J. Bradley Elder and E. Antonio Chiocca
Jacob A. Miller, Ehsan H. Balagamwala, Samuel T. Chao, Todd Emch, John H. Suh, Toufik Djemil and Lilyana Angelov
The objective of this study was to define symptomatic and radiographic outcomes following spine stereotactic radiosurgery (SRS) for the treatment of multiple myeloma.
All patients with pathological diagnoses of myeloma undergoing spine SRS at a single institution were included. Patients with less than 1 month of follow-up were excluded. The primary outcome measure was the cumulative incidence of pain relief after spine SRS, while secondary outcomes included the cumulative incidences of radiographic failure and vertebral fracture. Pain scores before and after treatment were prospectively collected using the Brief Pain Inventory (BPI), a validated questionnaire used to assess severity and impact of pain upon daily functions.
Fifty-six treatments (in 38 patients) were eligible for inclusion. Epidural disease was present in nearly all treatment sites (77%). Moreover, preexisting vertebral fracture (63%), thecal sac compression (55%), and neural foraminal involvement (48%) were common. Many treatment sites had undergone prior local therapy, including external beam radiation therapy (EBRT; 30%), surgery (23%), and kyphoplasty (21%). At the time of consultation for SRS, the worst, current, and average BPI pain scores at these treatment sites were 6, 4, and 4, respectively. The median prescription dose was 16 Gy in a single fraction. The median clinical follow-up duration after SRS was 26 months. The 6- and 12-month cumulative incidences of radiographic failure were 6% and 9%, respectively. Among painful treatment sites, 41% achieved pain relief adjusted for narcotic usage, with a median time to relief of 1.6 months. The 6- and 12-month cumulative incidences of adjusted pain progression were 13% and 15%, respectively. After SRS, 1-month and 3-month worst, current, and average BPI scores all significantly decreased (p < 0.01). Vertebral fracture occurred following 12 treatments (21%), with an 18% cumulative incidence of fracture at 6 and 12 months. Two patients (4%) developed pain flare following spine SRS.
This study reports the largest series of myeloma lesions treated with spine SRS. A rapid and durable symptomatic response was observed, with a median time to pain relief of 1.6 months. This response was durable among 85% of patients at 12 months following treatment, with 91% local control. The efficacy and minimal toxicity of spine SRS is likely related to the delivery of ablative and conformal radiation doses to the target. SRS should be considered with doses of 14–16 Gy in a single fraction for patients with multiple myeloma and limited spinal disease, myelosuppression requiring “marrow-sparing” radiation therapy, or recurrent disease after EBRT.
Veronica L. Chiang, Samuel T. Chao, Constantin Tuleasca, Matthew C. Foote, Cheng-chia Lee, David Mathieu, Hany Soliman and Arjun Sahgal
In order to determine what areas of research are a clinical priority, a small group of young Gamma Knife investigators was invited to attend a workshop discussion at the 19th International Leksell Gamma Knife Society Meeting. Two areas of interest and the need for future radiosurgical research involving multiple institutions were identified by the young investigators working group: 1) the development of additional imaging sequences to guide the understanding, treatment, and outcome tracking of diseases such as tremor, radiation necrosis, and AVM; and 2) trials to clarify the role of hypofractionation versus single-fraction radiosurgery in the treatment of large lesions such as brain metastases, postoperative cavities, and meningiomas.
E. Emily Bennett, Camille Berriochoa, Ghaith Habboub, Scott Brigeman, Samuel T. Chao and Lilyana Angelov
Stereotactic radiosurgery (SRS) has emerged as a treatment option for patients with spinal metastatic disease. Although SRS has been shown to be successful in a multitude of extradural metastatic tumors causing cord compression, very few cases of intradural treatment have been reported. The authors present a rare case of an intradural extramedullary metastatic small cell lung cancer lesion to the cervical spine resulting in cord compression in an area that had also been extensively pretreated with conventional external-beam radiation therapy. The patient underwent successful SRS to this metastatic site, with rapid and complete resolution of his lesion.
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
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.
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.
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.
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.
