Preoperative stereotactic radiosurgery for cerebral metastases: safe, effective, and decreases steroid dependency.

OBJECTIVE: Preoperative stereotactic radiosurgery (SRS) is emerging as a viable alternative to standard postoperative SRS. Studies have suggested that preoperative SRS provides comparable tumor control and overall survival (OS) and may reduce the incidence of leptomeningeal disease (LMD) and adverse radiation effects (AREs). It is unknown, however, if preoperative SRS remains effective in cohorts including large brain metastases (> 14 cm3) or if preoperative SRS affects steroid taper/immunotherapy. Here, the authors report the results of a phase 2 single-arm trial assessing a prospectively acquired series of 26 patients who underwent preoperative SRS, without a volumetric cutoff, compared with a propensity score-matched concurrent cohort of 30 patients who underwent postoperative SRS to address these salient questions. METHODS: Demographics, oncological history, surgical details, and outcomes were collected from the medical records. Coprimary endpoints were local tumor control (LTC) and a composite outcome of LTC, ARE, and LMD. Additional outcomes were OS, steroid taper details, and immunotherapy resumption. For survival analyses, cohorts were propensity score matched. RESULTS: Preoperative and postoperative SRS patients were comparable in terms of age, sex, Karnofsky Performance Status score, oncological history, and operative details. Gross tumor volume (GTV) was significantly higher in the preoperative group (median 12.2 vs 5.3 cm3, p < 0.001). One-year LTC (preoperative SRS: 77.2% vs postoperative SRS: 82.5%, p = 0.61) and composite outcome (68.3% vs 72.7%, p = 0.38) were not significantly different between the groups. In multivariable analysis, preoperative SRS did not have a significant effect on LTC (HR 1.57 [95% CI 0.38-6.49], p = 0.536) or the composite outcome (HR 1.18 [95% CI 0.38-3.72], p = 0.771), although the confidence intervals were large. The median OS (preoperative SRS: 17.0 vs postoperative SRS: 14.0 months, p = 0.61) was not significantly different. Rates of LMD were nonsignificantly lower in the preoperative SRS group (3.8% vs 16.7%, p = 0.200). Greater GTV volume was associated with prolonged (> 10 days) steroid taper (OR 1.24 [95% CI 1.04-1.55], p = 0.032). However, in multivariable analysis, preoperative SRS markedly reduced the steroid taper length (OR 0.13 [95% CI 0.02-0.61], p = 0.016). Time to immunotherapy was shorter in the preoperative SRS group (36 [IQR 26, 76] vs OR 228 [IQR 129, 436] days, p = 0.02). CONCLUSIONS: Compared with postoperative SRS, preoperative SRS is a safe and effective strategy in the management of cerebral metastases of all sizes and provides comparable tumor control without increased adverse effects. Notably, preoperative SRS enabled rapid steroid taper, even in larger tumors. Future studies should specifically examine the interaction of preoperative SRS with steroid usage and resumption of systemic therapies and the subsequent effects on systemic progression and OS.

A phase â ¡ prospective trial of photobiomodulation therapy in limiting oral mucositis in the treatment of locally advanced head and neck cancer patients.

Objective: This study aimed to compare the historical incidence rate of severe oral mucositis (OM) in head and neck cancer patients undergoing definitive concurrent chemoradiation therapy (CRT) versus a prospective cohort of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with prophylactic photobiomodulation therapy (PBMT). Methods: This US-based, institutional, single-arm, phase Ⅱ prospective clinical trial was initiated in 50 patients (age ≥ 18 years, Karnofsky Performance Scale Index > 60, with locally advanced HNSCC (excluding oral cavity) receiving definitive or adjuvant radiation therapy (RT) with concurrent platinum-based chemotherapy (CT). PBMT was delivered three times per week throughout RT utilizing both an intraoral as well extraoral delivery system. Primary outcome measure was incidence of severe OM utilizing both the National Cancer Institute Common Toxicity Criteria, version 4.0 (NCI-CTCAE) Grade ≥3 and the World Health Organization Mucositis Grading Scale (WHO) Grade ≥3 versus historical controls; secondary outcome measures included time to onset of severe OM following therapy initiation. Results: At baseline, all patients included in final analysis (N = 47) had OM Grade 0. Average RT and CT dose was (66.3 ± 5.1) Gy and (486.1 ± 106.8) mg/m2, respectively. Severe OM was observed in 11 of 47 patients (23%, confidence interval: 12, 38). OM toxicity grade trended upward during treatment, reaching a maximum at 7 weeks (WHO: 1.8 vs. NCI-CTCAE: 1.7). Subsequently, OM grade returned to baseline 3 months following completion of RT. The mean time to onset of severe OM was (35 ± 12) days. The mean time to resolution of severe OM was (37 ± 37) days. Conclusions: Compared to historical outcomes, PBMT aides in decreasing severe OM in patients with locally advanced HNSCC. PBMT represents a minimally invasive, prophylactic intervention to decrease OM as a major treatment-related side effect.

