Influence of respiratory motion management technique on radiation pneumonitis risk with robotic stereotactic body radiation therapy.

PURPOSE/OBJECTIVES: For lung stereotactic body radiation therapy (SBRT), real-time tumor tracking (RTT) allows for less radiation to normal lung compared to the internal target volume (ITV) method of respiratory motion management. To quantify the advantage of RTT, we examined the difference in radiation pneumonitis risk between these two techniques using a normal tissue complication probability (NTCP) model. MATERIALS/METHOD: 20 lung SBRT treatment plans using RTT were replanned with the ITV method using respiratory motion information from a 4D-CT image acquired at the original simulation. Risk of symptomatic radiation pneumonitis was calculated for both plans using a previously derived NTCP model. Features available before treatment planning that identified significant increase in NTCP with ITV versus RTT plans were identified. RESULTS: Prescription dose to the planning target volume (PTV) ranged from 22 to 60 Gy in 1-5 fractions. The median tumor diameter was 3.5 cm (range 2.1-5.5 cm) with a median volume of 14.5 mL (range 3.6-59.9 mL). The median increase in PTV volume from RTT to ITV plans was 17.1 mL (range 3.5-72.4 mL), and the median increase in PTV/lung volume ratio was 0.46% (range 0.13-1.98%). Mean lung dose and percentage dose-volumes were significantly higher in ITV plans at all levels tested. The median NTCP was 5.1% for RTT plans and 8.9% for ITV plans, with a median difference of 1.9% (range 0.4-25.5%, pairwise P < 0.001). Increases in NTCP between plans were best predicted by increases in PTV volume and PTV/lung volume ratio. CONCLUSIONS: The use of RTT decreased the risk of radiation pneumonitis in all plans. However, for most patients the risk reduction was minimal. Differences in plan PTV volume and PTV/lung volume ratio may identify patients who would benefit from RTT technique before completing treatment planning.

Hybrid minimally invasive Ivor Lewis esophagectomy after neoadjuvant chemoradiation yields excellent long-term survival outcomes with minimal morbidity.

BACKGROUND: There is a clear survival benefit to neoadjuvant chemoradiation prior to esophagectomy for patients with stages II-III esophageal cancer. A minimally invasive esophagectomy approach may decrease morbidity but is more challenging in a previously radiated field and therefore patients who undergo neoadjuvant chemoradiation may experience more postoperative complications. METHODS: A prospective database of all esophageal cancer patients who underwent attempted hybrid minimally invasive Ivor Lewis esophagectomy was maintained between 2006 and 2015. The clinical characteristics, neoadjuvant treatments, perioperative complications, and survival outcomes were reviewed. RESULTS: Overall 30- and 90-day mortality rates were 0.8% (1/131) and 2.3% (3/131), respectively. The majority of patients 58% (76/131) underwent induction treatment without significant adverse impact on mortality, major complications, or hospital stay. Overall survival at 1, 3, and 5 years was 85.9%, 65.3%, and 53.9%. Five-year survival by pathologic stage was stage I 68.9%, stage II 54.0%, and stage III 29.6%. CONCLUSIONS: The hybrid minimally invasive Ivor Lewis esophagectomy approach results in low perioperative morbidity and mortality and is well tolerated after neoadjuvant chemoradiation. Good long-term overall survival rates likely resulted from combined concurrent neoadjuvant chemoradiation in the majority of patients, which did not impact the ability to safely perform the operation or postoperative complications rates. J. Surg. Oncol. 2016;114:838-847. © 2016 2016 Wiley Periodicals, Inc.

Investigating the clinical advantages of a robotic linac equipped with a multileaf collimator in the treatment of brain and prostate cancer patients.

The purpose of this study was to evaluate the performance of a commercially avail-able CyberKnife system with a multileaf collimator (CK-MLC) for stereotactic body radiotherapy (SBRT) and standard fractionated intensity-modulated radiotherapy (IMRT) applications. Ten prostate and ten intracranial cases were planned for the CK-MLC. Half of these cases were compared with clinically approved SBRT plans generated for the CyberKnife with circular collimators, and the other half were compared with clinically approved standard fractionated IMRT plans generated for conventional linacs. The plans were compared on target coverage, conformity, homogeneity, dose to organs at risk (OAR), low dose to the surrounding tissue, total monitor units (MU), and treatment time. CK-MLC plans generated for the SBRT cases achieved more homogeneous dose to the target than the CK plans with the circular collimators, for equivalent coverage, conformity, and dose to OARs. Total monitor units were reduced by 40% to 70% and treatment time was reduced by half. The CK-MLC plans generated for the standard fractionated cases achieved prescription isodose lines between 86% and 93%, which was 2%-3% below the plans generated for conventional linacs. Compared to standard IMRT plans, the total MU were up to three times greater for the prostate (whole pelvis) plans and up to 1.4 times greater for the intracranial plans. Average treatment time was 25min for the whole pelvis plans and 19 min for the intracranial cases. The CK-MLC system provides significant improvements in treatment time and target homogeneity compared to the CK system with circular collimators, while main-taining high conformity and dose sparing to critical organs. Standard fractionated plans for large target volumes (> 100 cm3) were generated that achieved high prescription isodose levels. The CK-MLC system provides more efficient SRS and SBRT treatments and, in select clinical cases, might be a potential alternative for standard fractionated treatments.

