Pain/Discomfort (55%), and Anxiety/Depression (52.5%). Nearly twenty-eight percent reported no problems in any domain. KPS correlated with Mobility (r=-.48, p< 0.01), Self-Care (r=-.49, p< 0.01), and Usual Activities (r=-.44, p< 0.01). There was no association between EQ-5D-5L items and number/volume of metastases. Patients’ baseline rating of current health on a 0-100 scale (VAS) ranged from 30-100 (mean (SD)=72.25 (19.18)). VAS correlated most with Anxiety/Depression (r=-.40, p=.01). VAS also correlated significantly with MDASI-BT Affective Factor (r=-.541, p< .001) but not with Cognitive or Neurologic Factors. There was no correlation between VAS and KPS or number/volume of metastases. As previously reported, objective measures of cognitive function are associated with disease characteristics. PROs were associated with performance status but not disease characteristics. Mood was more strongly associated with patients’ self-perception of overall health status than clinical or disease characteristics. At baseline, a high proportion of patients report no adverse symptoms, suggesting use of these outcomes is best suited to trials measuring worsening of symptoms.

QLTI-03. FRACTIONATED PREOPERATIVE VS POSTOPERATIVE STEREOTACTIC RADIOTHERAPY FOR PATIENTS WITH MELANOMA BRAIN METASTASES: A COST UTILITY ANALYSIS

Abstract INTRODUCTION Stereotactic radiosurgery (SRS) followed by surgical resection is an emerging treatment paradigm for brain metastases. Preoperative SRS may improve outcomes such as rates of radiation necrosis (RN) and leptomeningeal disease (LMD) compared to postoperative SRS. However, the impact of this paradigm shift on metrics such as cost of care and hospital length of stay is unclear. In this study, we sought to categorize these metrics for melanoma metastases, specifically. METHODS A retrospective analysis identified patients who underwent surgical resection and fractionated stereotactic radiation therapy (FSRT) for melanoma brain metastases. Demographics, medical history, systemic and local treatment modalities, imaging, and postoperative course were collected. Perioperative cost of care was analyzed beginning two weeks preoperatively and concluded at four-weeks postoperatively. Continuous variables were analyzed via non-parametric two-sided t-tests and ANOVAs. Categorical variables were analyzed via Chi-squared tests. RESULTS Forty-two patients underwent 43 craniotomies for melanoma metastases. The mean age at surgery was 59.6 years-old and the male predominance was 65.1%. Total cost of perioperative care was more expensive among those treated with neoadjuvant (n = 11) FSRT compared to those who underwent postoperative (n = 32) FSRT ($262,072 vs $174,646; p = 0.0254). Mean length of stay for craniotomies was similar between groups (p = 0.1674), although trending down among the neoadjuvant FSRT group (4.5 days) among the neoadjuvant FSRT group versus the postoperative FSRT group (7.0 days). CONCLUSIONS In this study, neoadjuvant FSRT had an increased cost of care in the perioperative period, and similar lengths of hospital stay for craniotomy. Preoperative FSRT for melanoma metastases may result in shorter LOS, however, comes with an increased cost of care. Further investigation of itemization of healthcare costs to identify areas of improvement for neoadjuvant therapy is warranted.

LMAP-16 THE EFFECTS OF POSTOPERATIVE STEREOTACTIC RADIOSURGERY TIMING ON CLINICAL OUTCOMES IN PATIENTS WITH INTRACRANIAL METASTASES: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract Stereotactic radiosurgery (SRS) after neurosurgical resection improves local tumor control in patients with metastatic brain cancer. However, the influence of timing on its therapeutic efficacy is unclear, and a lack of consensus and standardization limits its optimization. We performed a systematic review and meta-analysis examining publications that reported the timing of postoperative SRS for patients with intracranial metastases. Our primary outcomes included median overall survival and rates of local and regional failure, while our secondary outcomes examined the incidence of treatment-related adverse events. Correlations between median SRS timing and these variables were assessed using linear regression and publication bias was appraised via Egger’s test. Our systematic review resulted in 22 articles comprising 1338 patients who met the criteria for inclusion. The median timing of adjuvant SRS spanned 14.5 to 41 days. There was a significant positive study-level correlation of median time to SRS with regional failure (P=0.043, R2=0.32) but not with overall survival (P=0.54, R2=0.03) or local failure (P=0.16, R2= 0.14). Data regarding adverse events related to treatment was limited in the literature and there was significant heterogeneity within the reports (P<0.0001). Overall, our results demonstrate institutions with a longer time between surgery and SRS had lower rates of regional failure, however, this did not affect rates of local failure or patient survival. Further research is warranted to elucidate the role of timing for postoperative SRS on oncologic outcomes as well as the factors that contribute to optimal radiosurgery workflow in this patient population.

