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The impact of selection of prescription isodose line (IDL) on plan quality has not been well evaluated during inverse planning (IP). In this study, a total of 180 IP plans at five levels of IDL were generated for 30 brain metastases (BMs). For each BM, one round of IP was performed with typical IP settings, followed by a quick fine‐tuning to ensure the same target coverage and comparable conformality index. The impact of the IDL on the quality metrics (selectivity, gradient index [GI], and treatment time) was evaluated. The decrease of selectivity and increase of GI meant inferior target dose conformality and more dose spillage. Additionally, a metric directly correlated to the treatment time was proposed. For all cases, the mean GI decreased monotonically as IDL decreased from 70% to 30%, and the decreasing rate was significantly different based on tumor size. The mean selectivity and number of shots decreased monotonically as IDL decreased for all the tumors. From 70% to 30% IDL, the decreasing rate of the mean selectivity was 2.8% (p = 0.020), 7.7% (p = 0.005), and 15.4% (p = 0.020) and that of the number of shots was 75.4% (p = 0.001), 73.2% (p = 0.001), and 50.7% (p = 0.009), for the large, medium, and small tumors, respectively. For the medium and small tumor groups, the mean treatment time increased monotonically when IDLs decreased (increasing rate was 80.0% [p = 0.002] for medium tumors [p = 0.001] and 130.8% [p = 0.001] for small tumors from 70% to 30%). For the large tumors, the mean treatment time was the shortest at 50% IDL (59.0 min) and higher at 70% (65.9 min) and 30% (71.9 min). Overall, the GammaPlan chose smaller sectors for plans with lower IDLs except for the large size group.

The purpose of the study was to introduce and evaluate a high-resolution diode array for patient-specific quality assurance (PSQA) of CyberKnife brain stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT). Thirty-three intracranial plans were retrospectively delivered on the SRS MapCHECK using fixed cone, Iris, and multileaf collimator (MLC). The plans were selected to cover a range of sites from large tumor bed, single/multiple small brain metastases (METs) to trigeminal neuralgia. Fiducial tracking using the four fiducials embedded around the detector plane was used as image guidance. Results were analyzed before and after registration based on absolute dose gamma criterion of 1 mm distance-to-agreement and 0.5%-3% dose-difference. Overall, the gamma passing rates (1 mm and 3% criterion) before registration for all the patients were above 90% for all three treatment modalities (96.8 ± 3.5%, the lowest passing rate of 90.4%), and were improved after registration (99.3 ± 1.5%). When tighter criteria (1 mm and 2%) were applied, the gamma passing rates after registration for all the cases dropped to 97.3 ± 3.2%. For trigeminal neuralgia cases, we applied 1 mm and 0.5% criterion and the passing rates dropped from 100 ± 0.0% to 98.5 ± 2.0%. The mean delivery time was 33.4 ± 11.7 min, 24.0 ± 4.9 min, and 17.1 ± 2.6 min for the fixed cone, Iris, and MLC, respectively. With superior gamma passing rates and reasonable quality assurance (QA) time, we believe the SRS MapCHECK could be a good option for routine PSQA for CyberKnife SRS/SRT.

This is a single arm phase 2 study (Clinical trials.gov NCT02568033) to examine the role of stereotactic body radiotherapy (SBRT) along with full dose systemic chemotherapy in the treatment of unresectable stage 2 and stage 3 nonsmall cell lung cancer. Primary endpoints are disease free survival and toxicity.Patients were treated with SBRT to all sites of gross disease. Dosing consisted of 60 Gy in 3 fractions for peripheral lung tumors, 50 Gy in 5 fractions for central lung tumors, and 40 to 50 Gy in 5 fractions for hilar and mediastinal lymph nodes. Chemotherapy consisted of 4 cycles of pemetrexed and cisplatin or carboplatin and paclitaxel for nonsquamous histology and cisplatin and docetaxel or cisplatin and paclitaxel for squamous histology. SBRT was given in between the chemotherapy cycles. There was a 7 days break between chemotherapy and SBRT. Quality of life was measured using functional assessment of cancer therapy-lung.Twenty two patients were enrolled and analyzed. Seventeen (77%) were stage III and 19 (86%) had lymph node involvement. Median follow-up for all patients was 23.1 months. Median overall survival is 27.2 months. Overall survival at 1 year was 82% and overall survival at 2 years was 53%. Median disease free survival is 16.0 months with a 2-year regional failure rate of 19% and 2-year distant failure rate of 47.2%. There were 6 grade 3 acute toxicities and 2 late grade 3 or higher toxicities including 1 grade 5 hemoptysis. Quality of life scores were unchanged compared with baseline.A combination of SBRT and full dose chemotherapy appears to be a safe and effective treatment for locally advanced NSCLC and warrants further investigation.

BACKGROUND Neuro-oncology care is becoming increasingly complex and patients often see multiple specialists. Multidisciplinary clinic (MDC) is a patient-centric option to allow multiple specialists to be involved where patients see multiple providers on the same day. OBJECTIVE The objective of this study was to evaluate the role of a neuro-oncology MDC on patient outcomes. MATERIALS AND METHODS Retrospective study was performed on consecutive patients who received radiosurgery for central nervous system (CNS) disease. We evaluated patients 2 years before and 2 years after the implementation of a MDC. RESULTS A total of 351 patients were analyzed, 163 patients before MDC and 188 after implementation of MDC. Before MDC the median follow-up was dependent on which department ordered follow-up radiographic imaging. This discrepancy decreased after the MDC. Overall survival for patients with CNS metastatic disease improved in the MDC cohort (median survival of 248 before MDC and 315 d after, P

Background Osteoradionecrosis (ORN) of the mandible is a well-known complication of radiation therapy for head and neck cancer. However, few reports have described hyoid bone ORN and its clinical implications. Methods We describe a retrospective case series of previously irradiated patients who were seen with sudden airway compromise, found to have underlying pathological hyoid fractures secondary to osteoradionecrosis. Results Six patients within postchemoradiation period (3-9 months) for oropharyngeal squamous cell carcinoma were seen with acute-onset dyspnea. Computed topography (CT) imaging was remarkable for severe airway luminal narrowing and pathological hyoid fractures. All six patients required urgent intervention with direct laryngoscopy and tracheostomy. Intraoperatively, five patients were seen with exposed necrotic hyoid bones. Conclusion The hyoid and its associated musculature strongly influence upper airway patency. ORN may compromise its physiological function and leads to acute airway compromise. Hyoid ORN may hold significant and imperative clinical implications in head and neck cancer post-treatment surveillance.