ACR appropriateness Criteria® Postradical prostatectomy irradiation in prostate cancer.

The purpose of this article is to present an updated set of American College of Radiology consensus guidelines formed from an expert panel on the appropriate use of radiation therapy in postprostatectomy prostate cancer. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Recent and relevant literature reviewed by the panel led to establishment of criteria for appropriate use of radiation therapy in postprostatectomy prostate cancer. The discussion includes treatment technique, appropriate dose, field design, and the role of prostate-specific antigen (PSA). Ratings and commentary of the panel on multiple treatment parameters were used to reach consensus. Patients with high-risk pathologic features benefit from postprostatectomy radiation therapy.

Deep match: A zero-shot framework for improved fiducial-free respiratory motion tracking.

BACKGROUND AND PURPOSE: Motion management is essential to reduce normal tissue exposure and maintain adequate tumor dose in lung stereotactic body radiation therapy (SBRT). Lung SBRT using an articulated robotic arm allows dynamic tracking during radiation dose delivery. Two stereoscopic X-ray tracking modes are available - fiducial-based and fiducial-free tracking. Although X-ray detection of implanted fiducials is robust, the implantation procedure is invasive and inapplicable to some patients and tumor locations. Fiducial-free tracking relies on tumor contrast, which challenges the existing tracking algorithms for small (e.g., <15 mm) and/or tumors obscured by overlapping anatomies. To markedly improve the performance of fiducial-free tracking, we proposed a deep learning-based template matching algorithm - Deep Match. METHOD: Deep Match consists of four self-definable stages - training-free feature extractor, similarity measurements for location proposal, local refinements, and uncertainty level prediction for constructing a more trustworthy and versatile pipeline. Deep Match was validated on a 10 (38 fractions; 2661 images) patient cohort whose lung tumor was trackable on one X-ray view, while the second view did not offer sufficient conspicuity for tumor tracking using existing methods. The patient cohort was stratified into subgroups based on tumor sizes (<10 mm, 10-15 mm, and >15 mm) and tumor locations (with/without thoracic anatomy overlapping). RESULTS: On X-ray views that conventional methods failed to track the lung tumor, Deep Match achieved robust performance as evidenced by >80 % 3 mm-Hit (detection within 3 mm superior/inferior margin from ground truth) for 70 % of patients and <3 mm superior/inferior distance (SID) ∼1 mm standard deviation for all the patients. CONCLUSION: Deep Match is a zero-shot learning network that explores the intrinsic neural network benefits without training on patient data. With Deep Match, fiducial-free tracking can be extended to more patients with small tumors and with tumors obscured by overlapping anatomy.

Improving plan quality and consistency by standardization of dose constraints in prostate cancer patients treated with CyberKnife.

Treatment plans for prostate cancer patients undergoing stereotactic body radiation therapy (SBRT) are often challenging due to the proximity of organs at risk. Today, there are no objective criteria to determine whether an optimal treatment plan has been achieved, and physicians rely on their personal experience to evaluate the plan's quality. In this study, we propose a method for determining rectal and bladder dose constraints achievable for a given patient's anatomy. We expect that this method will improve the overall plan quality and consistency, and facilitate comparison of clinical outcomes across different institutions. The 3D proximity of the organs at risk to the target is quantified by means of the expansion-intersection volume (EIV), which is defined as the intersection volume between the target and the organ at risk expanded by 5 mm. We determine a relationship between EIV and relevant dosimetric parameters, such as the volume of bladder and rectum receiving 75% of the prescription dose (V75%). This relationship can be used to establish institution-specific criteria to guide the treatment planning and evaluation process. A database of 25 prostate patients treated with CyberKnife SBRT is used to validate this approach. There is a linear correlation between EIV and V75% of bladder and rectum, confirming that the dose delivered to rectum and bladder increases with increasing extension and proximity of these organs to the target. This information can be used during the planning stage to facilitate the plan optimization process, and to standardize plan quality and consistency. We have developed a method for determining customized dose constraints for prostate patients treated with robotic SBRT. Although the results are technology specific and based on the experience of a single institution, we expect that the application of this method by other institutions will result in improved standardization of clinical practice.

