Engineering topics

Gillin, Michael

Publications and source records attributed to Gillin, Michael.

12 records

DOE OSTI2018

3D treatment planning systemâ€”Varian Eclipse for proton therapy planning

The capabilities of the Eclipse treatment planning system (TPS) (Varian Medical Systems, Palo Alto, CA) for proton therapy treatment planning are described. Various steps involved in the planning process to produce a 3-dimensional (3D) dose distribution both for the passive scattering and pencil beam scanning proton beam therapy are outlined. Mitigation of range and setup uncertainties through robust optimization is discussed. Use of verification plans for patient treatment field dosimetry quality assurance (QA) is presented. Limitations of the Eclipse TPS and future developments are discussed.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2015

Selective robust optimization: A new intensity-modulated proton therapy optimization strategy

Purpose: To develop a new robust optimization strategy for intensity-modulated proton therapy as an important step in translating robust proton treatment planning from research to clinical applications. Methods: In selective robust optimization, a worst-case-based robust optimization algorithm is extended, and terms of the objective function are selectively computed from either the worst-case dose or the nominal dose. Two lung cancer cases and one head and neck cancer case were used to demonstrate the practical significance of the proposed robust planning strategy. The lung cancer cases had minimal tumor motion less than 5 mm, and, for the demonstration of the methodology, are assumed to be static. Results: Selective robust optimization achieved robust clinical target volume (CTV) coverage and at the same time increased nominal planning target volume coverage to 95.8%, compared to the 84.6% coverage achieved with CTV-based robust optimization in one of the lung cases. In the other lung case, the maximum dose in selective robust optimization was lowered from a dose of 131.3% in the CTV-based robust optimization to 113.6%. Selective robust optimization provided robust CTV coverage in the head and neck case, and at the same time improved controls over isodose distribution so that clinical requirements may be readily met. Conclusions: Selective robust optimization may provide the flexibility and capability necessary for meeting various clinical requirements in addition to achieving the required plan robustness in practical proton treatment planning settings.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2014

Clinical Implementation of Intensity Modulated Proton Therapy for Thoracic Malignancies

Purpose: Intensity modulated proton therapy (IMPT) can improve dose conformality and better spare normal tissue over passive scattering techniques, but range uncertainties complicate its use, particularly for moving targets. We report our early experience with IMPT for thoracic malignancies in terms of motion analysis and management, plan optimization and robustness, and quality assurance. Methods and Materials: Thirty-four consecutive patients with lung/mediastinal cancers received IMPT to a median 66 Gy(relative biological equivalence [RBE]). All patients were able to undergo definitive radiation therapy. IMPT was used when the treating physician judged that IMPT conferred a dosimetric advantage; all patients had minimal tumor motion (<5 mm) and underwent individualized tumor-motion dose-uncertainty analysis and 4-dimensional (4D) computed tomographic (CT)-based treatment simulation and motion analysis. Plan robustness was optimized by using a worst-case scenario method. All patients had 4D CT repeated simulation during treatment. Results: IMPT produced lower mean lung dose (MLD), lung V{sub 5} and V{sub 20}, heart V{sub 40}, and esophageal V{sub 60} than did IMRT (P<.05) and lower MLD, lung V{sub 20}, and esophageal V{sub 60} than did passive scattering proton therapy (PSPT) (P<.05). D{sub 5} to the gross tumor volume and clinical target volume was higher with IMPT than with intensity modulated radiation therapy or PSPT (P<.05). All cases were analyzed for beam-angle-specific motion, water-equivalent thickness, and robustness. Beam angles were chosen to minimize the effect of respiratory motion and avoid previously treated regions, and the maximum deviation from the nominal dose-volume histogram values was kept at <5% for the target dose and met the normal tissue constraints under a worst-case scenario. Patient-specific quality assurance measurements showed that a median 99% (range, 95% to 100%) of the pixels met the 3% dose/3 mm distance criteria for the γ index. Adaptive replanning was used for 9 patients (26.5%). Conclusions: IMPT using 4D CT-based planning, motion management, and optimization was implemented successfully and met our quality assurance parameters for treating challenging thoracic cancers.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2014

Spot Scanning Proton Therapy for Malignancies of the Base of Skull: Treatment Planning, Acute Toxicities, and Preliminary Clinical Outcomes