TIPS-15 NEUROCOGNITIVE FUNCTION AND NEUROCOGNITIVE CONCERNS IN AN ONGOING PHASE III TRIAL OF PRE-OPERATIVE SRS VERSUS POST-OPERATIVE SRS FOR BRAIN METASTASES

Abstract In our ongoing phase III randomized trial (NCT03741673) evaluating risk of leptomeningeal disease (LMD) in patients with brain metastasis, patients are stratified by tumor size, location, and histology, and randomized to pre-operative SRS versus post-operative SRS. The primary endpoint is 1-year LMD-free rate, and exploratory endpoints include neurocognitive function (NCF). NCF is assessed prior to treatment and longitudinally (1.5, 6, and 12 months from the start of treatment) with the HVLT-R, TMT, and COWA yielding the Clinical Trial Battery Composite score (CTB COMP). Patients also complete the MDASI-BT, which includes a Cognitive Factor measuring patient reported cognitive concerns. Currently, 41 patients completed pre-treatment NCF baseline. Characteristics of patients with pre-treatment NCF baseline include mean (SD): age 60.0+/-11.7 years, 2.6+/-2.2 metastases, 15.2+/-10.1 cc brain metastases volume, median KPS 90 (range: 70-100), 83% white, 52% male, and 50% received AEDs at time of surgery. The most common primary cancers among this cohort were: 31% NSCLC, 19% RCC, 14% melanoma, 7% breast, 2% thyroid, and 26% other. Mean (SD) NCF z-scores ranged from z= -0.09 (1.08) to -3.09 (6.13), CTB COMP z=-1.13 (1.65), and the mean (SD) MDASI-BT Cognitive Factor score was 1.1 (1.3). Using multivariable linear regression including CTB COMP, MDASI-BT Cognitive and Affective Factor, KPS, number of and intracranial volume of metastases, only intracranial volume of metastases was statistically significantly associated with CTB COMP (B=-.058, p=.034) and only the MDASI-BT Affective Factor was statistically significantly associated with the MDASI-BT Cognitive Factor (B=.305, p=<.001). At baseline, disease factors such as tumor burden appear to be the primary driver of objectively measured neurocognitive dysfunction and mood factors appear to be the primary driver of subjective patient reported neurocognitive concerns. This has important implications for interpretation of these different clinical outcome assessments in clinical trials measuring objective neurocognitive function and subjective neurocognitive concerns.

Separation Operation Followed by Stereotactic Radiotherapy in the Treatment of Spinal Metastasis From Hepatocellular Carcinoma: A Retrospective Cohort Study.

Retrospective cohort study. Spinal metastasis from hepatocellular carcinoma is rapidly progressive and predisposes to spinal disability, cord compression and further neural injury, leading to poor prognosis. Currently, it is still challenging to look for a treatment strategy that can improve the quality of life of patients and even directly prolong the survival time. This study attempts to evaluate the clinical efficacy of separation operation combined with postoperative stereotactic radiotherapy (SRT/SRS) in the treatment of hepatocellular carcinoma patients developing spinal metastasis and epidural spinal cord compression. Patients with metastases spinal cord compression from hepatocellular carcinoma were studied retrospectively and divided into two groups, the SO group (who undergo separation operations combined with postoperative SRS, n = 32) and RT group (who received only SRS, n = 28). The visual Analogue Scale (VAS) pain score, Frankel grade, Karnofsky performance score, and Quality of Life (SF-36) score were comparatively analyzed between the two groups. Significantly higher VAS pain scores, Frankel grades, Karnofsky performance scores and Quality of Life (SF-36) scores were demonstrated in patients with combination treatment than in patients with SRS alone. Separation operations are effective surgical procedure for the treatment of spinal metastatic tumor from hepatocellular carcinoma with spinal cord compression. The combination with postoperative SRS can significantly improve the quality of life in this patient population via spinal canal decompression and spinal stability reconstruction.

INTRAMET: Results of a prospective, single-arm, open-label phase II trial of intraoperative radiotherapy after resection of brain metastases.

