Multiparametric Magnetic Resonance Imaging- Guided Dose-Escalated Radiation Therapy for Localized Prostate Cancer: A Prospective Phase 2 Trial.

PURPOSE: This trial's purpose was to determine the late toxicity associated with dose escalation to Prostate Imaging Reporting and Data System (PI-RADS) III-V lesions on multiparametric magnetic resonance imaging (MRI) with an image guided combined IMRT-stereotactic body radiation therapy (SBRT) approach in men with localized prostate cancer. METHODS AND MATERIALS: In this phase 2 trial patients with localized prostate cancer with clinical tumor stage T1-T3bN0 and at least one PIRADS III-V lesion were recruited to receive 45 Gy in 25 fractions to the prostate and seminal vesicles followed by a boost of 18 Gy in 3 fractions to the prostate with a simultaneous integrated boost 21 Gy in 3 fractions to the PI-RADS lesion(s). The primary endpoint was the cumulative incidence of late grade ≥3 genitourinary and gastrointestinal toxicity by 18 months (National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0). RESULTS: Overall, 50 patients were enrolled in this study, and 43 patients completed at least 18 months of follow-up. The cumulative incidence of grade 1, 2, and 3 late genitourinary toxicity at 18 months was 18%, 53%, and 2%. One patient was noted to have grade 3 hematuria and needed cystoscopy-guided cauterization. No acute grade 3 gastrointestinal or genitourinary toxicities were observed. The cumulative incidence of grade 1, 2, and 3 late gastrointestinal toxicity at 18 months was 31%, 4%, and 0%, respectively. At a median follow-up of 43.5 months, 3 patients developed biochemical recurrence, each with distant bone metastases without local or nodal recurrence. At 3 years, freedom from biochemical failure rate was 95.3% (95% CI, 89.2%-100%). CONCLUSIONS: Multiparametric MRI-guided dose escalation to PI-RADS III-V lesions using a combined image guided IMRT-SBRT approach is associated with an acceptable risk of late gastrointestinal and genitourinary toxicity. The results should be interpreted with caution considering their single institutional nature, small sample size, and short follow-up and should be validated in a larger study.

A novel use of 3D-printed template in vaginal HDR brachytherapy.

PURPOSE: The High-Dose-Rate (HDR) vaginal cylinder treatment is typically designed using the initial CT, while the subsequent implants are verified using rudimentary methods (i.e., visual inspection, ruler measurements, etc.) and/or X-ray imaging. We are proposing the use of a 3D-printed individualized template that could provide simple and reproducible vaginal cylinder insertion. MATERIAL AND METHODS: Six patients were included in the study with prescriptions of 6 Gy/fraction for 2 to 5 fractions (total 27 treatments). The first 1 to 2 treatments were delivered without the template and the rest with the CT-based 3D-printed templates. Cone beam CTs (CBCTs) were acquired to verify the cylinder placement for all treatments. D2cc of the bladder and rectum are recorded on both planning CT and the following on-treatment CBCTs. RESULTS: By using the templates, the tip position variation on average (±1 SD) reduced from 0.8±0.5 cm to 0.6±0.4 cm, and angular difference decreased from 5.3±3.5° to 4.7±2.4°. The pitch and yaw deviation are reduced from 0.9 ± 5.8° and 0.4±2.9° to 0.0±3.9° and -0.2±3.0°, respectively. The deviation of D2cc to bladder from the plan reduced from 6±4% to 5±3%, and rectum from 5±2% to 4±4%. CONCLUSION: The 3D-printed patient-specific cylinder templates could potentially improve the geometrical reproducibility of cylinder treatments at no cost of additional imaging. The D2cc for the bladder and rectum are determined by the treatment length rather than their respective volumes.

Initial Clinical Experience With Novel Directional Low-Dose Rate Brachytherapy for Retroperitoneal Sarcoma.

