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  • Author or Editor: Chandana A. Reddy x
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Ehsan H. Balagamwala, Lilyana Angelov, Shlomo A. Koyfman, John H. Suh, Chandana A. Reddy, Toufik Djemil, Grant K. Hunter, Ping Xia and Samuel T. Chao

Object

Stereotactic body radiotherapy (SBRT) has emerged as an important treatment option for spinal metastases from renal cell carcinoma (RCC) as a means to overcome RCC's inherent radioresistance. The authors reviewed the outcomes of SBRT for the treatment of RCC metastases to the spine at their institution, and they identified factors associated with treatment failure.

Methods

Fifty-seven patients (88 treatment sites) with RCC metastases to the spine received single-fraction SBRT. Pain relief was based on the Brief Pain Inventory and was adjusted for narcotic use according to the Radiation Therapy Oncology Group protocol 0631. Toxicity was scored according to Common Toxicity Criteria for Adverse Events version 4.0. Radiographic failure was defined as infield or adjacent (within 1 vertebral body [VB]) failure on follow-up MRI. Multivariate analyses were performed to correlate outcomes with the following variables: epidural, paraspinal, single-level, or multilevel disease (2–5 sites); neural foramen involvement; and VB fracture prior to SBRT. Kaplan-Meier analysis and Cox proportional hazards modeling were used for statistical analysis.

Results

The median follow-up and survival periods were 5.4 months (range 0.3–38 months) and 8.3 months (range 1.5–38 months), respectively. The median time to radiographic failure and unadjusted pain progression were 26.5 and 26.0 months, respectively. The median time to pain relief (from date of simulation) and duration of pain relief (from date of treatment) were 0.9 months (range 0.1–4.4 months) and 5.4 months (range 0.1–37.4 months), respectively. Multivariate analyses demonstrated that multilevel disease (hazard ratio [HR] 3.5, p = 0.02) and neural foramen involvement (HR 3.4, p = 0.02) were correlated with radiographic failure; multilevel disease (HR 2.3, p = 0.056) and VB fracture (HR 2.4, p = 0.046) were correlated with unadjusted pain progression. One patient experienced Grade 3 nausea and vomiting; no other Grade 3 or 4 toxicities were observed. Twelve treatment sites (14%) were complicated by subsequent vertebral fractures.

Conclusions

Stereotactic body radiotherapy for RCC metastases to the spine offers fast and durable pain relief with minimal toxicity. Stereotactic body radiotherapy seems optimal for patients who have solitary or few spinal metastases. Patients with neural foramen involvement are at an increased risk for failure.

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Ovidiu Marina, John H. Suh, Chandana A. Reddy, Gene H. Barnett, Michael A. Vogelbaum, David M. Peereboom, Glen H. J. Stevens, Heinrich Elinzano and Samuel T. Chao

Object

The object of this study was to determine the benefit of surgery, radiation, and chemotherapy for patients with glioblastoma multiforme (GBM) and a low Karnofsky Performance Scale (KPS) score.

Methods

The authors retrospectively evaluated the records of patients who underwent primary treatment for pathologically confirmed GBM and with a KPS score ≤ 50 on initial evaluation for radiation therapy at a tertiary care institution between 1977 and 2006. Seventy-four patients with a median age of 69 years (range 19–88 years) and a median KPS score of 50 (range 20–50) were retrospectively grouped into the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) Classes IV (11 patients), V (15 patients), and VI (48 patients). Patients underwent biopsy (38 patients) or tumor resection (36 patients). Forty-seven patients received radiation. Nineteen patients also received chemotherapy (53% temozolomide), initiated concurrently (47%) or after radiotherapy.

