In this study, we assess the dosimetric qualities and usability of planning for 1.5 T MR-Linac based intensity modulated radiotherapy (MRL-IMRT) for various clinical sites in comparison with IMRT plans using a conventional linac. In total of 30 patients with disease sites in the brain, esophagus, lung, rectum and vertebra were re-planned retrospectively for simulated MRL-IMRT using the Elekta Unity dedicated treatment planning system (TPS) Monaco (v5.40.01). Currently, the step-and-shoot (ss) is the only delivery technique for IMRT available on Unity. All patients were treated on an Elekta Versa HD TM with IMRT using the dynamic multileaf collimator (dMLC) technique, and the plans were designed using Monaco v5.11. For comparison, the same dMLC-IMRT plan was recalculated with the same machine and TPS but only changing the technique to step-and-shoot. The dosimetric qualities of the MRL-IMRT plans, to be evaluated by the Dose Volume Histograms (DVH) metrics, Homogeneity Index and Conformality Index, were compared with the clinical plans. The planning usability was measured by the optimization time and the number of Monitor Units (MUs). Comparing MRL-IMRT with conventional linac based plans, all created plans were clinically equivalent to current clinical practice. However, MRL-IMRT plans had higher dose to skin and larger low dose region of normal tissues. Furthermore, MRL-IMRT plans had significantly reduced optimization time by comparing conventional linac based plans. The number of MUs of MRL-IMRT was increased by 23% compared with ss-IMRT, and no difference from dMLC-IMRT. In conclusion, clinically acceptable plans can be achieved with 1.5 T MR-Linac system for multiple tumor sites. Given the differences in machine characteristics, some minor differences in plan quality were found between MR-Linac plans and current clinical practice and this should be considered in clinical practice.

Abstract Purpose The purpose of this study was to develop an auto‐planning platform to be interfaced with a commercial treatment planning system (TPS). The main goal was to obtain robust and high‐quality plans for different anatomic sites and various dosimetric requirements. Methods Monaco (Elekta, St. Louis, US) was the TPS in this work. All input parameters for inverse planning could be defined in a plan template inside Monaco. A software tool called Robot Framework was used to launch auto‐planning trials with updated plan templates. The template modifier external to Monaco was the major component of our auto‐planning platform. For current implementation, it was a rule‐based system that mimics the trial‐and‐error process of an experienced planner. A template was automatically updated by changing the optimization constraints based on dosimetric evaluation of the plan obtained in the previous trial, along with the data of the iterative optimization extracted from Monaco. Treatment plans generated by Monaco with all plan evaluation criteria satisfied were considered acceptable, and such plans would be saved for further evaluation by clinicians. The auto‐planning platform was validated for 10 prostate and 10 head‐and‐neck cases in comparison with clinical plans generated by experienced planners. Results The performance and robustness of our auto‐planning platform was tested with clinical cases of prostate and head and neck treatment. For prostate cases, automatically generated plans had very similar plan quality with the clinical plans, and the bladder volume receiving 62.5 Gy, 50 Gy, and 40 Gy in auto‐plans was reduced by 1%, 3%, and 5%, respectively. For head and neck cases, auto‐plans had better conformity with reduced dose to the normal structures but slightly higher dose inhomogeneity in the target volume. Remarkably, the maximum dose in the spinal cord and brain stem was reduced by more than 3.5 Gy in auto‐plans. Fluence map optimization only with less than 30 trials was adequate to generate acceptable plans, and subsequent optimization for final plans was completed by Monaco without further intervention. The plan quality was weakly dependent on the parameter selection in the initial template and the choices of the step sizes for changing the constraint values. Conclusion An automated planning platform to interface with Monaco was developed, and our reported tests showed preliminary results for prostate and head and neck cases.