Long-Term Outcomes After Stereotactic Radiosurgery for Spine Metastases: Radiation Dose-Response for Late Toxicity.

PURPOSE: To document the 5- and 10-year rates of late toxicity and vertebral compression fracture (VCF) in long-term survivors after stereotactic radiosurgery for spine metastases. METHODS AND MATERIALS: A retrospective review was performed on 562 patients treated with SRS for spine metastases between April 2001 and July 2011. Selecting those with at least 5-year survival after SRS, included were 43 patients who collectively underwent 84 treatments at 54 spine sites. Most were treated with single-fraction stereotactic radiosurgery to a median dose of 16 Gy (range, 12-24 Gy), and 56% of sites had received prior external beam radiation therapy. Late toxicities and VCFs occurring in the absence of tumor progression were recorded. Binary logistic regression was used to identify predictors of late complications. RESULTS: Nine patients (17% of treatment sites) developed grade ≥2 late toxicities at a median time of 12.8 months (range, 4.2-59.0 months). Actuarial 5- and 10-year rates of grade ≥2 late toxicity were 17% and 17%, respectively. On multivariate analysis, only cumulative biologically effective dose (BED3) > 200 Gy (or EQD22Gy [2-Gy equivalent dose calculated using an α/ß ratio of 2] > 130 Gy) was associated with grade ≥2 late toxicity (P = .036). Maximum point BED3 > 110 Gy (or EQD22Gy > 70 Gy) to spinal cord or cauda equina was associated with grade ≥2 late neuropathy (P = .017). Nine VCFs (18%) occurred at a median time of 10.2 months (range, 3.2-57.2 months), with 5- and 10-year VCF rates of 17% and 17%, respectively. CONCLUSION: Stereotactic radiosurgery for primary treatment and reirradiation of spinal metastases is associated with a moderate risk of late toxicity with 10-year follow-up. Risk of late toxicity significantly increases with cumulative BED3 > 200 Gy and spinal cord or cauda equina point BED3 > 110 Gy. Patients remain at moderate risk of VCF up to 5 years after treatment, with a plateau in incidence thereafter up to 10 years.

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.

Pretreatment SUVmax predicts progression-free survival in early-stage non-small cell lung cancer treated with stereotactic body radiation therapy.

BACKGROUND: This retrospective study aims to assess the usefulness of SUV(max) from FDG-PET imaging as a prognosticator for primary biopsy-proven stage I NSCLC treated with SBRT. METHODS: This study includes 95 patients of median age 77 years, with primary, biopsy-confirmed peripheral stage IA/IB NSCLC. All patients were treated with 60 Gy in 3 fractions with a median treatment time of six days. Local, regional, and distant failures were evaluated independently according to the terms of RTOG1021. Local, regional, and distant control, overall- and progression-free survival were estimated by the Kaplan-Meier method. Cox proportional hazards regression was performed to determine whether SUV(max), age, KPS, gender, tumor size/T stage, or smoking history influenced outcomes. SUV(max) was evaluated as both a continuous and as a dichotomous variable using a cutoff of <5 and ≥ 5. RESULTS: Median follow-up for the cohort was 16 months. Median OS and PFS were 25.3 and 40.3 months, respectively. SUV with a cutoff value of 5 predicted for OS and PFS (p = .024 for each) but did not achieve significance for LC (p = .256). On Cox univariate regression analysis, SUV as a dichotomous variable predicted for both OS and PFS (p = .027 and p = .030, respectively). Defined as a continuous variable, SUV(max) continued to predict for OS and PFS (p = .032 and p = .003), but also predicted LC (p = .045) and trended toward significance for DC (p = .059). SUV(max) did not predict for OS as a dichotomous or continuous variable. It did, however, predict for PFS as a continuous variable (p = .008), neared significance for local control (p = .057) and trended towards, significance for distant control (p = .092). CONCLUSIONS: SUV(max) appears to be a statistically and clinically significant independent prognostic marker for progression-free survival in patients with stage I NSCLC treated with SBRT. Prospective studies to more accurately define the role of tumor FDG uptake in the prognosis of NSCLC are warranted.

