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.

Single isocenter HyperArc treatment of multiple intracranial metastases: Targeting accuracy.

PURPOSE/OBJECTIVES: (A) To examine the alignment accuracy of CBCT guidance for brain metastases with off centered isocenters, (B) to test dose delivery and targeting accuracy for single isocenter treatments with multiple brain metastases. We report the results of the end-to-end test for Truebeam stereotactic radiosurgery (SRS). MATERIALS/METHODS: An anthropomorphic CT head phantom was drilled with five MOSFET inserts and two PTW Pinpoint chamber inserts. The phantom was simulated, planned, and delivered. For the purpose of comparing the accuracy of alignment, CBCTs were acquired with the isocenter centered and offset superiorly 8 cm, inferiorly 8 cm, anteriorly 7 cm, posteriorly 7 cm, and right 5 cm. There were six degrees of freedom corrections applied to the plans, as well as intentional rotational and translational errors for dose comparisons. Dose accuracy checks were performed with MOSFET and PTW Pinpoint chamber, and targeting accuracy was assessed with GafChromic films. RESULT: (A) Compared to centered CBCT, off-centered CBCT scan showed some alignment errors, with a maximum difference of 0.6-degree pitch and 0.9 mm translation when the phantom was placed 8 cm inferior off center. (B) For the single isocenter plan, measured doses of the five MOSFET were 95%-100% of the planned dose, whereas the multiple isocenter plans were 96%-100%. With intentional setup errors of 1-degree pitch, doses were 97.1%-100.4% compared to the perfect setup. The same was found for the two pinpoint chamber readings with 1-degree rotation and 1 mm translation. (C) Targeting accuracy for targets at the isocenter is 0.67 mm, within the machine specification of 0.75 mm. Targeting accuracy for isocenters 6-12 cm away from the target is in the range 0.67-1.18 mm. CONCLUSION: (A) Single isocenter HyperArc treatments for multiple brain metastases are feasible and targeting accuracy is clinically acceptable. (B) The vertex in a cranial scan is very important for proper alignment.

A 3D correction method for predicting the readings of a PinPoint chamber on the CyberKnife® M6™ machine.

The use of small fields in radiation therapy techniques has increased substantially in particular in stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT). However, as field size reduces further still, the response of the detector changes more rapidly with field size, and the effects of measurement uncertainties become increasingly significant due to the lack of lateral charged particle equilibrium, spectral changes as a function of field size, detector choice, and subsequent perturbations of the charged particle fluence. This work presents a novel 3D dose volume-to-point correction method to predict the readings of a 0.015 cc PinPoint chamber (PTW 31014) for both small static-fields and composite-field dosimetry formed by fixed cones on the CyberKnife® M6™ machine. A 3D correction matrix is introduced to link the 3D dose distribution to the response of the PinPoint chamber in water. The parameters of the correction matrix are determined by modeling its 3D dose response in circular fields created using the 12 fixed cones (5 mm-60 mm) on a CyberKnife® M6™ machine. A penalized least-square optimization problem is defined by fitting the calculated detector reading to the experimental measurement data to generate the optimal correction matrix; the simulated annealing algorithm is used to solve the inverse optimization problem. All the experimental measurements are acquired for every 2 mm chamber shift in the horizontal planes for each field size. The 3D dose distributions for the measurements are calculated using the Monte Carlo calculation with the MultiPlan® treatment planning system (Accuray Inc., Sunnyvale, CA, USA). The performance evaluation of the 3D conversion matrix is carried out by comparing the predictions of the output factors (OFs), off-axis ratios (OARs) and percentage depth dose (PDD) data to the experimental measurement data. The discrepancy of the measurement and the prediction data for composite fields is also performed for clinical SRS plans. The optimization algorithm used for generating the optimal correction factors is stable, and the resulting correction factors were smooth in the spatial domain. The measurement and prediction of OFs agree closely with percentage differences of less than 1.9% for all the 12 cones. The discrepancies between the prediction and the measurement PDD readings at 50 mm and 80 mm depth are 1.7% and 1.9%, respectively. The percentage differences of OARs between measurement and prediction data are less than 2% in the low dose gradient region, and 2%/1 mm discrepancies are observed within the high dose gradient regions. The differences between the measurement and prediction data for all the CyberKnife based SRS plans are less than 1%. These results demonstrate the existence and efficiency of the novel 3D correction method for small field dosimetry. The 3D correction matrix links the 3D dose distribution and the reading of the PinPoint chamber. The comparison between the predicted reading and the measurement data for static small fields (OFs, OARs and PDDs) yield discrepancies within 2% for low dose gradient regions and 2%/1 mm for high dose gradient regions; the discrepancies between the predicted and the measurement data are less than 1% for all the SRS plans. The 3D correction method provides an access to evaluate the clinical measurement data and can be applied to non-standard composite fields intensity modulated radiation therapy point dose verification.