Addition of Enzalutamide to Leuprolide and Definitive Radiation Therapy Is Tolerable and Effective in High-Risk Localized or Regional Nonmetastatic Prostate Cancer: Results From a Phase 2 Trial.

Background: Enzalutamide is an antiandrogen used to treat both metastatic and nonmetastatic prostate cancer. Here we present results from a phase 2 trial designed to determine the safety, tolerability, and efficacy of adding enzalutamide to standard androgen deprivation therapy with radiation therapy in high-risk localized or regional, nonmetastatic patients with prostate cancer. Methods and Materials: Enrollment criteria included at least 2 of the following: stage cT3a/b, prostate specific antigen (PSA) ≥20 ng/mL, Gleason grade 8 to 10, ≥33% core involvement on biopsy, or pelvic lymph node involvement on computed tomography or magnetic resonance imaging. Patients with metastatic disease were excluded. All patients received 24 months of leuprolide and enzalutamide, and 5 weeks of intensity modulated radiation therapy followed by a brachytherapy boost. Adverse events (AE), PSA, testosterone, and basic laboratory tests were then followed for up to 36 months. Primary outcomes were safety and tolerability and PSA complete response rate (PSA-CR, defined as PSA ≤0.3). Secondary outcomes included time to biochemical recurrence (BCR; nadir + 2 ng/mL). Results: Sixteen patients were enrolled; 2 were ineligible and 3 withdrew before starting treatment. Median age at enrollment was 69.0 years (interquartile range [IQR] 11.5). Median treatment duration was 24.0 months (IQR 11.9). Median follow-up time was 35.5 months (IQR 11.2), and 9 of 11 (81.8%) patients completed the 36 months of follow-up. One of 11 (9%) patients had grade 4 AE (seizure), and no grade 5 AE were reported. Four of 11 (36.4%) patients had grade 3 AE, such as erectile dysfunction and hot flashes. All patients achieved PSA-CR, and median time to PSA-CR was 4.2 months (IQR 1.4). At 24 months follow-up, 0 of 11 (0%) patients had a biochemical recurrence. At 36 months, 1 of 9 (11.1%) patient had a biochemical recurrence. Of note, this patient did not complete the full 24 months of enzalutamide and leuprolide due to AEs. Conclusions: Enzalutamide in combination with standard androgen deprivation therapy and radiation therapy was well-tolerated and effective warranting further study in a randomized controlled trial.

Comparison of patient megavoltage cone beam CT images acquired with an unflattened beam from a carbon target and a flattened treatment beam.

PURPOSE: To use an imaging beam line (IBL) to obtain the first megavoltage cone-beam computed tomography (MV CBCT) images of patients with a low atomic number (Z) target, and to compare these images to those taken of the same patients with the 6 MV flattened beam from the treatment beam line (TBL). METHODS: The IBL, which produces a 4.2 MV unflattened beam from a carbon target, was installed on a linear accelerator in use for radiotherapy. Provision was made for switching between the IBL and TBL for imaging the same patient with beams from the low-Z and high-Z targets. Dose was quoted as monitor units times the dose per monitor unit for the standard calibration geometry. Images were acquired with institutional approval and patient consent with both the IBL and TBL on a series of 23 patients undergoing radiotherapy. Patients were imaged daily to weekly and aligned to the planning CT using the images. Doses were reduced over the course of treatment to determine the minimum doses required for alignment. Images were assessed offline. RESULTS: IBL MV CBCT images of prostate, head and neck, lung, and abdomen showed improvement in soft tissue contrast for the same dose as the TBL images. Bony anatomy, air cavities, and fiducial markers were sharper. CBCT with a dose of 1 cGy was sufficient for alignment of prostate and head and neck patients based on bony anatomy or implanted gold seeds, 2-4 cGy for lung, abdomen, and pelvis. Photon scatter in the patient had minimal effect on image quality. The metallic hip prosthesis in one patient showed reduced artifacts compared to diagnostic CT. CONCLUSIONS: The IBL has the advantage of improved image quality at the same dose, or reduced dose for the same image quality, over the TBL.

Evaluation of a National Comprehensive Cancer Network Guidelines-Based Decision Support Tool in Patients With Non-Small Cell Lung Cancer: A Nonrandomized Clinical Trial.