Treatment outcomes in patients treated with CyberKnife radiosurgery for vestibular schwannoma.

OBJECTIVE: To evaluate tumor control, hearing, tinnitus, and balance outcomes of patients treated with CyberKnife (CK) radiosurgery for vestibular schwannoma (VS). STUDY DESIGN: Retrospective series review. SETTING: Tertiary referral center. PATIENTS: All patients treated with CK radiosurgery for vestibular schwannoma by a multidisciplinary radiosurgical team from August 2005 to November 2011. The median age was 59 years, and mean follow-up was 40 months. Seventy-three patients were treated (63 primary radiosurgery and 10 postsurgical). INTERVENTIONS: CK radiosurgery, serial MRI imaging, comprehensive audiometry, Tinnitus Handicap Inventory (THI) scores, and Activities-Specific Balance Confidence Scale (ABC). MAIN OUTCOME MEASURES: Tumor control defined as 2 mm linear growth or lower or less than 20% increase in tumor volume (TV), measured in cubic centimeter, after a minimum of 12 months of monitoring, audiogram profiles, THI, and ABC surveys. RESULTS: Of those treated with CK as primary modality, 83% had 0- to 2-mm growth (tumor control or stable) and 17% grew greater than 2 mm. Of the tumors that were stable, 29% shrank 2 mm or greater. Volumetric analysis found that 74% of tumors had less than 20% TV growth, whereas 26% exhibited 20% or greater increase in TV. Of those deemed stable, 65% shrank 20% or greater TV; 95% of patients did not need additional surgical intervention, 3 required salvage surgery and 1 underwent additional radiosurgery. The majority of patients started with Class D hearing, but of those with Class A or B hearing before treatment, 53.5% maintained serviceable hearing at 3 years of follow-up. The pretreatment and posttreatment median THI Grades were both 1. The pretreatment and posttreatment ABC scores were unchanged at 81%. CONCLUSION: The LINAC-based CK (18 Gy over 3 fractions at 80% isodose line) provides tumor control rates comparable to other forms of radiosurgery. Analysis for tumor growth was positive for 17% using maximum linear diameters and 26% with a volumetric workstation. This discrepancy is consistent with previous reports where volumetric models were found to be more sensitive in establishing growth. Serviceable hearing was comparable to previous SRS and SRT reports with an overall hearing preservation of 53.5%. This number was 77% in those with pre-Class A hearing. SRS did not affect pretreatment tinnitus or vestibular function.

Pathologic response with neoadjuvant chemotherapy and stereotactic body radiotherapy for borderline resectable and locally-advanced pancreatic cancer.

BACKGROUND: Neoadjuvant stereotactic body radiotherapy (SBRT) has potential applicability in the management of borderline resectable and locally-advanced pancreatic adenocarcinoma. In this series, we report the pathologic outcomes in the subset of patients who underwent surgery after neoadjuvant SBRT. METHODS: Patients with borderline resectable or locally-advanced pancreatic adenocarcinoma who were treated with SBRT followed by resection were included. Chemotherapy was to the discretion of the medical oncologist and preceded SBRT for most patients. RESULTS: Twelve patients met inclusion criteria. Most (92%) received neoadjuvant chemotherapy, and gemcitabine/capecitabine was most frequently utilized (n = 7). Most were treated with fractionated SBRT to 36 Gy/3 fractions (n = 7) and the remainder with single fraction to 24 Gy (n = 5). No grade 3+ acute toxicities attributable to SBRT were found. Two patients developed post-surgical vascular complications and one died secondary to this. The mean time to surgery after SBRT was 3.3 months. An R0 resection was performed in 92% of patients (n = 11/12). In 25% (n = 3/12) of patients, a complete pathologic response was achieved, and an additional 16.7% (n = 2/12) demonstrated <10% viable tumor cells. Kaplan-Meier estimated median progression free survival is 27.4 months. Overall survival is 92%, 64% and 51% at 1-, 2-, and 3-years. CONCLUSIONS: This study reports the pathologic response in patients treated with neoadjuvant chemotherapy and SBRT for borderline resectable and locally-advanced pancreatic cancer. In our experience, 92% achieved an R0 resection and 41.7% of patients demonstrated either complete or extensive pathologic response to treatment. The results of a phase II study of this novel approach will be forthcoming.

Target delineation in stereotactic body radiation therapy for recurrent head and neck cancer: a retrospective analysis of the impact of margins and automated PET-CT segmentation.