Purpose: To describe treatment planning techniques and early clinical outcomes in patients treated with spot scanning proton therapy for chordoma or chondrosarcoma of the skull base. Methods and Materials: From June 2010 through August 2011, 15 patients were treated with spot scanning proton therapy for chordoma (n=10) or chondrosarcoma (n=5) at a single institution. Toxicity was prospectively evaluated and scored weekly and at all follow-up visits according to Common Terminology Criteria for Adverse Events, version 3.0. Treatment planning techniques and dosimetric data were recorded and compared with those of passive scattering plans created with clinically applicable dose constraints. Results: Ten patients were treated with single-field-optimized scanning beam plans and 5 with multifield-optimized intensity modulated proton therapy. All but 2 patients received a simultaneous integrated boost as well. The mean prescribed radiation doses were 69.8 Gy (relative biological effectiveness [RBE]; range, 68-70 Gy [RBE]) for chordoma and 68.4 Gy (RBE) (range, 66-70) for chondrosarcoma. In comparison with passive scattering plans, spot scanning plans demonstrated improved high-dose conformality and sparing of temporal lobes and brainstem. Clinically, the most common acute toxicities included fatigue (grade 2 for 2 patients, grade 1 for 8 patients) and nausea (grade 2 for 2 patients, grade 1 for 6 patients). No toxicities of grades 3 to 5 were recorded. At a median follow-up time of 27 months (range, 13-42 months), 1 patient had experienced local recurrence and a second developed distant metastatic disease. Two patients had magnetic resonance imaging-documented temporal lobe changes, and a third patient developed facial numbness. No other subacute or late effects were recorded. Conclusions: In comparison to passive scattering, treatment plans for spot scanning proton therapy displayed improved high-dose conformality. Clinically, the treatment was well tolerated, and with short-term follow-up, disease control rates and toxicity profiles were favorable.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2014

Multifield Optimization Intensity Modulated Proton Therapy for Head and Neck Tumors: A Translation to Practice

Background: We report the first clinical experience and toxicity of multifield optimization (MFO) intensity modulated proton therapy (IMPT) for patients with head and neck tumors. Methods and Materials: Fifteen consecutive patients with head and neck cancer underwent MFO-IMPT with active scanning beam proton therapy. Patients with squamous cell carcinoma (SCC) had comprehensive treatment extending from the base of the skull to the clavicle. The doses for chemoradiation therapy and radiation therapy alone were 70 Gy and 66 Gy, respectively. The robustness of each treatment plan was also analyzed to evaluate sensitivity to uncertainties associated with variations in patient setup and the effect of uncertainties with proton beam range in patients. Proton beam energies during treatment ranged from 72.5 to 221.8 MeV. Spot sizes varied depending on the beam energy and depth of the target, and the scanning nozzle delivered the spot scanning treatment “spot by spot” and “layer by layer.” Results: Ten patients presented with SCC and 5 with adenoid cystic carcinoma. All 15 patients were able to complete treatment with MFO-IMPT, with no need for treatment breaks and no hospitalizations. There were no treatment-related deaths, and with a median follow-up time of 28 months (range, 20-35 months), the overall clinical complete response rate was 93.3% (95% confidence interval, 68.1%-99.8%). Xerostomia occurred in all 15 patients as follows: grade 1 in 10 patients, grade 2 in 4 patients, and grade 3 in 1 patient. Mucositis within the planning target volumes was seen during the treatment of all patients: grade 1 in 1 patient, grade 2 in 8 patients, and grade 3 in 6 patients. No patient experienced grade 2 or higher anterior oral mucositis. Conclusions: To our knowledge, this is the first clinical report of MFO-IMPT for head and neck tumors. Early clinical outcomes are encouraging and warrant further investigation of proton therapy in prospective clinical trials.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2014

