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Debra A. Goldman, Koos Hovinga, Anne S. Reiner, Yoshua Esquenazi, Viviane Tabar and Katherine S. Panageas

OBJECTIVE

Previous studies assessed the relationship between repeat resection and overall survival (OS) in patients with glioblastoma, but ignoring the timing of repeat resection may have led to biased conclusions. Statistical methods that take time into account are well established and applied consistently in other medical fields. The goal of this study was to illustrate the change in the effect of repeat resection on OS in patients with glioblastoma once timing of resection is incorporated.

METHODS

The authors conducted a retrospective study of patients initially diagnosed with glioblastoma between January 2005 and December 2014 who were treated at Memorial Sloan Kettering Cancer Center. Patients underwent at least 1 craniotomy with both pre- and postoperative MRI data available. The effect of repeat resection on OS was assessed with time-dependent extended Cox regression controlling for extent of resection, initial Karnofsky Performance Scale score, sex, age, multifocal status, eloquent status, and postoperative treatment.

RESULTS

Eighty-nine (55%) of 163 patients underwent repeat resection with a median time between resections of 7.7 months (range 0.5–50.8 months). Median OS was 18.8 months (95% confidence interval [CI] 16.3–20.5 months) from initial resection. When timing of repeat resection was ignored, repeat resection was associated with a lower risk of death (hazard ratio [HR] 0.62, 95% CI 0.43–0.90, p = 0.01); however, when timing was taken into account, repeat resection was associated with a higher risk of death (HR 2.19, 95% CI 1.47–3.28, p < 0.001).

CONCLUSIONS

In this study, accounting for timing of repeat resection reversed its protective effect on OS, suggesting repeat resection may not benefit OS in all patients. These findings establish a foundation for future work by accounting for timing of repeat resection using time-dependent methods in the evaluation of repeat resection on OS. Additional recommendations include improved data capture that includes mutational data, development of algorithms for determining eligibility for repeat resection, more rigorous statistical analyses, and the assessment of additional benefits of repeat resection, such as reduction of symptom burden and enhanced quality of life.

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Jennifer Moliterno, William P. Cope, Emma D. Vartanian, Anne S. Reiner, Roselyn Kellen, Shahiba Q. Ogilvie, Jason T. Huse and Philip H. Gutin

OBJECT

While most meningiomas are benign, 1%–3% display anaplastic features, with little current understanding regarding the molecular mechanisms underlying their formation. In a large single-center cohort, the authors tested the hypothesis that two distinct subtypes of anaplastic meningiomas, those that arise de novo and those that progress from lower grade tumors, exist and exhibit different clinical behavior.

METHODS

Pathology reports and clinical data of 37 patients treated between 1999 and 2012 for anaplastic meningioma at Memorial Sloan–Kettering Cancer Center (MSKCC) were retrospectively reviewed. Patients were divided into those whose tumors arose de novo and those whose tumors progressed from previously documented benign or atypical meningiomas.

RESULTS

Overall, the median age at diagnosis was 59 years and 57% of patients were female. Most patients (38%) underwent 2 craniotomies (range 1–5 surgeries) aimed at gross-total resection (GTR; 59%), which afforded better survival when compared with subtotal resection according to Kaplan-Meier estimates (median overall survival [OS] 3.2 vs 1.3 years, respectively; p = 0.04, log-rank test). Twenty-three patients (62%) presented with apparently de novo anaplastic meningiomas. Compared with patients whose tumors had progressed from a lower grade, those patients with de novo tumors were significantly more likely to be female (70% vs 36%, respectively; p = 0.04), experience better survival (median OS 3.0 vs 2.4 years, respectively; p = 0.03, log-rank test), and harbor cerebral hemispheric as opposed to skull base tumors (91% vs 43%, respectively; p = 0.002).

CONCLUSIONS

Based on this single-center experience at MSKCC, anaplastic meningiomas, similar to glial tumors, can arise de novo or progress from lower grade tumors. These tumor groups appear to have distinct clinical behavior. De novo tumors may well be molecularly distinct, which is under further investigation. Aggressive GTR appears to confer an OS advantage in patients with anaplastic meningioma, and this is likely independent of tumor progression status. Similarly, those patients with de novo tumors experience a survival advantage likely independent of extent of resection.

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Ibrahim Hussain, Ori Barzilai, Anne S. Reiner, Lily McLaughlin, Natalie M. DiStefano, Shahiba Ogilvie, Anne L. Versteeg, Charles G. Fisher, Mark H. Bilsky and Ilya Laufer

OBJECTIVE

The Spinal Instability Neoplastic Score (SINS) correlates with preoperative disability and response to stabilization, with patients with higher scores experiencing greater relief after surgery. However, there is a paucity of data demonstrating the extent to which each component contributes to preoperative clinical status and response to stabilization surgery. The objectives of this study were 2-fold. First, to determine how SINS components correlate with pre- and postoperative patient-reported outcomes (PROs). Second, to determine whether patients with higher SINS (10–12) in the “indeterminate” group respond differently to surgery compared to patients with lower SINS (7–9).