BACKGROUND: A novel Palladium-103 low-dose rate (LDR) brachytherapy device was developed to provide dose-escalation to the tumor bed after resection while shielding adjacent tissues. This multicenter report describes the initial experience with this device in patients with retroperitoneal sarcoma (RPS). MATERIALS AND METHODS: Patients with recurrent RPS, prior radiotherapy, and/or concern for positive margins were considered. An LDR brachytherapy dose of 20-60 Gy was administered, corresponding to biologically effective dose values of 15-53 Gy and equivalent dose values of 12-43 Gy. RESULTS: Six patients underwent implantation at four institutions. Of these, five had recurrent disease in the retroperitoneum or pelvic sidewall, one had untreated locally advanced leiomyosarcoma, two had prior external beam radiation therapy at the time of initial diagnosis, and four received neoadjuvant external beam radiation therapy plus brachytherapy. The device was easily implanted and conformed to the treatment area. Median follow-up was 16 mo; radiation was delivered to the at-risk margin with minimal irradiation of adjacent structures. No local recurrences at the site of implantation, device migration, or radiation-related toxicities were observed. CONCLUSIONS: The novel LDR directional brachytherapy device successfully delivered a targeted dose escalation to treat RPS high-risk margins. Lack of radiation-related toxicity demonstrates its safety.

Quantitative Medical Physics National Job Data Distribution Analysis.

PURPOSE: The purpose of this study was to investigate the contemporary distribution of medical physics (MP) employment opportunities across the United States. METHODS AND MATERIALS: An annual record (2018-2019) of advertised full-time MP jobs was created using publicly available information from the American Association of Physicists in Medicine and Indeed websites. Listed jobs were categorized based on position name, work experience, job function, and geographic region. To account for regional population differences, a preponderance of employment opportunities per 10 million people was computed. Using Commission on Accreditation of Medical Physics Education Programs residency accreditation data, the nationwide locations of the MP training centers and the number of residency positions per annum were identified. A chi-square goodness-of-fit test was used for statistical analysis. RESULTS: A total of 441 unique MP jobs were identified nationwide per annum (2018-2019). The highest percentage of MP jobs was reported from the South region (33.6%), and the lowest (17.2%) was from the West. Analysis revealed that 148 jobs (33.6%) were academic and 293 (66.4%) were nonacademic. The South had the most academic jobs overall (31.8%), whereas the West had the fewest (13.5%). Regionally, the highest percentage of academic jobs (46.9%) was reported from the Northeast, whereas the West had the lowest percentage (26.3%). The analysis of academic versus nonacademic job comparison by regions showed statistically significant differences (P = .0133). The Midwest and the West regions, respectively, showed the highest (18.2) and lowest (10.24) number of jobs per unit population, measured in 10 million. CONCLUSIONS: To our knowledge, this is one of the first national quantitative job data analyses of MP job distributions. This study revealed the level of demand for qualified candidates in 2018 to 2019, showing an imbalance between academic and nonacademic positions across the regions of the United States. Moreover, the geographic distribution of job listings deviated significantly from expectation given the relative population of each region.

Scatter imaging during lung stereotactic body radiation therapy characterized with phantom studies.

By collecting photons scattered out of the therapy beam, scatter imaging creates images of the treated volume. Two phantoms were used to assess the possible application of scatter imaging for markerless tracking of lung tumors during stereotactic body radiation therapy (SBRT) treatment. A scatter-imaging camera was assembled with a CsI flat-panel detector and a 5 mm diameter pinhole collimator. Scatter images were collected during the irradiation of phantoms with megavoltage photons. To assess scatter image quality, spherical phantom lung tumors of 2.1-2.8 cm diameters were placed inside a static, anthropomorphic phantom. To show the efficacy of the technique with a moving target (3 cm diameter), the position of a simulated tumor was tracked in scatter images during sinusoidal motion (15 mm amplitude, 0.25 Hz frequency) in a dynamic lung phantom in open-field, dynamic conformal arc (DCA), and volumetric modulated arc therapy (VMAT) deliveries. Anatomical features are identifiable on static phantom scatter images collected with 10 MU of delivered dose (2.1 cm diameter lung tumor contrast-to-noise ratio of 4.4). The contrast-to-noise ratio increases with tumor size and delivered dose. During dynamic motion, the position of the 3.0 cm diameter lung tumor was identified with a root-mean-square error of 0.8, 1.2, and 2.9 mm for open field (0.3 s frame integration), DCA (0.5 s), and VMAT (0.5 s), respectively. Based on phantom studies, scatter imaging is a potential technique for markerless lung tumor tracking during SBRT without additional imaging dose. Quality scatter images may be collected at low, clinically relevant doses (10 MU). Scatter images are capable of sub-millimeter tracking precision, but modulation decreases accuracy.

