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Purpose The purpose of this study was to quantify the relationship of bone marrow response to radiation dose, using 3’-deoxy-3’-[18F]fluorothymidine ([18F]FLT)-labeled uptake quantified in positron-emission tomography (PET) scans. Methods and Materials Pre- and post-Week 1 treatment [18F]FLT PET images were registered to the CT images used to create the radiation treatment plan. Changes in [18F]FLT uptake values were measured using profile data of standardized uptake values (SUVs) and doses along the vertebral bodies located at a field border where a range of radiation doses were present for 10 patients. Data from the profile measurements were grouped into 1 Gy dose bins from 1 to 9 Gy to compare SUV changes for all patients. Additionally, the maximum pretreatment, the post-Week 1 treatment, and the dose values located within the C6–T7 vertebrae that straddled the field edge were measured for all patients. Results Both the profile and the individual vertebral data showed a strong correlation between SUV change and radiation dose. Relative differences in SUVs between bins >1 Gy and Conclusions The change in SUV observed in head and neck cancer patients treated with chemoradiation shows the potential for using [18F]FLT PET images for identifying active bone marrow and monitoring changes due to radiation dose. Additionally, the change in [18F]FLT uptake observed in bone marrow for different weekly doses suggests potential dose thresholds for reducing bone marrow toxicity.

The growth of functional and metabolically informative imaging is eclipsing anatomic imaging alone in clinical practice. The recognition that magnetic resonance (MR) and positron emission tomography (PET)-based treatment planning and response assessment are essential components of clinical practice and furthermore offer the potential of quantitative analysis being important. Extracting the greatest benefit from these imaging techniques will require refining the best combinations of multimodality imaging through well-designed clinical trials that use robust image-analysis tools and require substantial computer based infrastructure. Through these changes and enhancements, image-based biomarkers will enhance clinical decision making and accelerate the progress that is made through clinical trial research.

Purpose: A ketogenic diet (KD) is a high fat, low carbohydrate diet that forces cells to utilize mitochondrial fatty acid oxidation for energy production. It has been previously shown that cancer cells have defects in mitochondrial oxidative metabolism resulting in increased oxidative stress relative to non-malignant cells. Because radiation and platinum based chemotherapy also induce oxidative damage, we hypothesized that a KD may enhance radiation and platinum chemotherapy efficacy in head and neck cancer. The KD's ability to enhance radiation and chemotherapy efficacy were assessed in murine head and neck cancer xenograft models. The safety and tolerability of a KD in combination with standard of care radiation and platinum-based chemotherapy in head and neck cancer patients was assessed in a phase I clinical trial. Methods: Mice bearing FaDu human head and neck cancer xenografts were fed either standard mouse chow or commercially prepared KD and treated with varying combination of cetuximab (CTX), cisplatin, and/or radiation (IR) and tumor growth was measured via calipers. Tumor homogenates and mice serum were harvested to test for markers including glutathione, 4HNE, PCNA, and IL6. Based on this study and other previously published pre-clinical studies, a phase I clinical trial in locally advanced head and neck cancer combining standard radiation and chemotherapy while consuming a KD was initiated. Subjects consumed a KD by PEG or nasogastric-tube and were also allowed to orally consume water, sugar-free drinks approved by the dietician, and approved snacks and meals approved by the dietician. Oxidative stress markers including protein carbonyl and glutathione were assessed. Results: Mice bearing xenografts treated with KD + IR + CTX had significantly increased survival relative to mice treated with IR + CTX. Collected tumor homogenates in KD + IR + CTX treated mice demonstrated increased 4HNE modified proteins relative to tumor homogenates from IR +CTX mice. In the phase I clinical trial, a total of twelve subjects were enrolled in the study. Four subjects completed five weeks of the KD as per protocol. Median follow-up from completion of RT was 13.1 months (range 8.0-26.7 months). Of the eight subjects that did not tolerate the diet, median number of days subjects stayed on diet was 5.5 (range: 2-8 days). Reasons for discontinuation included “stress of diet compliance” (1), grade 2 nausea (3), and grade 3 fatigue (1). Three subjects were removed for dose limiting toxicities: grade 4 hyperuricemia (2) and grade 3 acute pancreatitis (1). Median weight loss was 2.95% for the KD group and 7.92% for subjects that did not tolerate the diet. Subject serums demonstrated increased oxidative stress as they continued the diet. Conclusions: KD shows promise as adjuvant treatment in mouse xenograft model of head and neck cancer but in our small study there was difficulty with compliance and tolerability when combined with standard of care radiation and chemotherapy. Citation Format: Daniel MA, Carryn Anderson, Samuel N. Rodmann, Kayla Follmer, Visarut Buranasudja, Kellie Bodeker, Jessica R. Parkhurst, Michael McCormack, Andrew Davis, Douglas R. Spitz, John Buatti, Bryan G. Allen, Melissa A. Fath. Ketogenic diet with concurrent chemoradiation in head and neck squamous cell carcinoma: Pre-clinical and phase I trial results [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-252.

6006Background: Intensity-modulated radiotherapy (IMRT) plus cisplatin is established treatment for locally advanced OC/OP cancer, but appx. 70% of patients develop SOM, defined as WHO Grade 3 or 4...

Purpose: Radiation therapy (RT) for lung cancer is commonly limited to subtherapeutic doses due to unintended toxicity to normal lung tissue. Reducing the frequency of occurrence and magnitude of normal lung function loss may benefit from treatment plans that incorporate the regional lung and radiation dose information. In this article, the authors propose a method that quantitatively measures the regional changes in lung tissue function following a course of radiation therapy by using 4DCT and image registration techniques. Methods: 4DCT data sets before and after RT from two subjects are used in this study. Nonlinear 3D image registration is applied to register an image acquired near end inspiration to an image acquired near end expiration to estimate the pulmonary function. The Jacobian of the image registration transformation, indicating local lung expansion or contraction, serves as an index of regional pulmonary function. Approximately 120 annotated vascular bifurcation points are used as landmarks to evaluate registration accuracy. The authors compare regional pulmonary function before and after RT to the planned radiation dose at different locations of the lung. Results: In all registration pairs, the average landmark distances after registration are on the order of 1 mm. The pulmonary function change as indicated by the Jacobian change ranges from −0.15 to 0.1 in the contralateral lung and −0.22 to 0.23 in the ipsilateral lung for subject A, and ranges from −0.4 to 0.39 in the contralateral lung and −0.25 to 0.5 in the ipsilateral lung for subject B. Both of the subjects show larger range of the increase in the pulmonary function in the ipsilateral lung than the contralateral lung. For lung tissue regions receiving a radiation dose larger than 24 Gy, a decrease in pulmonary function was observed. For regions receiving a radiation dose smaller than 24 Gy, either an increase or a decrease in pulmonary function was observed. The relationship between the pulmonary function change and the radiation dose varies at different locations. Conclusions: With the use of 4DCT and image registration techniques, the pulmonary function prior to and following a course of radiation therapy can be measured. In the preliminary application of this approach for two subjects, changes in pulmonary function were observed with a weak correlation between the dose and pulmonary function change. In certain sections of the lung, detected locally compromised pulmonary function may have resulted from radiation injury.