To develop a warm-start strategy for template-based auto-planning method and to evaluate the planning efficiency and plan quality of this method in comparison with cold-start auto-planning. For both methods, an acceptable plan could be achieved with no more than 30 trials. However, the plan quality in 10 prostate cases indicated warm start auto-planning was consistently better than “cold-start” auto-planning, especially in rectal dose sparing and in target dose uniformity. Most importantly, warm start optimization (WSO) auto planning improved the planning efficiency tremendously. The average time for a planning trial was reduced from 2.1 minute to 0.5 minute. As an approach using machine decision making to modify the optimization parameters, WSO in auto-planning has a great potential for more clinical trials and clinical applications.

Purpose: The AAPM TG-135 report is a landmark recommendation for the quality assurance (QA) of image-guided robotic radiosurgery. The purpose of this paper is to present results pertaining to intentionally offsetting the phantom as recommended by TG-135 and to present data on targeting algorithm accuracy as a function of imager parameters in less than ideal circumstances, which had not been available at the time of publication of TG-135.Methods: All tests in this study were performed at the Cooper University Hospital CyberKnife Center in Mt. Laurel, NJ. For intentional offsets, initial tests were performed on the Accuray-supplied anthropomorphic head and neck phantom, whereas for subsequent tests, the Accuray-supplied alignment quality assurance (AQA) phantom was used. To simulate the effects of imager parameters for larger patients, slabs of Blue Water (Standard Imaging, Inc., Middleton, WI) were added to attenuate the x-ray images in some of the tests. In conjunction with attenuated x-ray tests, the number of fiducials was varied by systematically deselecting them one at a time at the CyberKnife console.Results: Tests using the AQA phantom verified that submillimeter alignments were consistently achieved even with intentional shifts and rotations of up to 10.0 mm and 1.0 degrees, respectively. An analysis of 17 months of daily QA alignment tests showed that submillimeter alignments were achieved more than 99% of the time even with such intentional shifts and rotations of the phantom. When additional slabs of Blue Water were added to simulate patient attenuation of the x-ray images, targeting errors could be induced depending on imager parameters and the amount of Blue Water used. A series of consecutive tests showed that two helpful variables to ensure good accuracy of the system were (1) the fiducial extraction confidence level (FECL) system parameter and (2) the number of targeted fiducials. When fewer than four fiducials were used, the FECL reported by the CyberKnife was sometimes high even when a false lock occurred, so using multiple fiducials helped to ensure reliable targeting.Conclusions: Radiosurgery requires the highest degree of targeting accuracy, and in our experience, the CyberKnife has been able to maintain submillimeter accuracy consistently. It has been verified that our CyberKnife can correct for phantom shifts of up to 10.0 mm and rotations of up to 1.0 degrees. It has also been discovered that false locks are more likely to occur with a single fiducial than with multiple fiducials. Although targeting accuracy can only be measured on a phantom, the insight gained from analyzing the QA tests can help us in devising better strategies for achieving the best treatment for our patients. (C) 2015 American Association of Physicists in Medicine.

The purpose of this study was to develop a system of clinical application of reconstructed dose that includes dose reconstruction, reconstructed dose registration between fractions of treatment, and dose-volume-histogram generation and to demonstrate the system on a deformable prostate phantom. To achieve this purpose, a deformable prostate phantom was embedded into a 20 cm-deep and 40 cm-wide water phantom. The phantom was CT scanned and the anatomical models of prostate, seminal vesicles, and rectum were contoured. A coplanar 4-field intensity modulated radiation therapy (IMRT) plan was used for this study. Organ deformation was simulated by inserting a “transrectal” balloon containing 20 ml of water. A new CT scan was obtained and the deformed structures were contoured. Dose responses in phantoms and electronic portal imaging device (EPID) were calculated by using the XVMC Monte Carlo code. The IMRT plan was delivered to the two phantoms and integrated EPID images were respectively acquired. Dose reconstruction was performed on these images using the calculated responses. The deformed phantom was registered to the original phantom using an in-house developed software based on the Demons algorithm. The transfer matrix for each voxel was obtained and used to correlate the two sets of the reconstructed dose to generate a cumulative reconstructed dose on the original phantom. Forwardly calculated planning dose in the original phantom was compared to the cumulative reconstructed dose from EPID in the original phantom. The prescribed 200 cGy isodose lines showed little difference with respect to the “prostate” and “seminal vesicles”, but appreciable difference (3%) was observed at the dose level greater than 210 cGy. In the rectum, the reconstructed dose showed lower volume coverage by a few percent than the plan dose in the dose range of 150 to 200 cGy. Through this study, the system of clinical application of reconstructed dose was successfully developed and demonstrated. The organ deformation simulated in this study resulted in small but observable dose changes in the target and critical structure.