Heart dose and coronary artery calcification in patients receiving thoracic irradiation for lung cancer.

BACKGROUND: Thoracic irradiation (TIR) is associated with an increased risk of coronary artery disease (CAD) and coronary-related death. Lung cancer patients receive considerable doses of TIR, making them a high-risk population that may benefit from post-therapy surveillance. Coronary artery calcium (CAC) is a known biomarker of CAD development and may serve as a useful indicator of disease progression in this population. We hypothesized greater CAC progression in lung cancer patients subjected to higher whole heart radiation doses. METHODS: CAC progression (pre- and >2 years post-TIR) from chest CT scans of lung cancer patients were evaluated. A 2:1 matched control population was established controlling for age, gender, race, and CT scan interval. Vessel-specific CAC presence, progression, and extension in pre- and post-interval CT studies was evaluated by two blinded reviewers using the ordinal method. Dosimetric treatment files were restored and contours of the whole heart and proximal left anterior descending artery (LAD) were created within existing plans to compute radiation doses (Pinnacle Treatment Planning Software). Binary logistic regression analysis identified factors predictive for CAC development. Multiple logistic regression analysis with hierarchal method was used to assess covariates. RESULTS: Thirty-five patients and 65 controls (50% female) were evaluated; mean age 57 years, mean follow-up post-radiation 4.9±2.2 years. Average mean and maximum left anterior descending coronary artery (LAD) radiation doses were 19.9 Gy (95% CI, 14.1-25.7) and 30.7 Gy (95% CI, 23.8-37.5), respectively; 91.6% inter-observer variability. There was greater incidence of coronary calcification in irradiated patients (48.6% vs. 24.6%; P=0.01). In interval CT scans, a greater proportion of radiated patients demonstrated new coronary calcification (P=0.007) and extension within the LAD (P=0.003). Radiation exposure was the only independent predictor of new calcification (OR 3.1; 95% CI: 1.09-9.2). CONCLUSIONS: We identified both an increase in the development and progression of CAC in lung cancer patients receiving TIR. Future studies utilizing alternative cancer populations and larger sample sizes are necessary to further correlate radiographic and dosimetric observations to cardiovascular events.

Compton scatter imaging: A promising modality for image guidance in lung stereotactic body radiation therapy.

PURPOSE: Lung stereotactic body radiation therapy (SBRT) requires delivering large radiation doses with millimeter accuracy, making image guidance essential. An approach to forming images of patient anatomy from Compton-scattered photons during lung SBRT is presented. METHODS: To investigate the potential of scatter imaging, a pinhole collimator and flat-panel detector are used for spatial localization and detection of photons scattered during external beam therapy using lung SBRT treatment conditions (6 MV FFF beam). MCNP Monte Carlo software is used to develop a model to simulate scatter images. This model is validated by comparing experimental and simulated phantom images. Patient scatter images are then simulated from 4DCT data. RESULTS: Experimental lung tumor phantom images have sufficient contrast-to-noise to visualize the tumor with as few as 10 MU (0.5 s temporal resolution). The relative signal intensity from objects of different composition as well as lung tumor contrast for simulated phantom images agree quantitatively with experimental images, thus validating the Monte Carlo model. Scatter images are shown to display high contrast between different materials (lung, water, bone). Simulated patient images show superior (~double) tumor contrast compared to MV transmission images. CONCLUSIONS: Compton scatter imaging is a promising modality for directly imaging patient anatomy during treatment without additional radiation, and it has the potential to complement existing technologies and aid tumor tracking and lung SBRT image guidance.

Acoustic-based proton range verification in heterogeneous tissue: simulation studies.