BACKGROUND: The authors prospectively evaluated magnetic resonance imaging (MRI) parameters quantifying heterogeneous perfusion pattern and residual tumor volume early during treatment in cervical cancer, and compared their predictive power for primary tumor recurrence and cancer death with the standard clinical prognostic factors. A novel approach of augmenting the predictive power of clinical prognostic factors with MRI parameters was assessed. METHODS: Sixty-two cervical cancer patients underwent dynamic contrast-enhanced (DCE) MRI before and during early radiation/chemotherapy (2-2.5 weeks into treatment). Heterogeneous tumor perfusion was analyzed by signal intensity (SI) of each tumor voxel. Poorly perfused tumor regions were quantified as lower 10th percentile of SI (SI[10%]). DCE-MRI and 3-dimensional (3D) tumor volumetry MRI parameters were assessed as predictors of recurrence and cancer death (median follow-up, 4.1 years). Their discriminating capacity was compared with clinical prognostic factors (stage, lymph node status, histology) using sensitivity/specificity and Cox regression analysis. RESULTS: SI(10%) and 3D volume 2-2.5 weeks into therapy independently predicted disease recurrence (hazard ratio [HR], 2.6; 95% confidence interval [95% CI], 1.0-6.5 [P = .04] and HR, 1.9; 95% CI, 1.1-3.5 [P = .03], respectively) and death (HR, 1.9; 95% CI, 1.0-3.5 [P = .03] and HR, 1.9; 95% CI, 1.2-2.9 [P = .01], respectively), and were superior to clinical prognostic factors. The addition of MRI parameters to clinical prognostic factors increased sensitivity and specificity of clinical prognostic factors from 71% and 51%, respectively, to 100% and 71%, respectively, for predicting recurrence, and from 79% and 54%, respectively, to 93% and 60%, respectively, for predicting death. CONCLUSIONS: MRI parameters reflecting heterogeneous tumor perfusion and subtle tumor volume change early during radiation/chemotherapy are independent and better predictors of tumor recurrence and death than clinical prognostic factors. The combination of clinical prognostic factors and MRI parameters further improves early prediction of treatment failure and may enable a window of opportunity to alter treatment strategy. Cancer 2010. © 2010 American Cancer Society.

In this paper, we study an interesting matrix decomposition problem that seeks to decompose a "complicated" matrix into two "simpler" matrices while minimizing the sum of the horizontal complexity of the first sub-matrix and the vertical complexity of the second sub-matrix. The matrix decomposition problem is crucial for improving the "step-and-shoot" delivery efficiency in Intensity-Modulated Radiation Therapy, which aims to deliver a highly conformal radiation dose to a target tumor while sparing the surrounding normal tissues. Our algorithm is based on a non-trivial graph construction scheme, which enables us to formulate the decomposition problem as computing a minimum s-t cut in a 3-D geometric multi-pillar graph. Experiments on randomly generated intensity map matrices and on clinical data demonstrated the efficacy of our algorithm.

Hypo-fractionated radiation schemes may be used for patients with a poor prognosis and limited survival without compromising response. Hyper-fractionation and accelerated fractionation have not been shown to be superior to conventional fractionation and are not recommended. Brachytherapy or stereotactic radiosurgery as a boost to external beam radiotherapy have not been shown to be beneficial and are not recommended in the routine management of newly diagnosed malignant glioma.

Adjuvant radiation treatment is often offered for lacrimal sac tumors. However, due to the adjacent critical structures, conventional radiation technique may result in severe side effects. We have treated two patients with lacrimal sac tumors using optically guided stereotactic radiotherapy. One patient with lacrimal sac melanoma was treated with optical-guidance intensity-modulated radiotherapy (IMRT). The other with mixed transitional and squamous cell carcinoma was treated with optical-guidance 3-D conformal radiation. Dose volume analysis revealed excellent target coverage and sparing of critical structures. Both patients tolerated the treatment well with no significant acute or late side effects. One patient died of metastatic melanoma 30 months after radiation; another died of coexisting disease 41 months after radiation. Both had no clinical evidence of local recurrence at the time of death. Our report show that optically guided stereotactic radiotherapy is well tolerated. It offers excellent tumor coverage and sparing of critical structures. It can be used for tumors adjacent to radiation sensitive critical structures such as skull base tumors.

Purpose To determine whether the response of human head and neck cancer xenografts to cisplatin (CIS) could be enhanced with 2-deoxy-d-glucose (2DG); whether 2-[ 18 F]-fluoro-2-deoxy-d-glucose (FDG) uptake correlated with responses to this drug combination; and whether 2DG would enhance CIS-induced radiosensitization. Methods and Materials Clonogenic survival responses to CIS + 2DG were determined in FaDu and Cal-27 cells and reduced/oxidized glutathione levels were monitored as parameters indicative of oxidative stress. The efficacy of CIS + 2DG was determined in FaDu and Cal-27 xenografts, and FDG uptake was determined by using positron emission tomography. Results Use of CIS + 2DG enhanced cell killing of FaDu and Cal-27 cells compared with either drug alone while increasing the percentage of oxidized glutathione in vitro. Use of CIS + 2DG inhibited FaDu and Cal-27 tumor growth and increased disease-free survival compared with either drug alone. The Cal-27 tumors showed greater pretreatment FDG uptake and increased disease-free survival when treated with 2DG + CIS relative to FaDu tumors. Treatment with 2DG enhanced CIS-induced radiosensitization in FaDu tumor cells grown in vitro and in vivo and resulted in apparent cures in 50% of tumors. Conclusions These results show the enhanced therapeutic efficacy of CIS + 2DG in human head and neck cancer cells in vitro and in vivo compared with either drug alone, as well as the potential for FDG uptake to predict tumor sensitivity to 2DG + CIS. These findings provide a strong rationale for evaluating 2DG + CIS in combined-modality head and neck cancer therapy with radiation in a clinical setting.

To test the hypothesis that radiation dose to key sites in the upper aerodigestive tract is associated with long-term functional outcome after (chemo)radiotherapy for head-and-neck cancers.This study examined the outcome for 27 patients treated with intensity-modulated radiotherapy for definitive management of their head-and-neck cancer who were disease free for at least 1 year after treatment. Head-and-neck cancer-specific quality of life (QoL) was assessed before treatment and at 1 year after treatment. Type of diet tolerated, presence of a feeding tube, and degree of weight loss 1 year after treatment were also used as outcome measures. Radiation doses delivered to various points along the upper aerodigestive tract, including base of tongue, lateral pharyngeal walls, and laryngeal structures, were determined from each treatment plan. Radiation doses for each of these points were tested for correlation with outcome measures.Higher doses delivered to the aryepiglottic folds, false vocal cords, and lateral pharyngeal walls near the false cords correlated with a more restrictive diet, and higher doses to the aryepiglottic folds correlated with greater weight loss (p0.05) 1 year after therapy. Better posttreatment speech QoL scores were associated with lower doses delivered to structures within and surrounding the larynx.Our data show an inverse relationship between radiation dose delivered to laryngeal structures and speech and diet and QoL outcomes after definitive (chemo)radiation treatment. These findings suggest that efforts to deliver lower doses to laryngeal structures may improve outcomes after definitive (chemo)radiation therapy.