Long-Term Survivorship Following Stereotactic Radiosurgery Alone for Brain Metastases: Risk of Intracranial Failure and Implications for Surveillance and Counseling.

BACKGROUND: Historically, survival for even highly select cohorts of brain metastasis patients selected for SRS alone is <2 yr; thus, limited literature on risks of recurrence exists beyond 2 yr. OBJECTIVE: To investigate the possibility that for subsets of patients the risk of intracranial failure beyond 2 yr is less than the commonly quoted 50% to 60%, wherein less frequent screening may be appropriate. METHODS: As a part of our institutional radiosurgery database, we identified 132 patients treated initially with stereotactic radiosurgery (SRS) alone (± pre-SRS surgical resection) with at least 2 yr of survival and follow-up from SRS. Primary study endpoints were rates of actuarial intracranial progression beyond 2 yr, calculated using the Kaplan-Meier and Cox regression methods. RESULTS: The median follow-up from the first course of SRS was 3.5 yr. Significant predictors of intracranial failure beyond 2 yr included intracranial failure before 2 yr (52% vs 25%, P < .01) and total SRS tumor volume ≥5 cc (51% vs 25%, P < .01). On parsimonious multivariate analysis, failure before 2 yr (HR = 2.2, 95% CI: 1.2-4.3, P = .01) and total SRS tumor volume ≥5 cc (HR = 2.3, 95% CI: 1.2-4.3, P = .01) remained significant predictors of intracranial relapse beyond 2 yr. CONCLUSION: Relapse rates beyond 2 yr following SRS alone for brain metastases are low in patients who do not suffer intracranial relapse within the first 2 yr and with low-volume brain metastases, supporting a practice of less frequent screening beyond 2 yr. For remaining patients, frequent (every 3-4 mo) screening remains prudent, as the risk of intracranial failure after 2 yr remains high.

Dosimetric comparison between cone/Iris-based and InCise MLC-based CyberKnife plans for single and multiple brain metastases.

We performed an evaluation of the CyberKnife InCise MLC by comparing plan qualities for single and multiple brain lesions generated using the first version of InCise MLC, fixed cone, and Iris collimators. We also investigated differences in delivery efficiency among the three collimators. Twenty-four patients with single or multiple brain mets treated previously in our clinic on a CyberKnife M6 using cone/Iris collimators were selected for this study. Treatment plans were generated for all lesions using the InCise MLC. Number of monitor units, delivery time, target coverage, conformity index, and dose falloff were compared between MLC- and clinical cone/Iris-based plans. Statistical analysis was performed using the non-parametric Wilcoxon-Mann-Whitney signed-rank test. The planning accuracy of the MLC-based plans was validated using chamber and film measurements. The InCise MLC-based plans achieved mean dose and target coverage comparable to the cone/Iris-based plans. Although the conformity indices of the MLC-based plans were slightly higher than those of the cone/Iris-based plans, beam delivery time for the MLC-based plans was shorter by 30% ~ 40%. For smaller targets or cases with OARs located close to or abutting target volumes, MLC-based plans provided inferior dose conformity compared to cone/Iris-based plans. The QA results of MLC-based plans were within 5% absolute dose difference with over 90% gamma passing rate using 2%/2 mm gamma criteria. The first version of InCise MLC could be a useful delivery modality, especially for clinical situations for which delivery time is a limiting factor or for multitarget cases.