OBJECT: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.METHODS: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.RESULTS: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.CONCLUSIONS: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 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 Elekta Infinity is the one of the latest generation LINAC with unique features. Two Infinity LINACs are recently commissioned at our institution. The dosimetric and mechanical characteristics of the machines are presented. METHODS Both Infinity LINACs with Agility MLC (160 leaves with 0.5 cm leaf width) are configured with five electron energies (6, 9, 12, 15, and 18 MeV) and two photon energies (6 and 15 MV). One machine has additional photon energy (10 MV). The commissioning was performed by following the manufacturer's specifications and AAPM TG recommendations. Beam data of both electron and photon beams are measured with scanning ion chambers and linear diode array. Machines are adjusted to have the dosimetrically equivalent characteristics. RESULTS The commissioning of mechanical and imaging system meets the tolerances by TG recommendations. The PDD1 0 of various field sizes for 6 and 15 MV shows < 0.5% difference between two machines. For each electron beams, R8 0 matches with < 0.4 mm difference. The symmetry and flatness agree within 0.8% and 0.9% differences for photon beams, respectively. For electron beams, the differences of the symmetry and flatness are within 1.2% and 0.8%, respectively. The mean inline penumbras for 6, 10, and 15 MV are respectively 5.1±0.24, 5.6±0.07, and 5.9±0.10 mm for 10×10 cm at 10 cm depth. The crossline penumbras are larger than inline penumbras by 2.2, 1.4, and 1.0 mm, respectively. The MLC transmission factor with interleaf leakage is 0.5 % for all photon energies. CONCLUSION The dosimetric and mechanical characteristics of two Infinity LINACs show good agreements between them. Although the Elekta Infinity has been used in many institutions, the detailed characteristics of the machine have not been reported. This study provides invaluable information to understand the Infinity LINAC and to compare the quality of commissioning data for other LINACs.

Objectives: Published local control rates for certain stereotactic body radiotherapy (SBRT) lung cancer treatments have exceeded 97%, but several serious adverse events have been reported. No five-year normal tissue complication probability (NTCP) statistical analysis SBRT results have been published yet for skin. While we expectantly await these publications, the goal of this manuscript is to glean the published expert opinion and ongoing clinical trials for skin dose tolerance limits in one to five fractions for clinical application and research. Methods: All 42 lung tumors treated with the CyberKnife at Cooper University Hospital from July 2008 to May 2010 that had skin contours and Monte Carlo dose calculations with heterogeneity corrections were reviewed for toxicity. Twenty-one published dose tolerance limits for skin were partitioned into high-risk and low-risk categories. The DVH Evaluator software tool was developed by the first author and used to conveniently assess the dose tolerance limits for each case prior to treatment and to analyze the followup data. Results: Three of the 42 patients experienced mild Grade 1 erythema that resolved within a few months. No Grade 2 or higher adverse events of skin toxicity were encountered. A unified framework of high-risk and low-risk skin dose limits in one to five fractions at specific dose-volume levels is presented. Conclusions: When the dose tolerance limits are diligently studied and respected, SBRT has potential to be a safe and effective form of radiation therapy. Longer follow-up will still be required to statistically analyze late effects and long-term outcomes.