Stereotactic radiosurgery and image-guided radiotherapy (IGRT) place enhanced demands on treatment delivery machines. In this study, we describe a high-dose-rate output accelerator as a part of our stereotactic IGRT delivery system. The linac is a Siemens Oncor without a flattening filter, and enables dose rates to reach 1000 monitor units (MUs) per minute. Even at this high-dose-rate, the linac dosimetry system remains robust; constancy, linearity, and beam energy remain within 1% for 3 to 1000 MU. Dose profiles for larger field sizes are not flat, but they are radially symmetric and, as such, able to be modeled by a treatment planning system. Target localization is performed via optical guidance utilizing a 3-dimensional (3D) ultrasound probe coupled to an array of 4 infrared light-emitting diodes. These diodes are identified by a fixed infrared camera system that determines diode position and, by extension, all objects imaged in the room coordinate system. This system provides sub-millimeter localization accuracy for cranial applications and better than 1.5 mm for extracranial applications. Because stereotactic IGRT can require significantly longer times for treatment delivery, the advantages of the high-dose-rate design and its direct impact on IGRT are discussed.

This study determines if postradiotherapy [18F]fluorodeoxyglucose positron emission tomography (FDG PET) can predict the pathology status of residual cervical lymph nodes in patients undergoing definitive radiotherapy for head and neck squamous cell carcinoma (HNSCC).Patients with stage N2 or higher HNSCC underwent PET and CT imaging after definitive radiotherapy. Patients with radiographically persistent lymphadenopathy underwent either neck dissection or fine needle aspiration (FNA) of the lymph nodes under ultrasound guidance. PET scan results were correlated with the pathologic findings of the residual lymphadenopathy.Twenty-four hemi-necks in 23 patients with residual lymphadenopathy had neck dissection or FNA. The pathology correlated strongly with the post-RT FDG PET studies. All patients with a negative post-RT FDG PET and those with a maximum standardized uptake value (SUVmax) of less than 3.0 in the post-RT FDG PET were found to be free from residual viable tumor. Using a SUVmax of less than 3.0 as the criterion for a negative FDG PET study, the sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 84.2%, 62.5%, and 100%, respectively.A negative post-RT FDG PET is very predictive of negative pathology in the residual lymph node after definitive radiotherapy for advanced HNSCC. A prospective clinical trial is warranted to determine if neck dissection can be withheld in these patients.

Purpose: The authors present a novel paddle-based rotating-shield brachytherapy (P-RSBT) method, whose radiation-attenuating shields are formed with a multileaf collimator (MLC), consisting of retractable paddles, to achieve intensity modulation in high-dose-rate brachytherapy. Methods: Five cervical cancer patients using an intrauterine tandem applicator were considered to assess the potential benefit of the P-RSBT method. The P-RSBT source used was a 50 kV electronic brachytherapy source (Xoft Axxent™). The paddles can be retracted independently to form multiple emission windows around the source for radiation delivery. The MLC was assumed to be rotatable. P-RSBT treatment plans were generated using the asymmetric dose–volume optimization with smoothness control method [Liu et al., Med. Phys. 41(11), 111709 (11pp.) (2014)] with a delivery time constraint, different paddle sizes, and different rotation strides. The number of treatment fractions (fx) was assumed to be five. As brachytherapy is delivered as a boost for cervical cancer, the dose distribution for each case includes the dose from external beam radiotherapy as well, which is 45 Gy in 25 fx. The high-risk clinical target volume (HR-CTV) doses were escalated until the minimum dose to the hottest 2 cm3 (D 2cm3 ) of either the rectum, sigmoid colon, or bladder reached their tolerance doses of 75, 75, and 90 Gy3, respectively, expressed as equivalent doses in 2 Gy fractions (EQD2 with α/β = 3 Gy). Results: P-RSBT outperformed the two other RSBT delivery techniques, single-shield RSBT (S-RSBT) and dynamic-shield RSBT (D-RSBT), with a properly selected paddle size. If the paddle size was angled at 60°, the average D 90 increases for the delivery plans by P-RSBT on the five cases, compared to S-RSBT, were 2.2, 8.3, 12.6, 11.9, and 9.1 Gy10, respectively, with delivery times of 10, 15, 20, 25, and 30 min/fx. The increases in HR-CTV D 90, compared to D-RSBT, were 16.6, 12.9, 7.2, 3.7, and 1.7 Gy10, respectively. P-RSBT HR-CTV D 90-values were insensitive to the paddle size for paddles angled at less than 60°. Increasing the paddle angle from 5° to 60° resulted in only a 0.6 Gy10 decrease in HR-CTV D 90 on average for five cases when the delivery times were set to 15 min/fx. The HR-CTV D 90 decreased to 2.5 and 11.9 Gy10 with paddle angles of 90° and 120°, respectively. Conclusions: P-RSBT produces treatment plans that are dosimetrically and temporally superior to those of S-RSBT and D-RSBT, although P-RSBT systems may be more mechanically challenging to develop than S-RSBT or D-RSBT. A P-RSBT implementation with 4–6 shield paddles would be sufficient to outperform S-RSBT and D-RSBT if delivery times are constrained to less than 15 min/fx.

For 75% of patients with trigeminal neuralgia (TN), the pain can be controlled with medication. For those who fail medication therapy, surgical options include microvascular decompression (MVD), percutaneous radiofrequency rhizotomy (RFR), and stereotactic radiosurgery (SRS). Few studies have explored the relative cost-effectiveness of these interventions, particularly in surgically naïve patients.A retrospective chart review performed between January 2003 and January 2013 identified a total of 89 patients who underwent surgical treatment for TN (MVD=27, RFR=23, SRS=39). Outcome measures included facial pain (excellent=no pain, no medications; good=no pain, medications required; fair=50% decrease in pain; and poor=50% decrease in pain/secondary surgery), numbness, cost, and the need for a subsequent procedure.The average age of patients for each procedure was MVD=53.9±16, RFR=76.2±16, and SRS=74.5±12 (p0.001 MVD vs. other modalities). Total charges for the procedures (US dollars) were MVD=50,100±9600, RFR=4700±2200, and SRS=39,300±6000 (p0.001). Actual collections varied by insurance. Percentages of postoperative facial numbness were MVD=11%, RFR=52%, and SRS=28% (p0.01). At two years, the rates of recurrence requiring a second procedure were MVD=22%, RFR=74%, and SRS=31% (p0.01). Average times to secondary procedure in months were MVD=26±29, RFR=59±76, and SRS=35±25. Mean quality adjusted pain-free years were MVD=1.58, RFR=2.28, and SRS=0.99. Cost-effectiveness calculations in US dollars showed MVD=31,800, RFR=2100, and SRS=39,600 (p0.001).There are significant cost differences among the three most common surgical procedures for TN. MVD was the most expensive procedure, was more likely to be performed on younger patients, had the lowest rate of facial numbness, and had the lowest rate of recurrence requiring a secondary procedure. SRS was slightly less costly, more likely to be performed on an older population, and had a rate of recurrence similar to MVD. RFR was the least expensive procedure, provided immediate relief, but was associated with the highest rates of facial numbness and recurrence. Based on cost-effectiveness, considering both cost and outcome, RFR was the most cost-effective, followed by MVD, and finally SRS.