A method to improve dose gradient for robotic radiosurgery.

For targets with substantial volume, collimators of relatively large size are usually selected to minimize the treatment time in robotic radiosurgery. Their large penumbrae may adversely affect the dose gradient around the target. In this study, we implement and evaluate an inner-shell planning method to increase the dose gradient and reduce dose to normal tissues. Ten patients previously treated with CyberKnife M6 system were randomly selected with the only criterion being that PTV be larger than 2 cm(3). A new plan was generated for each patient in which the PTV was split into two regions: a 5 mm inner shell and a core, and a 7.5 mm Iris collimator was exclusively applied to the shell, with other appropriate collimators applied to the core depending on its size. The optimization objective, functions, and constraints were the same as in the corresponding clinical plan. The results were analyzed for V12 Gy, V9 Gy, V5 Gy, and gradient index (GI). Volume reduction was found for the inner-shell method at all studied dose levels as compared to the clinical plans. The absolute dose-volume reduction ranged from 0.05 cm(3) to 18.5 cm(3) with a mean of 5.6 cm(3) for 12 Gy, from 0.2 cm(3) to 38.1 cm(3) with a mean of 9.8 cm(3) for 9 Gy, and from 1.5 cm(3) to 115.7 cm(3) with a mean of 24.8 cm(3) for 5 Gy, respectively. The GI reduction ranged from 3.2% to 23.6%, with a mean of 12.6%. Paired t-test for GI has a p-value of 0.0014. The range for treatment time increase is from -3 min to 20 min, with a mean of 7.0 min. We conclude that irradiating the PTV periphery exclusively with the 7.5 mm Iris collimator, rather than applying mixed collimators to the whole PTV, can substantially improve the dose gradient, while maintaining good coverage, conformity, and reasonable treatment time.

Stereotactic Radiosurgery/Stereotactic Body Radiotherapy for Recurrent Lung Neoplasm: An Analysis of Outcomes in 100 Patients.

BACKGROUND: A significant number of patients have recurrent or persistent lung cancer despite complete resection or treatment with definitive chemoradiation. Stereotactic radiosurgery (SRS)/stereotactic body radiation therapy is emerging as an important modality for the treatment of early-stage lung neoplasm; SRS may also offer an alternative treatment option for patients with recurrent lung disease. We evaluated outcomes after treatment with SRS for recurrent lung neoplasm in a large series of patients. METHODS: Selected patients with limited recurrent, persistent, or progressive disease after one or more prior treatments for lung cancer were offered SRS. Thoracic surgeons evaluated all patients, placed fiducials when needed, and planned treatment in close collaboration with radiation oncologists and medical physicists. In our early experience, a single fraction of 20 Gy radiation was prescribed and was subsequently increased to 45 to 60 Gy in three to five fractions. The primary endpoint evaluated was overall survival. RESULTS: We treated 100 patients with recurrent lung cancer (median age 72 years) with SRS. The postprocedure 30-day mortality rate was 0%; median follow-up was 51 months (range, 5 to 123). The median overall survival for the entire group was 23 months (95% confidence interval: 19 to 41). The probability of 2-year and 5-year overall survival was 49% (95% confidence interval: 40% to 60%) and 31% (95% confidence interval: 23% to 43%), respectively. CONCLUSIONS: Our experience indicates that SRS is safe, and offers an alternative modality for selected patients with recurrent oligometastatic or persistent lung cancer. Thoracic surgeons should actively participate in SRS and continue to evaluate the efficacy of this treatment strategy.

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.

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.

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.

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 radiosurgery to the resection cavity of brain metastases: a retrospective analysis and literature review.