Mayur Sharma, Jason L. Schroeder, Paul Elson, Antonio Meola, Gene H. Barnett, Michael A. Vogelbaum, John H. Suh, Samuel T. Chao, Alireza M. Mohammadi, Glen H. J. Stevens, Erin S. Murphy and Lilyana Angelov
Glioblastoma (GBM) is the most malignant form of astrocytoma. The average survival is 6–10 months in patients with recurrent GBM (rGBM). In this study, the authors evaluated the role of stereotactic radiosurgery (SRS) in patients with rGBMs.
The authors performed a retrospective review of their brain tumor database (1997–2016). Overall survival (OS) and progression-free survival (PFS) after salvage SRS were the primary endpoints evaluated. Response to SRS was assessed using volumetric MR images.
Fifty-three patients with rGBM underwent salvage SRS targeting 75 lesions. The median tumor diameter and volume were 2.55 cm and 3.80 cm3, respectively. The median prescription dose was 18 Gy (range 12–24 Gy) and the homogeneity index was 1.90 (range 1.11–2.02). The median OS after salvage SRS was estimated to be 11.0 months (95% CI 7.1–12.2) and the median PFS after salvage SRS was 4.4 months (95% CI 3.7–5.0). A Karnofsky Performance Scale score ≥ 80 was independently associated with longer OS, while small tumor volume (< 15 cm3) and less homogeneous treatment plans (homogeneity index > 1.75) were both independently associated with longer OS (p = 0.007 and 0.03) and PFS (p = 0.01 and 0.002, respectively). Based on these factors, 2 prognostic groups were identified for PFS (5.4 vs 3.2 months), while 3 were identified for OS (median OS of 15.2 vs 10.5 vs 5.2 months).
SRS is associated with longer OS and/or PFS in patients with good performance status, small-volume tumor recurrences, and heterogeneous treatment plans. The authors propose a prognostic model to identify a cohort of rGBM patients who may benefit from SRS.
Rupesh Kotecha, Lilyana Angelov, Gene H. Barnett, Chandana A. Reddy, John H. Suh, Erin S. Murphy, Gennady Neyman and Samuel T. Chao
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.
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.
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.
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.
Robert J. Weil, Gaurav G. Mavinkurve, Samuel T. Chao, Michael A. Vogelbaum, John H. Suh, Matthew Kolar and Steven A. Toms
The authors assessed the feasibility of intraoperative radiotherapy (IORT) using a portable radiation source to treat newly diagnosed, surgically resected, solitary brain metastasis (BrM).
In a nonrandomized prospective study, 23 patients with histologically confirmed BrM were treated with an Intrabeam device that delivered 14 Gy to a 2-mm depth to the resection cavity during surgery.
In a 5-year minimum follow-up period, progression-free survival from the time of surgery with simultaneous IORT averaged (± SD) 22 ± 33 months (range 1–96 months), with survival from the time of BrM treatment with surgery+IORT of 30 ± 32 months (range 1–96 months) and overall survival from the time of first cancer diagnosis of 71 ± 64 months (range 4–197 months). For the Graded Prognostic Assessment (GPA), patients with a score of 1.5–2.0 (n = 12) had an average posttreatment survival of 21 ± 26 months (range 1–96 months), those with a score of 2.5–3.0 (n = 7) had an average posttreatment survival of 52 ± 40 months (range 5–94 months), and those with a score of 3.5–4.0 (n = 4) had an average posttreatment survival of 17 ± 12 months (range 4–28 months). A BrM at the treatment site recurred in 7 patients 9 ± 6 months posttreatment, and 5 patients had new but distant BrM 17 ± 3 months after surgery+IORT. Six patients later received whole-brain radiation therapy, 7 patients received radiosurgery, and 2 patients received both treatments. The median Karnofsky Performance Scale scores before and 1 and 3 months after surgery were 80, 90, and 90, respectively; at the time of this writing, 3 patients remain alive with a CNS progression-free survival of > 90 months without additional BrM treatment.
The results of this study demonstrate the feasibility of resection combined with IORT at a dose of 14 Gy to a 2-mm peripheral margin to treat a solitary BrM. Local control, distant control, and long-term survival were comparable to those of other commonly used modalities. Surgery combined with IORT seems to be a potential adjunct to patient treatment for CNS involvement by systemic cancer.