2031 Background: Brain metastases (BM) occur in about 10-20% of all cancer patients during the course of their disease. The current standard of care for lesions that cause mass effects is neurosurgical resection followed by adjuvant radiotherapy of the resection cavity. We here report efficacy data of the INTRAMET trial (NCT03226483), which tested intraoperative radiation therapy (IORT) using a high-dose, single fraction to the tumor bed. Methods: Patients ≥18 years and Karnofsky (KPS) ≥50 with suspected BM were included. A frozen-section confirmed metastasis and technically applicable IORT were mandatory. Exclusion criteria were surgical or MRI contraindications, meningeal infiltration, or IORT Dmax doses exceeding 8 Gy at risk structures. IORT was performed after tumor resection in the operating room with a mobile low energy X-ray device emitting a spherical radiation field with a sharp dose gradient. A dose of 30Gy was prescribed to the surface of the resection cavity. The primary endpoint was cumulative local control rate (LCR). Secondary endpoints were incidence of other (distant) BM (RCR), overall survival (OS), time to the next systemic treatment and adverse event rates (AE). Results: In total, 35 of the originally 50 planned patients were recruited. After a pre-specified interim analysis, the study was prematurely halted due to good safety and outcomes profiles. 54.3% were men, the mean age was 64 (45-85) years. The mean follow-up was 25.7 (0.8-64.5) month. At the time of this report, 51.4% of patients were alive. 68.6% primary histologies corresponded to lung primaries. The LCR was 94.3% (95% CI 82.9-98.8%) and RCR was 57.1% (95% CI 40.7-72.4%,). 8.6% patients or lesions developed out of field leptomeningeal progression. The mean OS was 37.4 months (95% CI 28.9-46.9). For those patients undergoing salvage whole brain RT (WBRT), the median initiation time was 147 (20-601) days with a significant survival benefit for those not requiring WBRT (p = 0.027). No significant survival differences were identified according to primary histology (p = 0.618), immunotherapy (p = 0.928), seizures at baseline (p = 0.169), KPS (p = 0.056) or radionecrosis appearance (p = 0.214). Mean time to next systemic treatment was 45.0 (95% CI 35.1-54.8) days. No G4-5 AE related to IORT occurred. The overall radionecrosis (RN) rate was 20% (n = 5 G1, n = 1 G2, n = 1 G3). No risk factors could be associated to RN. Post-surgical seizures were present in 28.6% patients, with eloquent localizations as the only predictive factor (p = 0.008). Conclusions: IORT for resected BM yields excellent local control rates and has a toxicity profile similar to those reported in post-operative SRS trials. By easing a prompt initiation of subsequent systemic treatments, IORT might shorten the overall treatment courses of many cancer patients. Clinical trial information: NCT03226483 .

What if: A retrospective reconstruction of resection cavity stereotactic radiosurgery to mimic neoadjuvant stereotactic radiosurgery.

Neoadjuvant stereotactic radiosurgery (NaSRS) of brain metastases has gained importance, but it is not routinely performed. While awaiting the results of prospective studies, we aimed to analyze the changes in the volume of brain metastases irradiated pre- and postoperatively and the resulting dosimetric effects on normal brain tissue (NBT). We identified patients treated with SRS at our institution to compare hypothetical preoperative gross tumor and planning target volumes (pre-GTV and pre-PTV) with original postoperative resection cavity volumes (post-GTV and post-PTV) as well as with a standardized-hypothetical PTV with 2.0mm margin. We used Pearson correlation to assess the association between the GTV and PTV changes with the pre-GTV. A multiple linear regression analysis was established to predict the GTV change. Hypothetical planning for the selected cases was created to assess the volume effect on the NBT exposure. We performed a literature review on NaSRS and searched for ongoing prospective trials. We included 30 patients in the analysis. The pre-/post-GTV and pre-/post-PTV did not differ significantly. We observed a negative correlation between pre-GTV and GTV-change, which was also a predictor of volume change in the regression analysis, in terms of a larger volume change for a smaller pre-GTV. In total, 62.5% of cases with an enlargement greater than 5.0 cm3 were smaller tumors (pre-GTV < 15.0 cm3), whereas larger tumors greater than 25.0 cm3 showed only a decrease in post-GTV. Hypothetical planning for the selected cases to evaluate the volume effect resulted in a median NBT exposure of only 67.6% (range: 33.2-84.5%) relative to the dose received by the NBT in the postoperative SRS setting. Nine published studies and twenty ongoing studies are listed as an overview. Patients with smaller brain metastases may have a higher risk of volume increase when irradiated postoperatively. Target volume delineation is of great importance because the PTV directly affects the exposure of NBT, but it is a challenge when contouring resection cavities. Further studies should identify patients at risk of relevant volume increase to be preferably treated with NaSRS in routine practice. Ongoing clinical trials will evaluate additional benefits of NaSRS.