Purpose: Our purpose was to establish the prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in asymptomatic patients scheduled to receive radiation therapy and its effect on management decisions. Methods and Materials: Between April 2020 and July 2020, patients without influenza-like illness symptoms at four radiation oncology departments (two academic university hospitals and two community hospitals) underwent polymerase chain reaction testing for SARS-CoV-2 before the initiation of treatment. Patients were tested either before radiation therapy simulation or after simulation but before treatment initiation. Patients tested for indications of influenza-like illness symptoms were excluded from this analysis. Management of SARS-CoV-2-positive patients was individualized based on disease site and acuity. Results: Over a 3-month period, a total of 385 tests were performed in 336 asymptomatic patients either before simulation (n = 75), post-simulation, before treatment (n = 230), or on-treatment (n = 49). A total of five patients tested positive for SARS-CoV-2, for a pretreatment prevalence of 1.3% (2.6% in north/central New Jersey and 0.4% in southern New Jersey/southeast Pennsylvania). The median age of positive patients was 58 years (range, 38-78 years). All positive patients were white and were relatively equally distributed with regard to sex (2 male, 3 female) and ethnicity (2 Hispanic and 3 non-Hispanic). The median Charlson comorbidity score among positive patients was five. All five patients were treated for different primary tumor sites, the large majority had advanced disease (80%), and all were treated for curative intent. The majority of positive patients were being treated with either sequential or concurrent immunosuppressive systemic therapy (80%). Initiation of treatment was delayed for 14 days with the addition of retesting for four patients, and one patient was treated without delay but with additional infectious-disease precautions. Conclusions: Broad-based pretreatment asymptomatic testing of radiation oncology patients for SARS-CoV-2 is of limited value, even in a high-incidence region. Future strategies may include focused risk-stratified asymptomatic testing.

Stereotactic body radiotherapy (SBRT) has become one of the main options for treatment of thoracic malignancies, leading to the need for more fiducial marker placement. We report cases where these fiducials were placed transthoracically by interventional pulmonologists using ultrasound (US) and electronic navigational bronchoscopy (ENB) needle guidance. Six cases were identified in the Cooper University Hospital medical records where such procedures were performed, alone or in combination with other interventions. All six patients underwent successful placement of fiducials. Concomitant bronchoscopic procedures were performed in four cases. All patients proceeded to SBRT without the need for further interventions. The overall retention rate of fiducials was 80%. No complications were noted. Fiducials' placement by interventional pulmonologists using US or ENB needle guidance is safe and effective, and may be combined with other procedures in a single setting., In this study, we aim to evaluate the feasibility and safety of transthoracic ultrasound or electronic navigational bronchoscopy (ENB) needle‐guided fiducial placement in the chest performed by interventional pulmonologists in the bronchoscopy suite. We describe six such cases performed at Cooper University Hospital in Camden, New Jersey, USA.

Key Clinical Message Our patient's clinical history and preoperative radiographic evaluation suggested central nervous system (CNS) metastatic disease. Ultimately, final pathology revealed epithelioid glioblastoma (eGBM), a newly classified CNS primary tumor. This reinforces the importance of direct tissue sampling and including eGBM on the differential for young patients with histories of systemic cancer presenting with new CNS lesions.

Spinal cord dose constraints are a critical feature for stereotactic body radiation therapy (SBRT). Spinal cord maximum point dose (Dmax) by Monte Carlo (MC) calculations is used as a critical cord tolerance limit for SBRT, but information is lacking about its reproducibility. This study examines uncertainty of MC dose calculations for small volumes in spine SBRT. Seven consecutive spine radiosurgery cases were randomly selected to measure precision of the Dmax calculation in comparison to other volumes. Each plan was calculated five times using MC with a 2% uncertainty objective, and variabilities in dose-volume histogram (DVH) parameters across recalculations were evaluated with coefficient of variation (standard deviation divided by mean). The average ratio of D0.03 cc/Dmax was calculated across a larger series of 130 cases. The variability of Dmax was twice as high for D0.03 cc and five times as high for D1 cc across recalculations for the seven cases. For larger volumes, the variability was lower. The standard deviation of Dmax was 0.1959 Gy, compared to 0.0931 Gy, 0.0569 Gy, and 0.0364 Gy for D0.03 cc, D0.1 cc, and D1 cc, respectively. The average D0.03 cc/Dmax among 130 cases was 0.93. Dmax has greater variability compared to D0.03 cc, D0.1 cc, and D1 cc, potentially creating risks when used for guidance for spinal cord. D0.03 cc may be an attractive alternative with higher reliability while its limits could be obtained by scaling the reported Dmax limit by a factor of 0.93. This may help guide treatment planning and aid in discovering true dose constraints for spine SBRT.

Stereotactic radiosurgery (SRS), stereotactic body radiotherapy (SBRT), and stereotactic ablative body radiotherapy (SABR) are commonly used in the treatment of central nervous system (CNS) disease. This study has refined the radiation toxicity estimates for some normal tissues of the CNS based on review and analysis of the clinical evidence for single fraction radiosurgery, hypofractionated SBRT, and conventionally fractionated radiation therapy. Published guidelines and protocols are reviewed. In the past, many normal tissue tolerances were compiled based on the experience of the investigators and publications in the literature. Some tolerances were determined by modeling or calculation using the existing biological formulas, in particular the linear quadratic (LQ) model. In the present study, the estimate of risk for each dose tolerance limit in some CNS tissues is provided exclusively with normal tissue complication probability (NTCP). The clinical outcomes are compared to understand the difference in biological effect between radiosurgery and radiotherapy. Normal tissue dose tolerances and the corresponding complication rates are provided for brainstem, optic nerves, cochlea, and spinal cord, including single fraction SRS, five-fraction SBRT, and conventional radiation therapy. Calculation of biologically effective dose (BED) or single fraction equivalent dose (SFED) alone using the LQ model conveys no consensus on the biological effect across different fractionations. Comparison of conventional radiation therapy to brain and spinal cord with single fraction equivalent dose leads to even conflicting clinical outcomes. Effective differences between single fraction SRS and conventional radiotherapy need to be better understood. The existing biological model might not be valid to predict the radiosurgical outcomes based on conventionally fractionated radiotherapy. However, application of the statistical dose response models of clinical SRS and SBRT outcomes data to selected current dose tolerance guidelines into simple tables can be a clinically useful resource.