On the interplay effects with proton scanning beams in stage III lung cancer

Purpose: To assess the dosimetric impact of interplay between spot-scanning proton beam and respiratory motion in intensity-modulated proton therapy (IMPT) for stage III lung cancer. Methods: Eleven patients were sampled from 112 patients with stage III nonsmall cell lung cancer to well represent the distribution of 112 patients in terms of target size and motion. Clinical target volumes (CTVs) and planning target volumes (PTVs) were defined according to the authors' clinical protocol. Uniform and realistic breathing patterns were considered along with regular- and hypofractionation scenarios. The dose contributed by a spot was fully calculated on the computed tomography (CT) images corresponding to the respiratory phase that the spot is delivered, and then accumulated to the reference phase of the 4DCT to generate the dynamic dose that provides an estimation of what might be delivered under the influence of interplay effect. The dynamic dose distributions at different numbers of fractions were compared with the corresponding 4D composite dose which is the equally weighted average of the doses, respectively, computed on respiratory phases of a 4DCT image set. Results: Under regular fractionation, the average and maximum differences in CTV coverage between the 4D composite and dynamic doses after delivery of all 35 fractions were no more than 0.2% and 0.9%, respectively. The maximum differences between the two dose distributions for the maximum dose to the spinal cord, heart V40, esophagus V55, and lung V20 were 1.2 Gy, 0.1%, 0.8%, and 0.4%, respectively. Although relatively large differences in single fraction, correlated with small CTVs relative to motions, were observed, the authors' biological response calculations suggested that this interfractional dose variation may have limited biological impact. Assuming a hypofractionation scenario, the differences between the 4D composite and dynamic doses were well confined even for single fraction. Conclusions: Despite the presence of interplay effect, the delivered dose may be reliably estimated using the 4D composite dose. In general the interplay effect may not be a primary concern with IMPT for lung cancers for the authors' institution. The described interplay analysis tool may be used to provide additional confidence in treatment delivery.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2013

Quality of Life and Toxicity From Passively Scattered and Spot-Scanning Proton Beam Therapy for Localized Prostate Cancer

Purpose: To report quality of life (QOL)/toxicity in men treated with proton beam therapy for localized prostate cancer and to compare outcomes between passively scattered proton therapy (PSPT) and spot-scanning proton therapy (SSPT). Methods and Materials: Men with localized prostate cancer enrolled on a prospective QOL protocol with a minimum of 2 years' follow-up were reviewed. Comparative groups were defined by technique (PSPT vs SSPT). Patients completed Expanded Prostate Cancer Index Composite questionnaires at baseline and every 3-6 months after proton beam therapy. Clinically meaningful differences in QOL were defined as ≥0.5 × baseline standard deviation. The cumulative incidence of modified Radiation Therapy Oncology Group grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity and argon plasma coagulation were determined by the Kaplan-Meier method. Results: A total of 226 men received PSPT, and 65 received SSPT. Both PSPT and SSPT resulted in statistically significant changes in sexual, urinary, and bowel Expanded Prostate Cancer Index Composite summary scores. Only bowel summary, function, and bother resulted in clinically meaningful decrements beyond treatment completion. The decrement in bowel QOL persisted through 24-month follow-up. Cumulative grade ≥2 GU and GI toxicity at 24 months were 13.4% and 9.6%, respectively. There was 1 grade 3 GI toxicity (PSPT group) and no other grade ≥3 GI or GU toxicity. Argon plasma coagulation application was infrequent (PSPT 4.4% vs SSPT 1.5%; P=.21). No statistically significant differences were appreciated between PSPT and SSPT regarding toxicity or QOL. Conclusion: Both PSPT and SSPT confer low rates of grade ≥2 GI or GU toxicity, with preservation of meaningful sexual and urinary QOL at 24 months. A modest, yet clinically meaningful, decrement in bowel QOL was seen throughout follow-up. No toxicity or QOL differences between PSPT and SSPT were identified. Long-term comparative results in a larger patient cohort are warranted.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2013

Quality assurance of proton beams using a multilayer ionization chamber system

Purpose: The measurement of percentage depth-dose (PDD) distributions for the quality assurance of clinical proton beams is most commonly performed with a computerized water tank dosimetry system with ionization chamber, commonly referred to as water tank. Although the accuracy and reproducibility of this method is well established, it can be time-consuming if a large number of measurements are required. In this work the authors evaluate the linearity, reproducibility, sensitivity to field size, accuracy, and time-savings of another system: the Zebra, a multilayer ionization chamber system.Methods: The Zebra, consisting of 180 parallel-plate ionization chambers with 2 mm resolution, was used to measure depth-dose distributions. The measurements were performed for scattered and scanned proton pencil beams of multiple energies delivered by the Hitachi PROBEAT synchrotron-based delivery system. For scattered beams, the Zebra-measured depth-dose distributions were compared with those measured with the water tank. The principal descriptors extracted for comparisons were: range, the depth of the distal 90% dose; spread-out Bragg peak (SOBP) length, the region between the proximal 95% and distal 90% dose; and distal-dose fall off (DDF), the region between the distal 80% and 20% dose. For scanned beams, the Zebra-measured ranges were compared with those acquired using a Bragg peak chamber during commissioning.Results: The Zebra demonstrated better than 1% reproducibility and monitor unit linearity. The response of the Zebra was found to be sensitive to radiation field sizes greater than 12.5 × 12.5 cm; hence, the measurements used to determine accuracy were performed using a field size of 10 × 10 cm. For the scattered proton beams, PDD distributions showed 1.5% agreement within the SOBP, and 3.8% outside. Range values agreed within −0.1 ± 0.4 mm, with a maximum deviation of 1.2 mm. SOBP length values agreed within 0 ± 2 mm, with a maximum deviation of 6 mm. DDF values agreed within 0.3 ± 0.1 mm, with a maximum deviation of 0.6 mm. For the scanned proton pencil beams, Zebra and Bragg peak chamber range values demonstrated agreement of 0.0 ± 0.3 mm with a maximum deviation of 1.3 mm. The setup and measurement time for all Zebra measurements was 3 and 20 times less, respectively, compared to the water tank measurements.Conclusions: Our investigation shows that the Zebra can be useful not only for fast but also for accurate measurements of the depth-dose distributions of both scattered and scanned proton beams. The analysis of a large set of measurements shows that the commonly assessed beam quality parameters obtained with the Zebra are within the acceptable variations specified by the manufacturer for our delivery system.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