Dosimetric feasibility of direct post-operative MR-Linac-based stereotactic radiosurgery for resection cavities of brain metastases

BackgroundPost-operative radiosurgery (SRS) of brain metastases patients is typically planned on a post-recovery MRI, 2–4 weeks after resection. However, the intracranial metastasis may (re-)grow in this period. Planning SRS directly on the post-operative MRI enables shortening this time interval, anticipating the start of adjuvant systemic therapy, and so decreasing the chance of extracranial progression. The MRI-Linac (MRL) allows the simultaneous execution of the post-operative MRI and SRS treatment. The aim of this work was investigating the dosimetric feasibility of MRL-based post-operative SRS. MethodsMRL treatments based on the direct post-operative MRI were simulated, including thirteen patients with resectable single brain metastases. The gross tumor volume (GTV) was contoured on the direct post-operative scans and compared to the post-recovery MRI GTV.Three plans for each patient were created: a non-coplanar VMAT CT-Linac plan (ncVMAT) and a coplanar IMRT MRL plan (cIMRT) on the direct post-operative MRI, and a ncVMAT plan on the post-recovery MRI as the current clinical standard. ResultsBetween the direct post-operative and post-recovery MRI, 15.5 % of the cavities shrunk by > 2 cc, and 46 % expanded by ≥ 2 cc. Although the direct post-operative cIMRT plans had a higher median gradient index (3.6 vs 2.7) and median V3Gy of the skin (18.4 vs 1.1 cc) compared to ncVMAT plans, they were clinically acceptable. ConclusionDirect post-operative MRL-based SRS for resection cavities of brain metastases is dosimetrically acceptable, with the advantages of increased patient comfort and logistics.Clinical benefit of this workflow should be investigated given the dosimetric plausibility.

Staged radiosurgery alone versus postoperative cavity radiosurgery for patients with midsize-to-large brain metastases: a propensity score matching analysis.

The authors investigated and compared the results of staged stereotactic radiosurgery (S-SRS) alone and those of postoperative cavity SRS (C-SRS) for patients with midsize-to-large brain metastases (BMs). Patients with BMs who had undergone S-SRS or C-SRS during the period from 2010 to 2020 were retrospectively identified from an institutional database. The two treatment groups were generated by propensity score matching (PSM; match ratio 2:1) based on 13 potential prognostic covariates: sex, age, Karnofsky Performance Status, type of primary cancer, timing of BM diagnosis, extracranial disease status, driver mutations, molecular target therapy, neurological symptoms, number of BMs, location of BMs treated with S-SRS or C-SRS, maximal tumor or cavity volume, and cumulative intracranial tumor volume. Patient survival and control of intracranial disease were compared between the S-SRS and C-SRS groups using time-dependent analyses taking into account competing events. In total, 110 patients in the S-SRS group and 62 in the C-SRS group were selected by PSM. In the S-SRS group, the median interval between the two radiosurgical sessions was 21 days, and the median total prescription dose was 28 Gy at 50%. In the C-SRS group, the median time from surgery to C-SRS was 16 days, and the median prescription dose delivered to the surgical cavity was 15 Gy at 55%. At the time point of data set fixation, 129 patients had died, 43 were alive, and none had been lost to follow-up. The 2-year survival rates for the S-SRS and C-SRS groups after the initial intervention were 33% and 37% and the median survival times were 14.8 and 17.5 months, respectively (p = 0.33). The 2-year cumulative neurological mortality rates were 11% and 9%, respectively (p = 0.65). The 2-year local failure rates were 32% and 12% (p = 0.036) and the 2-year distant recurrence rates were 55% and 58%, respectively (p = 0.53). The 2-year leptomeningeal disease development rates were 9% and 25%, respectively (p = 0.007). The present study revealed no significant difference in overall survival or cumulative neurological mortality between the S-SRS and C-SRS groups. The local control failure rate was significantly higher in the S-SRS group, whereas the incidence of leptomeningeal disease development was significantly higher in the C-SRS group.

Pre-operative stereotactic radiosurgery for cerebral metastatic disease: A retrospective dose-volume study

Background and purposeStereotactic radiosurgery (SRS) after maximal safe resection is an accepted treatment strategy for patients with cerebral metastatic disease. Despite its high conformality profile, the incidence of radionecrosis (RN) remains high. SRS delivered pre-operatively could be associated with a reduced incidence of RN. We sought to evaluate whether neoadjuvant SRS could reduce radiotherapy doses in a cohort of patients treated with post-operative SRS. MethodsA cohort of 47 brain metastases (BM) treated at 2 academic institutions was retrospectively analyzed. Subjects underwent surgical extirpation of BMs and subsequent SRS to surgical bed. Post-operative volumetric and dosimetric data was collected from records or recreations of delivered plans; pre-operative data were derived from hypothetical radiotherapy courses and compared using Wilcoxon signed-rank tests. ResultsHigher planned tumor volume post-operatively (median[IQR] 12.28 [6.54, 18.69]cc vs 10.20 [4.53, 21.70]cc respectively, p = 0.4150) was observed. The median prescribed radiotherapy dose (DRx) was 16 Gy pre-operatively and 24 Gy post-operatively (p < 0.0001). Further investigations revealed improved pre-operative conformity index (1.23[1.20, 1.29] vs 1.29[1.23, 1.39], p = 0.0098) and gradient index (2.72[2.59, 2.98] vs 2.94[2.69, 3.47], p = 0.0004). A significant difference was found in normal brain tissue exposed to 10 Gy (12.97[6.78, 25.54]cc vs 32.13[19.42, 48.40]cc, p < 0.0001), 12 Gy (9.31[4.56, 17.43]cc vs 23.80[14.74, 36.56]cc, p < 0.0001), and 14 Gy (5.62[3.23, 11.61]cc vs 17.47[9.00, 28.31]cc, p < 0.0001), favoring pre-operative SRS. ConclusionsNeoadjuvant SRS is associated reduced DRx, better conformality profile and decreased radiation to normal tissue. These findings could support the use of neoadjuvant SRS for the treatment of BMs.