Purpose We proposed a planning strategy that utilized tuning targets to guide GammaKnife (GK) Inverse Planning (IP) to deliver higher dose to the tumor, while keeping acceptable dose to the abutting organ at risk (OAR). Methods Ten patients with a large portion of brain tumor abutting the OAR previously treated with GK stereotactic radiosurgery (SRS) were selected. For each patient, multiple tuning targets were created by cropping the target contour from three-dimensional (3D) expansions of the OAR. The number of the tuning targets depended on the complexity of the planning process. To demonstrate dose sparing effect, an IP plan was generated for each tuning target after one round of optimization without shot fine-tuning. In the dose enhancement study, a more aggressive target dose was prescribed to the tuning target with a larger margin and one to two shots were filled in the region with missing dose. The resulting plans were compared to the previously approved clinical plans. Results For all 10 patients, a dose sparing effect was observed, i.e. both target coverage and dose to the OARs decreased when the margins of 3D expansion increased. For one patient, a margin of 6 mm was needed to decrease the maximum dose to the optical chiasm and optical nerve by 44.3% and 28.4%, respectively. For the other nine patients, the mean dropping rate of V12Gyto brain stem were 28.2% and 59.5% for tuning targets of 1 and 2 mm margins, respectively. In the dose enhancement study, the tuning-target-guided plans were hotter than the approved treatment plans, while keeping similar dose to the OARs. The mean of the treatment and enhancement dose was 15.6 ± 2.2 Gy and 18.5 ± 3.2 Gy, respectively. The mean coverage of the target by prescription dose was slightly higher in the enhancement plans (96.9 ± 2.6% vs 96.3 ± 3.6%), whereas the mean coverage of the enhancement dose was 20.1% higher in the enhancement plans (89.6 ± 9.0% vs 74.6 ± 19.9%). Conclusions We demonstrated that an inverse planning strategy could facilitate target dose enhancement for challenging GK cases while keeping acceptable OAR dose.

The Leksell GammaPlan (LGP) with an inverse planning (IP) tool has been upgraded to version 11.1 since its launch in 2010. We evaluated its IP planning performance by re-planning 16 targets that had been planned using forward planning (FP). The FP and IP plans were compared. A planning guideline for IP process was developed aiming for an unbiased comparison. Sixteen brain metastases (BMs) without nearby critical structures were included in the study (size > 1 cm for all targets). All prior FP were re-planned in the LGP using IP and maintaining the same beam-on time and coverage. The dose to all the targets was scaled to 20 Gy in a single fraction at 50% isodose line (IDL) for FP and IP comparison purpose. The coverage and beam-on time were nearly the same for both the FP and IP plans. For all the IP plans, the mean selectivity was 0.85 ± 0.04 (vs 0.83 ± 0.04 in FP plans, p = 0.02), the mean GI was 2.92 ± 0.21 (vs 3.18 ± 0.60 in FP plans, p = 0.047), the mean V12Gy was 8.18 ± 8.57 cc (vs 9.09 ± 9.08 cc in FP plans, p = 0.001), the mean V8Gy was 14.63 ± 15.14 cc (vs 16.34 ± 16.17 cc in FP plans, p = 0.001), and the mean V5Gy was 29.01 ± 28.77 cc (vs 32.77 ± 31.41 cc in FP plans, p = 0.001). The number of shots was higher in IP plans (means of 16.69 ± 8.11 vs 10.81 ± 6.87 in FP plans, p = 0.001). We retrospectively re-planned 16 FP plans using the IP tool while meeting the quality limiting factors for the FP plans. The dosimetry parameters from the IP plans outperformed the treated FP plans and the IP tool should be preferred for tumors with size > 1 cm.

PURPOSE: Next-generation sequencing (NGS) is increasingly used to identify actionable mutations for oncology treatment. We examined the results and use of NGS assays at our institution. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 305 consecutive patients who had NGS testing of tumor samples from March 2014 to April 2017. NGS was performed by FoundationOne. RESULTS: Of the 305 tissue samples sent to FoundationOne, 189 reports were potentially usable. Of these reports, 76 (40.21%) demonstrated an aberration targetable by on-label therapies and 126 (66.67%) by off-label therapies, and 170 (89.94%) revealed actionable aberrations via all potential avenues, including clinical trials; 21 of these 189 potentially usable reports (11.1%) yielded a change in management, including use of on-label therapies (n = 7), use of off-label therapies (n = 6), enrollment in a clinical trial (n = 6), and discontinuation of a medication with a predicted poor response (n = 3; one report was used twice). For the six patients with off-label use, median duration of treatment was 46 days and discontinued after death (n = 3) or progression (n = 3). CONCLUSION: Only a minority of NGS assay results (6.9% percent of all tests ordered and 11.1% of useable tests) resulted in a management change. A small minority of patients started off-label therapy on the basis of NSG assay results and overall had poor responses to off-label treatment. Although in theory NGS assays may improve oncologic outcomes, the results of our initial 305 patients showed low clinical utility.