DOE OSTI2013

Phase 1 Study of Dose Escalation in Hypofractionated Proton Beam Therapy for Non-Small Cell Lung Cancer

Background: Many patients with locally advanced non-small cell lung cancer (NSCLC) cannot undergo concurrent chemotherapy because of comorbidities or poor performance status. Hypofractionated radiation regimens, if tolerable, may provide an option to these patients for effective local control. Methods and Materials: Twenty-five patients were enrolled in a phase 1 dose-escalation trial of proton beam therapy (PBT) from September 2010 through July 2012. Eligible patients had histologically documented lung cancer, thymic tumors, carcinoid tumors, or metastatic thyroid tumors. Concurrent chemotherapy was not allowed, but concurrent treatment with biologic agents was. The dose-escalation schema comprised 15 fractions of 3 Gy(relative biological effectiveness [RBE])/fraction, 3.5 Gy(RBE)/fraction, or 4 Gy(RBE)/fraction. Dose constraints were derived from biologically equivalent doses of standard fractionated treatment. Results: The median follow-up time for patients alive at the time of analysis was 13 months (range, 8-28 months). Fifteen patients received treatment to hilar or mediastinal lymph nodes. Two patients experienced dose-limiting toxicity possibly related to treatment; 1 received 3.5-Gy(RBE) fractions and experienced an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab. The other patient received 4-Gy(RBE) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT. Conclusion: Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures. Phase 2/3 trials are needed to compare the efficacy of this technique with standard treatment for locally advanced NSCLC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2013

Spot-scanning beam proton therapy vs intensity-modulated radiation therapy for ipsilateral head and neck malignancies: A treatment planning comparison

Radiation therapy for head and neck malignancies can have side effects that impede quality of life. Theoretically, proton therapy can reduce treatment-related morbidity by minimizing the dose to critical normal tissues. We evaluated the feasibility of spot-scanning proton therapy for head and neck malignancies and compared dosimetry between those plans and intensity-modulated radiation therapy (IMRT) plans. Plans from 5 patients who had undergone IMRT for primary tumors of the head and neck were used for planning proton therapy. Both sets of plans were prepared using computed tomography (CT) scans with the goals of achieving 100% of the prescribed dose to the clinical target volume (CTV) and 95% to the planning TV (PTV) while maximizing conformity to the PTV. Dose-volume histograms were generated and compared, as were conformity indexes (CIs) to the PTVs and mean doses to the organs at risk (OARs). Both modalities in all cases achieved 100% of the dose to the CTV and 95% to the PTV. Mean PTV CIs were comparable (0.371 IMRT, 0.374 protons, p = 0.953). Mean doses were significantly lower in the proton plans to the contralateral submandibular (638.7 cGy IMRT, 4.3 cGy protons, p = 0.002) and parotid (533.3 cGy IMRT, 48.5 cGy protons, p = 0.003) glands; oral cavity (1760.4 cGy IMRT, 458.9 cGy protons, p = 0.003); spinal cord (2112.4 cGy IMRT, 249.2 cGy protons, p = 0.002); and brainstem (1553.52 cGy IMRT, 166.2 cGy protons, p = 0.005). Proton plans also produced lower maximum doses to the spinal cord (3692.1 cGy IMRT, 2014.8 cGy protons, p = 0.034) and brainstem (3412.1 cGy IMRT, 1387.6 cGy protons, p = 0.005). Normal tissue V{sub 10}, V{sub 30}, and V{sub 50} values were also significantly lower in the proton plans. We conclude that spot-scanning proton therapy can significantly reduce the integral dose to head and neck critical structures. Prospective studies are underway to determine if this reduced dose translates to improved quality of life.