Are patients who return for 10-year follow-up after AIS surgery different from those who do not?

To evaluate the impact of patients lost to follow-up on outcomes of surgery for adolescent idiopathic scoliosis (AIS) at 10-year postoperative. Preoperative, 2-year, and 5-year postoperative demographic, radiographic, and SRS-22 data from a prospective multi-center registry were compared between patients with a 10-year follow-up visit versus those without. A second analysis utilized variables that were different between the groups, along with SRS scores, in a cohort of patients with preoperative, 2-, 5-, and 10-year postoperative SRS scores (complete cohort) to impute missing 10-year data (imputed cohort) utilizing Markov chain Monte Carlo simulation. 250 patients had 10-year follow-up (21%). Those with 10-year follow-up had a greater percentage of patients who underwent anterior procedures (p < 0.05). Radiographically, the groups were similar at all three time points. SRS-22 scores demonstrated slightly worse pain and function preoperatively and at 2year in those lost to follow-up (effect size eta = 0.11-0.12), with no differences at 5year. Imputed data analysis demonstrated similar trends over time in SRS-22 scores compared to the complete cohort for total score and all domains except pain. There was no significant difference in imputed versus complete 10-year SRS-22 scores (p > 0.05). This study identified early differences between patients with 10-year follow-up and those without, though effect sizes were small and non-existent at 5years. SRS-22 scores at 10year between the complete and imputed data sets did not differ. Clinically relevant outcomes of the subset who followed-up at 10year are likely generalizable to the entire eligible AIS population.

From Postoperative to Preoperative: A Case Series of Hypofractionated and Single-Fraction Neoadjuvant Stereotactic Radiosurgery for Brain Metastases.

Postoperative stereotactic radiosurgery after resection of brain metastases is currently the standard of care. However, rates of leptomeningeal disease (LMD) after postoperative stereotactic radiosurgery have been reported to be >30%. Neoadjuvant stereotactic radiosurgery (NaSRS) has been proposed as an alternative treatment approach to decrease this risk. To report the local control (LC) and LMD rates in patients undergoing NaSRS. Our retrospective multicenter case series included consecutive patients planned for SRS followed by resection of intracranial lesions with a confirmed primary malignancy. Concurrent SRS alone to other intracranial lesions was permitted. Exclusion criteria included previous local treatment to that particular lesion and Eastern Cooperative Oncology Group performance status ≥3. Outcomes reported included LC, distant intracranial control (DC), overall survival, LMD, and radionecrosis (RN) rates. Overall, 28 patients with 29 lesions were eligible for analysis. The median follow-up was 12.8 months. The mean age was 62.5 (range 43-80) years, and 55% were Eastern Cooperative Oncology Group performance status 0 to 1. The most common primary malignancies included non-small cell lung cancer (43%) and melanoma (32%). Hypofractionated SRS was used in 62.1%. The 12-month LC and LMD rates were 91.3% and 4.0%, respectively. The 12-month RN, DC, and overall survival rates were 5.0%, 51.5%, and 60.1%, respectively. Compared with postoperative SRS, our study suggests that NaSRS leads to comparable local control with a decreased risk of LMD and RN. This is the first NaSRS series with a majority of patients treated with fractionated SRS. NaSRS is a promising approach for appropriate patients where surgical resection is a component of local therapy.