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 degrees +/- 1.8 degrees, 1.8 degrees +/- 2.4 degrees, and 1.7 degrees +/- 2.1 degrees, 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. (C) 2014 Elsevier Inc.

Introduction. Brachytherapy plays a key role in the treatment of many gynecologic cancers. However, some patients are unable to tolerate brachytherapy for medical or other reasons. For these patients, stereotactic body radiotherapy (SBRT) offers an alternative form of treatment. Methods. Retrospective review of patients prospectively collected on SBRT database is conducted. A total of 11 gynecologic patients who could not have brachytherapy received SBRT for treatment of their malignancies. Five patients have been candidates for interstitial brachytherapy, and six have required tandem and ovoid brachytherapy. Median SBRT dose was 25 Gy in five fractions. Results. At last followup, eight patients were alive, and three patients had died of progressive disease. One patient had a local recurrence. Median followup for surviving patients was 420 days (median followup for all patients was 120 days). Two patients had acute toxicity (G2 dysuria and G2 GI), and one patient had late toxicity (G3 GI, rectal bleeding requiring cauterization). Conclusions. Our data show acceptable toxicity and outcome for gynecologic patients treated with SBRT who were unable to receive a brachytherapy boost. This treatment modality should be further evaluated in a phase II study.

Objectives: Published local control rates for certain stereotactic body radiotherapy (SBRT) lung cancer treatments have exceeded 97%, but several serious adverse events have been reported. No five-year normal tissue complication probability (NTCP) statistical analysis SBRT results have been published yet for skin. While we expectantly await these publications, the goal of this manuscript is to glean the published expert opinion and ongoing clinical trials for skin dose tolerance limits in one to five fractions for clinical application and research. Methods: All 42 lung tumors treated with the CyberKnife at Cooper University Hospital from July 2008 to May 2010 that had skin contours and Monte Carlo dose calculations with heterogeneity corrections were reviewed for toxicity. Twenty-one published dose tolerance limits for skin were partitioned into high-risk and low-risk categories. The DVH Evaluator software tool was developed by the first author and used to conveniently assess the dose tolerance limits for each case prior to treatment and to analyze the followup data. Results: Three of the 42 patients experienced mild Grade 1 erythema that resolved within a few months. No Grade 2 or higher adverse events of skin toxicity were encountered. A unified framework of high-risk and low-risk skin dose limits in one to five fractions at specific dose-volume levels is presented. Conclusions: When the dose tolerance limits are diligently studied and respected, SBRT has potential to be a safe and effective form of radiation therapy. Longer follow-up will still be required to statistically analyze late effects and long-term outcomes.