61 RADIATION PROTECTION AND DOSIMETRY↗

DOE OSTI2012

Long-Term Results of an RTOG Phase II Trial (00-19) of External-Beam Radiation Therapy Combined With Permanent Source Brachytherapy for Intermediate-Risk Clinically Localized Adenocarcinoma of the Prostate

Purpose: External-beam radiation therapy combined with low-doserate permanent brachytherapy are commonly used to treat men with localized prostate cancer. This Phase II trial was performed to document late gastrointestinal or genitourinary toxicity as well as biochemical control for this treatment in a multi-institutional cooperative group setting. This report defines the long-term results of this trial. Methods and Materials: All eligible patients received external-beam radiation (45 Gy in 25 fractions) followed 2-6 weeks later by a permanent iodine 125 implant of 108 Gy. Late toxicity was defined by the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme. Biochemical control was defined by the American Society for Therapeutic Radiology and Oncology (ASTRO) Consensus definition and the ASTRO Phoenix definition. Results: One hundred thirty-eight patients were enrolled from 20 institutions, and 131 were eligible. Median follow-up (living patients) was 8.2 years (range, 2.7-9.3 years). The 8-year estimate of late grade >3 genitourinary and/or gastrointestinal toxicity was 15%. The most common grade >3 toxicities were urinary frequency, dysuria, and proctitis. There were two grade 4 toxicities, both bladder necrosis, and no grade 5 toxicities. In addition, 42% of patients complained of grade 3 impotence (no erections) at 8 years. The 8-year estimate of biochemical failure was 18% and 21% by the Phoenix and ASTRO consensus definitions, respectively. Conclusion: Biochemical control for this treatment seems durable with 8 years of follow-up and is similar to high-dose external beam radiation alone or brachytherapy alone. Late toxicity in this multi-institutional trial is higher than reports from similar cohorts of patients treated with high-dose external-beam radiation alone or permanent low-doserate brachytherapy alone, perhaps suggesting further attention to strategies that limit doses to normal structures or to unimodal radiotherapy techniques.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2011

Long-Term Results of a Phase II Trial of Ultrasound-Guided Radioactive Implantation of the Prostate for Definitive Management of Localized Adenocarcinoma of the Prostate (RTOG 98-05)

Purpose: To evaluate the long-term effectiveness of transrectal ultrasound-guided permanent radioactive I{sup 125} implantation of the prostate for organ confined adenocarcinoma of the prostate compared with historical data of prostatectomy and external beam radiotherapy within a cooperative group setting. Methods and Materials: Patients accrued to this study had histologically confirmed, locally confined adenocarcinoma of the prostate clinical stage T1b, T1c, or T2a; no nodal or metastatic disease; prostate-specific antigen level of {<=}10 ng/ml; and a Gleason score of {<=}6. All patients underwent transrectal ultrasound-guided radioactive I{sup 125} seed implantation into the prostate. The prescribed dose was 145 Gy to the prostate planning target volume. Results: A total of 101 patients from 27 institutions were accrued to this protocol; by design, no single institution accrued more than 8 patients. There were 94 eligible patients. The median follow up was 8.1 years (range, 0.1-9.2 years). After 8 years, 8 patients had protocol-defined biochemical (prostate-specific antigen) failure (cumulative incidence, 8.0%); 5 patients had local failure (cumulative incidence, 5.5%); and 1 patient had distant failure (cumulative incidence, 1.1%; this patient also had biochemical failure and died of causes not related to prostate cancer). The 8-year overall survival rate was 88%. At last follow-up, no patient had died of prostate cancer or related toxicities. Three patients had maximum late toxicities of Grade 3, all of which were genitourinary. No Grade 4 or 5 toxicities were observed. Conclusions: The long-term results of this clinical trial have demonstrated that this kind of trial can be successfully completed through the RTOG and that results in terms of biochemical failure and toxicity compare very favorably with other brachytherapy published series as well as surgical and external beam radiotherapy series. In addition, the prospective, multicenter design highlights the probable generalizability of the outcomes.

62 RADIOLOGY AND NUCLEAR MEDICINE↗