Rupesh Kotecha, Camille A. Berriochoa, Erin S. Murphy, Andre G. Machado, Samuel T. Chao, John H. Suh and Kevin L. Stephans
Patients with implanted neuromodulation devices present potential challenges for radiation therapy treatment planning and delivery. Although guidelines exist regarding the irradiation of cardiac pacemakers and defibrillators, fewer data and less clinical experience exist regarding the effects of radiation therapy on less frequently used devices, such as deep brain stimulators. A 79-year-old woman with a history of coarse tremors effectively managed with deep brain stimulation presented with multiple intracranial metastases from a newly diagnosed lung cancer and was referred for whole-brain radiation therapy. She was treated with a German helmet technique to a total dose of 30 Gy in 10 fractions using 6 MV photons via opposed lateral fields with the neurostimulator turned off prior to delivery of each fraction. The patient tolerated the treatment well with no acute complications and no apparent change in the functionality of her neurostimulator device or effect on her underlying neuromuscular disorder.
This represents the first reported case of the safe delivery of whole-brain radiation therapy in a patient with an implanted neurostimulator device. In cases such as this, neurosurgeons and radiation oncologists should have discussions with patients about the risks of brain injury, device malfunction or failure of the device, and plans for rigorous testing of the device before and after radiation therapy.
Mayur Sharma, Elizabeth E. Bennett, Gazanfar Rahmathulla, Samuel T. Chao, Hilary K. Koech, Stephanie N. Gregory, Todd Emch, Anthony Magnelli, Antonio Meola, John H. Suh and Lilyana Angelov
Stereotactic radiosurgery (SRS) of the spine is a conformal method of delivering a high radiation dose to a target in a single or few (usually ≤ 5) fractions with a sharp fall-off outside the target volume. Although efforts have been focused on evaluating spinal cord tolerance when treating spinal column metastases, no study has formally evaluated toxicity to the surrounding organs at risk (OAR), such as the brachial plexus or the oropharynx, when performing SRS in the cervicothoracic region. The aim of this study was to evaluate the radiation dosimetry and the acute and delayed toxicities of SRS on OAR in such patients.
Fifty-six consecutive patients (60 procedures) with a cervicothoracic spine tumor involving segments within C5–T1 who were treated using single-fraction SRS between February 2006 and July 2014 were included in the study. Each patient underwent CT simulation and high-definition MRI before treatment. The clinical target volume and OAR were contoured on BrainScan and iPlan software after image fusion. Radiation toxicity was evaluated using the common toxicity criteria for adverse events and correlated to the radiation doses delivered to these regions. The incidence of vertebral body compression fracture (VCF) before and after SRS was evaluated also.
Metastatic lesions constituted the majority (n = 52 [93%]) of tumors treated with SRS. Each patient was treated with a median single prescription dose of 16 Gy to the target. The median percentage of tumor covered by SRS was 93% (maximum target dose 18.21 Gy). The brachial plexus received the highest mean maximum dose of 17 Gy, followed by the esophagus (13.8 Gy) and spinal cord (13 Gy). A total of 14 toxicities were encountered in 56 patients (25%) during the study period. Overall, 14% (n = 8) of the patients had Grade 1 toxicity, 9% (n = 5) had Grade 2 toxicity, 2% (n = 1) had Grade 3 toxicity, and none of the patients had Grade 4 or 5 toxicity. The most common (12%) toxicity was dysphagia/odynophagia, followed by axial spine pain flare or painful radiculopathy (9%). The maximum radiation dose to the brachial plexus showed a trend toward significance (p = 0.066) in patients with worsening post-SRS pain. De novo and progressive VCFs after SRS were noted in 3% (3 of 98) and 4% (4 of 98) of vertebral segments, respectively.
From the analysis, the current SRS doses used at the Cleveland Clinic seem safe and well tolerated at the cervicothoracic junction. These preliminary data provide tolerance benchmarks for OAR in this region. Because the effect of dose-escalation SRS strategies aimed at improving local tumor control needs to be balanced carefully with associated treatment-related toxicity on adjacent OAR, larger prospective studies using such approaches are needed.