Acoustic-based proton range verification (protoacoustics) is a potential in vivo technique for determining the Bragg peak position. Previous measurements and simulations have been restricted to homogeneous water tanks. Here, a CT-based simulation method is proposed and applied to a liver and prostate case to model the effects of tissue heterogeneity on the protoacoustic amplitude and time-of-flight range verification accuracy. For the liver case, posterior irradiation with a single proton pencil beam was simulated for detectors placed on the skin. In the prostate case, a transrectal probe measured the protoacoustic pressure generated by irradiation with five separate anterior proton beams. After calculating the proton beam dose deposition, each CT voxel's material properties were mapped based on Hounsfield Unit values, and thermoacoustically-generated acoustic wave propagation was simulated with the k-Wave MATLAB toolbox. By comparing the simulation results for the original liver CT to homogenized variants, the effects of heterogeneity were assessed. For the liver case, 1.4 cGy of dose at the Bragg peak generated 50 mPa of pressure (13 cm distal), a 2× lower amplitude than simulated in a homogeneous water tank. Protoacoustic triangulation of the Bragg peak based on multiple detector measurements resulted in 0.4 mm accuracy for a δ-function proton pulse irradiation of the liver. For the prostate case, higher amplitudes are simulated (92-1004 mPa) for closer detectors (<8 cm). For four of the prostate beams, the protoacoustic range triangulation was accurate to ⩽1.6 mm (δ-function proton pulse). Based on the results, application of protoacoustic range verification to heterogeneous tissue will result in decreased signal amplitudes relative to homogeneous water tank measurements, but accurate range verification is still expected to be possible.

Dosimetric effects of saline- versus water-filled balloon applicators for IORT using the model S700 electronic brachytherapy source.

PURPOSE: The Xoft Axxent Electronic Brachytherapy System (Xoft, Inc., San Jose, CA) is a viable option for intraoperative radiation therapy (IORT) treatment of early-stage breast cancer. The low-energy (50-kVp) X-ray source simplifies shielding and increases relative biological effectiveness but increases dose distribution sensitivity to medium composition. Treatment planning systems typically assume homogenous water for brachytherapy dose calculations, including precalculated atlas plans for Xoft IORT. However, Xoft recommends saline for balloon applicator filling. This study investigates dosimetric differences due to increased effective atomic number (Zeff) for saline (Zeff = 7.56) versus water (Zeff = 7.42). METHODS: Balloon applicator diameters range from 3 to 6 cm. Monte Carlo N-Particle software is used to calculate dose at the surface (Ds) of and 1 cm away (D1cm) from the water-/saline-filled balloon applicator using a single dwell at the applicator center as a simple estimation of the dosimetry and multiple dwells simulating the clinical dose distributions for the atlas plans. RESULTS: Single-dwell plans show a 4.4-6.1% decrease in Ds for the 3- to 6-cm diameter applicators due to the saline. Multidwell plans show similar results: 4.9% and 6.4% Ds decrease, for 4-cm and 6-cm diameter applicators, respectively. For the single-dwell plans, D1cm decreases 3.6-5.2% for the 3- to 6-cm diameter applicators. For the multidwell plans, D1cm decreases 3.3% and 5.3% for the 4-cm and 6-cm applicators, respectively. CONCLUSIONS: The dosimetric effect introduced by saline versus water filling for Xoft balloon applicator-based IORT treatments is ∼5%. Users should be aware of this in the context of both treatment planning and patient outcome studies.

A model for predicting the dose to the parotid glands based on their relative overlapping with planning target volumes during helical radiotherapy.

