Annette E. Quinn

Radiosurgery for the treatment of spinal melanoma metastases

Background: The role of stereotactic radiosurgery in treating metastatic melanoma involving the spine has previously been limited. Conventional external beam radiotherapy lacks the precision to allow delivery of large single-fraction doses of radiation and simultaneously to limit the dose delivered to radiosensitive structures such as the spinal cord. This study evaluated the clinical efficacy of radiosurgery for the treatment of melanoma spinal metastases in 28 patients.Methods: Thirty-six melanoma spine metastases were treated with a single-session radiosurgery technique (1 cervical, 11 thoracic, 13 lumbar, and 11 sacral) with a follow-up period of 3–43 months (median 13 months). Tumor volume ranged from 4.1 to 153 cm3 (mean 47.6 cm3). Twenty-three of the 36 lesions had received prior external beam irradiation. Results: Maximum tumor dose was maintained at 17.5–25 Gy (mean 21.7 Gy). Spinal cord volume receiving >8 Gy ranged from 0.0 to 0.7 cm3 (mean 0.26 cm3); spinal canal volume at the cauda equina level receiving >8 Gy ranged from 0.0 to 3.5 cm3 (mean 0.98 cm3). No radiation-induced toxicity occurred during the follow-up period. Axial and radicular pain improved in 27 of 28 patients (96%) who were treated primarily for pain. Long-term tumor control was seen in 3 of 4 cases treated primarily for radiographic tumor progression. Two patients went on to require open surgical intervention for tumor progression resulting in neurological deficit. Conclusions: Spinal radiosurgery offers a therapeutic modality for the safe delivery of large dose fractions of radiation therapy in a single fraction for the management of spinal metastases in patients with advanced melanoma that are often poorly controlled with alternative conventional external beam radiation therapy, and is successful even in patients with previously irradiated lesions.

Stereotactic body radiotherapy in the treatment of advanced adenocarcinoma of the pancreas.

Objectives: The aim of the study was to assess the feasibility and safety of stereotactic body radiotherapy (SBRT) in patients with advanced pancreatic adenocarcinoma. Methods: We reviewed outcomes of 71 patients treated with SBRT for pancreatic cancer between July 2004 and January 2009. Forty patients (56%) had locally unresectable disease, 11 patients (16%) had local recurrence following surgical resection, 8 patients (11%) had metastatic disease, and 12 patients (17%) received adjuvant SBRT for positive margins. The median dose was 24 Gy (18–25 Gy), given in a single-fraction SBRT (n = 67) or fractionated SBRT (n = 4). Kaplan-Meyer survival analyses were used to estimate freedom from local progression (FFLP) and overall survival (OS) rates. Results: The median follow-up among surviving patients was 12.7 months (4–26 months). The median tumor volume was 17 mL (5.1–249 mL). The overall FFLP rates at 6 months/1 year were 71.7%/48.5%, respectively. Among those with macroscopic disease, FFLP was achieved in 77.3% of patients with tumor size <15 mL (n = 22), and 59.5% for ≥15 mL (n = 37) (P = 0.02). FFLP was achieved in 73% following 24 to 25 Gy, and 45% with 18 to 22 Gy (P = 0.004). The median OS was 10.3 months, with 6 month/1 year OS rates of 65.3%/41%, respectively. Grade 1–2 acute and late GI toxicity were seen in 39.5% of patients. Three patients experienced acute grade 3 toxicities. Conclusions: SBRT is feasible, with minimal grade ≥3 toxicity. The overall FFLP rate for all patients was 64.8%, comparable to rates with external beam radiotherapy. This shorter treatment course can be delivered without delay in adjuvant systemic therapy.