Importance: The association of guideline-based decision support with the quality of care in patients with non-small cell lung cancer (NSCLC) is not known. Objective: To evaluate the association of exposure to the National Comprehensive Cancer Center (NCCN) guidelines with guideline-concordant care and patients' decisional conflict. Design, Setting, and Participants: A nonrandomized clinical trial, conducted at a tertiary care academic institution, enrolled patients from February 23, 2015, to September 28, 2017. Data analysis was conducted from July 19, 2019, to April 22, 2020. A cohort of 76 patients with NSCLC seen at diagnosis or disease progression and a retrospective cohort of 157 patients treated before the trial were included. Adherence to 6 NCCN recommendations were evaluated: (1) smoking cessation counseling, (2) adjuvant chemotherapy for patients with stage IB to IIB NSCLC after surgery, (3) pathologic mediastinal staging in patients with stage III NSCLC before surgery, (4) pathologic mediastinal staging in patients with stage III NSCLC before nonsurgical treatment, (5) definitive chemoradiotherapy for patients with stage III NSCLC not having surgery, and (6) molecular testing for epidermal growth factor receptor and anaplastic lymphoma kinase alterations for patients with stage IV NSCLC. Subgroup analysis was conducted to compare the rates of guideline concordance between the prospective and retrospective cohorts. Secondary end points included decisional conflict and satisfaction. Interventions: An online tool customizing the NCCN guidelines to patients' clinical and pathologic features was used during consultation, facilitated by a trained coordinator. Main Outcomes and Measures: Concordance of practice with 6 NCCN treatment recommendations on NSCLC and patients' decisional conflict. Results: Of the 76 patients with NSCLC, 44 were men (57.9%), median age at diagnosis was 68 years (interquartile range [IQR], 41-87 years), and 59 patients (77.6%) had adenocarcinoma. In the retrospective cohort, 91 of 157 patients (58.0%) were men, median age at diagnosis was 66 years (IQR, 61-65 years), and 105 patients (66.9%) had adenocarcinoma. After the intervention, patients received more smoking cessation counseling (4 of 5 [80.0%] vs 1 of 24 [4.2%], P < .001) and less adjuvant chemotherapy (0 of 7 vs 7 of 11 [63.6%]; P = .012). There was no significant change in mutation testing of non-squamous cell stage IV disease (20 of 20 [100%] vs 48 of 57 [84.2%]; P = .10). There was no significant change in pathologic mediastinal staging or initial chemoradiotherapy for patients with stage III disease. After consultation with the tool, decisional conflict scores improved by a median of 20 points (IQR, 3-34; P < .001). Conclusions and Relevance: The findings of this study suggest that exposure to the NCCN guidelines is associated with increased guideline-concordant care for 2 of 6 preselected recommendations and improvement in decisional conflict. Trial Registration: ClinicalTrials.gov Identifier: NCT03982459.

High-dose-rate brachytherapy for localized prostate adenocarcinoma post abdominoperineal resection of the rectum and pelvic irradiation: Technique and experience.

PURPOSE: Treatment options are limited for patients with localized prostate cancer and a prior history of abdominoperineal resection (APR) and pelvic irradiation. We have previously reported on the successful utility of high-dose-rate (HDR) brachytherapy salvage for prostate cancer failing definitive external beam radiation therapy (EBRT). In this report, we describe our technique and early experience with definitive HDR brachytherapy in patients post APR and pelvic EBRT. PATIENTS AND METHODS: Six men with newly diagnosed localized prostate cancer had a prior history of APR and pelvic EBRT. Sixteen to 18 HDR catheters were placed transperineally under transperineal ultrasound-guidance. The critical first two catheters were placed freehand posterior to the inferior rami on both sides of the bulbar urethra under cystoscopic visualization. A template was used for subsequent catheter placement. Using CT-based planning, 5 men received 36Gy in six fractions as monotherapy. One patient initially treated with EBRT to 30Gy, received 24Gy in four fractions. RESULTS: Median age was 67.5 (56-74) years. At a median followup of 26 (14-60) months, all patients are alive and with no evidence of disease per the Phoenix definition of biochemical failure, with a median prostate-specific antigen nadir of 0.19ng/mL. Three men have reported grade 2 late genitourinary toxicity. There has been no report of grade 3-5 toxicity. CONCLUSION: Transperineal ultrasound-guided HDR brachytherapy using the above technique should be considered as definitive therapy for patients with localized prostate cancer and a prior history of APR and pelvic EBRT.

Impact of Staging 68Ga-PSMA-11 PET Scans on Radiation Treatment Plansin Patients With Prostate Cancer.