Understanding dose constraints for critical structures in stereotactic body radiation therapy (SBRT) is essential to generate a plan for optimal efficacy and safety. Published dose constraints are derived by a variety of methods, including crude statistics, actuarial analysis, modeling, and simple biologically effective dose (BED) conversion. Many dose constraints reported in the literature are not consistent with each other, secondary to differences in clinical and dosimetric parameters. Application of a dose constraint without discriminating the variation of all the factors involved may result in suboptimal treatment. This issue of Seminars in Radiation Oncology validates dose tolerance limits for 10 critical anatomic structures based on dose response modeling of clinical outcomes data to include detailed dose-volume metrics. This article presents a logistic dose-response model for aorta and major vessels based on 238 cases from the literature in addition to 387 cases from MD Anderson Cancer Center at Cooper University Hospital, for a total of 625 cases. The Radiation Therapy Oncology Group (RTOG) 0813 dose-tolerance limit of Dmax = 52.5Gy in 5 fractions was found to have a 1.2% risk of grade 3-5 toxicity, and the Timmerman 2008 limit of Dmax = 45Gy in 3 fractions had 2.3% risk. From the model, the 1% and 2% risk levels for D4cc, D1cc, and D0.5cc are also provided in 1-5 fractions, in the form of a dose-volume histogram (DVH) Risk Map.

Inconsistencies permeate the literature regarding small bowel dose tolerance limits for stereotactic body radiation therapy (SBRT) treatments. In this review, we organized these diverse published limits with MD Anderson at Cooper data into a unified framework, constructing the dose-volume histogram (DVH) Risk Map, demonstrating low-risk and high-risk SBRT dose tolerance limits for small bowel. Statistical models of clinical data from 2 institutions were used to assess the safety spectrum of doses used in the exposure of the gastrointestinal tract in SBRT; 30% of the analyzed cases had vascular endothelial growth factor inhibitors (VEGFI) or other biological agents within 2 years before or after SBRT. For every dose tolerance limit in the DVH Risk Map, the probit dose-response model was used to estimate the risk level from our clinical data. Using the current literature, 21Gy to 5cc of small bowel in 3 fractions has low toxicity and is reasonably safe, with 6.5% estimated risk of grade 3 or higher complications, per Common Terminology Criteria for Adverse Events version 4.0. In the same fractionation for the same volume, if lower risk is required, 16.2Gy has an estimated risk of only 2.5%. Other volumes and fractionations are also reviewed; for all analyzed high-risk small bowel limits, the risk is 8.2% or less, and the low-risk limits have 4% or lower estimated risk. The results support current clinical practice, with some possibility for dose escalation.

Purpose In the current Gamma Knife (GK) planning system (GammaPlan, version 10.2, Elekta AB, Stockholm, Sweden), multiple adjacent brain metastasis (BMs) had to be planned sequentially if BMs were drawn separately, leading to less conformal target dose in the composite plan due to inter-target dose contribution and fine-tuning of the shots being quite tedious. We proposed a method to improve target dose conformality and planning efficiency for such cases. Methods and Materials Fifteen patients with multiple BMs treated on the Leksell GK Perfexion system were retrospectively replanned in the Institutional Review Board (IRB) approved study. The recruitment criterion was all the BMs should be entirely encompassed within the maximum dose grid allowed in the GammaPlan. The BMs were first planned sequentially as routine clinic cases. The contours of the BMs were then exported to the VelocityAI (Varian, CA, USA) to generate a composite contour after a union operation, and all the BMs were planned again simultaneously using this composite contour in the GammaPlan. The inverse planning (IP) was employed in both methods with the same treatment time allowed for a fair plan comparison. Dose evaluation was performed in the VelocityAI with all planning magnetic resonance (MR) images, structure set and dose were exported to the VelocityAI. The dosimetery parameters, including conformality index (CI), V20Gy, V16Gy, V12Gy, and V5Gy, were compared between the two methods. Results The planning results from both methods were reviewed qualitatively and quantitatively. The proposed method exhibited superior CI, except for an outlier case with very tiny BMs. The mean and standard deviation (std.) of the Paddick CI for all patients were 0.76±0.11 for the proposed method, comparing to 0.69±0.13 for the sequential method. The V20Gy, V16Gy, V12Gy, and V5Gy for the proposed method were 10.9±0.9%, 9.5±10.2%, 6.2±16.4% and 3.3±21.8%, all lower than those from the sequential method. Conclusions The proposed method showed improved target dose conformality for all cases except for very tiny BMs. Planning efficiency is considerably better with the combined target technique. The improved dose conformality will be beneficial to patients in long term with lowered risk of radiation necrosis after GK stereotactic radiosurgery (SRS).

Purpose: Locally recurrent, previously irradiated primary head and neck tumors have historically been associated with poor outcomes. Stereotactic body radiation therapy has emerged as a feasible and promising treatment option for tumor recurrence, particularly in nonsurgical candidates. This study aimed to assess the associated outcomes of stereotactic body radiation therapy used in this setting. Methods: Retrospective analysis of a prospectively collected database of 25 patients treated with CyberKnife for unresectable, recurrent head and neck cancer in a previously irradiated field. The primary end points evaluated were rates of survival, tumor control, and treatment-related toxicities. Results: Median survival of the study population was 7.5 months (range, 1.5-47.0 months). Median survival of the 20 (80%) patients who were treated with curative purpose was 8.3 months. One-year overall survival rate for the entire population was 32%. The respective 1-year and 2-year survival rates for the curative subcohort were 40% and 20%, respectively. Local and locoregional failure occurred in 8 (32%) and 7 (28%) patients, respectively. Low severe acute (4%) and late (6%) treatment-related toxicity rates were observed. No grade 4 or 5 toxicities were observed. Conclusion: Stereotactic body radiation therapy is a viable treatment option for patients with unresectable, recurrent head and neck cancer. Significant tumor control rates are achievable with minimal severe toxicity. Although perhaps associated with patient selection and a heterogeneous sample, overall survival of stereotactic body radiation therapy outcomes appears unfavorable.