RADIOSURGERY FOR BENIGN INTRADURAL SPINAL TUMORS

OBJECTIVEThe role of stereotactic radiosurgery for the treatment of intracranial benign tumors is well established. There is less experience and more controversy regarding its use for benign tumors of the spine. This study evaluated the clinical efficacy of radiosurgery as part of the treatment paradigm of selected benign tumors of the spine. METHODSSeventy-three benign intradural extramedullary spinal tumors were treated with a radiosurgery technique and prospectively evaluated. Patient ages ranged from 18 to 85 years (mean age, 44 yr); the follow-up period was 8 to 71 months (median, 37 mo). Lesion location included 43 cervical, five thoracic, 19 lumbar, and six sacral. Tumor histology included neurofibroma (25 cases), schwannoma (35 cases), and meningioma (13 cases). Twenty-one cases were associated with neurofibromatosis Type 1, and nine patients had neurofibromatosis Type 2. Nineteen tumors (26%) had previously undergone open surgical resection, and six tumors (8%) had previously been treated with conventional external beam irradiation techniques. RESULTSSimilar radiation doses were prescribed for all three histopathologies. The maximum intratumoral dose was 1500 to 2500 cGy (mean, 2164 Gy). Tumor volume ranged from 0.3 to 93.4 cm3 (mean, 10.5 cm3; median, 4.11 cm3). Radiosurgery was used for the treatment of postsurgical radiographic progression in 18 cases; it was used as the primary treatment modality in 14 cases; it was used for treatment of radiographic tumor progression in nine cases; and it was used for the treatment of postsurgical residual tumor in two cases. Long-term pain improvement occurred in 22 out of 30 cases (73%). Long-term radiographic tumor control was demonstrated in all cases. Three patients experienced new symptoms attributed to radiation-induced spinal cord toxicity 5 to 13 months after treatment. CONCLUSIONSingle fraction radiosurgery was found to be clinically effective for the treatment of benign extramedullary spinal neoplasms. Although surgical extirpation remains the primary treatment option for most benign spinal tumors, radiosurgery was demonstrated to have short-term clinical benefits for the treatment of such lesions. The long-term efficacy of spinal radiosurgery for such tumors will be determined with longer follow-up periods. Its role in patients with neurofibromatosis will also be further defined with greater clinical experience.

Frameless stereotactic radiosurgery for recurrent head and neck carcinoma.

The aim of this study was to assess the feasibility and toxicity of stereotactic radiosurgery (CK-SRS) using the CyberKnife® Frameless Radiosurgery System (Accuray Inc., Sunnyvale, CA) in the management of recurrent squamous cell carcinoma of the head and neck region (SCCHN). Between November 2001 and February 2004, 22 patients with recurrent, previously irradiated SCCHN were treated with CK-SRS. The following endpoints were assessed post-CK-SRS: local control (LC), cause-specific survival (CSS), overall survival (OS), symptom relief, and acute and late toxicity. Kaplan-Meier survival analyses were used to estimate the LC, CSS, and OS rates. Clinical symptoms were graded as “improved,” “stable,” or “progressed” after CK-SRS. Acute and late toxicity were graded according to the National Cancer Institute Common Toxicity Criteria (CTC) scale, version 2.0. Seventeen patients were followed until their death. The median follow-up in the remaining five patients was 19 months (range 11–40 months). The median survival time for the entire cohort was 12 months from the time of CK-SRS. The 2-year LC, CSS, and OS rates were 26%, 26%, and 22%, respectively. After CK-SRS, symptoms were improved or stable in all but one patient who reported increasing pain. The treatment was well tolerated, with one case each of Grade 2 and 3 mucositis. There were no acute Grade 4 or 5 CTC toxicities. There were no late toxicities in this cohort. Frameless stereotactic radiosurgery for recurrent SCCHN is feasible and safe in the setting of high doses of prior irradiation. The majority of patients experienced palliation of disease without excess toxicity.

Concurrent cetuximab with stereotactic body radiotherapy for recurrent squamous cell carcinoma of the head and neck: a single institution matched case-control study.