OBJECTIVE: To evaluate the impact of staging 68Ga-PSMA-11 PET imaging on radiotherapy (RT) dose and volumes in patients with prostate cancer. METHODS: Forty-five patients (89% high or very high risk by NCCN criteria) who underwent 68Ga-PSMA-11 PET imaging prior to definitive treatment for prostate cancer between December 2015 and December 2016 were included. Locations of 68Ga-PSMA-11-avid lesions were compared to Radiation Therapy Oncology Group consensus pelvic nodal volumes (clinical target volume [CTV]); coverage of lesions outside the consensus CTV was considered a major change, while dose-escalation to lesions within the consensus CTV was considered a minor change. RESULTS: All patients had 68Ga-PSMA-11 PET uptake in the prostate. Twenty-five patients (56%) had N1/M1a disease on 68Ga-PSMA-11 PET scan, of whom 21 (47%) were previously N0. Six patients (13%) had bone metastases on 68Ga-PSMA-11 PET scan, of whom 4 had prior negative bone scans. Eight patients (18%) had lymph node metastases outside the consensus CTV. Twelve patients (27%) received a RT boost to nodes within the consensus CTV. Six patients (13%) had limited bone metastases treated with focal RT. Overall PSMA PET imaging resulted in major and/or minor changes to RT plans in 24 patients (53%). CONCLUSION: 68Ga-PSMA-11 PET imaging resulted in RT changes in 53% of patients. Prospective investigation is needed to evaluate the clinical benefit of RT changes based on staging 68Ga-PSMA-11 PET imaging.

Proposed rectal dose constraints for patients undergoing definitive whole pelvic radiotherapy for clinically localized prostate cancer.

PURPOSE: Although several institutions have reported rectal dose constraints according to threshold toxicity, the plethora of trials has resulted in multiple, confusing dose-volume histogram recommendations. A set of standardized, literature-based constraints for patients undergoing whole pelvic radiotherapy (RT) for prostate cancer would help guide the practice of prostate RT. The purpose of this study was to develop these constraints, demonstrate that they are achievable, and assess the corresponding rectal toxicity. METHODS AND MATERIALS: An extensive literature search identified eight key studies relating dose-volume histogram data to rectal toxicity. A correction factor was developed to address differences in the anatomic definition of the rectum across studies. The dose-volume histogram constraints recommended by each study were combined to generate the constraints. The data from all patients treated with definitive intensity-modulated RT were then compared against these constraints. Acute rectal toxicity was assessed. RESULTS: A continuous, proposed rectal dose-constraint curve was generated. Intensity-modulated RT not only met this constraint curve, but also was able to achieve at least 30-40% lower dose to the rectum. The preliminary clinical results were also positive: 50% of patients reported no acute bowel toxicity, 33% reported Grade 1 toxicity, and 17% reported Grade 2 toxicity. No patients reported Grade 3-4 acute rectal toxicity. CONCLUSIONS: In this study, we developed a set of proposed rectal dose constraints. This allowed for volumetric assessment of the dose-volume relationship compared with single dose-volume histogram points. Additional research will be performed to validate this threshold as a class solution for rectal dose constraints.

Simulated real time image guided intrafraction tracking-delivery for hypofractionated prostate IMRT.

Hypofractionated stereotactic body radiotherapy (SBRT) has been tested for prostate cancer radiotherapy. This study aims to investigate the dosimetric effects of intrafraction prostate motion on the target and the normal structures for SBRT. For prostate cancer patients treated with an image-tracking CyberKnife system, the intrafraction prostate movements were recorded during 50-70 min treatment time. Based on the recorded intrafraction prostate movements, treatment plans were created for these cases using intensity modulated beams while scaling the average time patterns from the CyberKnife treatment to simulate hypofractionated intensity modulated radiotherapy (IMRT) delivery. The effect of delivery time on the intrafraction organ motion was investigated. For a nominal single fraction delivery of 9.5 Gy with IMRT, we found that the dosimetric effect of the intrafraction prostate movement is case dependent. For most cases, the dose volume histograms exhibited very small changes from the treatment plans that assumed no intrafractional prostate motion when the maximum intrafraction movements were within +/-5 mm. However, when sporadic prostate movements greater than 5 mm were present in any one direction, significant changes were found. For example, the V100, for the prostate could be reduced by more than 10% to less than 85% of the prostate volume coverage. If these large movements could be excluded by some active correction strategies, then the average V100% for the simulated plan could be restored to within approximately 2% of the ideal treatment plans. On average, the sporadic intrafraction motion has less dosimetric impact on the prolonged treatment delivery versus fast treatment delivery. For example, the average V100% for the clinical target volume was reduced from the original 95.1% to 92.1 +/- 3.7% for prolonged treatment, and to 91.3 +/- 5.4% when the treatment time was shortened by 50%. Due to the observed large sporadic prostate motions, we conclude that an on-line target motion monitoring and correction strategy is necessary to implement hypofractionated SBRT with intensity modulated beams for prostate cancer treatments.