The sparing of the parotid glands in the treatment of head and neck cancers is of clinical relevance as high doses to the salivary glands may result in xerostomia. Xerostomia is a major cause of decreased quality of life for head and neck patients. This paper explores the relationship between the overlap of the target volumes and their expansions with the parotid glands for helical delivery plans and their ability to be spared. Various overlapping volumes were examined, and an overlap with a high statistical relevance was found. A model that predicts exceeding tolerance parotid mean dose based on its fractional overlapping volume with PTVs was developed. A fractional overlapping volume of 0.083 between the parotid gland and the high dose PTV plus 5 mm expansion - was determined to be the threshold value to predict parotid Dmean  > 26 Gy for parotids that overlap with the high dose PTV plus 5 mm expansion. If the parotid gland only overlaps with the intermediate dose target (and/or low dose target) and the overlapping volume of the parotid gland and the intermediate dose target is less than 25%, the parotid mean dose is likely less than 26 Gy. If the parotid overlaps with the low dose target only then the mean dose to the parotid is likely to be less than 26 Gy. This finding will prove as a very useful guide for the physicians and planners involved in the planning process to know prior whether the parotid glands will be able to be spared with the current set of target volumes or if revisions are necessary. This work will serve as a helpful guide in the planning process of head and neck target cases.

Characterization of Compton-scatter imaging with an analytical simulation method.

By collimating the photons scattered when a megavoltage therapy beam interacts with the patient, a Compton-scatter image may be formed without the delivery of an extra dose. To characterize and assess the potential of the technique, an analytical model for simulating scatter images was developed and validated against Monte Carlo (MC). For three phantoms, the scatter images collected during irradiation with a 6 MV flattening-filter-free therapy beam were simulated. Images, profiles, and spectra were compared for different phantoms and different irradiation angles. The proposed analytical method simulates accurate scatter images up to 1000 times faster than MC. Minor differences between MC and analytical simulated images are attributed to limitations in the isotropic superposition/convolution algorithm used to analytically model multiple-order scattering. For a detector placed at 90° relative to the treatment beam, the simulated scattered photon energy spectrum peaks at 140-220 keV, and 40-50% of the photons are the result of multiple scattering. The high energy photons originate at the beam entrance. Increasing the angle between source and detector increases the average energy of the collected photons and decreases the relative contribution of multiple scattered photons. Multiple scattered photons cause blurring in the image. For an ideal 5 mm diameter pinhole collimator placed 18.5 cm from the isocenter, 10 cGy of deposited dose (2 Hz imaging rate for 1200 MU min-1 treatment delivery) is expected to generate an average 1000 photons per mm2 at the detector. For the considered lung tumor CT phantom, the contrast is high enough to clearly identify the lung tumor in the scatter image. Increasing the treatment beam size perpendicular to the detector plane decreases the contrast, although the scatter subject contrast is expected to be greater than the megavoltage transmission image contrast. With the analytical method, real-time tumor tracking may be possible through comparison of simulated and acquired patient images.

Truebeam Radiosurgery for the Treatment of Trigeminal Neuralgia: Preliminary Results at a Single Institution.

INTRODUCTION: Radiosurgery is now an established method of satisfactory pain control in patients with trigeminal neuralgia (TN). The Varian Truebeam STx (Varian Medical Systems, Palo Alto, CA) linear accelerator (LINAC) system is an arc-based, frameless stereotactic radiosurgery system used for the treatment of TN. To our knowledge, there has been only one published series of patient histories that documents the use of a frameless LINAC system for the treatment of TN. We describe the treatment parameters, patient outcomes, and complications associated with the treatment of TN. METHODS: All patients treated with the Truebeam system for TN between 2012 and 2015, with at least a six-month follow-up, were identified. A dose of 90 Gy was delivered to the isocenter using a 0.5 cm diameter cone. The cisternal segment of the trigeminal nerve was placed at the location of the LINAC isocenter using an ExacTrac™ (Brainlab, Munich, Germany) image guidance system. The radiosurgical dose, Barrow Neurologic Institute pain score (BNI PS), symptom recurrence, magnetic resonance imaging (MRI) radiographic changes, and other complications, including Barrow Neurologic Institute facial numbness score (BNI FN), were analyzed. RESULTS: A total of 18 patients-15 women and 3 men-with a mean age of 58 years (median: 59 years; range: 22-84 years) were treated at our institution. Fourteen patients (78%) had a BNI PS of IIIb or better, which was considered successful treatment. Twelve patients had excellent (BNI PS I) pain relief and two patients had good (BNI PS II-IIIB; recurrence after one year) pain relief. The pain of four patients recurred after a mean of 10 months. CONCLUSION: Truebeam radiosurgery can provide effective and safe treatment for patients suffering from TN. The efficacy appears similar to other frame- and frameless-based systems.