Radiation therapy indications in the postprostatectomy setting are evolving. Several retrospective series have identified a number of "high-risk" pathologic features associated with an elevated risk of disease recurrence after radical prostatectomy. More recently, several randomized phase III trials demonstrated superior biochemical relapse-free survival for adjuvant radiation therapy after prostatectomy for patients with these high-risk pathologic features, including positive margin status, extraprostatic extension, and/or seminal vesicle invasion. These series further suggested improvement in distant metastasis control and overall survival after 15 years. However, not all patients with high-risk features experience disease recurrence after surgery alone, and some subsets of patients experience suboptimal disease control and survival despite immediate postoperative radiotherapy. Furthermore, some patients without high-risk features will develop recurrence. The present review discusses the current data and potential future directions to improve individualization of therapy after prostatectomy.

To compare the interobserver and intermodality differences in image-based identification of head and neck primary site gross tumor volumes (GTV). Modalities compared include: contrast-enhanced CT, F-18 fluorodeoxyglucose positron emission tomography (PET/CT) and contrast-enhanced MRI.Fourteen patients were simulated after immobilization for all 3 imaging modalities (CT, PET/CT, MRI). Three radiation oncologists (RO) contoured GTVs as seen on each modality. The GTV was contoured first on the contrast-enhanced CT (considered the standard), then on PET/CT, and finally on post-contrast T1 MRI. Interobserver and intermodality variability were analyzed by volume, intersection, union, and volume overlap ratio (VOR).Analysis of RO contours revealed the average volume for CT-, PET/CT-, and MRI-derived GTVs were 45cc, 35cc and 49cc, respectively. In 93% of cases PET/CT-derived GTVs had the smallest volume and in 57% of cases MRI-derived GTVs had the largest volume. CT showed the largest variation in target definition (standard deviation amongst observers 35%) compared to PET/CT (28%) and MRI (27%). The VOR was largest (indicating greatest interobserver agreement) in PET/CT (46%), followed by MRI (36%), followed by CT (34%). For each observer, the least agreement in GTV definition occurred between MRIPET/CT (average VOR = 41%), compared to CTPET/CT (48%) and CTMRI (47%).A nonsignificant interobserver difference in GTVs for each modality was seen. Among three modalities, CT was least consistent, while PET/CT-derived GTVs had the smallest volumes and were most consistent. MRI combined with PET/CT provided the least agreement in GTVs generated. The significance of these differences for headneck cancer is important to explore as we move to volume-based treatment planning based on multi-modality imaging as a standard method for treatment delivery.

Objective: Review the University of Iowa experience with intensity modulated radiation treatment (IMRT) in oropharyngeal squamous cell carcinoma. Methods: From January 2000 to July 2004, 66 patients with oropharyngeal cancer were treated with IMRT, 62 with definitive IMRT and 4 postoperative IMRT. Three target volumes (CTV1, CTV2, and CTV3) were defined. The prescribed doses to CTV1, CTV2, and CTV3 were 70 to 74 Gy, 60 Gy, and 54 Gy, respectively, for definitive IMRT, and 60 to 66 Gy, 60 Gy, and 54 Gy, respectively, for postoperative IMRT. Results: Median follow-up was 27.3 months and all living patients had a follow-up of at least 11.5 months. The 3-year estimate of locoregional progression free survival was 98.8%. However, there is a high incidence of distant metastasis with a 3-year estimate of distant metastasis-free survival of 80.4%. In addition, there is a high incidence of second primary tumor. The 3-year overall survival and 3-year disease-free survival were 78.1% and 64.4%, respectively. Treatment was well tolerated with 1 death resulting from treatment toxicity. Conclusions: IMRT offers an excellent locoregional control for oropharyngeal cancer patients. Failure patterns have changed with an increased portion of patients who failed distantly, either with metastasis or second primary tumor. Therefore, survival for these patients is still poor. Future research should focus on identifying patients at high risk of distant diseases and developing effective systemic treatment and prevention for distant diseases.

Acoustic schwannomas, skull base meningiomas, and pituitary adenomas are benign intracranial tumors frequently managed with radiotherapy. Control rates after treatment for each of these tumors are generally high, and toxicity from treatment is relatively low. Side effect profiles depend on the tumor location, the volume treated, the dose delivered, and the presence of nearby critical structures. In addition, patient-specific factors, such as hypertension and diabetes, may increase a patient's risk for complications. This article reviews radiotoxicity after conformal radiation therapy for acoustic schwannomas, skull base meningiomas, and pituitary adenomas.

Purpose: To review the University of Iowa experience with intensity-modulated radiotherapy (IMRT) in the treatment of head-and-neck squamous cell carcinoma. Methods and Materials: From October 1999 to April 2004, 151 patients with head-and-neck squamous cell carcinoma were treated with IMRT for curative intent. One patient was lost to follow-up 2 months after treatment and therefore excluded from analysis. Of the remaining 150 patients, 99 were treated with definitive IMRT, and 51 received postoperative IMRT. Sites included were nasopharynx, 5; oropharynx, 56; larynx, 33; oral cavity, 29; hypopharynx, 8; nasal cavity/paranasal sinus, 8; and unknown primary, 11. None of the patients treated with postoperative IMRT received chemotherapy. Of 99 patients who had definitive IMRT, 68 patients received concurrent cisplatin-based chemotherapy. One patient received induction cisplatin-based chemotherapy, but no concurrent chemotherapy was given. Three clinical target volumes (CTV1, CTV2, and CTV3) were defined. The prescribed doses to CTV1, CTV2, and CTV3 in the definitive cohort were 70–74 Gy, 60 Gy, and 54 Gy, respectively. For high-risk postoperative IMRT, the prescribed doses to CTV1, CTV2, and CTV3 were 64–66 Gy, 60 Gy, and 54 Gy, respectively. For intermediate-risk postoperative IMRT, the prescribed doses to CTV1, CTV2, and CTV3 were 60 Gy, 60 Gy, and 54 Gy. Results: The median follow-up was 18 months (range, 2–60 months). All living patients were followed for at least 6 months. There were 11 local–regional failures: 7 local failures, 3 regional failures, and 1 failure both in the primary tumor and regional lymph node. There were 16 patients who failed distantly, either with distant metastasis or new lung primaries. The 2-year overall survival, local progression-free survival, locoregional progression-free survival, and distant disease-free survival rates were 85%, 94%, 92%, and 87%, respectively. The median time from treatment completion to local–regional recurrence was 4.7 months (range, 1.8 to 15.6 months). Only one marginal failure was noted in a patient who had extensive tonsil cancer with tumor extension into the orbit and cavernous sinus. Patients with oropharyngeal cancer did significantly better than patients with oral cavity and laryngeal cancer, with a 2-year local–regional control rate of 98%, compared with 78% for oral cavity cancer and 85% for laryngeal cancer ( p = 0.005). There was no significant difference in local–regional control for patients who received postoperative radiation or definitive radiation ( p = 0.339) and for patients who had chemotherapy or not ( p = 0.402). Neither T stage nor N stage had a significant effect on local–regional control ( p = 0.722 and 0.712, respectively). Conclusions: Our results have confirmed the effectiveness of IMRT in head-and-neck cancer. It offers excellent outcomes in local–regional control and overall survival. More studies are necessary to further improve the outcomes of laryngeal cancer as well as oral cavity cancer.