Phase I study of dose escalation to dominant intraprostatic lesions using high-dose-rate brachytherapy.

PURPOSE: Radiation dose escalation for prostate cancer improves biochemical control but is limited by toxicity. Magnetic resonance spectroscopic imaging (MRSI) can define dominant intraprostatic lesions (DIL). This phase I study evaluated dose escalation to MRSI-defined DIL using high-dose-rate (HDR) brachytherapy. MATERIAL AND METHODS: Enrollment was closed early due to low accrual. Ten patients with prostate cancer (T2a-3b, Gleason 6-9, PSA < 20) underwent pre-treatment MRSI, and eight patients had one to three DIL identified. The eight enrolled patients received external beam radiation therapy to 45 Gy and HDR brachytherapy boost to the prostate of 19 Gy in 2 fractions. MRSI images were registered to planning CT images and DIL dose-escalated up to 150% of prescription dose while maintaining normal tissue constraints. The primary endpoint was genitourinary (GU) toxicity. RESULTS: The median total DIL volume was 1.31 ml (range, 0.67-6.33 ml). Median DIL boost was 130% of prescription dose (range, 110-150%). Median urethra V120 was 0.15 ml (range, 0-0.4 ml) and median rectum V75 was 0.74 ml (range, 0.1-1.0 ml). Three patients had acute grade 2 GU toxicity, and two patients had late grade 2 GU toxicity. No patients had grade 2 or higher gastrointestinal toxicity, and no grade 3 or higher toxicities were noted. There were no biochemical failures with median follow-up of 4.9 years (range, 2-8.5 years). CONCLUSIONS: Dose escalation to MRSI-defined DIL is feasible. Toxicity was low but incompletely assessed due to limited patients' enrollment.

Feasibility of high-dose-rate brachytherapy salvage for local prostate cancer recurrence after radiotherapy: the University of California-San Francisco experience.

PURPOSE: The aim of this study was to evaluate the feasibility and safety of salvage high-dose-rate (HDR) brachytherapy for locally recurrent prostate cancer after external beam radiotherapy (EBRT). METHODS AND MATERIALS: We retrospectively analyzed 21 consecutively accrued patients undergoing salvage HDR brachytherapy for locally recurrent prostate cancer after EBRT between November 1998 and December 2005. After pathologic confirmation of locally recurrent disease, all patients were treated with 36 Gy in six fractions using two transrectal ultrasound-guided HDR prostate implants, separated by 1 week. Eleven patients received neoadjuvant hormonal therapy immediately presalvage, whereas none received adjuvant hormonal therapy postsalvage. Median follow-up time from recurrence was 18.7 months (range, 6-84 months). Determination of subsequent biochemical failure after brachytherapy was based on the definition by the American Society for Therapeutic Radiology and Oncology. RESULTS: Based on the Common Terminology Criteria for Adverse Events (CTCAE version 3), 18 patients reported Grade 1 to 2 genitourinary symptoms by 3 months postsalvage. Three patients developed Grade 3 genitourinary toxicity. Maximum observed gastrointestinal toxicity was Grade 2; all cases spontaneously resolved. The 2-year Kaplan-Meier estimate of biochemical control after recurrence was 89%. Thirteen patients have achieved a PSA nadir < or =0.1 ng/ml, but at the time of writing this endpoint has not yet been reached for all patients. All patients are alive; however 2 have experienced biochemical failure, both with PSA nadirs > or =1, and have subsequently been found to have distant metastases. CONCLUSIONS: Salvage HDR prostate brachytherapy appears to be feasible and effective.

Daily electronic portal imaging of implanted gold seed fiducials in patients undergoing radiotherapy after radical prostatectomy.