Reporting small bowel dose in cervix cancer high-dose-rate brachytherapy.

Small bowel (SB) is an organ at risk (OAR) that may potentially develop toxicity after radiotherapy for cervix cancer. However, its dose from brachytherapy (BT) is not systematically reported as in other OARs, even with image-guided brachytherapy (IGBT). This study aims to introduce consideration of quantified objectives for SB in BT plan optimization and to evaluate the feasibility of sparing SB while maintaining adequate target coverage. In all, 13 patients were included in this retrospective study. All patients were treated with external beam radiotherapy (EBRT) 45Gy in 25 fractions followed by high dose rate (HDR)-BT boost of 28Gy in 4 fractions using tandem/ring applicator. Magnetic resonance imaging (MRI) and computed tomographic (CT) images were obtained to define the gross tumor volume (GTV), high-risk clinical target volume (HR-CTV) and OARs (rectum, bladder, sigmoid colon, and SB). Treatment plans were generated for each patient using GEC-ESTRO recommendations based on the first CT/MRI. Treatment plans were revised to reduce SB dose when the [Formula: see text] dose to SB was > 5Gy, while maintaining other OAR constraints. For the 7 patients with 2 sets of CT and MRI studies, the interfraction variation of the most exposed SB was analyzed. Plan revisions were done in 6 of 13 cases owing to high [Formula: see text] of SB. An average reduction of 19% in [Formula: see text] was achieved. Meeting SB and other OAR constraints resulted in less than optimal target coverage in 2 patients (D90 of HR-CTV < 77Gyαß10). The highest interfraction variation was observed for SB at 16 ± 59%, as opposed to 28 ± 27% for rectum and 21 ± 16% for bladder. Prospective reporting of SB dose could provide data required to establish a potential correlation with radiation-induced late complication for SB.

The sensitivity of ArcCHECK-based gamma analysis to manufactured errors in helical tomotherapy radiation delivery.

Three-dimensional measurement arrays are an efficient means of acquiring a distribution of data for patient plan delivery QA. However, the tie between plan integrity and traditional gamma-based analysis of these data are not clear. This study explores the sensitivity of such analysis by creating errors in Helical Tomotherapy delivery and measuring the passing rates with an ArcCHECK cylindrical diode array. Errors were introduced in each of the couch speed, leaf open time, and gantry starting position in increasing magnitude while the resulting gamma passing rates were tabulated. The error size required to degrade the gamma passing rate to 90% or below was on average a 3% change in couch speed, 5° in gantry synchronization, or a 5 ms in leaf closing speed for a 3%/3 mm Van Dyk gamma analysis. This varied with plan type, with prostate plans exhibiting less sensitivity than head and neck plans and with gamma analysis criteria, but in all cases the error magnitudes were large compared to actual machine tolerances. These findings suggest that the sensitivity of ArcCHECK-based gamma analysis to single-mode errors in tomotherapy plans is dependent upon plan and analysis type and at traditional passing thresholds unable to detect small defects in the plan.

Patterns of locoregional failure in stage III non-small cell lung cancer treated with definitive chemoradiation therapy.

PURPOSE: Chemoradiation therapy (CRT) is the core treatment of locally advanced non-small cell lung cancer (LA-NSCLC), but potential toxicities limit radiation therapy dose. These toxicities, plus the advent of increasingly conformal radiation therapy, have prioritized target definition and the use of involved-field radiation therapy (IFRT). Published data largely focus on regional rather than local failure patterns. We report our pattern-of-failure experience treating patients with LA-NSCLC with definitive CRT, focusing on both local and regional recurrences with detailed dosimetric analyses of failure location. METHODS AND MATERIALS: Patients treated between December 2004-2010 were included. Imaging scans from date of failure were fused with the RT-planning CT scan, and recurrent nodes were contoured to determine if the recurrence was in a previously irradiated region, defined as involved nodal recurrence (INR) versus elective nodal recurrence (ENR). Local failures were contoured and identified as in-field, marginal, or out-of-field based on dose received. Actuarial overall survival (OS) and progression-free survival (PFS) were calculated, and the cumulative incidences of local, regional, locoregional, and distant recurrence (CILR, CIRR, CILRR, CIDR) were determined with death as a competing risk. RESULTS: One hundred five patients were included with a median survival of 21.8 months. The 3-year OS and PFS were 36% and 22%, respectively. The 3 year CILRR, CILR, CIRR, CIDR were 41%, 38%, 40%, and 58%, respectively. Thirty patients failed regionally, but only 7 patients developed an ENR with no concurrent local failure or INR, and only 1 of these patients did not develop distant metastases within 1 month of recurrence. A total of 21 patients (20%) developed an ENR with or without other areas of recurrence. CONCLUSIONS: Elective regional recurrences rarely occurred as the sole site of failure, despite the use of IFRT. Moreover, the pattern of local failure was entirely in-field. These data strongly support field design focusing on gross nodal and primary disease.