Purpose: To report the local control, survival, and low toxicity observed at the Cooper University Hospital CyberKnife Center post stereotactic body radiation therapy (SBRT) in the treatment of lung tumors near the mediastinum.Methods and Materials: Twenty-four medically inoperable lung cancer patients with tumors near the mediastinum were treated using the Accuray CyberKnife system (Accuray, Sunnyvale, CA) with Monte Carlo dose calculations and heterogeneity corrections from July 2008 to May 2010. The prescription dose ranged from 28.5 Gy to 60 Gy in 3-5 fractions. For conventional fractionation schemes, Emami et al 1 organized the dose tolerance limits into a unified format for clinical utility and partitioned them into 2 risk levels (5% and 50%) with preset volumes for most critical structures throughout the body. In contrast, statistical SBRT dose tolerance limits for mediastinal structures have not been established yet. We have sufficient experience at least to begin organizing a unified format with low-risk and high-risk partitions and preset volumes for 1-5 fractions exposing mediastinal structures. With the help of the (dose-volume histogram) DVH Evaluator, a software tool developed by our senior author, each treatment plan was assessed for safety and feasibility prior to treatment. The DVH Evaluator was also used to analyze the follow-up data and to create graphs of risk, called DVH Risk Maps, superimposing clinical data onto the unified SBRT dose tolerance limits.Results: It was not feasible to prescribe the doses of peripheral lung lesions for all tumors near the mediastinum because of known toxicity. The crude local tumor control rate achieved in our series was 92%. Median survival was 26.8 months for the primary lung cases and 9.6 months for the metastatic cases. No patients experienced grade 3 or higher toxicities.Conclusions: We affirm that SBRT is feasible in the treatment of centrally located lung cancers when the dose tolerance limits of critical structures are diligently respected. The low adverse event rates that we have experienced, combined with a good local tumor control rate, are encouraging. (C) 2013 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Purpose:To investigate the dosimetric feasibility of accelerated partial breast irradiation (APBI) using CyberKnife.Methods:Fourteen previously treated patients with early‐stage breast cancer were selected for a retrospective study. Six of these patients had been treated to 38.5 Gy in 10 fractions in a phase III accelerated partial breast trial and the rest of the patients were treated to 50.4 Gy in 28 fractions. In this planning study, the guidelines in the protocol for the phase III partial breast trial were followed for organ delineation and CyberKnife planning. The achievable dosimetric parameters from all CyberKnife plans were compared to Intensity‐modulated radiation therapy (IMRT) and 3D‐CRT methods. The reproducibility of the dose delivery with and without respiratory motion was assessed through delivering a patient plan to a breast phantom. Different dose calculation algorithms were also compared between ray tracing and Monte Carlo.Results:For all the patients in the study, the dosimetric parameters met the guidelines from the NSABP B39/RTOG 0413 protocol strictly. The mean PTV volume covered by 100% of the prescription dose was 95.7 ± 0.7% (94.7%–97.1%). The mean maximal dose was 104 ± 2% of the prescription dose. The mean V50% and mean V100% to the ipsilateral normal breast were 23.1 ± 11.6% and 9.0 ± 5.8%, respectively. The conformity index of all plans was 1.14 ± 0.04. The maximum dose to the contralateral breast varied from 1.3 cGy to 111 cGy. The mean V5% and mean V30% to the contralateral and ipsilateral lungs were 1.0 ± 1.6% and 1.3 ± 1.2%, respectively. In our study, the mean V5% to the heart was 0.2 ± 0.5% for right‐sided tumors and 9.4 ± 10.1% for left‐sided tumors. Compared with IMRT and 3D‐CRT planning, the PTV coverage from CyberKnife planning was the highest, and the ratio of V20% to V100% of the breast from CyberKnife planning was the smallest. The heart and lung doses were similar in all the techniques except that the V5% for the lung and heart in CyberKnife planning was slightly higher.Conclusions:The dosimetric feasibility of APBI using CyberKnife was investigated in this retrospective study. All the dosimetric parameters strictly met the guidelines from the NSABP B39/RTOG 0413 protocol. With advanced real‐time tracking capability, CyberKnife should provide better target coverage and spare nearby critical organs for APBI treatment.

Current gated radiation therapy starts with simulation 4DCT images of a patient with lung cancer. We propose a method to confirm the phase of 4DCT for planning and setup position at the time of treatment. An intensity-based rigid algorithm was developed in this work to register an orthogonal set of on-board projection X-ray images with each phase of the 4DCT. Multiple DRRs for one of ten 4DCT phases are first generated and the correlation coefficient (CC) between the projection X-ray image and each DRR is computed. The maximum value of CC for the phase is found via a simulated annealing optimization process. The whole process repeats for all ten phases. The 4DCT phase that has the highest CC is identified as the breathing phase of the X-ray. The phase verification process is validated by a moving phantom study. Thus, the method may be used to independently confirm the correspondence between the gating phase at the times of 4DCT simulation and radiotherapy delivery. When the intended X-ray phase and actual gating phase are consistent, the registration of the DRRs and the projection images may also yield the values of patient shifts for treatment setup. This method could serve as the 4D analog of the conventional setup film as it provides both verification of the specific phase at the time of treatment and isocenter positioning shifts for treatment delivery.