PURPOSE: The aim of this study was to measure interfraction prostate bed motion, setup error, and total positioning error in 10 consecutive patients undergoing postprostatectomy radiotherapy. METHODS AND MATERIALS: Daily image-guided target localization and alignment using electronic portal imaging of gold seed fiducials implanted into the prostate bed under transrectal ultrasound guidance was used in 10 patients undergoing adjuvant or salvage radiotherapy after prostatectomy. Prostate bed motion, setup error, and total positioning error were measured by analysis of gold seed fiducial location on the daily electronic portal images compared with the digitally reconstructed radiographs from the treatment-planning CT. RESULTS: Mean (+/- standard deviation) prostate bed motion was 0.3 +/- 0.9 mm, 0.4 +/- 2.4 mm, and -1.1 +/- 2.1 mm in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) axes, respectively. Mean set-up error was 0.1 +/- 4.5 mm, 1.1 +/- 3.9 mm, and -0.2 +/- 5.1 mm in the LR, SI, and AP axes, respectively. Mean total positioning error was 0.2 +/- 4.5 mm, 1.2 +/- 5.1 mm, and -0.3 +/- 4.5 mm in the LR, SI, and AP axes, respectively. Total positioning errors >5 mm occurred in 14.1%, 38.7%, and 28.2% of all fractions in the LR, SI, and AP axes, respectively. There was no significant migration of the gold marker seeds. CONCLUSIONS: This study validates the use of daily image-guided target localization and alignment using electronic portal imaging of implanted gold seed fiducials as a valuable method to correct for interfraction target motion and to improve precision in the delivery of postprostatectomy radiotherapy.

Patient dose considerations for routine megavoltage cone-beam CT imaging.

Megavoltage cone-beam CT (MVCBCT), the recent addition to the family of in-room CT imaging systems for image-guided radiation therapy (IGRT), uses a conventional treatment unit equipped with a flat panel detector to obtain a three-dimensional representation of the patient in treatment position. MVCBCT has been used for more than two years in our clinic for anatomy verification and to improve patient alignment prior to dose delivery. The objective of this research is to evaluate the image acquisition dose delivered to patients for MVCBCT and to develop a simple method to reduce the additional dose resulting from routine MVCBCT imaging. Conventional CT scans of phantoms and patients were imported into a commercial treatment planning system (TPS: Phillips, Pinnacle) and an arc treatment mimicking the MVCBCT acquisition process was generated to compute the delivered acquisition dose. To validate the dose obtained from the TPS, a simple water-equivalent cylindrical phantom with spaces for MOSFETs and an ion chamber was used to measure the MVCBCT image acquisition dose. Absolute dose distributions were obtained by simulating MVCBCTs of 9 and 5 monitor units (MU) on pelvis and head and neck patients, respectively. A compensation factor was introduced to generate composite plans of treatment and MVCBCT imaging dose. The article provides a simple equation to compute the compensation factor. The developed imaging compensation method was tested on routinely used clinical plans for prostate and head and neck patients. The quantitative comparison between the calculated dose by the TPS and measurement points on the cylindrical phantom were all within 3%. The dose percentage difference for the ion chamber placed in the center of the phantom was only 0.2%. For a typical MVCBCT, the dose delivered to patients forms a small anterior-posterior gradient ranging from 0.6 to 1.2 cGy per MVCBCT MU. MVCBCT acquisitions in the pelvis and head and neck areas deliver slightly more dose than current portal imaging but render soft tissue information for positioning. Overall, the additional dose from daily 9 MU MVCBCTs of prostate patients is small compared to the treatment dose (<4%). Dose-volume histograms of compensated plans for pelvis and head and neck patients imaged daily with MVCBCT showed no additional dose to the target and small increases at low doses. The results indicate that the dose delivered for MVCBCT imaging can be precisely calculated in the TPS and therefore included in the treatment plan. This allows simple plan compensations, such as slightly reducing the treatment dose, to minimize the total dose received by critical structures from daily positioning with MVCBCT. The proposed compensation factor reduces the number of MU per treatment beam per fraction. Both the number of fractions and the beam arrangement are kept unchanged. Reducing the imaging volume in the cranio-caudal direction can further reduce the dose delivered for MVCBCT. This is a useful feature to eliminate the imaging dose to the eyes or to focus on a specific region of interest for alignment.

Receiver operating curves and dose-volume analysis of late toxicity with stereotactic body radiation therapy for prostate cancer.