Patterns-of-failure after helical tomotherapy-based chemoradiotherapy for head and neck cancer: implications for CTV margin, elective nodal dose and bilateral parotid sparing.

OBJECTIVES: There is debate about the optimal clinical target volume (CTV) expansion and prophylactic nodal dose (PND) in head and neck IMRT. We evaluated our patterns-of-failure (POF) after helical tomotherapy-based concurrent chemoradiotherapy (CCRT) to assess the oncologic safety of reducing the CTV, PND, and bilateral parotid sparing (BPS). MATERIALS AND METHODS: All patients with locally advanced squamous cell carcinoma of the head and neck treated with curative intent CCRT between January 2007 and April 2013 at a single institution were included in this retrospective study. Locoregional recurrences (LRR) were overlaid on the treatment plan, and POF was determined relative to planned dose. RESULTS: One hundred and fourteen patients treated with CCRT were evaluated, 74% of whom underwent BPS. The median follow-up for surviving patients was 29.3 months. The 3-year cumulative incidence of locoregional failure, distant metastasis, progression-free and overall survival were 20%, 20%, 56% and 73% respectively. The local failures (n = 12) were either entirely contained within or centered on the original gross tumor volume (GTV), and all but 2 regional recurrences were in GTV. There were no nodal failures in the low-dose or peri-parotid neck (including ipsilateral neck). DISCUSSION: Nearly all LRR were located within the GTV suggesting that minimal-to-zero margin is required for CTV 70. The nodal recurrence pattern suggests the safety of routine bilateral parotid sparing and relatively low biologically equivalent dose (54 Gy in 33fx) to the low-risk neck.

Optimization for high-dose-rate brachytherapy of cervical cancer with adaptive simulated annealing and gradient descent.

PURPOSE: To validate an in-house optimization program that uses adaptive simulated annealing (ASA) and gradient descent (GD) algorithms and investigate features of physical dose and generalized equivalent uniform dose (gEUD)-based objective functions in high-dose-rate (HDR) brachytherapy for cervical cancer. METHODS: Eight Syed/Neblett template-based cervical cancer HDR interstitial brachytherapy cases were used for this study. Brachytherapy treatment plans were first generated using inverse planning simulated annealing (IPSA). Using the same dwell positions designated in IPSA, plans were then optimized with both physical dose and gEUD-based objective functions, using both ASA and GD algorithms. Comparisons were made between plans both qualitatively and based on dose-volume parameters, evaluating each optimization method and objective function. A hybrid objective function was also designed and implemented in the in-house program. RESULTS: The ASA plans are higher on bladder V75% and D2cc (p=0.034) and lower on rectum V75% and D2cc (p=0.034) than the IPSA plans. The ASA and GD plans are not significantly different. The gEUD-based plans have higher homogeneity index (p=0.034), lower overdose index (p=0.005), and lower rectum gEUD and normal tissue complication probability (p=0.005) than the physical dose-based plans. The hybrid function can produce a plan with dosimetric parameters between the physical dose-based and gEUD-based plans. The optimized plans with the same objective value and dose-volume histogram could have different dose distributions. CONCLUSIONS: Our optimization program based on ASA and GD algorithms is flexible on objective functions, optimization parameters, and can generate optimized plans comparable with IPSA.