Results

The median survival overall was 2.3 months (range 0.2–48 months). Median survival stratified by RPA Classes IV, V, and VI was 6.6, 6.6, and 1.8 months, respectively (p < 0.001, log-rank test). Median survival for patients receiving radiation (5.2 months) was greater than that for patients who declined radiation (1.6 months, p < 0.001). Patients in RPA Class VI appeared to benefit from radiotherapy only when tumor resection was also performed. The median survival from treatment initiation was greater for patients receiving chemotherapy concomitantly with radiotherapy (9.8 months) as compared with radiotherapy alone (1.7 months, p = 0.002). Of 20 patients seen for follow-up in the clinic at a median of 48 days (range 24–196 days) following radiotherapy, 70% were noted to have an improvement in the KPS score of between 10 and 30 points from the baseline score. On multivariate analysis, only RPA class (p = 0.01), resection (HR = 0.37, p = 0.001), and radiation therapy (HR = 0.39, p = 0.02) were significant predictors of a decreased mortality rate.

Conclusions

Patients with a KPS score ≤ 50 appear to have increased survival and functional status following tumor resection and radiation. The extent of benefit from concomitant chemotherapy is unclear. Future studies may benefit from reporting that utilizes a prognostic classification system such as the RTOG RPA class, which has been shown to be effective at separating outcomes even in patients with low performance status. Patients with GBMs and low KPS scores need to be evaluated in prospective studies to identify the extent to which different therapies improve outcomes.

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Rupesh Kotecha, Lilyana Angelov, Gene H. Barnett, Chandana A. Reddy, John H. Suh, Erin S. Murphy, Gennady Neyman and Samuel T. Chao

Object

Traditionally, the treatment of choice for patients with metastases to the calvaria or skull base has been conventional radiation therapy. Because patients with systemic malignancies are also at risk for intracranial metastases, the utility of Gamma Knife surgery (GKS) for these patients has been explored to reduce excess radiation exposure to the perilesional brain parenchyma. The purpose of this study was to report the efficacy of GKS for the treatment of calvarial metastases and skull base lesions.

Methods

The authors performed a retrospective chart review of 21 patients with at least 1 calvarial or skull base metastatic lesion treated with GKS during 2001–2013. For 7 calvarial lesions, a novel technique, in which a bolus was placed over the treatment site, was used. For determination of local control or disease progression, radiation therapy data were examined and posttreatment MR images and oncology records were reviewed. Survival times from the date of procedure were estimated by using Kaplan-Meier analyses.

Results

The median patient age at treatment was 57 years (range 29–84 years). A total of 19 (90%) patients received treatment for single lesions, 1 patient received treatment for 3 lesions, and 1 patient received treatment for 4 lesions. The most common primary tumor was breast cancer (24% of patients). Per lesion, the median clinical and radiographic follow-up times were 10.3 months (range 0–71.9 months) and 7.1 months (range 0–61.3 months), respectively. Of the 26 lesions analyzed, 14 (54%) were located in calvarial bones and 12 (46%) were located in the skull base. The median lesion volume was 5.3 cm3 (range 0.3–55.6 cm3), and the median prescription margin dose was 15 Gy (range 13–24 Gy). The median overall survival time for all patients was 35.9 months, and the 1-year local control rate was 88.9% (95% CI 74.4%–100%). Local control rates did not differ between lesions treated with the bolus technique and those treated with traditional methods or between calvarial lesions and skull base lesions (p > 0.05). Of the 3 patients for whom local treatment failed, 1 patient received no further treatment and 2 patients responded to salvage chemotherapy. Subsequent brain parenchymal metastases developed in 2 patients, who then underwent GKS.

Conclusions

GKS is an effective treatment modality for patients with metastases to the calvarial bones or skull base. For patients with superficial calvarial lesions, a novel approach with bolus application resulted in excellent rates of local control. GKS provides an effective therapeutic alternative to conventional radiation therapy and should be considered for patients at risk for calvarial metastases and brain parenchymal metastases.

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Samuel T. Chao, Taisei Kobayashi, Edward Benzel, Chandana A. Reddy, Glen H. J. Stevens, Richard A. Prayson, Iain Kalfas, Richard Schlenk, Ajit Krishnaney, Michael P. Steinmetz, William Bingaman, Joseph Hahn and John H. Suh

Object

The goal in this study was to determine the role of radiation therapy (RT) in the treatment of spinal myxopapillary ependymomas (MPEs).