Preoperative Radiosurgery for Resected Brain Metastases: The PROPS-BM Multicenter Cohort Study

Preoperative (pre-op) SRS has been demonstrated to be a feasible alternative to postoperative (post-op) SRS primarily based on single institution studies with potential benefits in adverse radiation effect (ARE) and leptomeningeal disease (LMD) compared to post-op SRS. This study (Preoperative Radiosurgery for Brain Metastases - PROPS-BM) reports pre-op SRS treatment details and outcomes from a large multicenter cohort.Patients (pts) with brain metastases (BM) from solid cancers, of which at least 1 lesion was treated with pre-op SRS and underwent planned resection were included from 5 institutions. SRS to synchronous intact BM was allowed. Exclusion criteria included classically radiosensitive or non-solid cancers, prior or planned whole brain radiotherapy (WBRT), and < 3 months of cranial imaging follow-up. SRS dose, fractionation, and interval between pre-op SRS and surgery was as per individual institutional protocol. Intracranial outcomes were estimated using cumulative incidence with competing risk of death and overall survival (OS) was estimated using the Kaplan-Meier method with the date of resection considered time 0. Radiographic LMD was categorized as nodular (nLMD) or classical "sugarcoating" (cLMD).The cohort included 242 pts with 253 pre-op treated index lesions. The majority of pts (62.4%) had a single BM, 93.7% underwent gross total resection (GTR), and 98.8% were treated with a single fraction to a median dose of 15 Gy to a median gross tumor volume (GTV) of 9.9 cc. Median interval between pre-op SRS and surgery was 1 day. Most pts had non-small cell lung (43.4%), breast (20.2%), or melanoma (12.8%) cancer. The table below details 1 and 2-year outcomes. Extent of resection was a strong independent predictor of cavity local recurrence (LR) with LR occurring in 7 of 16 cavities (43.8%) status post subtotal resection (STR) compared with 32 of 237 (13.5%) cavities status post GTR (P = 0.005). The majority of LMD was cLMD type (13 of 19 pts with LMD, 68.4%). Ten of 242 pts (4.1%) experienced grade ≥3 post-op surgical complications.This multicenter cohort study represents the largest population of pts treated with pre-op SRS to our knowledge. Approximately half of the pts included are from previously unpublished cohorts. The favorable oncologic outcomes, especially the notably low rates of LMD and ARE, previously demonstrated in single institution studies are confirmed in this expanded multicenter analysis without evidence of excessive post-op surgical complications. STR, though infrequent, is associated with significantly worse cavity LR in this setting. A randomized trial between pre-op and post-op SRS is warranted and is currently being designed.

Preoperative Radiosurgery for Resected Brain Metastases: The PROPS-BM Multicenter Cohort Study

Preoperative radiosurgery (SRS) is a feasible alternative to postoperative SRS, with potential benefits in adverse radiation effect (ARE) and leptomeningeal disease (LMD) relapse. However, previous studies are limited by small patient numbers and single-institution designs. Our aim was to evaluate preoperative SRS outcomes and prognostic factors from a large multicenter cohort (Preoperative Radiosurgery for Brain Metastases [PROPS-BM]). Patients with brain metastases (BM) from solid cancers who had at least 1 lesion treated with preoperative SRS and underwent a planned resection were included from 5 institutions. SRS to synchronous intact BM was allowed. Radiographic meningeal disease (MD) was categorized as either nodular or classical "sugarcoating" (cLMD). The cohort included 242 patients with 253 index lesions. Most patients (62.4%) had a single BM, 93.7% underwent gross total resection, and 98.8% were treated with a single fraction to a median dose of 15 Gray to a median gross tumor volume of 9.9 cc. Cavity local recurrence (LR) rates at 1 and 2 years were 15% and 17.9%, respectively. Subtotal resection (STR) was a strong independent predictor of LR (hazard ratio, 9.1; P < .001). One and 2-year rates of MD were 6.1% and 7.6% and of any grade ARE were 4.7% and 6.8% , respectively. The median overall survival (OS) duration was 16.9 months and the 2-year OS rate was 38.4%. The majority of MD was cLMD (13 of 19 patients with MD; 68.4%). Of 242 patients, 10 (4.1%) experienced grade ≥3 postoperative surgical complications. To our knowledge, this multicenter study represents the largest cohort treated with preoperative SRS. The favorable outcomes previously demonstrated in single-institution studies, particularly the low rates of MD and ARE, are confirmed in this expanded multicenter analysis, without evidence of an excessive postoperative surgical complication risk. STR, though infrequent, is associated with significantly worse cavity LR. A randomized trial between preoperative and postoperative SRS is warranted and is currently being designed.

The effects of thoracoplasty on immediate post-operative recovery in adolescent idiopathic scoliosis.