METHODS

SINS and PROs were prospectively collected in 131 patients undergoing stabilization surgery for metastatic spinal disease. Association of SINS components and their individual scores with preoperative symptom burden and PRO symptom change after surgery was analyzed using the Spearman rank correlation coefficient (rho) and the Kruskal-Wallis test. SINS and association with preoperative PRO scores and mean differences in post- and preoperative PRO scores were compared for 2 SINS categories within the indeterminate group (7–9 vs 10–12) using the Wilcoxon 2-sample test and Wilcoxon signed-rank test.

RESULTS

The presence of mechanical pain, followed by metastatic location, correlated most strongly with preoperative functional disability measures and lower disability PRO scores following surgical stabilization. Blastic rather than lytic bone lesions demonstrated stronger association with pain reduction following stabilization. Following surgery, patients with SINS 10–12 demonstrated markedly greater improvement in pain and disability PRO scores nearly across the board compared to patients with SINS 7–9.

CONCLUSIONS

The presence of mechanical pain has the strongest correlation with preoperative disability and improvement in pain and disability PRO scores after surgery. Radiographic components of SINS also correlate with preoperative symptom severity and postoperative PRO, supporting their utilization in evaluation of spinal instability. Among patients with indeterminate SINS, patients with higher scores experience greater reduction in pain and disability PRO scores following surgical stabilization, suggesting that the indeterminate-SINS group includes distinct populations.

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Michael S. Virk, James E. Han, Anne S. Reiner, Lily A. McLaughlin, Daniel M. Sciubba, Eric Lis, Yoshiya Yamada, Mark Bilsky and Ilya Laufer

OBJECTIVE

The purpose of this study was to determine the rate of symptomatic vertebral body compression fractures (VCFs) requiring kyphoplasty or surgery in patients treated with 24-Gy single-fraction stereotactic radiosurgery (SRS).

METHODS

This retrospective analysis included all patients who had been treated with 24-Gy, single-fraction, image-guided intensity-modulated radiation therapy for histologically confirmed solid tumor metastases over an 8-year period (2005–2013) at Memorial Sloan Kettering Cancer Center. Charts and imaging studies were reviewed for post-SRS kyphoplasty or surgery for mechanical instability. A Spinal Instability Neoplastic Score (SINS) was calculated for each patient both at the time of SRS and at the time of intervention for VCF.

RESULTS

Three hundred twenty-three patients who had undergone single-fraction SRS between C-1 and L-5 were included in this analysis. The cumulative incidence of VCF 5 years after SRS was 7.2% (95% CI 4.1–10.2), whereas that of death following SRS at the same time point was 82.5% (95% CI 77.5–87.4). Twenty-six patients with 36 SRS-treated levels progressed to symptomatic VCF requiring treatment with kyphoplasty (6 patients), surgery (10 patients), or both (10 patients). The median time to symptomatic VCF was 13 months. Seven patients developed VCF at 11 levels adjacent to the SRS-treated level. Fractured levels had no evidence of tumor progression. The median SINS changed from 6.5 at SRS (interquartile range [IQR] 4.3–8.8) to 11.5 at stabilization (IQR 9–13). In patients without prior stabilization at the level of SRS, there was an association between the SINS and the time to fracture.

CONCLUSIONS

Five years after ablative single-fraction SRS to spinal lesions, the cumulative incidence of symptomatic VCF at the treated level without tumor recurrence was 7.2%. Higher SINSs at the time of SRS correlated with earlier fractures.

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Chunzi Jenny Jin, John Berry-Candelario, Anne S. Reiner, Ilya Laufer, Daniel S. Higginson, Adam M. Schmitt, Eric Lis, Ori Barzilai, Patrick Boland, Yoshiya Yamada and Mark H. Bilsky

OBJECTIVE

The current treatment of chordomas is associated with significant morbidity, high rates of local recurrence, and the potential for metastases. Stereotactic radiosurgery (SRS) as a primary treatment could reduce the need for en bloc resection to achieve wide or marginal margins. Spinal SRS outcomes support the exploration of SRS’s role in the durable control of these conventionally radioresistant tumors. The goal of the study was to evaluate outcomes of patients with primary chordomas treated with spinal SRS alone or in combination with surgery.

METHODS

Clinical records were reviewed for outcomes of patients with primary chordomas of the mobile spine and sacrum who underwent single-fraction SRS between 2006 and 2017. Radiographic local recurrence-free survival (LRFS), overall survival (OS), symptom response, and toxicity were assessed in relation to the extent of surgery.