Increasing the dose rate offers time saving for IMRT delivery but the dosimetric accuracy is a concern, especially in the case of treating a moving target. The objective of this work is to determine the effect of dose rate associated with organ motion and gated treatment using step-and-shoot IMRT delivery. Both measurements and analytical simulation on clinical plans are performed to study the dosimetric differences between high dose rate and low dose rate gated IMRT step-and-shoot delivery. Various sites of IMRT plans for liver, lung, pancreas, and breast cancers were delivered to a custom-made motorized phantom, which simulated sinusoidal movement. Repeated measurements were taken for gated and nongated delivery with different gating settings and three dose rates, 100, 500, and 1000 MU/min using ion chambers and extended dose range films. For the study of the residual motion effect for individual segment dose and composite dose of IMRT plans, our measurements with 30%-60% phase gating and without gating for various dose rates were compared. A small but clinically acceptable difference in delivered dose was observed between 1000, 500, and 100 MU/min at 30%-60% phase gating. A simulation is presented, which can be used for predicting dose profiles for patient cases in the presence of motion and gating to confirm that IMRT step-and-shoot delivery with gating for 1000 MU/min are not much different from 500 MU/min. Based on the authors sample plan analyses, our preliminary results suggest that using 1000 MU/Min dose rate is dosimetrically accurate and efficient for IMRT treatment delivery with gating. Nonetheless, for the concern of patient care and safety, a patient specific QA should be performed as usual for IMRT plans for high dose rate deliveries.

To analyze the evolution of treatment and outcome for esophageal cancer at a single institution, we performed retrospective analysis for patients with esophageal cancer who received radiotherapy as the sole modality or as a component of multimodality treatment at our institution. Six hundred thirty-five consecutive patients with primary esophageal cancer received radiotherapy as a sole treatment modality or as a component of multimodality therapy from 1/1985, when CT scan became available for routine pretreatment evaluation, to 12/2002. Change in patient demographics was analyzed in this population. Patients who did not have metastatic disease were included in a multivariate analysis to identify factors associated with long-term survival. Patients were divided into 4 cohorts at 5-year interval starting from 1985 for comparison. From 1985 to 2002, there was a progressive white (79% to 87%) male (65% to 83%) predominance, increased incidence of adenocarcinoma (37.5% to 68%) located in the lower esophagus and the gastraesophageal junction (36% to 66%) in the population studied. The median age remained stable at 62–63 years. At diagnosis, the proportion of patients currently smoking decreased from 44% to 20%, whereas the proportion of patients who quit smoking increased from 35% to 74%. The median radiation dose was 45 to 50 Gy in all cohorts except the cohort from 1990–1994, when median radiation dose was 30 Gy in 10 fractions. The proportion of patients who received chemotherapy increased from 64% to 94%, while the proportion of patients who underwent surgery remained stable at about 50% at all time intervals. For all comers during the study period, the rates of 5-year overall survival (OS), disease free survival (DFS), distant metastasis free survival (DMFS), and locoregional control (LRC) were 20.2%, 22.3%, 63.6% and 43.2%, respectively. Table 1 shows the patients demographics and 3 -yr survival. Multiple drug chemotherapy, concurrent chemoradiation, surgery, 3-Dimensional radiation technique with 18 Mv photons, total radiation dose were significant predictive therapeutic factors for overall survival in multivariate analysis. There has been a change in patient demographics with an increased incidence of adenocarcinoma at the lower esophagus/GEJ. However, there was not a significant change in median radiation dose or the proportion of patients undergoing surgery. The most striking change in therapeutic modality for this disease was increased utilization of concurrent chemoradiation, intensity of chemotherapy, and improved radiation technique. Overall survival of patients with esophageal cancer who received radiation therapy has increased over time.