Optical tracking determines an object's position by measuring light either emitted or reflected from the object. The hallmark of optical tracking systems is their high spatial resolution and measurement in real time; such systems can resolve the position of a point source within a fraction of a millimeter and report at a rate of 10 Hz or faster. Several systems have been developed for radiation therapy, all of which track infrared markers attached to the patient's external surface. The positions of the optical markers relative to the target volume, together with the desired marker positions relative to treatment isocenter, are determined during computed tomography simulation. In the treatment room, the real marker positions are measured relative to isocenter; rigid-body mathematics then determine marker displacements from their desired positions and hence target displacement from isocenter. Real-time feedback allows one to correct the patient's position. The first systems were used for intracranial stereotaxis radiotherapy; rigid arrays of optical markers were attached to the patient via a biteplate linkage. Subsequent systems for extracranial radiotherapy tracked external markers to determine patient position and/or gate the radiation beam based on patient motion. Lastly, optical tracking has been integrated with ultrasound or stereoscopic x-ray imaging to determine the position of internal anatomy targets relative to isocenter.

Intracranial atypical teratoid/rhabdoid tumors (AT/RT) are rare with a poor prognosis. We report one case of a 7-year old girl living over 17 months after the diagnosis of AT/RT in the left frontal lobe. Treatment was partial surgical resection and post-operative radiation therapy. Radiation therapy resulted in complete response with no evidence of residual or recurrent disease more than 17 months after diagnosis. The patient has been maintained on an extensive regimen of alternative therapies since completion of radiation therapy.

Purpose [ 18 F] fluorodeoxyglucose positron emission tomography (FDG PET) imaging has been shown to be valuable in early detection of persistent and recurrent head-and-neck cancer after treatment. Previous studies have reported its use in patients treated with conventional radiation. Many patients are now treated with intensity-modulated radiation treatment (IMRT). We evaluated the value of FDG PET in the assessment of treatment response and surveillance in head-and-neck cancer patients treated with IMRT. Methods and materials We performed a retrospective review of 85 head-and-neck cancer patients treated with IMRT at our institution between December 2000 and September 2003 who had FDG PET in their follow-up. Of these, 58 were treated with primary IMRT with or without chemotherapy, and 27 were treated with postoperative IMRT. Results Sixty-four patients had negative initial FDG PET after treatment. Forty of them, who had 6 to 24 months of follow-up after the imaging study, had no evidence of local or regional recurrence, although three of them developed distant disease. Twenty-one patients had a positive initial FDG PET after treatment, with 11 positive at the primary site, 9 positive in the neck, and 3 positive distantly. Six of 11 patients with a positive FDG PET at the primary site were true positive, and 3 had salvage surgery. Eight of 9 patients positive in the neck had a salvage neck dissection. One had fine needle aspiration of the lymph node with positive cytology but refused surgery later. For patients with follow-up of 6 months and longer, only 1 of 45 patients with a negative initial FDG PET at the primary site developed a local recurrence. None of 49 patients with a negative initial FDG PET in the neck developed a regional recurrence. Two cases are presented in which abnormal FDG PET preceded laryngoscopy or computed tomography in detection of tumor recurrences. Conclusions FDG PET is useful in the posttreatment management of head-and-neck cancer patients treated with IMRT. It is highly accurate in the detection of persistent and recurrent disease after treatment and allows salvage treatment to be initiated in a timely manner. It also provides prognostic information concerning the risk of recurrence after curative therapy.

This update addressing head and neck sarcoma presents new data published after January 2003. This new information is presented following review of contemporary management principles established before 2003.The application of advances in molecular and genetic techniques to characterize individual sarcomas has improved classification schemes and hopefully will lead to individually tailored therapy. Maturation and refinements of large tumor registries are permitting more detailed analysis of larger contemporary series of the rare head and neck sarcomas. Improved long-term survival of patients treated for sarcoma in their childhood has allowed study of the morbidity induced by treatment. Novel treatment strategies are under study to decrease morbidity without diminishing the chance for cure.Progress in improving the treatment of sarcoma of the head and neck has been slow due to the lack of a large clinical experience with this rare neoplasm. Advances continue and are anticipated to be most striking in the study of genetic mechanisms.

For static beam conformal intracranial radiosurgery, geometry of the beam arrangement dominates overall dose distribution. Maximizing beam separation in three dimensions decreases beam overlap, thus maximizing dose conformality and gradient outside of the target volume. Webb proposed arrangements of isotropically convergent beams that could be used as the starting point for a radiotherapy optimization process. We have developed an extracranial radiosurgery optimization method by extending Webb's isotropic beam arrangements to deliverable beam arrangements. This method uses an arrangement of N maximally separated converging vectors within the space available for beam delivery. Each bouquet of isotropic beam vectors is generated by a random sampling process that iteratively maximizes beam separation. Next, beam arrangement is optimized for critical structure avoidance while maintaining minimal overlap between beam entrance and exit pathways. This geometrically optimized beam set can then be used as a template for either conformal beam or intensity modulated extracranial radiosurgery. Preliminary results suggest that using this technique with conformal beam planning provides high plan conformality, a steep dose gradient outside of the tumour volume and acceptable critical structure avoidance in the majority of clinical cases.

Surgical resection followed by post-operative radiation is used as a standard treatment approach for locally advanced head and neck squamous cell cancer (HNSCC) patients. Unfortunately, even with aggressive approaches roughly 40% of patients with locoregionally advanced disease will ultimately succumb. 18F- Fluorothymidine Positron Emission Tomography (FLT PET) is a non-invasive imaging method that can be used in vivo to assess tumor proliferative status. Results showed that FLT PET successfully images HNSCC subjects with high lesion-to-background contrast. Surprisingly, our results also showed that HNSCC subjects with low FLT uptake (indicative of low proliferative index; LPI) in the primary tumor at base line have significantly poorer outcome compared to subjects with high tumor FLT uptake (indicative of high proliferative index; HPI). This intriguing clinical observation suggests that HNSCC growth-state significantly impacts therapy outcome. Consistent with this hypothesis, results from in vitro HNSCC cell culture studies showed that LPI-HNSCC cultures ( 20% S-phase cells). Radioresistance of LPI-HNSCC cultures is associated with a higher basal manganese superoxide dismutase activity, increases in radiation induced forkhead box M1 expression, suppression of late accumulation of reactive oxygen species (ROS), and absence of a radiation induced shift in cellular metabolism towards mitochondrial respiration. Interestingly, treatment with palmitate (substrate for the TCA cycle) increased oxygen consumption rate and ROS levels resulting in radiation sensitization of LPI-HNSCC cultures. These results support the hypothesis that metabolic plasticity regulates HNSCC growth-state specific radiation sensitivity.