Purpose:Locally recurrent head and neck squamous cell carcinoma can be treated with curative intent by surgical salvage or reirradiation with or without chemotherapy. We have previously demonstrated the feasibility and safety of stereotactic body reirradiation at our institution; however, efficacy has been unsatisfactory. Based on the successful combination of cetuximab with radiotherapy in locally-advanced squamous cell carcinoma of the head and neck, we compared stereotactic body radiotherapy alone with combination therapy, using concomitant cetuximab with stereotactic body radiotherapy, to enhance clinical efficacy while minimizing toxicity. Methods:In a retrospective-matched cohort study, we compared 2 groups of patients treated over a 6-year period with stereotactic body radiation therapy alone (n = 35) or with weekly cetuximab infusion during stereotactic body radiotherapy (n = 35), and evaluated clinical response, local control, overall survival, and toxicity. Cox proportional hazard models were used to assess independent prognostic factors. Results:The median follow-ups for patients alive at last contact were 21.3 months and 24.8 months for stereotactic body radiotherapy only (n = 13) and stereotactic body radiotherapy plus cetuximab (n = 22), respectively. Our results indicate that cetuximab conferred an overall survival advantage (24.5 vs. 14.8 months) when compared with the stereotactic body radiotherapy alone arm, without a significant increase in grade 3/4 toxicities. This survival advantage was also observed in the subgroup that had received cetuximab therapy during their prior therapeutic regimen. Conclusions:Our results suggest an overall survival benefit of concomitant cetuximab with stereotactic body radiotherapy in locally recurrent head and neck squamous cell carcinoma, and suggest a role in this setting. Concomitant cetuximab with stereotactic body radiotherapy is a reasonable approach for unresectable recurrent squamous cell carcinoma of the head and neck, and should be tested in prospective randomized trials to validate its clinical efficacy.

Radiosurgery for the treatment of spinal lung metastases.

Spinal metastases are a common source of pain as well as neurologic deficit in patients with lung cancer. Metastases from lung cancer traditionally have been believed to be relatively responsive to radiation therapy. However, conventional external beam radiotherapy lacks the precision to allow delivery of large single‐fraction doses of radiation and simultaneously limit the dose to radiosensitive structures such as the spinal cord. The current study evaluated the efficacy of single‐fraction radiosurgery for the treatment of spinal lung cancer metastases.

Fractionated stereotactic body radiation therapy in the treatment of previously-irradiated recurrent head and neck carcinoma: updated report of the University of Pittsburgh experience.

Objectives:The aim of this study was to assess the safety and outcome of stereotactic body radiotherapy (SBRT) in patients with recurrent previously irradiated squamous cell carcinoma of the head and neck (rSCCHN). Methods:We reviewed our experience with 85 patients who received SBRT for rSCCHN between January 2003 and May 2008. The mean dose of SBRT was 35 Gy (range: 15–44 Gy). The following end points were evaluated: tumor response, time-to-progression, acute and late toxicities, local control (LC) rates and impact of tumor dose and tumor size on LC, and overall survival. Results:The median follow-up of all patients was 6 months (range: 1.3–39 months). For those patients who were alive at last follow-up (40%) the median follow-up was 17.6 months. The mean total dose of prior radiation to the primary site was 74 Gy (range: 32–170 Gy). Those patients who received SBRT <35 Gy had significantly lower LC than those with ≥35 Gy at 6 months the median follow-up time (P = 0.014). Tumor responses were 34% complete response, 34% partial response, 20% stable disease, and 12% progressive disease. Among those with an initial tumor response followed by progression (58 patients), there was a median interval of 5.5 months for time-to-progression. The 1-year and 2-year LC and overall survival rates for all patients were 51.2% and 30.7%, and 48.5% and 16.1%, respectively. Overall, the median survival for all patients was 11.5 months (range: 3–51). Treatment was well-tolerated with no grade 4 or 5 treatment-related toxicities. Conclusions:SBRT is feasible and safe with minimal toxicities for treatment of rSCCHN patients with prior radiation therapy deemed to be poor candidates for reirradiation by conventional means.