PURPOSE: The aim of this study was to analyze results of stereotactic radiosurgery (SRS) as adjuvant therapy for resected brain metastases. METHODS: Medical records of patients treated at a single institution with SRS to the postoperative cavity of brain metastases were retrospectively reviewed. Patients who completed the prescribed SRS regimen following gross-total resection and had no previous whole brain radiotherapy were included in the study. Kaplan-Meier analyses were used to estimate local (LC) and intracranial control (IC), and overall survival (OS) rates. RESULTS: Between April 2005 and July 2010, 77 patients (median age 63 years) with 89 metastases met the inclusion criteria. The median prescription dose was 18 Gy (12-27 Gy) delivered in 1-3 fractions for a median target volume of 7.6 cm(3) (0.5-59 cm(3)). The 6-month, 1-year, and 2-year LC rates were 76.1, 76.1, and 74.3%, respectively. The 6-month, 1-year, and 2-year IC rates were 75.2, 54, and 43.6%, respectively. With a median follow-up of 13.8 months, the median OS was 14.5 months (1.9-51.4 months) after SRS. The overall 6-month, 1-year, and 2-year OS rates were 91, 62.5, and 43.6%, respectively. Complications included 2 patients with radiation necrosis. CONCLUSION: Adjuvant radiosurgery to the tumor cavity of resected brain metastases is well-tolerated and achieves LC in the majority of patients.

The impact of tumor volume and radiotherapy dose on outcome in previously irradiated recurrent squamous cell carcinoma of the head and neck treated with stereotactic body radiation therapy.

PURPOSE: To assess the effect of stereotactic body radiotherapy (SBRT) dose and tumor volume on outcomes in patients with recurrent, previously irradiated squamous cell carcinoma of the head and neck. MATERIALS AND METHODS: A total of 96 patients with recurrent, previously irradiated squamous cell carcinoma of the head and neck were treated with SBRT using Cyberknife and Trilogy-intensity-modulated radiosurgery. Kaplan-Meier survival analyses were used to estimate locoregional control (LRC) and overall survival rates. Response was evaluated using positron emission tomography/computed tomography or computed tomography and detailed physical examination. RESULTS: The median follow-up for all patients was 14 months (2-39 months). The median dose of prior radiation was 68.4 Gy (32-170 Gy). Patients were divided into 4 SBRT dose groups: I (15-28 Gy/n = 29), II (30-36 Gy/n = 22), III (40 Gy/n = 18), and IV (44-50 Gy/n = 27). The median gross tumor volume (GTV) was 24.3(3) cm (2.5-162 cm). For GTV ≤25 cm(3) (n = 50), complete response rates were 27.8%/30%/45.5%/45.5%, and for GTV >25 cm(3) (n = 46), complete response rates were 20%/25%/42.8%/50% for SBRT groups I-IV, respectively. The 1-/2-/3-year LRC rates for doses 40 to 50 Gy were 69.4%/57.8%/41.1%, respectively, whereas for 15 to 36 Gy, they were 51.9%/31.7%/15.9%, respectively (P = 0.02). The overall 1- and 2-year overall survival rates were 58.9% and 28.4%, respectively. Treatment was well tolerated with no grade 4/5 toxicities. CONCLUSIONS: Dose escalation up to 50 Gy in 5 fractions is feasible with SBRT for recurrent head and neck squamous cell carcinoma. Higher SBRT doses were associated with significantly higher LRC rates. Large tumor volume required higher SBRT doses to achieve optimal response rates compared with smaller tumor volume.

Stereotactic body radiotherapy for the treatment of presacral recurrences from rectal cancers.