BACKGROUND: Few guidelines exist on stereotactic body radiation therapy (SBRT) treatment planning for recurrent head and neck cancer. We assessed the impact of retrospectively adding margins/automated PET volumes to the gross tumor volume (GTV) in patients with post-SBRT recurrences. MATERIALS AND METHODS: We reviewed 89 patients with recurrent head and neck cancer treated with SBRT using no margin around the GTV. GTVs were recontoured with 1-5mm margins. PET-CT planned GTVs were also recontoured by adding PET-standardized uptake value (SUV)(3.5), SUV(4.5), SUV(40% max), and signal/background ratio (SBR) to the original GTV. We deformably registered recontoured GTVs to post-SBRT scans and assessed fraction of recurrence volume (RV) falling within the GTV, the "RV-GTV overlap." RESULTS: With non-PET-CT planning, median RV-GTV overlap increased from 11.7% to 48.2% using 5mm margins, and median GTV size increased by 41.8 cc (156%). With PET-CT planning, RV-GTV overlap increased from 45% to 93.6% using 5mm margins, and GTV size increased by 34.8 cc (140%). Adding SUV(3.5) and SBR increased RV-GTV overlap from 45% to 73.3% and 73.6%, with GTV size increases of 0.8 (3%) and 3.1 cc (11%), respectively. CONCLUSIONS: Recontouring increased recurrence coverage and also GTV size. Margins up to 5mm may reduce failures but could possibly increase toxicities. Automated PET contours may reduce near-miss failures with smaller increases in GTV size.

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.

A retrospective, deformable registration analysis of the impact of PET-CT planning on patterns of failure in stereotactic body radiation therapy for recurrent head and neck cancer.

BACKGROUND: Stereotactic body radiation therapy (SBRT) has seen increasing use as a salvage strategy for selected patients with recurrent, previously-irradiated squamous cell carcinoma of the head and neck (rSCCHN). PET-CT may be advantageous for tumor delineation and evaluation of treatment failures in SBRT. We analyzed the patterns of failure following SBRT for rSCCHN and assessed the impact of PET-CT treatment planning on these patterns of failure. METHODS: We retrospectively reviewed 96 patients with rSCCHN treated with SBRT. Seven patients (7%) were treated after surgical resection of rSCCHN and 89 patients (93%) were treated definitively. PET-CT treatment planning was used for 45 patients whereas non-PET-CT planning was used for 51 patients. Categories of failure were assigned by comparing recurrences on post-treatment scans to the planning target volume (PTV) from planning scans using the deformable registration function of VelocityAI™. Failures were defined: In-field (>75% inside PTV), Overlap (20-75% inside PTV), Marginal (<20% inside PTV but closest edge within 1cm of PTV), or Regional/Distant (more than 1cm from PTV). RESULTS: Median follow-up was 7.4 months (range, 2.6-52 months). Of 96 patients, 47 (49%) developed post-SBRT failure. Failure distribution was: In-field-12.3%, Overlap-24.6%, Marginal-36.8%, Regional/Distant-26.3%. There was a significant improvement in overall failure-free survival (log rank p = 0.037) and combined Overlap/Marginal failure-free survival (log rank p = 0.037) for those receiving PET-CT planning vs. non-PET-CT planning in the overall cohort (n = 96). Analysis of the definitive SBRT subgroup (n = 89) increased the significance of these findings (overall failure: p = 0.008, Overlap/Marginal failure: p = 0.009). There were no significant differences in age, gender, time from prior radiation, dose, use of cetuximab with SBRT, tumor differentiation, and tumor volume between the PET-CT and non-PET-CT groups. CONCLUSIONS: Most failures after SBRT treatment for rSCCHN were near misses, i.e. Overlap/Marginal failures (61.4%), suggesting an opportunity to improve outcomes with more sensitive imaging. PET-CT treatment planning showed the lowest rate of overall and near miss failures and is beneficial for SBRT treatment planning.

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

BACKGROUND: 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). METHODS: In all, 34 patients with pathologically proven NSCHN were re-irradiated with SBRT to a median dose of 40 Gy in 5 fractions (interquartile range, 30-44 Gy). Toxicity and quality of life were followed prospectively. RESULTS: Median follow-up was 10 months (absolute range, 0-55 months). The 6-month/1-year local control rate was 77/59%, with a 6-month/1-year overall survival of 76/59%. Local control was significantly improved for tumors <25 mL (p = .030). Acute/late grade 3 toxicity was 15/6%, with no grade 4-5 toxicity. CONCLUSIONS: SBRT for previously irradiated, locally recurrent NSCHN provides promising local control, especially for tumors <25 mL, with minimal toxicity. The optimal dose for larger tumors remains to be defined.