In-stent restenosis is commonly observed in coronary arteries after intervention. Intravascular brachytherapy has been found effective in reducing the recurrence of restenosis after stent placement. Conventional dosing models for brachytherapy with beta (/spl beta/) radiation neglect vessel geometry as well as the position of the delivery catheter. This paper demonstrates in computer simulations on phantoms and on in vivo patient data that the estimated dose distribution varies substantially in curved vessels. In simulated phantoms of 50-mm length with a shape corresponding to a 60/spl deg/-180/spl deg/ segment of a respectively sized torus, the average dose in 2-mm depth was decreased by 2.70%-7.48% at the outer curvature and increased by 2.95%-9.70% at the inner curvature as compared with a straight phantom. In vivo data were represented in a geometrically correct three-dimensional model that was derived by fusion of intravascular ultrasound (IVUS) and biplane angiography. These data were compared with a simplified tubular model reflecting common assumptions of conventional dosing schemes. The simplified model yielded significantly lower estimates of the delivered radiation and the dose variability as compared with a geometrically correct model (p < 0.001). The estimated dose in ten vessel segments of eight patients was on average 8.76% lower at the lumen/plaque and 6.52% lower at the media/adventitia interfaces (simplified tubular model relative to geometrically correct model). The differences in dose estimates between the two models were significantly higher in the right coronary artery as compared with the left coronary artery (p < 0.001).

Purpose Intensity-modulated radiotherapy (IMRT) has been shown to reduce the radiation dose to small bowel in pelvic RT in gynecology patients. Prone positioning has also been used to decrease small bowel dose by displacement of small bowel from the RT field in these patients. The purpose of this study was to determine whether the combination of both IMRT and prone positioning on a belly board can reduce small bowel dose further in gynecologic cancer patients undergoing pelvic RT. Methods and materials IMRT plans for pelvic RT were computed in 16 patients with gynecologic cancer who had undergone planning CT scans in both the supine and the prone positions on a belly board. For the gross tumor volume, the uterus, cervix, and tumor (or postoperative region) were traced. The clinical target volume was defined as the vessels and lymph nodes from the obturator level to the aortic bifurcation, presacral region, and upper 4 cm of the vagina, in addition to gross tumor volume. The planning target volume was defined as a 2-cm margin in addition to the gross tumor volume and upper 4 cm of the vagina, and 1.5 cm for lymph nodes and vessels. Normal tissue regions of interest included small bowel, large bowel, and bladder. IMRT plans using ( 1 ) the limited arc technique (180° arc length) and ( 2 ) the extended arc technique (340° arc length) were computed. Dose–volume histograms for normal tissue structures and target were compared between the supine and prone IMRT plans using the paired t test. Results Prone positioning on a belly board decreased the small bowel dose in gynecologic pelvic IMRT, and the magnitude of improvement depended on the specific IMRT technique used. With the limited arc technique, prone positioning significantly decreased the irradiated small bowel volume at the 25–50-Gy dose levels compared with supine positioning. Small bowel volumes receiving ≥45 Gy decreased from 19% to 12.5% ( p = 0.005) with prone positioning. With the extended arc technique, the decrease in irradiated small bowel volume was less marked, but remained detectable in the 35–45-Gy dose levels. Small bowel volumes receiving ≥45 Gy decreased from 13.6% to 10.1% ( p = 0.03) with prone positioning. The effect of prone positioning on large bowel and bladder was variable. Large bowel volumes receiving ≥45 Gy increased with prone positioning from 16.5% to 20.6% ( p = 0.02) in the limited arc technique and was unaffected in the extended arc technique. Conclusion These preliminary data suggest that prone positioning on a belly board can reduce the small bowel dose further in gynecology patients treated with pelvic RT, and that the dose reduction depends on the IMRT technique used.

Purpose: Stereotactic radiosurgery is an effective treatment modality for many intracranial lesions, but target mobility limits its utility for extracranial applications. We have developed a new technique for extracranial radiosurgery based on optically guided three-dimensional ultrasound (3DUS). The 3DUS system provides the ability to image the target volume and critical structures in real time and determine any misregistration of the target volume with the linear accelerator. In this paper, we describe the system and its initial clinical application in the treatment of localized metastatic disease. Methods and Materials: The extracranial stereotactic system consists of an ultrasound unit that is optically tracked and registered with the linear accelerator coordinate system. After an initial patient positioning based on computed tomographic (CT) simulation, stereotactic ultrasound images are acquired and correlated with the CT-based treatment plan to determine any soft-tissue shifts between the time of the planning CT and the actual treatment. Optical tracking is used to correct any patient offsets that are revealed by the real-time imaging. Results: Preclinical testing revealed that the ultrasound-based stereotactic navigation system is accurate to within 1.5 mm in comparison with an absolute coordinate phantom. Between March 2001 and March 2002, the system was used to deliver extracranial radiosurgery to 17 metastatic lesions in 16 patients. Treatments were delivered in 1 or 2 fractions, with an average fractional dose of 16 Gy (range 12.5–24 Gy) delivered to the 80% isodose surface. Before each fraction, the target misalignment from isocenter was determined using the 3DUS system and the misalignments averaged over all patients were anteroposterior = 4.8 mm, lateral = 3.6 mm, axial = 2.1 mm, and average total 3D displacement = 7.4 mm (range = 0–21.0 mm). After correcting patient misalignment, each plan was delivered as planned using 6–11 noncoplanar fields. No acute complications were reported. Conclusions: A system for high-precision radiosurgical treatment of metastatic tumors has been developed, tested, and applied clinically. Optical tracking of the ultrasound probe provides real-time tracking of the patient anatomy and allows computation of the target displacement before treatment delivery. The patient treatments reported here suggest the feasibility and safety of the technique.

Object. The goal of this study was to evaluate the outcomes of patients who underwent repeated radiosurgery to treat a residual intracranial arteriovenous malformation (AVM) after an initial radiosurgical treatment failure. Methods. The authors reviewed the cases of 52 patients who underwent repeated radiosurgery for residual AVM at the University of Florida between December 1991 and June 1998. In each case, residual arteriovenous shunting persisted longer than 36 months after the initial treatment; the mean interval between the first and second treatment was 41 months. Each AVM nidus was measured at the time of the original treatment and again at the time of retreatment, and the dosimetric parameters of the two treatments were compared. After retreatment, patients were followed up and their outcomes were evaluated according to a standard posttreatment protocol for radiosurgery for AVMs. The mean original lesion volume was 13.8 cm3 and the mean volume at retreatment was 4.7 cm3, for an average volume reduction of 66% after the initial treatment failure. Only two AVMs (3.8%) failed to demonstrate size reduction after the primary treatment. The median doses on initial and repeated treatment were 12.5 and 15 Gy, respectively. Five patients were lost to follow up and five refused neuroimaging follow up. One patient died of a hemorrhage shortly after retreatment. Of the remaining 41 patients, 24 had evidence of cure, 15 on angiographic studies and nine on magnetic resonance (MR) images. Seventeen had evidence of treatment failure, 10 on angiographic studies and seven on MR images. By angiographic criteria alone, the cure rate after retreatment was 60%, whereas according to angiographic and MR imaging results, the cure rate was 59%. Conclusions. Although initial radiosurgical treatment failed to obliterate the AVM in these 52 patients, it did produce a substantial therapeutic effect (volume reduction). This size reduction commonly allowed higher doses to be delivered during radiosurgical retreatment. The results show rates of angiographically confirmed cure comparable to primary treatment and a low incidence of complications, indicating that salvage radiosurgical retreatment is a safe and effective therapy in cases of failed AVM radiosurgery.