PURPOSE: Management of recurrent presacral rectal cancer is often not amenable to curative surgery. The goal of this study is to evaluate the safety and efficacy of cyberknife stereotactic body radiotherapy (SBRT) in the management of presacral recurrences. MATERIALS AND METHODS: Between April 2003 and October 2008, 14 patients with presacral tumors from rectal adenocarcinoma were SBRT treated. Eleven patients were treated with 36 Gy in 3 fractions and 3 patients were treated with single fraction of 12, 16 or 18 Gy. Tumor response was assessed using response evaluation and criteria in solid tumor (RECIST) criteria. Toxicities were assessed with common terminology criteria adverse events v 3.0. Pain control was assessed. RESULTS: One patient (6.7%) received SBRT as boost therapy. All patients had prior radiotherapy [median 50.4 Gy (20 - 81 Gy)]. Median tumor volume was 52.5 cc (19 - 110 cc). At initial follow-up of a median 4.9 months (1 - 16.3 months), treatment responses were complete response (n=3) and stable disease (n=8). With a median follow-up of 16.5 months (6 - 69 months), the one- and two-year LC rates were 90.9 and 68.2%, respectively, and the one- and two-year OS rates were 90 and 78.8%, respectively. No factors were significantly predictive of LC and OS. There were no grade 3 or 4 toxicities. Fifty percent (n=7) of our patients experienced pain with recurrence before treatment and 4 (57.1%) of them reported no pain after completion of their SBRT. CONCLUSIONS: Stereotactic body radiotherapy for presacral recurrence of rectal adenocarcinoma is an efficacious and well-tolerated treatment modality which allows for palliation of pain.

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.

Stereotactic radiosurgery for the treatment of lung neoplasm: experience in 100 consecutive patients.

BACKGROUND: Surgical resection is the standard of care for patients with resectable non-small cell lung cancer or selected patients with pulmonary metastases. Stereotactic radiosurgery may offer an alternative option for high-risk patients who are not surgical candidates. We report our initial experience with stereotactic radiosurgery in the treatment of lung neoplasm in 100 consecutive patients. METHODS: Patients who were medically inoperable were offered stereotactic radiosurgery. Thoracic surgeons evaluated all patients, placed fiducials, and performed treatment planning in collaboration with radiation oncologists. Initially, a median dose of 20 Gy prescribed to the 80% isodose line was administered in a single fraction, and this was subsequently increased to a total of 60 Gy in three fractions. The primary end point evaluated was overall survival. RESULTS: We treated 100 patients (median age, 70 years; 51 men, 49 women) with stereotactic radiosurgery: 46 (46%) with primary lung neoplasm, 35 (35%) with recurrent cancer, and 19 (19%) with pulmonary metastases. The median follow-up was 20 months. The median overall survival was 24 months. Local recurrence occurred in 25 patients. The probability of 2-year overall survival was 50% for the entire group, 44% for primary lung cancer, 41% for recurrent cancer, and 84% for metastatic cancer. CONCLUSIONS: Our initial experience indicates that stereotactic radiosurgery has reasonable results in these high-risk patients. Resection continues to remain the standard treatment; however, stereotactic radiosurgery may offer an alternative in high-risk patients. Further prospective studies with different dose schema are needed to evaluate the efficacy of stereotactic radiosurgery.

Stereotactic radiosurgery for the treatment of stage I non-small cell lung cancer in high-risk patients.

OBJECTIVE: Surgical resection is the standard of care for patients with stage I non-small cell lung cancer. For high-risk patients, however, stereotactic radiosurgery may offer an alternative. We report our initial experience with stereotactic radiosurgery for treatment of stage I non-small cell lung cancer by a team of thoracic surgeons and radiation oncologists. METHODS: Patients medically ineligible for operation were offered stereotactic radiosurgery. Thoracic surgeons evaluated all patients, placed fiducials, and performed treatment planning in collaboration with radiation oncologists. Median dose of 20 Gy to 80% isodose line was administered as single fraction (range 20-60 Gy,1-3 fractions). Initial response rate, progression, and survival were monitored. RESULTS: Twenty-one patients underwent stereotactic radiosurgery in 3 years. Fiducial placement resulted in pneumothorax requiring a pigtail catheter in 10 of 21 patients (47%). Disease showed initial response in 12 of 21 patients (57%), was stable in 5 (24%), progressed in 3 (14%), and was not evaluable in 1 (5%). Procedure-related mortality was zero. With mean 24-month follow-up, estimated 1-year survival probability was 81% (68% confidence interval 0.73-0.90). Median survival was 26.4 months (confidence interval 19.6 months-not reached). Local progression occurred in 9 patients (42%). Median time to local progression was 12.3 months (confidence interval 12 months-not reached). CONCLUSION: Preliminary experience indicates that stereotactic radiosurgery (median dose 20 Gy) is safe in this high-risk group; however, it was associated with significant local progression. Further prospective studies with multiple fractions are needed to evaluate its efficacy in this population.