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.

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.

Combined endoscopic endonasal surgery and fractionated stereotactic radiosurgery (fSRS) for complex cranial base tumors-early clinical outcomes.

Endoscopic endonasal surgery (EES) has been shown to be a feasible approach to cranial base tumors while reducing post-operative morbidity. Using the endoscopic endonasal approach alone or in combination with open approaches may provide advantages over conventional approaches. However, the balance between maximal resection and minimal injury to neurovascular structures frequently precludes gross total resection (GTR). Consequently, adjuvant radiation therapy may be an important option to improve local control (LC) of residual disease. In this retrospective series, we report clinical outcomes, morbidity, and LC of 40 patients with cranial base tumors treated with EES +/- combined open approach followed by fSRS (CyberKnife, Accuray Inc.). 26 patients had benign disease, 7 had newly diagnosed malignant disease, and 7 had previously resected malignant disease. Surgical outcomes were evaluable in all patients. LC after fSRS was evaluable in 39 patients and defined as no evidence of regrowth by MRI, CT, & physical examination. GTR was achieved in 12/40. Median post-operative length of stay (LOS) was 3 days. In multivariable analysis controlling for anatomic location and malignant histology, post-operative complications (n = 10) were significantly associated with patients having combined open and EES (p < 0.01, OR = 16.9). SRS was delivered in 1-5 sessions to a median marginal dose of 24.9 Gy. Median follow-up was 24.7 months (range, 1.5 to 61 months). LC was achieved in 89.7% (35/39) of evaluable patients. LC was achieved in 11/12 patients who had GTR. Median progression-free survival was 19.7 months (21.0 months for benign tumors (n = 26), 5.8 months for previously resected malignant disease (n = 7), and 21.2 months for newly diagnosed malignant disease (n = 7). Of the 31 patients who had symptomatic disease at presentation, 18 (58%) reported complete symptom resolution, 9 partial, and 4 no improvement. One patient who received two prior courses of radiation therapy developed osteosclerosis (grade III). Other adverse events were erythema (grade I, n = 5), nausea (grade II, n = 2), conjunctivitis (grade II, n = 1). EES followed by fSRS is a safe and effective management strategy for selected cranial base tumors. EES combined with an open surgical approach may result in increased complications. However, initial follow-up offers encouraging results indicating shorter time to recovery, acceptable LC rates compared to conventional approaches, and similar median time to progression for benign and newly diagnosed malignant disease.

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 > or =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 re-irradiation by conventional means.

Percutaneous tibial nerve stimulation for treatment of overactive bladder and urinary retention in an elderly population.

Percutaneous tibial nerve stimulation (PTNS) is a treatment option for patients who present with urinary urgency, frequency, urge incontinence, or urinary retention. When behavior modification and/or pharmacotherapy did not adequately relieve symptoms, this treatment was found to decrease incidence of overactive bladder or retention symptoms in the authors' patient population.

Radiosurgery for benign intradural spinal tumors.

OBJECTIVE: The 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. METHODS: Seventy-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. RESULTS: Similar 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 cm (mean, 10.5 cm; median, 4.11 cm). 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. CONCLUSION: Single 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.

Radiosurgery for the treatment of spinal lung metastases.

BACKGROUND: 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. METHODS: In the current prospective cohort evaluation, 87 lung cancer metastases to the spine in 77 patients were treated with a single-fraction radiosurgery technique with a follow-up period of 6 to 40 months (median, 12 months). The indication for radiosurgery treatment was pain in 73 cases, as a primary treatment modality in 7 cases, for radiographic tumor progression in 4 cases, and for progressive neurologic deficit in 3 cases. RESULTS: Tumor volume ranged from 0.2 to 264 cm(3) (mean, 25.7 cm(3)). The maximum tumor dose was maintained at 15 to 25 grays (Gy) (mean, 20 Gy; median, 20 Gy). No radiation-induced toxicity occurred during the follow-up period. Long-term axial and radicular pain improvement occurred in 65 of 73 patients (89%) who were treated primarily for pain. Long-term radiographic tumor control was observed in all patients who underwent radiosurgery as their primary treatment modality or for radiographic tumor progression. CONCLUSIONS: Spinal radiosurgery was found to be feasible, safe, and clinically effective for the treatment of spinal metastases from lung cancer. The results of the current study indicate the potential of radiosurgery in the treatment of patients with spinal lung metastases, especially those with solitary sites of spine involvement, to improve long-term palliation.

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.