The purpose of this study was to evaluate differences in pain, opiate utilization and oxygen (O2) consumption during the immediate post-operative course for patients undergoing posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) with and without thoracoplasty. Patients aged 10-21years old that had undergone PSF for AIS were identified from 1/1/16-8/1/18. A cohort of patients that did not have a thoracoplasty group was used as a control group. A standardized pain protocol (rapid response pathway) was implemented on all patients. A retrospective chart review was performed. Pre-operative, operative and post-operative data and SRS scores were analyzed. Forty-six patients (38 girls, 8 boys) were included, 23 in each group. The average age was 15.2years (range 12.0-19.3) and BMI was 20.9 (range 13.1-37.6). Differences in visual analog scores, post-operative oxygen and narcotic consumption were not statistically significant on any POD. Total opiate utilization was 146.06 morphine milligram equivalents (MME) in the control group and 149.41 MME in the thoracoplasty group (p = 0.78). One-year SRS self-image scores were higher in the thoracoplasty group (4.24 vs 3.96) (p = 0.007). There was no difference in length of hospitalization (3.6 vs 3.5days), levels fused (12.9 vs 12.9) or blood loss (334.1 vs 413.5mL). There was one pleural effusion and no instances of intercostal neuralgia or pneumothorax in the thoracoplasty group. There is no increase in immediate post-operative pain, narcotic use or oxygen consumption when a thoracoplasty is performed with a PSF for AIS. Improved SRS self-image scores were seen after thoracoplasty.

Minimum 2-Year Analysis of S2-Alar-Iliac Screw Fixation for Adult Spinal Deformity.

Study Design:Retrospective cohort.Objective:Determine the rate and risk factors for S2AI screw-related pain after adult spinal deformity surgery with a minimum 2-year follow-up.Methods:A consecutive 83 spinal deformity patients undergoing surgical treatment between August 2015 and December 2017 with minimum 2-year follow-up for S2AI screw complication and screw-related pain were included. Linear regression was performed on various risk factors and postoperative S2AI screw-related pain. Subset analysis of 53 patients was performed on preoperative and postoperative SRS and ODI scores, operative data, and radiographic data.Results:The overall proportion of S2AI screw-related pain was 9.6%. An S2AI screw complication was identified radiographically in 10.8% of patients; among these, 22.2% experienced S2AI screw-related pain. 3.4% of all patients underwent S2A1 screw removal. The SRS, ODI, sagittal vertical axis (SVA), and coronal alignment scores/measurements improved following treatment in all patients. However, the mean difference for the pre and postoperative SRS function score (1.2 ± 0.5 vs 0.9 ± 0.8) and SVA (4.0 ± 4.9 cm vs 2.1 ± 4.8 cm) were higher for the pain group.Conclusions:A minimum 2-year analysis of S2AI screw fixation in adult spinal deformity patients showed that 9.6% of patients experienced S2AI screw-related pain and 3.4% of patients had S2A1 screws removed. The size and the number of S2AI screws did not predict postoperative pain, nor were radiographic findings correlated with clinical outcomes. The patient outcome scores, coronal alignment, and SVA improved for all patients, but within the pain group there was an overall larger change in the SVA and SRS function score.

Surgical management of complex post-tuberculous kyphosis among African patients: clinical and radiographic outcomes for a consecutive series treated at a single institution in West Africa.

Retrospective review of consecutive series. To assess the clinical and radiographic outcomes after surgical management of post-tuberculous kyphosis. Post-tuberculous (TB) kyphosis can lead to progressive pulmonary and neurological deterioration. Surgery is indicated to decompress neural elements and correct the spine deformity. Although posterior vertebral column resection (PVCR) has been established as the treatment of choice for severe TB kyphosis, there is paucity of studies on the clinical outcomes among patients treated in West Africa. Clinical and radiographic data of 57 patients (pts) who underwent surgical correction of post-TB kyphosis at a single site in West Africa between 2013 and 2018 (≥ 2-year follow-up in 36 pts, ≥ 1-year FU in 21 pts). Pre- and post-op SRS scores and radiographic outcomes were compared using Paired t test. 57 patients, 36M:21F. Mean age 19 (11-57years). 22/57 pts (39.3%) underwent pre-op halo gravity traction (HGT) for an average duration of 86days (8-144days). HGT pts had a higher baseline regional kyphosis (125.1 ± 20.9) compared to non-HGT pts (64.6 ± 31.8, p < 0.001). Post-HGT regional kyphosis corrected to 101.2 ± 23 (24° correction). 53 pts (92.9%) underwent posterior-only surgery and 4 (7.0%) combined anterior-posterior surgery. 39 (68.4%) had PVCR, 11 (19.3%) PSO, and 16 (28.1%) thoracoplasty. Intraoperative neuromonitoring (IOM) signal changes occurred in 23/57 pts (≈ 40%), dural tear in 5 pts (8.8%), pleural tear in 3 pts (5.3%), ureteric injury in 1 pt (1.7%), and vascular injury in 1 pt (1.7%). Post-op complications included four (7.0%) infection, three (5.3%) implant related, two (3.5%) radiographic (one PJK and one DJK), one (1.7%) neurologic, one (1.7%) wound problem, and two (3.5%) sacral ulcers. IOM changes were similar in the VCR (48.7%) and non-VCR (23.5%) pts, p > 0.05. Complication rates were similar among HGT and non-HGT groups. Significant improvements from baseline were seen in the average SRS Total and domains scores and radiographic measurements for patients who attained 2-year follow-up. PVCR ± HGT can provide safe and optimal correction in cases of severe post-TB kyphosis with good clinical and radiographic outcomes in underserved regions.