Fractionated stereotactic body radiation therapy in the treatment of primary, recurrent, and metastatic lung tumors: the role of positron emission tomography/computed tomography-based treatment planning.

PURPOSE: The aim of this study was to assess the outcomes of patients treated with stereotactic body radiation therapy (SBRT) in patients with primary, recurrent, or metastatic lung lesions, with a focus on positron emission tomography (PET)/computed tomography (CT)-based management. PATIENTS AND METHODS: Fifty-one patients with primary stage I non-small-cell lung cancer (NSCLC; n = 26), recurrent lung cancer after definitive treatment (n = 12), or solitary lung metastases (n = 13) were treated with SBRT between 2005 and 2007. Patients were treated with the CyberKnife Robotic Radiosurgery System with Synchrony respiratory tracking. A dose of 60 Gy was delivered in 3 fractions. All patients had CT or PET/CT performed at approximately 3-month intervals after treatment. RESULTS: The median follow-up was 12 months. Local control at median follow-up was 85% in patients with stage I NSCLC, 92% in patients with recurrent lung cancer, and 62% in the patients with solitary lung metastasis. Analysis of the 28 patients with pre- and post-treatment PET/CT scans demonstrated that those with stable disease (n = 4) had a mean standardized uptake value (SUV) decrease of 28%, partial responders (n = 11) had a decrease of 48%, and patients with a complete response (n = 11) had a decrease of 94%. Patients with progressive disease (n = 2) had an SUV decrease of only 0.4%. Only 2 patients (7%) who had reduced fluorodeoxyglucose avidity later progressed locally. No correlations were found between pretreatment SUV and tumor response, disease progression, or survival. Overall 1-year survival rates were 81%, 67%, and 85% among the patients with primary NSCLC, recurrent lung cancer, and solitary lung metastases, respectively. CONCLUSION: Stereotactic body radiation therapy with CyberKnife is an effective treatment for patients with medically inoperable recurrent or metastatic lung cancer. Positron emission tomography/CT is valuable in staging, planning, and evaluating treatment response and might predict long-term outcome.

Synchrony--cyberknife respiratory compensation technology.

Studies of organs in the thorax and abdomen have shown that these organs can move as much as 40 mm due to respiratory motion. Without compensation for this motion during the course of external beam radiation therapy, the dose coverage to target may be compromised. On the other hand, if compensation of this motion is by expansion of the margin around the target, a significant volume of normal tissue may be unnecessarily irradiated. In hypofractionated regimens, the issue of respiratory compensation becomes an important factor and is critical in single-fraction extracranial radiosurgery applications. CyberKnife is an image-guided radiosurgery system that consists of a 6-MV LINAC mounted to a robotic arm coupled through a control loop to a digital diagnostic x-ray imaging system. The robotic arm can point the beam anywhere in space with 6 degrees of freedom, without being constrained to a conventional isocenter. The CyberKnife has been recently upgraded with a real-time respiratory tracking and compensation system called Synchrony. Using external markers in conjunction with diagnostic x-ray images, Synchrony helps guide the robotic arm to move the radiation beam in real time such that the beam always remains aligned with the target. With the aid of Synchrony, the tumor motion can be tracked in three-dimensional space, and the motion-induced dosimetric change to target can be minimized with a limited margin. The working principles, advantages, limitations, and our clinical experience with this new technology will be discussed.