Treatment option of stereotactic radiosurgery versus whole brain radiotherapy for multiple brain metastases (10) is an ongoing debate. Detailed dosimetric and biological information are presented in this study to investigate the possible clinical outcomes.Materials and Methods: Nine patients with multiple brain metastases (11-25) underwent stereotactic radiosurgery. Whole brain radiotherapy plans are retrospectively designed with the same MR image set and the same structure set for each patient using the standard opposing lateral beams and fractionation (3 Gy × 10).Physical doses and biologically effective doses are calculated for each lesion target and the CNS normal tissues and they are compared between whole brain radiotherapy and stereotactic radiosurgery in the context of clinical efficacy and published toxicities.Tumor biologically effective dose is higher in radiosurgery than in whole brain radiotherapy by factors of 3.2-5.3 in maximum dose and of 2.4-3.1 in mean dose. Biologically effective mean dose in radiosurgery is 1.3-34.3% for normal brain, 0.7-31.6% for brainstem, 0.5-5.7% for chiasm, 0.2-5.7% for optic nerves and 0.6-18.1% for hippocampus of that in whole brain radiotherapy over nine cases presented here. We also presented the dose-volume relationship for normal brain to address the dosimetric concerns in radiosurgery.Dose-volume metrics presented in this study are essential to understanding the safety and efficacy of whole brain radiotherapy and/or radiosurgery for multiple brain metastases. Whole brain radiotherapy has resulted in higher incidence of radiation-related toxicities than radiosurgery. Even for patients with more than 10 brain metastases, the CNS normal tissues receive significantly lower doses in radiosurgery. Mean normal brain dose in SRS is found to correlate with the total volume of lesions rather than the number of lesions treated.

Background Patients with primary head and neck cancer managed with radiation therapy (RT) +/- chemotherapy may experience significant treatment-related toxicities. We assessed hospitalization as a metric for severe treatment-related toxicities and evaluated patient and treatment factors for possible association. Methods A retrospective review was performed on 147 patients with head and neck cancer treated with definitive or adjuvant intensity-modulated radiation therapy (IMRT) +/- chemotherapy. Multiple Poisson regression model was used to analyze relationships between patient or treatment factors and number of hospital stays during RT and within 8 weeks after RT. Results Multivariate analysis showed preexisting diabetes or pulmonary disease, primary carcinoma of oral cavity, and prescribed radiation dose (p

ObjectThe efficacy and safety of treatment with whole-brain radiotherapy (WBRT) or with stereotactic radiosurgery (SRS) for multiple brain metastases (> 10) are topics of ongoing debate. This study presents detailed dosimetric and biological information to investigate the possible clinical outcomes of these 2 modalities.MethodsFive patients with multiple brain metastases (n = 11–23) underwent SRS. Whole-brain radiotherapy plans were retrospectively designed with the same MR image set and the same structure set for each patient, using the standard opposing lateral beams and fractionation (3 Gy × 10).Physical radiation doses and biologically effective doses (BEDs) in WBRT and SRS were calculated for each lesion target and for the normal brain tissues for comparison of the 2 modalities in the context of clinical efficacy and published toxicities.ResultsThe BEDs targeted to the tumor were higher in SRS than in WBRT by factors ranging from 2.4- to 3.0- fold for the mean dose and from 3.2- to 5.3-fold for the maximum dose. In the 5 patients, mean BEDs in SRS (calculated as percentages of BEDs in WBRT) were 1.3%–34.3% for normal brain tissue, 0.7%–31.6% for the brainstem, 0.5%–5.7% for the chiasm, 0.2%–5.7% for optic nerves, and 0.6%–18.1% for the hippocampus.ConclusionsThe dose-volume metrics presented in this study were essential to understanding the safety and efficacy of WBRT and SRS for multiple brain metastases. Whole-brain radiotherapy results in a higher incidence of radiation-related toxicities than SRS. Even in patients with > 10 brain metastases, the normal CNS tissues receive significantly lower doses in SRS. The mean normal brain dose in SRS correlated with the total volume of the lesions rather than with the number of lesions treated.

Purpose To quantify rigid and nonrigid motion of liver tumors using reconstructed 3-dimensional (3D) fiducials from stereo imaging during CyberKnife-based stereotactic body radiation therapy (SBRT). Methods and Materials Twenty-three liver patients treated with 3 fractions of SBRT were used in this study. After 2 orthogonal kilovoltage images were taken during treatment, the 3D locations of the fiducials were generated by the CyberKnife system and validated using geometric derivations. A total of 4824 pairs of kilovoltage images from start to end of treatment were analyzed. For rigid motion, the rotational angles and translational shifts were reported by aligning 3D fiducial groups from different image pairs, using least-squares fitting. For nonrigid motion, we quantified interfractional tumor volume variations by using the proportional volume derived from the fiducials, which correlates to the sum of interfiducial distances. The individual fiducial displacements were also reported (1) after rigid corrections and (2) without angle corrections. Results The proportional volume derived by the fiducials demonstrated a volume-increasing trend in the second (101.9% ± 3.6%) and third (101.0 ± 5.9%) fractions among most patients, possibly due to radiation-induced edema. For all patients, the translational shifts in left-right, anteroposterior, and superoinferior directions were 2.1 ± 2.3 mm, 2.9 ± 2.8 mm, and 6.4 ± 5.5 mm, respectively. The greatest translational shifts occurred in the superoinferior direction, likely due to respiratory motion from the diaphragm. The rotational angles in roll, pitch, and yaw were 1.2° ± 1.8°, 1.8° ± 2.4°, and 1.7° ± 2.1°, respectively. The 3D individual fiducial displacements with rigid corrections were 0.2 ± 0.2 mm and increased to 0.5 ± 0.4 mm without rotational corrections. Conclusions Accurate 3D locations of internal fiducials can be reconstructed from stereo imaging during treatment. As an effective surrogate to tumor motion, fiducials provide a close estimation of both rigid and nonrigid motion of liver tumors. The reported displacements could be further utilized for tumor margin definition and motion management in conventional linear accelerator–based liver SBRT.