Single-session and multisession CyberKnife radiosurgery for spine metastases—University of Pittsburgh and Georgetown University experience

OBJECT The authors compared the effectiveness of single-session (SS) and multisession (MS) stereotactic radiosurgery (SRS) for the treatment of spinal metastases. METHODS The authors conducted a retrospective review of the clinical outcomes of 348 lesions in 228 patients treated with the CyberKnife radiosurgery at the University of Pittsburgh Cancer Institute and Georgetown University Medical Center. One hundred ninety-five lesions were treated using an SS treatment regimen (mean 16.3 Gy), whereas 153 lesions were treated using an MS approach (mean 20.6 Gy in 3 fractions, 23.8 Gy in 4 fractions, and 24.5 Gy in 5 fractions). The primary end point was pain control. Secondary end points included neurological deficit improvement, toxicity, local tumor control, need for retreatment, and overall survival. RESULTS Pain control was significantly improved in the SS group (SSG) for all measured time points up to 1 year posttreatment (100% vs 88%, p = 0.003). Rates of toxicity and neurological deficit improvement were not statistically different. Local tumor control was significantly better in the MS group (MSG) up to 2 years posttreatment (96% vs 70%, p = 0.001). Similarly, the need for retreatment was significantly lower in the MSG (1% vs 13%, p < 0.001). One-year overall survival was significantly greater in the MSG than the SSG (63% vs 46%, p = 0.002). CONCLUSIONS Single-session and MS SRS regimens are both effective in the treatment of spinal metastases. While an SS approach provides greater early pain control and equivalent toxicity, an MS approach achieves greater tumor control and less need for retreatment in long-term survivors.

Stereotactic body radiation therapy for locally recurrent, previously irradiated nonsquamous cell cancers of the head and neck

Stereotactic body radiotherapy (SBRT) has emerged as a promising salvage strategy for patients with recurrent, previously irradiated head and neck cancer; however, data are limited predominantly to squamous cell carcinomas. Herein, we report the efficacy of SBRT in recurrent, nonsquamous cell cancers of the head and neck (NSCHNs).

Postoperative stereotactic radiosurgery to the resection cavity for large brain metastases: clinical outcomes, predictors of intracranial failure, and implications for optimal patient selection.

BACKGROUND Postoperative stereotactic radiosurgery for brain metastases potentially offers similar local control rates and fewer long-term neurocognitive sequelae compared to whole brain radiation therapy, although patients remain at risk for distant brain failure (DBF). OBJECTIVE To describe clinical outcomes of adjuvant stereotactic radiosurgery for large brain metastases and identify predictors of intracranial failure and their implications on optimal patient selection criteria. METHODS We performed a retrospective review on 100 large (>3 cm) brain metastases in 99 patients managed by resection followed by postoperative stereotactic radiosurgery to a median dose of 22 Gy (range, 10-28) in 1 to 5 fractions (median, 3). Primary histology was nonsmall cell lung in 40%, breast cancer in 18%, and melanoma in 17%. Forty (40%) patients had uncontrolled systemic disease. RESULTS With a median follow-up of 12.2 months (range, 0.6-87.4), the 1-year Kaplan-Meier local control was 72%, DBF 64%, and overall survival 55%. Nine patients (9%) developed evidence of radiation injury, and 6 (6%) developed leptomeningeal disease. Uncontrolled systemic disease (P=.03), melanoma histology (P=.04), and increasing number of brain metastases (P<.001) were significant predictors of DBF on Cox multivariate analysis. Patients with <4 metastases, controlled systemic disease, and nonmelanoma primary (n=47) had a 1-year DBF of 48.6% vs 80.1% for all others (P=.01). CONCLUSION Postoperative stereotactic radiosurgery to the resection cavity safely and effectively augments local control of large brain metastases. Patients with <4 metastases and controlled systemic disease have significantly lower rates of DBF and are ideal treatment candidates.