Purpose: Data collected from 10 institutions were reviewed to compare survival probabilities of patients with newly diagnosed brain metastases managed initially with radiosurgery (RS) alone vs. RS + whole brain radiotherapy (WBRT). Methods and Materials: A database was created from raw data submitted from 10 institutions on patients treated with RS for brain metastases. The major exclusion criteria were resection of a brain metastasis and interval from the end of WBRT until RS >1 month (to try to ensure that the up-front intent was to combine RS + WBRT and that RS was not given for recurrent brain metastases). Survival was estimated using the Kaplan-Meier method from the date of first treatment for brain metastases until death or last follow-up. Survival times were compared for patients managed initially with RS alone vs. RS + WBRT using the Cox proportional hazards model to adjust for known prognostic factors or Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class. Results: Out of 983 patients, 31 were excluded because treatment began after 6/1/98; 159 were excluded because brain metastases were resected; 179 were excluded because there was an interval >1 month from WBRT until RS; and 45 were excluded for other reasons. Of the 569 evaluable patients, 268 had RS alone initially (24% of whom ultimately had salvage WBRT), and 301 had RS + up-front WBRT. The median survival times for patients treated with RS alone initially vs. RS + WBRT were 14.0 vs. 15.2 months for RPA Class 1 patients, 8.2 vs. 7.0 months for Class 2, and 5.3 vs. 5.5 months for Class 3, respectively. With adjustment by RPA class, there was no survival difference comparing RS alone initially to RS + up-front WBRT ( p = 0.33, hazard ratio=1.09). Conclusions: Omission of up-front WBRT does not seem to compromise length of survival in patients treated with RS for newly diagnosed brain metastases.

Currently, optimally precise delivery of intracranial radiotherapy is possible with stereotactic radiosurgery and fractionated stereotactic radiotherapy. We present in this article a review of the underlying basic physical and radiobiological principles of fractionated stereotactic radiotherapy and review the clinical experience for ateriovenus malformations, pituitary adenomas, mengiomas, vestibular schwanomas, low grade astrocytomas, malignant gliomas, and brain metatases.

To review patterns of failure in infants with neuroblastoma and determine late toxicity and efficacy of radiotherapy (RT) on locoregional control.From 1955 to 1998, 53 children (35 males and 18 females)1 year old with neuroblastoma were seen at our institution. Twenty-one (40%) were/=1 month of age (neonates). Seven congenital anomalies were seen in 4 children (atrial septal defect, pulmonary valve stenosis, and absent corpus callosum were seen in 1 patient each; the other child had atrial and ventricular septal defect, aortic arch hypoplasia, and mitral valve stenosis). Primary tumor was located in the adrenal gland in 26 (49%), abdomen/nonadrenal in 14 (26%), thorax in 9 (17%), neck in 2 (4%), and pelvis in 2 (4%). All infants were retrospectively staged according to the International Neuroblastoma Staging System (INSS); 8 had Stage 1, 7 Stage 2A, 6 Stage 2B, 15 Stage 3, 6 Stage 4, and 11 Stage 4S. All patients, except 11 with Stage 4S and 4 with Stage 4, had resection of the primary tumor. Sixteen infants had pathologic involvement of regional lymph nodes (LN+). Twenty patients received RT. Kilovoltage beams were used in 10, megavoltage photons in 9, and electrons in 1 child. Fifteen received RT to the primary site and regional nodes (postoperative 8, preoperative 7). Postoperative doses ranged from 15 to 25 Gy whereas preoperative doses ranged from 12 to 31 Gy using a median fraction size of 1.5 Gy. Chemotherapy was employed in 22 of 53 patients (42%) with the most common agents being cyclophosphamide in 22 and doxorubicin in 11. Median follow-up was 13.1 years (range, 2-41 years).Tumor control: The 5-year overall and freedom from progression rates were 79 +/- 9% and 81 +/- 11%; the locoregional control rate was 88 +/- 9%. INSS Stage was a prognostic factor for overall survival (p = 0.03) and freedom from progression (p = 0.035). Gender, age (/=1 month vs.1 month), and primary site were not found to impact on survival or progression. None of the Stage 1, 2A, or 2B patients recurred. One of 15 Stage 3 and 5 of 6 Stage 4 children recurred (6 distant metastases, 4 local failure). Four of 6 (67%) LN+ patients treated with locoregional RT and 8 of 10 (80%) LN+ patients treated without RT were locally controlled. There was no isolated locoregional relapse. Two Stage 4S patients died of respiratory compromise secondary to hepatomegaly. RT toxicity: For the 20 infants who received RT, 13 are alive with long-term follow-up ranging from 9.3 to 41 years, median 23 years. The 10 and 15-year musculoskeletal toxicity rates were 38.5% and 47.3% for those receiving RT and 3.3% for no RT (p = 0.02, log-rank test). Five of 6 infants6 months of age and 1 of 7/=6 months developed musculoskeletal toxicity. Musculoskeletal effects were seen in 6 RT patients and included bony hypoplasia in 6, scoliosis in 5, soft tissue hypoplasia in 3, slipped capital femoral epiphysis in 2, kyphosis in 1, and osteochondroma in 1. Three required orthopedic intervention, all receiving/=20 Gy. One child developed bowel obstruction at 21 months and another developed a leiomyosarcoma in the treatment field 34 years after RT.Our study shows that most LN+ infants achieve locoregional control without RT. Infants6 months receiving RT were the most susceptible to musculoskeletal abnormalities. Further studies are needed to determine if cardiovascular anomalies are more frequently seen in children with neuroblastoma.

61 Background: In published series of extended pelvic LN dissection (LND), an association between higher number of LNs resected and both higher rate of occult LN disease discovery and long-term bRFS (for pN0) was observed. Despite this, practice patterns of LND extent (and associated number of LNs examined) vary, with the majority being limited to local nodal sampling. It remains unclear whether the LN yield correlates with bRFS in this context. The present investigation examines whether the number of LNs examined at RP is associated with bRFS. Methods: Patients with clinically localized prostate cancer, initial PSA < 30, and pT2-3a/N0 disease at RP were retrospectively identified for inclusion. Those who received pre-RP or adjuvant radiotherapy or hormone therapy were excluded. Kaplan-Meier method was employed for survival probability estimation. Cox regression models were used to assess bRFS differences. Results: From 2002 to 2010, 672 patients were eligible for this analysis. The median age was 61 yrs (range, 43-76). Most patients had cT1c (83%), Gleason Score (GS) 4-6 (63%), and were low risk by D’Amico classification (56%), with median PSA of 5.6 ng/dL (0.9-28.0). At RP, 213 (32%) patients had positive margins (M+). At a median follow-up of 82 months, 140 patients (21%) experienced PSA failure with estimated bRFS of 81%/76% at 5/8 years. Univariate analysis identified GS ³ 7 (biopsy or RP), intermediate/high risk, M+, higher percentage of biopsy cores involved, and performance of LND as adversely associated with bRFS (all p < 0.01). Of 446 patients (66%) who had LN sampling , 396 had a specific number of LNs reported (median 5; range 1-24, with single outlier case [33] excluded for statistical analysis). A higher number of LNs excised was not associated with bRFS for the entire cohort (HR = 0.99, p = 0.60), or for any biopsy GS subgroup (GS4-6 HR = 0.92, GS7 HR = 1.00, GS8-10 HR = 0.11). Conclusions: In the context of limited LND, this study did not demonstrate an association between LN yield and bRFS in patients with clinically localized pT2-3a/pN0 prostate cancer managed with RP alone, either in the entire population or with stratification by GS.