Objectives/Hypothesis Locoregional recurrence remains the primary failure pattern following salvage surgery for previously irradiated head and neck cancer; randomized trials have suggested a complimentary role for adjuvant chemotherapy and conventional reirradiation at the expense of significant increases in toxicity. We aimed to identify if stereotactic body radiotherapy (SBRT) ± cetuximab improves tumor control while reducing treatment-related toxicity following salvage surgery. Study Design Retrospective review (2005–2011) of 28 patients with high-risk features (positive surgical margins or extranodal extension) following macroscopic complete (R0/R1) salvage surgery treated with adjuvant SBRT ± cetuximab. Methods SBRT consisted of 40 to 44 Gy in five fractions over 1 to 2 weeks with concurrent cetuximab (n = 7) administered at 400 mg/m2 day −7 + 250 mg/m2 days 0 and +8. Toxicity was physician recorded, and University of Washington Quality of Life Revised surveys were prospectively collected. Results All patients received prior radiotherapy (median, 70 Gy; range, 54–99 Gy) with a median reirradiation interval of 25 months (range, 6–156 months). At a median follow-up of 14 months (range, 2–69 months), the 1-year locoregional control, distant control, disease-free survival, and overall survival were 51%, 90%, 49%, and 64%, respectively. Rates of acute and late severe (≥grade 3) toxicity were low at 0% and 8%, respectively. At a median follow-up survey time of 6 months, 56% of patients reported improved/stable overall quality-of-life scores. Conclusions Adjuvant SBRT ± cetuximab following salvage surgery is well tolerated with acceptable oncologic outcomes and little toxicity. Future prospective trials should evaluate adjuvant SBRT ± cetuximab versus a wait-and-see approach for recurrent head and neck cancers with high-risk features following salvage surgery. Level of Evidence 4 Laryngoscope, 124:1579–1584, 2014

Background: Whole brain radiation therapy is commonly used in the treatment of patients with CNS metastatic disease. Radiation to other areas of the body is associated with decrease in bone marrow proliferation. It is unclear what the effects ofWBRT have on blood counts. Methods: Retrospective chart review of patients with brain metastases treated with WBRT with recorded hematologic valuesbefore and after treatment. Univariate analysis was performed to identify statistical differences in outcome via paired t -testing. Results: Forty-nine patients were analyzed. Median age was 61 and 36 subjects were female. Analysis revealed significantly amedian decrease of 0.87 g/dL in hemoglobin values ( p .05). Conclusion: WBRT leads to a decrease in Hgb and platelets but does not appear to affect WBC counts. Physicians and patientsshould be aware of this side effect of WBRT.KeyWords: Whole brain radiotherapy, Anemia, Metastatic brain cancer

BACKGROUND AND PURPOSE: Optimizing the utilization of surveillance PET/CT in treated HNSCC is an area of ongoing research. Our aim was to determine the negative predictive value of PET/CT in patients with treated head and neck squamous cell cancer and to determine whether negative PET/CT reduces the need for further imaging surveillance. MATERIALS AND METHODS: We evaluated patients with treated HNSCC who underwent posttreatment surveillance PET/CT. During routine clinical readouts, scans were categorized as having negative, probably negative, probably malignant, or malignant findings. We followed patients clinically and radiographically for at least 12 months from their last PET/CT (mean, 26 months; median, 28 months; range, 12–89 months) to determine recurrence rates. All suspected recurrences underwent biopsy for confirmation. RESULTS: Five hundred twelve patients (1553 scans) were included in the study. Two hundred fourteen patients had at least 1 PET/CT with negative findings. Of the 214 patients with a scan with negative findings, 19 (9%) eventually experienced recurrence, resulting in a NPV of 91%. In addition, a subgroup of 114 patients with 2 consecutive PET/CT examinations with negative findings within a 6-month period was identified. Only 2 recurrences were found in this group, giving a NPV of 98%. CONCLUSIONS: In patients treated for HNSCC, a single PET/CT with negative findings carries a NPV of 91%, which is not adequate to defer further radiologic surveillance. Two consecutive PET/CT examinations with negative findings within a 6-month period, however, resulted in a NPV of 98%, which could obviate further radiologic imaging in the absence of clinical signs of recurrence.

Background Stereotactic body radiotherapy (SBRT) is a well-established treatment option for early stage non–small-cell lung cancer (NSCLC) tumors 5 cm. Patients and Methods We performed retrospective data collection of patients enrolled onto a prospective SBRT registry study. Eligible patients for this study had node-negative NSCLC measuring > 5 cm in any dimension. Data from 41 patients were analyzed. Median patient age was 75 years, and median tumor size was 5.6 cm (range, 5.0-12.2 cm). Sixteen patients had squamous disease, 20 patients adenocarcinoma, and 1 mixed tumor; 4 patients had no biopsy. Median radiation dose per fraction was 50 Gy in 5 fractions. Radiation was prescribed to isodose line, median 66% (range, 50%-84%). Results Before SBRT, 6 patients had previous chemotherapy and 7 patients had previous radiation. Median follow-up for all patients was 15.2 months (range, 0.56-48.1 months). At last follow-up, 16 patients were still alive, with a median follow-up of 16.1 months for surviving patients. The median survival was 17.5 months with 1- and 2-year survivals of 65% and 34%. Two patients (4.8%) had local failure, and 13 patients (31%) had distant failure. Four patients (9.8%) had acute toxicity, and 7 patients (17.1%) had late toxicity, including 2 (4.8%) grade 3 late toxicities. Conclusion SBRT for tumors > 5 cm is effective, with good local control rates and acceptable toxicity. The main pattern of failure is distant, suggesting a possible role for systemic chemotherapy in these patients.

OBJECTIVES The role of positron emission tomography (PET) scans in the staging of head and neck cancer (HNC) is unclear. The National Comprehensive Cancer Network guidelines do not recommend routine metastatic workup beyond physical examination, chest x-ray, and laboratory tests. The purpose of this report is to examine the accuracy of staging PET scans for detecting distant metastatic disease in patients with HNC. METHODS Retrospective review of 182 consecutive newly diagnosed HNC patients who had a staging PET scan at Thomas Jefferson University Hospital between 2003 and 2007. RESULTS The overall incidence of confirmed distant metastatic disease in this population was 5.0%. About 26 of the staging PET scans had areas suspicious for a metastatic lesion(s). Of total, 23 patients were further evaluated with imaging and/or biopsy, revealing 9 (39%) true positives, and 14 (60%) false positives. Of the 156 negative PET scans, there was 1 false negative and 155 true negatives. Thus, the sensitivity of PET was 90% and specificity was 92%. Positive predictive value was 39% and negative predictive value was 99.4%. No patients with pre-PET clinical stage I or II cancer had confirmed distant metastases. The only statistically significant predictor for metastatic disease was clinical stage IV versus all other stages (P=0.03). CONCLUSIONS Given the marked differences in the treatment of locally advanced/nonmetastatic HNC versus metastatic HNC, we recommend PET for clinical stage IV disease. Although the sensitivity, specificity, and negative predictive value rates were acceptable, the positive predictive value was suboptimal. Patients found to have a PET scan "positive" for metastatic disease require confirmatory imaging or ideally biopsy.