A new leaf-sequencing algorithm for step-and-shoot IMRT that is based on a graph-searching technique is described. An iterative process guided by a quantitative measure for the complexity of the initial or residual intensity pattern is used to identify the field segments shaped by a multileaf collimator (MLC). Given a user selected number of intensity levels, the algorithm searches deliverable segment candidates considering all intensity levels and two collimator positions separated by 90 degrees. The candidates for each intensity level are obtained as the least number of segments to cover the areas with equal or higher intensity. The shape of a deliverable segment is adjusted by leaving out certain beam elements for later delivery if this results in a simpler residual intensity pattern and the segment is still deliverable. For a MLC design that does not allow leaf interdigitation, it is initially assumed that a single segment cannot cover two disjoined areas. Among all candidates the segment with the greatest reduction of the complexity of the residual intensity distribution is chosen for the current step of iteration. The iterative process generates a set of deliverable segments of simply connected areas. These segments are combined later under specific MLC constraints. Different orders of segment combination are considered for minimizing the beam-on time. The final segments are sequenced to minimize the leaf travel. This algorithm has been tested using randomly generated intensity distributions and clinical cases for the Varian, Siemens, and Elekta MLC systems. The results show that as the number of intensity levels is increased, the numbers of segments and MUs increase only modestly. Using two collimator angles results in decreases in the required number of segments and the number of monitor units that can be as much as 20%.

Preclinical investigations have demonstrated that inhibition of COX-2 with selective COX-2 inhibitors preferentially enhances tumor response to radiation and chemotherapeutic agents, and suggested that these agents have potential to improve radiatiotherapy. This phase I study was designed to determine the maximum tolerated dose (MTD) of celecoxib, a selective COX-2 inhibitor, when used concurrently with standard fractionation thoracic radiotherapy for patients with poor prognosis NSCLC. The trial consisted of 3 separate patient groups. Group I was comprised of patients with locally advanced cancer who presented with obstructive pneumonia or minimal metastatic disease received palliative radiotherapy with 45 Gy total-dose delivered in 15 fractions. Patients in Group II presented with inoperable early stage tumors, and these patients received definitive radiation therapy consisting of 66 Gy total-dose delivered in 33 fractions. Group III included patients who received induction chemotherapy followed by radiotherapy to 63 Gy total-dose in 35 fractions. Three dimensional conformal treatment planning was used for all patients. Celecoxib in the escalation dose schedule of 200 mg, 400 mg, 600 mg, and 800 mg was administered orally in two equally divided daily doses starting 5 days prior to and continuing through the course of radiotherapy. Three to 4 patients of each radiotherapy group were assigned to each dose level of celecoxib. Forty-seven patients were enrolled in this protocol (19 in Group I, 22 in Group II, and 6 in Group III), with the 800 mg dose level completed only in Groups I and II. Group III was closed after 6 patients enrolled due to the fact that concurrent chemoradiation became a more accepted treatment modality. The main toxicities were grades 1 and 2 nausea and esophagitis. Two patients in Group II, one on 200mg and the other on 400mg celecoxib dose schedule developed grade 3 pneumonitis one month after radiotherapy plus celecoxib treatment. Two patients who were taking warfarin for other medical reasons had developed hemoragic episodes (one with hemotoma in the shoulder (grade 3) after 2 weeks of 200 mg per day celecoxib, the other had one episode of hemoptysis (grade 1) after one dose of 200 me per day celecoxib). One patient developed hypertension that did not normalize following discontinuation of the drug 2 weeks after starting 400mg celecoxib twice daily, and the event was considered grade 3 drug toxicity. In 23 patients evaluable for tumor response, 9 had complete response, 8 had partial response, 6 had stable or progression of the treated tumors radiographicly. The rate of local progression free survival was 67% at 20 months, following starting initiation of radiotherapy. These results suggest that celecoxib can be safely administered concurrently with thoracic radiotherapy. Importantly, the local progression free survival rate for all patients on the study was 67% at 20 months, a result similar to that after concurrent chemoradiotherapy, which is highly encouraging. A phase II/III trial is planned to test the efficacy of this treatment