RESULTS

In total, 35 patients with de novo chordomas of the mobile spine (n = 17) and sacrum (n = 18) received SRS and had a median post-SRS follow-up duration of 38.8 months (range 2.0–122.9 months). The median planning target volume dose was a 24-Gy single fraction (range 18–24 Gy). Overall, 12 patients (34%) underwent definitive SRS and 23 patients (66%) underwent surgery and either neoadjuvant or postoperative adjuvant SRS. Definitive SRS was selectively used to treat both sacral (n = 7) and mobile spine (n = 5) chordomas. Surgical strategies for the mobile spine were either intralesional, gross-total resection (n = 5) or separation surgery (n = 7) and for the sacrum en bloc sacrectomy (n = 11). The 3- and 5-year LRFS rates were 86.2% and 80.5%, respectively. Among 32 patients (91%) receiving 24-Gy radiation doses, the 3- and 5-year LRFS rates were 96.3% and 89.9%, respectively. The 3- and 5-year OS rates were 90.0% and 84.3%, respectively. The symptom response rate to treatment was 88% for pain and radiculopathy. The extent or type of surgery was not associated with LRFS, OS, or symptom response rates (p > 0.05), but en bloc resection was associated with higher surgical toxicity, as measured using the Common Terminology Criteria for Adverse Events (version 5.0) classification tool, than epidural decompression and curettage/intralesional resection (p = 0.03). The long-term rate of toxicity ≥ grade 2 was 31%, including 20% grade 3 tissue necrosis, recurrent laryngeal nerve palsy, myelopathy, fracture, and secondary malignancy.

CONCLUSIONS

High-dose spinal SRS offers the chance for durable radiological control and effective symptom relief with acceptable toxicity in patients with primary chordomas as either a definitive or adjuvant therapy.

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Rupa G. Juthani, Anne S. Reiner, Ankur R. Patel, Aimee Cowan, Marie Roguski, Katherine S. Panageas, Eliza B. Geer, Sasan Karimi, Marc A. Cohen and Viviane Tabar

OBJECTIVE

The utility and safety of intraoperative MRI (iMRI) for resection of pituitary adenomas is not clearly established in the context of advances in endoscopic approaches. The goal in this study was to evaluate the safety and efficacy of iMRI for pituitary adenoma resection, with endoscopic transsphenoidal (ETS) versus microscopic transsphenoidal (MTS) approaches.

METHODS

Radiographic and clinical outcomes of all pituitary adenomas resected using iMRI between 2008 and 2017 at a single institution were retrospectively evaluated.

RESULTS

Of 212 tumors treated, 131 (62%) underwent further resection based on iMRI findings, resulting in a significant increase in gross-total resection on postoperative MRI compared with iMRI (p = 0.0001) in both ETS and MTS groups. iMRI increased rates of gross-total resection for cavernous sinus invasion Knosp grades 1 and 2, but not in Knosp ≥ 3 across treatment groups (p < 0.0001). The extent of resection on postoperative MRI was significantly correlated with increased progression-free survival (p < 0.0001). Initial hormone remission off medical therapy was achieved in 64%, with a significantly higher rate of remission in tumors resected via the ETS approach (81%) compared with the MTS approach (55%) (p = 0.02). The rate of persistent new hormone deficit was low at 8%, including a 2.8% rate of permanent diabetes insipidus, and 45% of patients had improvement in preoperative hormone deficit following surgery. Serious postoperative complications including CSF leaks requiring reoperation were rare at 1%, with no postoperative infections.

CONCLUSIONS

These results suggest that iMRI is a safe and effective method of increasing the extent of resection for pituitary adenomas while preserving hormone function. When paired with the endoscope, iMRI may offer the ability to tailor more aggressive removal of tumors while optimizing pituitary function, resulting in high rates of secretory hormone remission. Secretory tumors and adenomas with Knosp grade < 3 cavernous sinus invasion may benefit most from the use of iMRI.

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Brad E. Zacharia, Sweena Kahn, Evan D. Bander, Gustav Y. Cederquist, William P. Cope, Lily McLaughlin, Alexa Hijazi, Anne S. Reiner, Ilya Laufer and Mark Bilsky

OBJECTIVE

The authors of this study aimed to identify the incidence of and risk factors for preoperative deep venous thrombosis (DVT) in patients undergoing surgical treatment for spinal metastases.

METHODS

Univariate analysis of patient age, sex, ethnicity, laboratory values, comorbidities, preoperative ambulatory status, histopathological classification, spinal level, and surgical details was performed. Factors significantly associated with DVT univariately were entered into a multivariate logistic regression model.

RESULTS

The authors identified 314 patients, of whom 232 (73.9%) were screened preoperatively for a DVT. Of those screened, 22 (9.48%) were diagnosed with a DVT. The screened patients were older (median 62 vs 55 years, p = 0.0008), but otherwise similar in baseline characteristics. Nonambulatory status, previous history of DVT, lower partial thromboplastin time, and lower hemoglobin level were statistically significant and independent factors associated with positive results of screening for a DVT. Results of screening were positive in only 6.4% of ambulatory patients in contrast to 24.4% of nonambulatory patients, yielding an odds ratio of 4.73 (95% CI 1.88–11.90). All of the patients who had positive screening results underwent preoperative placement of an inferior vena cava filter.

CONCLUSIONS

Patients requiring surgery for spinal metastases represent a population with unique risks for venous thromboembolism. This study showed a 9.48% incidence of DVT in patients screened preoperatively. The highest rates of preoperative DVT were identified in nonambulatory patients, who were found to have a 4-fold increase in the likelihood of harboring a DVT. Understanding the preoperative thrombotic status may provide an opportunity for early intervention and risk stratification in this critically ill population.