Integral dose delivered to normal brain with conventional intensity-modulated radiotherapy (IMRT) and helical tomotherapy IMRT during partial brain radiotherapy for high-grade gliomas with and without selective sparing of the hippocampus, limbic circuit and neural stem cell compartment.

INTRODUCTION: We compared integral dose with uninvolved brain (IDbrain ) during partial brain radiotherapy (PBRT) for high-grade glioma patients using helical tomotherapy (HT) and seven field traditional inverse-planned intensity-modulated radiotherapy (IMRT) with and without selective sparing (SPA) of contralateral hippocampus, neural stem cell compartment (NSC) and limbic circuit. METHODS: We prepared four PBRT treatment plans for four patients with high-grade gliomas (60 Gy in 30 fractions delivered to planning treatment volume (PTV60Gy)). For all plans, a structure denoted 'uninvolved brain' was created, which included all brain tissue not part of PTV or standard (STD) organs at risk (OAR). No dosimetric constraints were included for uninvolved brain. Selective SPA plans were prepared with IMRT and HT; contralateral hippocampus, NSC and limbic circuit were contoured; and dosimetric constraints were entered for these structures without compromising dose to PTV or STD OAR. We compared V100 and D95 for PTV46Gy and PTV60Gy, and IDbrain for all plans. RESULTS: There were no significant differences in V100 and D95 for PTV46Gy and PTV60Gy. IDbrain was lower in traditional IMRT versus HT plans for STD and SPA plans (mean IDbrain 23.64 Gy vs. 28 Gy and 18.7 Gy vs. 24.5 Gy, respectively) and in SPA versus STD plans both with IMRT and HT (18.7 Gy vs. 23.64 Gy and 24.5 Gy vs. 28 Gy, respectively). CONCLUSIONS: In the setting of PBRT for high-grade gliomas, IMRT reduces IDbrain compared with HT with or without selective SPA of contralateral hippocampus, limbic circuit and NSC, and the use of selective SPA reduces IDbrain compared with STD PBRT delivered with either traditional IMRT or HT.

Patterns of regional failure in stage III non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and resection.

PURPOSE: Treatment of locally advanced non-small cell lung cancer (LA-NSCLC) involves definitive chemoradiation therapy (CRT) or neoadjuvant CRT and resection, but radiation treatment volumes remain in question. With CRT, involved-field radiation therapy (IFRT) is replacing elective nodal irradiation, reducing toxicity, and allowing dose escalation. However, prior reports of IFRT describe failures only after radical CRT; with improved local control after resection, IFRT may lead to more regional recurrences. Our objective is to evaluate pattern-of-failure in patients with LA-NSCLC treated with split-course IFRT, chemotherapy, and subsequent surgery. METHODS AND MATERIALS: Patients treated between December 2004 and 2010 were included. Imaging scans demonstrating failure were fused into the radiation therapy planning computed tomography, and recurrent nodes were contoured to determine pattern-of-failure (involved versus elective nodal failure [INF vs ENF]). Locoregional progression-free survival and distant metastasis-free survival were calculated using Kaplan-Meier methodology. The cumulative incidence of regional recurrence (CIRR) was determined with death as a competing risk. RESULTS: Forty-five patients met inclusion criteria, and patients with RR had a lower rate of pN0 than those without RR (20% vs 60%, P = .02). With a median follow-up of 2.9 years, median survival was not reached, and 3-year locoregional progression-free survival and distant metastasis-free survival were 53% and 35%, respectively. Two and 3-year CIRR were 25% and 33%, respectively. There were no local failures. Thirteen (29%) patients had RR, 8 with INF only and 5 with ENF alone or both, totaling 27 recurrences. Only 2 (4%) ENF occurred without INF, both with distant metastasis, and no elective node was the first and only site of failure. CONCLUSIONS: Our data suggest that IFRT does not compromise regional control in the neoadjuvant management of LA-NSCLC. Tailoring nodal volumes may improve treatment-related morbidity and allow for dose intensification of involved nodes. Further research is necessary to improve regional and distant control.