Purpose Advanced head-and-neck cancer (HNC) remains a difficult disease to cure. Proteasome inhibitors such as bortezomib have the potential to improve survival over chemoradiotherapy alone. This Phase I dose-escalation study examined the potential of bortezomib in combination with cisplatin chemotherapy and concurrent radiation in the treatment of locally advanced and recurrent HNC. Methods and Materials Eligible patients received cisplatin once weekly at 30 mg/m 2 per week and bortezomib along with concurrent radiation. Bortezomib was given on Days 1, 4, 8, and 11 every 3 weeks, with an initial starting dose of 0.7 mg/m 2 and escalation levels of 1.0 and 1.3 mg/m 2 . Dose escalation was performed only after assessment to rule out any dose-limiting toxicity. Results We enrolled 27 patients with HNC, including 17 patients with recurrent disease who had received prior irradiation. Patients received bortezomib dose levels of 0.7 mg/m 2 (7 patients), 1.0 mg/m 2 (10 patients), and 1.3 mg/m 2 (10 patients). No Grade 5 toxicities, 3 Grade 4 toxicities (all hematologic and considered dose-limiting toxicities), and 39 Grade 3 toxicities (in 20 patients) were observed. With a median follow-up of 7.4 months, the overall median survival was 24.7 months (48.4 months for advanced HNC patients and 15.4 months for recurrent HNC patients). Conclusion Bortezomib in combination with radiation therapy and cisplatin chemotherapy is safe in the treatment of HNC with a bortezomib maximum tolerated dose of 1.0 mg/m 2 in patients previously treated for HNC and 1.3 mg/m 2 in radiation-naive patients.

The standard of care for patients with locally-advanced head and neck cancer is chemoradiation or surgical resection followed by radiation treatment with or without chemotherapy and despite aggressive, multimodality therapies with their associated toxicities, attempts are being made to improve efficacy while reducing toxicity. Cetuximab is a chimeric mAb directed against the EGFR that showed clinical activity in squamous cell carcinoma of head and neck (SCCHN).Cetuximab is beneficial in recurrent and metastatic setting, as well as in the definitive setting. In a landmark study by Bonner et al., cetuximab was found to be effective in prolonging survival in conjunction with radiation treatment in locally-advanced tumors versus radiation therapy alone. The Erbitux in First-Line Treatment of Recurrent or Metastatic Head and Neck Cancer (EXTREME) trial also showed an improvement in conjunction with chemotherapy in recurrent and metastatic tumors.Cetuximab is an important therapeutic option in SSCHN, and will continue to be used in metastatic and definitive settings. While cetuximab is a valuable tool in the treatment of SCCHN, more studies are needed to maximize the efficacy of this mAb in clinical settings and to identify the subpopulation of patients that truly benefit from its use.

Purpose Treatment of prostate cancer using higher doses of external beam radiation (EBRT) has been shown to improve results, but there are toxicity concerns with further dose escalation. A treatment option to safely increase total dose to the prostate includes combination therapy using EBRT and low-dose-rate transperineal brachytherapy seed implant. Our purpose was to report the results of combined modality therapy from a single institution in the community setting. Methods and Materials Retrospective review from single institution in the community setting. All patients were treated with a combination of EBRT followed by low-dose-rate brachytherapy seed placement. Results A total of 824 patients were analyzed with a median followup of 5.5 years, all censored patients had a minimum followup of 2 years. A total of 588 patients received hormone therapy before or concurrent with the radiation. Three hundred twenty-nine patients had low-risk disease, 300 patients had intermediate-risk disease, and 195 patients had high-risk disease. Five-year overall survivals were 86.1%, 85.0%, and 82.5% for low-, intermediate-, and high-risk patients. Five-year actuarial biochemical relapse-free survivals (bRFSs) were 85.4%, 83.2%, and 79.6% for low-, intermediate-, and high-risk patients. High-risk patients who received hormonal therapy had an improved bRFS vs. patients not receiving hormones. Conclusions Combination treatment using brachytherapy and EBRT is well tolerated, with acceptable overall survival and bRFS rates and should be considered a standard treatment option for patients. Hormones should be considered for high-risk patients.

Radiotherapy has an integral role in the treatment of head and neck cancer. Although radiotherapy has the potential to cure patients with advanced disease it also carries the potential for significant long-term morbidity. New technologies in the setting of head and neck radiotherapy are emerging, which have the potential to increase the cure rate and decrease toxicity. These new technologies include improved radiotherapy treatment design (intensity modulated radiation therapy) and improved planning and implementation (image-guided radiation therapy). Some of these advances are discussed in this article.

Background. The role of external beam radiation in the treatment of melanoma remains controversial. While melanoma is no longer considered radio-resistant, the indications and outcomes for adjuvant radiation therapy in melanoma patients are still evolving. Methods . A retrospective review was conducted of patients diagnosed with malignant melanoma and treated with postoperative radiation therapy at the University of Kansas Medical Center. Results. Forty-five patients (27 male; 18 female) with a diagnosis of malignant melanoma were treated with external beam radiation therapy for curative intent between 1985 and 2005. Local control at the treatment site was achieved in 42 of 45 patients and was maintained in 35 patients (78%) at a median follow-up of 14 months. The median time for freedom from any disease progression was 12 months. Conclusions . Radiation therapy is an effective option for management of patients with malignant melanoma with local control being achieved and maintained in the majority of patients. KJM 2008; 2(1):1-7.