Methods

Thirty-seven patients with histologically verified spinal MPEs were reviewed. Kaplan-Meier analyses and Cox proportional hazard regression were used to determine what patient and treatment factors influenced overall survival (OS) and recurrence.

Results

At the time of initial diagnosis, the median age was 33 years and the Karnofsky Performance Scale score was 80. In 86.5% of cases, the most common presenting symptom was pain. All patients received surgery as their initial treatment. Nine patients also received RT along with surgery, with a median total dose of 50.2 Gy. The mean survival time was 12.2 years; however, only 4 of 37 patients had died at the time of this study. None of the patient or treatment parameters significantly correlated with OS. Sixteen patients (43.2%) were found to have a recurrence, with a median time to recurrence of 7.7 years. None of the patient or treatment parameters correlated with recurrence-free survival for an initial recurrence. The median time to the second recurrence (recurrence following therapy for initial recurrence) was 1.6 years. Use of RT as salvage therapy after initial recurrence significantly correlated with longer times to a second recurrence. The median recurrence-free survival time before the second recurrence was 9.6 years for those who received RT versus 1.1 years for those who did not receive RT (p = 0.0093). None of the other parameters significantly correlated with a second recurrence.

Conclusions

Radiation therapy may have a role as salvage therapy in delaying recurrences of spinal MPEs.

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Rupesh Kotecha, Martin C. Tom, Mihir Naik, Lilyana Angelov, Edward C. Benzel, Chandana A. Reddy, Richard A. Prayson, Iain Kalfas, Richard Schlenk, Ajit Krishnaney, Michael P. Steinmetz, William Bingaman, John H. Suh and Samuel T. Chao

OBJECTIVE

The authors sought to describe the long-term recurrence patterns, prognostic factors, and effect of adjuvant or salvage radiotherapy (RT) on treatment outcomes for patients with spinal myxopapillary ependymoma (MPE).

METHODS

The authors reviewed a tertiary institution IRB-approved database and collected data regarding patient, tumor, and treatment characteristics for all patients treated consecutively from 1974 to 2015 for histologically confirmed spinal MPE. Key outcomes included relapse-free survival (RFS), postrecurrence RFS, failure patterns, and influence of timing of RT on recurrence patterns. Cox proportional hazards regression and Kaplan-Meier analyses were utilized.

RESULTS

Of the 59 patients included in the study, the median age at initial surgery was 34 years (range 12–74 years), 30 patients (51%) were female, and the most common presenting symptom was pain (n = 52, 88%). Extent of resection at diagnosis was gross-total resection (GTR) in 39 patients (66%), subtotal resection (STR) in 15 (25%), and unknown in 5 patients (9%). After surgery, 10 patients (17%) underwent adjuvant RT (5/39 GTR [13%] and 5/15 STR [33%] patients). Median follow-up was 6.2 years (range 0.1–35.3 years). Overall, 20 patients (34%) experienced recurrence (local, n = 15; distant, n = 5). The median RFS was 11.2 years (95% CI 77 to not reached), and the 5- and 10-year RFS rates were 72.3% (95% CI 59.4–86.3) and 54.0% (95% CI, 36.4–71.6), respectively.

STR was associated with a higher risk of recurrence (HR 6.45, 95% CI 2.15–19.23, p < 0.001) than GTR, and the median RFS after GTR was 17.2 years versus 5.5 years after STR. Adjuvant RT was not associated with improved RFS, regardless of whether it was delivered after GTR or STR. Of the 20 patients with recurrence, 12 (60%) underwent salvage treatment with surgery alone (GTR, n = 6), 4 (20%) with RT alone, and 4 (20%) with surgery and RT. Compared to salvage surgery alone, salvage RT, with or without surgery, was associated with a significantly longer postrecurrence RFS (median 9.5 years vs 1.6 years; log-rank, p = 0.006).

CONCLUSIONS

At initial diagnosis of spinal MPE, GTR is key to long-term RFS, with no benefit to immediate adjuvant RT observed in this series. RT at the time of recurrence, however, is associated with a significantly longer time to second disease recurrence. Surveillance imaging of the entire neuraxis remains crucial, as distant failure is not uncommon in this patient population.