Long Term Outcomes And Patterns Of Failure After Single Fraction Preoperative Radiosurgery For Brain Metastases

Postoperative (post-op) radiosurgery (SRS) after resection of brain metastases (BM) is associated with up to 30% risk of leptomeningeal disease (LMD). Approximately 60-70% of LMD is nodular pattern in this setting, which is thought to be associated with surgical tumor spillage. We have previously demonstrated that preoperative (pre-op) SRS is a feasible alternative to post-op SRS. Herein we report patterns of failure and long terms outcomes for patients (pts) treated with pre-op SRS. The records for pts with BM treated with pre-op SRS and planned surgical resection were reviewed. Pts with classically radiosensitive tumors, prior or planned adjuvant whole brain radiotherapy (WBRT), or no cranial imaging ≥ 1 month after surgery were excluded. Pre-op SRS dose was based on lesion size and was reduced approximately 10-20% from standard. No gross tumor volume (GTV) margin expansion was used. Surgery generally followed within 48 hours. Overall survival (OS) was estimated using the Kaplan-Meier method. Intracranial event rates were estimated using cumulative incidence with competing risk of death. Radiographic pattern of LMD was classified as classical “sugarcoating” (cLMD) vs. nodular (nLMD). The study cohort consisted of 141 pts with 150 lesions treated with single fraction pre-op SRS followed by planned surgery between 2005 – 2018. Most pts had a single BM (67%), underwent gross total resection (GTR, 96%), and had non-small cell lung cancer (41%). Median interval between pre-op SRS and surgery was 2 days, median SRS dose was 15 Gy, and median GTV volume was 8.4 cc (approximately equivalent to 2.5 cm diameter lesion). The 2-year cavity local recurrence (LR) rate was 23% overall and 20% in pts status post GTR. Five of 6 pts status post subtotal resection experienced LR. Multivariate analysis demonstrated GTR and renal cell histology as significantly associated with reduced risk of LR. SRS dose, lesion volume, and time between pre-op SRS and surgery were not significant. The 2-year LMD rate was 5%. Two of the 9 patients with LMD (22%) had nLMD while 78% had cLMD. The 2-year radiation necrosis (RN), symptomatic RN, and non-LMD distant brain failure rate was 7%, 4%, and 58%, respectively. Median OS was 19 months. Thirty-seven pts with 40 lesions had long term (≥2 years of cranial imaging) follow-up. In this subset, the 5-year cavity LR, symptomatic RN, and LMD rate was 25%, 8%, and 12%, respectively. Single fraction pre-op SRS is an effective treatment for surgically resected BM with low rates of cavity LR, RN, and LMD. LMD after pre-op SRS seems to be distinct from post-op SRS with a lower overall rate and lower proportion of nLMD pattern, which supports pre-op SRS sterilization of surgical tumor spillage. Outcomes in pts with long term imaging follow-up are consistent with the overall cohort. These data support further studies of pre-op SRS, including a randomized trial of pre-op vs. post-op SRS.

Preoperative Radiosurgery in Management of Brain Metastases

Brain metastases (BMs), the most frequent intracranial tumors, are diagnosed in approximately 30% of all adult patients over the span of planned treatment against a broad spectrum of solid cancers. The prognosis of patients presenting with BM is bleak with an expected median OS of only 4-7 months. However, some particular patients’ groups may enjoy longer survival durations with effective systemic and local therapies. At present, the feasible alternatives for active management of BMs typically include the whole-brain radiotherapy (WBRT), surgery, definitive SRS, postoperative SRS, systemic chemotherapy, targeted therapies, and their combination variants. Considering the local treatment, the severe neurotoxic effects of WBRT, and the increased risk for radionecrosis and leptomeningeal dissemination after postoperative SRS and together with the ineligibility of certain patients during the postoperative period prompted the energetic quest of alternative treatment strategies for such patients. In this respect, the novel preoperative SRS (PO-SRS) was proposed to provide at least equivalent local control rates with lesser radionecrosis and leptomeningeal dissemination risk. Respecting the scarcity of related literature, the present review aimed to meticulously detail theplausible rationale and accessible evidence for the novel PO-SRS in the management of patients presenting with BMs.