140 Background: Disease control and survival outcomes for LAEC are poor despite multimodality treatment with CRT with or without esophagectomy. Without comparative trial data, oncologists select a chemotherapy regimen based on clinical experience and toxicity profile. The present investigation compares LAEC progression free survival (PFS) and overall survival (OS) for CF versus CT. Methods: A retrospective analysis was performed for patients with LAEC from 2003-2012, treated with curative-intent neoadjuvant or definitive concurrent CRT with either CF or CT. Chi-squared tests, Fisher’s exact tests, and t-tests were used to identify significant differences between treatment groups. The Kaplan-Meier method was used to estimate PFS and OS. Results: Of 149 patients with non-metastatic LAEC, 82 met inclusion criteria (n=38 CF, n=44 CT), with 63, 2, and 2 excluded for non-CF/CT CRT, missing data, and

To determine the plan quality of proton spot scanning (SS) radiosurgery as a function of spot size (in-air sigma) in comparison to x-ray radiosurgery for treating peripheral brain lesions.Single-field optimized (SFO) proton SS plans with sigma ranging from 1 to 8 mm, cone-based x-ray radiosurgery (Cone), and x-ray volumetric modulated arc therapy (VMAT) plans were generated for 11 patients. Plans were evaluated using secondary cancer risk and brain necrosis normal tissue complication probability (NTCP).For all patients, secondary cancer is a negligible risk compared to brain necrosis NTCP. Secondary cancer risk was lower in proton SS plans than in photon plans regardless of spot size (p = 0.001). Brain necrosis NTCP increased monotonically from an average of 2.34/100 (range 0.42/100-4.49/100) to 6.05/100 (range 1.38/100-11.6/100) as sigma increased from 1 to 8 mm, compared to the average of 6.01/100 (range 0.82/100-11.5/100) for Cone and 5.22/100 (range 1.37/100-8.00/100) for VMAT. An in-air sigma less than 4.3 mm was required for proton SS plans to reduce NTCP over photon techniques for the cohort of patients studied with statistical significance (p = 0.0186). Proton SS plans with in-air sigma larger than 7.1 mm had significantly greater brain necrosis NTCP than photon techniques (p = 0.0322).For treating peripheral brain lesions--where proton therapy would be expected to have the greatest depth-dose advantage over photon therapy--the lateral penumbra strongly impacts the SS plan quality relative to photon techniques: proton beamlet sigma at patient surface must be small (7.1 mm for three-beam single-field optimized SS plans) in order to achieve comparable or smaller brain necrosis NTCP relative to photon radiosurgery techniques. Achieving such small in-air sigma values at low energy (70 MeV) is a major technological challenge in commercially available proton therapy systems.

Objective Chordomas carry significant morbidity due to their growth patterns and surgical constraints in resection. En bloc resection, when feasible, is the ideal treatment goal, but is associated with significant morbidity. We sought to elucidate the relationship between extent of surgery, location and radiotherapy in relation to overall disease and progression free survival (PFS). Methods We reviewed case records for all patients with a primary histopathological diagnosis of clival and spinal chordomas that was presented to our institution between 1978 and 2010. Results A total of 49 patients (location: n = 30, skull base/clival; n = 12 vertebral column; n = 7 sacrum) were identified with mean follow-up period of 6.3 years (range 0.25 months–33 years). Improved 5 year and 10 year survival rates were noted following gross total resection (n = 8, 5 year and 10 year survival = 88%) as compared to patients that underwent subtotal resection (n = 41, 55% and 31%, respectively), (p-value > 0.05, GTR versus STR). Adjuvant high-dose stereotactic fractionated radiotherapy (HS-FSRT) significantly improved 5 year PFS in craniocervical chordoma patients (70%, n = 13) as compared to standard dose radiation therapy (20%, n = 16; p-value = 0.03). Overall 10 year survival for craniocervical patients undergoing HD-FSRT (40%) was however not significantly different in comparison with conventional radiotherapy (45%). Sacral chordomas had the worst prognosis with 3 year survival of 28.6%. Conclusions GTR offers the best prognosis for improved long-term survival. Adjuvant HD FSRT for cranio-cervical/clival chordomas significantly improves disease free survival though the long-term benefits on survival have yet to be established. Sacral chordomas are associated with a worse prognosis and poor long-term survival.

The purpose of this correspondence is to alertcancer center directors and their associated biomedical imaging pro-grams about recent progress in quantitative imaging as a means topredictand/ormeasuretumorresponsetodrugorradiationtherapy,adevelopmentthatiscriticalto(forexample)implementingadaptivetherapy trial designs. There have been a number of initiatives in thisarea by the National Cancer Institute (NCI) and the RadiologicalSociety of North America (eg, the Quantitative Imaging BiomarkersAlliance

This study evaluates the potential efficacy and robustness of functional bone marrow sparing (BMS) using intensity-modulated proton therapy (IMPT) for cervical cancer, with the goal of reducing hematologic toxicity.IMPT plans with prescription dose of 45 Gy were generated for ten patients who have received BMS intensity-modulated X-ray therapy (IMRT). Functional bone marrow was identified by (18)F-flourothymidine positron emission tomography. IMPT plans were designed to minimize the volume of functional bone marrow receiving 5-40 Gy while maintaining similar target coverage and healthy organ sparing as IMRT. IMPT robustness was analyzed with ±3% range uncertainty errors and/or ±3 mm translational setup errors in all three principal dimensions.In the static scenario, the median dose volume reductions for functional bone marrow by IMPT were: 32% for V(5Gy), 47% for V(10Gy), 54% for V(20Gy), and 57% for V(40Gy), all with p0.01 compared to IMRT. With assumed errors, even the worst-case reductions by IMPT were: 23% for V(5Gy), 37% for V(10Gy), 41% for V(20Gy), and 39% for V(40Gy), all with p0.01.The potential sparing of functional bone marrow by IMPT for cervical cancer is significant and robust under realistic systematic range uncertainties and clinically relevant setup errors.

Radiation therapy of brain tumors in dogs typically involves administration of multiple fractions over several weeks. Fractionation is used to minimize damage to normal tissue. Radiosurgery uses multiple non-coplanar stereotactically focused beams of radiation in a series of arcs to deliver a single dose to the target with extreme accuracy. The large number of beams facilitates a high degree of conformation between the treatment area and the target tumor and allows for a steep dose gradient; the use of nonintersecting arcs minimizes exposure of normal tissue. Computed tomography with a stereotactic localizer secured to the skull allows generation of a 3-dimensional image of the target and provides accurate spatial coordinates for computerized treatment planning and delivery. Three dogs were treated with radiosurgery, using 1,000 to 1,500 cGy. A linear accelerator mounted on a rotating gantry was used to generate and deliver the radiation. Two dogs with meningiomas survived 227 and 56 weeks after radiosurgery. A dog with an oligodendroglioma survived 66 weeks. No complications were observed following the use of this technique.