Purpose Patients with poor performance status (PS), usually defined as a Karnofsky Performance Status of 60 or less, were not eligible for randomized stereotactic radiosurgery (SRS) studies, and many guidelines suggest that whole-brain radiation therapy (WBRT) is the most appropriate treatment for poor PS patients. Methods and Materials In this retrospective review of our SRS database, we identified 36 patients with PS of 60 or less treated with SRS for central nervous system (CNS) metastatic disease. PS, as defined by the Karnofsky Performance Status, was 60 (27 patients), 50 (8 patients), or 40 (1 patient). The median number of CNS lesions treated was 3. Results Median overall survival (OS) was 7.2 months (range, 0.73-25.6 months). Fifteen patients (41%) were alive at 6 months, and 6 patients (16.6%) were alive at 1 year. There was no difference in OS in patients who underwent previous WBRT. There were no local failures or cases of radiation toxicity. Distant CNS failures were seen in 9 patients (25%). Conclusions Our patients with poor PS had reasonable median OS and relatively low distant CNS failure rates. Patients in this patient population may be ideal candidates for SRS compared with WBRT given the low incidence of distant failure over their remaining lives and the favorable logistics of single-fraction treatment for these patients with debility and their caregivers.

Purpose: To assess brain tumor displacements between skull based and soft-tissue based matching during CTMRI fusion for a total of 35 brain lesions. Methods: Twenty-five patients who underwent CT and MRI scans in the same day were retrospectively recruited into the study. Semi-automatic skull based fusion was first performed and reviewed on a Treatment Planning System (TPS). A secondary fine-tuning of the fusion was then performed, if mismatch was observed in the tumor or neighboring soft-tissue, using nearby visible soft-tissue, such as gyri, sulci, and fissures. Two physicists fine-tuned the secondary fusion until the best match could be agreed upon. The resulting rotations and translations between the two fusions were recorded, which indicated local displacements between skull based and soft-tissue based matching. We further created a PTV by expanding a 2 mm margin around the GTV after skull-based fusion, and then evaluated the coverage of the GTV within the PTV after fine tuning with soft-tissue based fusion. Results: In 29 of the 35 lesions, minor to no mismatch was found between the soft-tissue and skull based fusions. The corresponding translational and rotational shifts were 0.05 ± 0.63 mm (LR), 0.01 ± 0.79 mm (AP), 0.37 ± 1.01 mm (SI); -0.15 ± 0.67° (pitch), -0.19 ± 0.34° (yaw), and -0.12 ± 0.49° (roll). Thus the GTV, after soft-tissue based fusion, was 100% covered by the PTV. However, in the remaining 6 lesions in the study, noticeable displacements were observed between the skull and soft-tissue based fusions. Excluding an outlier lesion, the mean translational and rotational shifts for 5 of the 6 remaining lesions were 0.90 ± 2.15 mm (LR), 1.50 ± 2.27 mm (AP), -1.01 ± 1.83 mm (SI); -1.42 ± 3.12°(pitch), 0.02 ± 0.83°(yaw), and -0.17 ± 0.68°(roll). For the outlier lesion, the GTV was nearly missed by the PTV, and for the rest of the 5 lesions, the mean coverage of the GTV was 98.9% within the PTV. Conclusion: In a small portion of lesions, our study showed noticeable brain tumor displacement with typical patient setup in CT and MRI scans when using skull based fusion in comparison with soft-tissue fusion. Careful review of the skull based fusion is recommended by examining the match with nearby soft-tissue and/or tumors. If fusion deviations are found, it is also recommended to consider adding a margin to the GTV to account for such variations, since such variations could potentially affect target localization accuracy at the time of treatment.

The efficacy and safety of treatment with whole-brain radiotherapy (WBRT) or with stereotactic radiosurgery (SRS) for multiple brain metastases (10) are topics of ongoing debate. This study presents detailed dosimetric and biological information to investigate the possible clinical outcomes of these 2 modalities.Five patients with multiple brain metastases (n = 11-23) underwent SRS. Whole-brain radiotherapy plans were retrospectively designed with the same MR image set and the same structure set for each patient, using the standard opposing lateral beams and fractionation (3 Gy × 10). Physical radiation doses and biologically effective doses (BEDs) in WBRT and SRS were calculated for each lesion target and for the normal brain tissues for comparison of the 2 modalities in the context of clinical efficacy and published toxicities.The BEDs targeted to the tumor were higher in SRS than in WBRT by factors ranging from 2.4- to 3.0- fold for the mean dose and from 3.2- to 5.3-fold for the maximum dose. In the 5 patients, mean BEDs in SRS (calculated as percentages of BEDs in WBRT) were 1.3%-34.3% for normal brain tissue, 0.7%-31.6% for the brainstem, 0.5%-5.7% for the chiasm, 0.2%-5.7% for optic nerves, and 0.6%-18.1% for the hippocampus.The dose-volume metrics presented in this study were essential to understanding the safety and efficacy of WBRT and SRS for multiple brain metastases. Whole-brain radiotherapy results in a higher incidence of radiation-related toxicities than SRS. Even in patients with10 brain metastases, the normal CNS tissues receive significantly lower doses in SRS. The mean normal brain dose in SRS correlated with the total volume of the lesions rather than with the number of lesions treated.

Patients with primary head and neck cancer managed with radiation therapy (RT) +/- chemotherapy may experience significant treatment-related toxicities. We assessed hospitalization as a metric for severe treatment-related toxicities and evaluated patient and treatment factors for possible association.A retrospective review was performed on 147 patients with head and neck cancer treated with definitive or adjuvant intensity-modulated radiation therapy (IMRT) +/- chemotherapy. Multiple Poisson regression model was used to analyze relationships between patient or treatment factors and number of hospital stays during RT and within 8 weeks after RT.Multivariate analysis showed preexisting diabetes or pulmonary disease, primary carcinoma of oral cavity, and prescribed radiation dose (p .05) were associated with increased number of patient hospital stays during or shortly after RT.We found that 34.7% of patients experienced a chemoradiation toxicity-related hospitalization during or shortly after treatment. Prior pulmonary disease, diabetes, and increasing prescribed radiation dose were associated with increased hospital stays.