PURPOSE: The purpose of this study was to evaluate a receiver operating characteristic (ROC) curve method to determine dose thresholds with late genitourinary (GU) toxicity after stereotactic body radiation therapy for prostate cancer. METHODS AND MATERIALS: Seventy-eight patients diagnosed with low- to intermediate-risk prostate cancer and treated with stereotactic body radiation therapy alone were reviewed retrospectively. All patients received a total dose of 38 Gy in 4 fractions with a planning target volume expansion of 2 mm. GU toxicity was documented according to the Common Terminology Criteria for Adverse Events, version 4. ROC analysis applied on a logistic regression model was used to determine optimal dosimetric parameters for GU toxicity. RESULTS: The median age at treatment was 69 years with a median prostate volume of 46.2 mL. The median prescription isodose line was 67% (interquartile range, 65, 70). The median clinical follow-up was 35.49 months. Late grade 1, 2, and 3 GU toxicity occurred in 21.8%, 19.2%, and 2.6% of cases, respectively. Late grade 2+ GU toxicity was associated with prescription to isodose line (P = .009) and normalized volumes for heterogeneity ≥46 Gy. The ROC method successfully produced thresholds for dose-volume recommendations for both prostate and urethra, including normalized prostate volumes from 46 to 50 Gy, such as volume of target tissue receiving 46% of the prescribed dose (V46) Gy of 36.7% (sensitivity, 71%; specificity, 61%; area under the curve, 0.67) with an associated probability of late GU grade 2+ toxicity of 21%. CONCLUSIONS: Intraprostatic heterogeneity should be controlled with potential thresholds at V46 Gy <36.7%, V48 Gy <21%, and V50 Gy <9.5% of the normalized prostate volume to keep late grade 2+ GU toxicity ≤20% with 4-fraction schemes. This may be facilitated with a higher prescription isodose line (>69%).

An Evaluation of Robotic and Conventional IMRT for Prostate Cancer: Potential for Dose Escalation.

This study compares conventional and robotic intensity modulated radiation therapy (IMRT) plans for prostate boost treatments and provides clinical insight into the strengths and weaknesses of each. The potential for dose escalation with robotic IMRT is further investigated using the "critical volume tolerance" method proposed by Roach et al. Three clinically acceptable treatment plans were generated for 10 prostate boost patients: (1) a robotic IMRT plan using fixed cones, (2) a robotic IMRT plan using the Iris variable aperture collimator, and (3) a conventional linac based IMRT (c-IMRT) plan. Target coverage, critical structure doses, homogeneity, conformity, dose fall-off, and treatment time, were compared across plans. The average bladder and rectum V75 was 17.1%, 20.0%, and 21.4%, and 8.5%, 11.9%, and 14.1% for the Iris, fixed, and c-IMRT plans, respectively. On average the conformity index (nCI) was 1.20, 1.30, and 1.46 for the Iris, fixed, and c-IMRT plans. Differences between the Iris and the c-IMRT plans were statistically significant for the bladder V75 (P= .016), rectum V75 (P= .0013), and average nCI (P =.002). Dose to normal tissue in terms of R50 was 4.30, 5.87, and 8.37 for the Iris, fixed and c-IMRT plans, respectively, with statistically significant differences between the Iris and c-IMRT (P = .0013) and the fixed and c-IMRT (P = .001) plans. In general, the robotic IMRT plans generated using the Iris were significantly better compared to c-IMRT plans, and showed average dose gains of up to 34% for a critical rectal volume of 5%.

Respiration-Induced Intraorgan Deformation of the Liver: Implications for Treatment Planning in Patients Treated With Fiducial Tracking.

Stereotactic body radiation therapy is a well-tolerated modality for the treatment of primary and metastatic liver lesions, and fiducials are often used as surrogates for tumor tracking during treatment. We evaluated respiratory-induced liver deformation by measuring the rigidity of the fiducial configuration during the breathing cycle. Seventeen patients, with 18 distinct treatment courses, were treated with stereotactic body radiosurgery using multiple fiducials. Liver deformation was empirically quantified by measuring the intrafiducial distances at different phases of respiration. Data points were collected at the 0%, 50%, and 100% inspiration points, and the distance between each pair of fiducials was measured at the 3 phases. The rigid body error was calculated as the maximum difference in the intrafiducial distances. Liver disease was calculated with Child-Pugh score using laboratory values within 3 months of initiation of treatment. A peripheral fiducial was defined as within 1.5 cm of the liver edge, and all other fiducials were classified as central. For 5 patients with only peripheral fiducials, the fiducial configuration had more deformation (average maximum rigid body error 7.11 mm, range: 1.89-11.35 mm) when compared to patients with both central and peripheral and central fiducials only (average maximum rigid body error 3.36 mm, range: 0.5-9.09 mm, P = .037). The largest rigid body errors (11.3 and 10.6 mm) were in 2 patients with Child-Pugh class A liver disease and multiple peripheral fiducials. The liver experiences internal deformation, and the fiducial configuration should not be assumed to act as a static structure. We observed greater deformation at the periphery than at the center of the liver. In our small data set, we were not able to identify cirrhosis, which is associated with greater rigidity of the liver, as predictive for deformation. Treatment planning based only on fiducial localization must take potential intraorgan deformation into account.