The role of image-guided intensity modulated proton therapy in glioma.
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ABSTRACT:
SUBMITTER: Grosshans DR
PROVIDER: S-EPMC5463497 | biostudies-literature | 2017 Apr
REPOSITORIES: biostudies-literature
Publications
The role of image-guided intensity modulated proton therapy in glioma.
Grosshans David R DR Mohan Radhe R Gondi Vinai V Shih Helen A HA Mahajan Anita A Brown Paul D PD
Neuro-oncology 20170401 suppl_2
Gliomas represent a broad spectrum of disease with life-expectancy outcomes ranging from months to decades. As our understanding of the molecular profiles of gliomas expands rapidly, practitioners are now better able to identify patients with favorable versus nonfavorable prognoses. Radiation therapy plays a key role in glioma treatment, improving disease control and oftentimes survival. However, for survivors, either long-term or short-term, radiation-induced cognitive impairments may negativel ...[more]
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Project description:PURPOSE:This study reported long-term outcomes of patients with cervical cancer who were treated with intensity modulated radiation therapy and 3-dimensional (3D) image-guided adapted brachytherapy (IMRT/3D-IGABT) compared with those treated with 2-dimensional (2D) external irradiation and 2D brachytherapy (2D EBRT/BT). METHODS AND MATERIALS:This study included patients with newly diagnosed cervical cancer and pretreatment fluorodeoxyglucose positron emission tomography scans who were treated with curative-intent irradiation from 1997 to 2013. The treatment policy changed from using 2D EBRT/BT to IMRT/3D-IGABT in 2005. Patterns of recurrence, cancer-specific survival (CSS), and overall survival (OS) were evaluated. Late gastrointestinal and genitourinary toxicity were scored with National Cancer Institute Common Terminology Criteria for Adverse Events. RESULTS:The median follow-up for patients alive at the time of last follow-up in the 2D EBRT/BT group (n = 300) was 15.3 years (range, 10.8-20.5 years). In the IMRT/3D-IGABT group (n = 300), it was 7 years (range, 5-12.4 years). According to the International Federation of Gynecology and Obstetrics, 33% of tumors were stage IB1 to IB2, 41% were stage IIA to IIB, and 26% were stage IIIA to IVA. The results after 5 years for patients treated with 2D EBRT/BT showed that freedom from relapse (FFR) was 57%, CSS was 62%, and OS was 57%. For the IMRT/3D-IGABT group, the 5-year results showed that FFR was 65% (P = .04), CSS was 69% (P = .01), and OS was 61% (P = .04). When stratified by lymph node status according to positron emission tomography scan results, disease control was most improved with IMRT/3D-IGABT versus 2D EBRT/BT in patients with positive pelvic lymph nodes only (P = .02). Cumulatively, 88 of 600 patients (15%) had grade ?3 late bowel/bladder toxicity. The 2D EBRT/BT group had 55 patients (18%), and the IMRT/3D-IGABT group had 33 patients (11%; P = .02). CONCLUSIONS:IMRT/3D-IGABT was associated with improved survival and decreased gastrointestinal and genitourinary toxicity in patients with cervical cancer compared with those who received 2D EBRT/BT.
| S-EPMC7065668 | biostudies-literature
Project description:This paper presents a concept for a proton therapy system capable of delivering intensity modulated proton therapy using a fan beam of protons. This system would allow present and future gantry-based facilities to deliver state-of-the-art proton therapy with the greater normal tissue sparing made possible by intensity modulation techniques.A method for producing a divergent fan beam of protons using a pair of electromagnetic quadrupoles is described and particle transport through the quadrupole doublet is simulated using a commercially available software package. To manipulate the fan beam of protons, a modulation device is developed. This modulator inserts or retracts acrylic leaves of varying thickness from subsections of the fan beam. Each subsection, or beam channel, creates what effectively becomes a beam spot within the fan area. Each channel is able to provide 0-255 mm of range shift for its associated beam spot, or stop the beam and act as an intensity modulator. Results of particle transport simulations through the quadrupole system are incorporated into the MCNPX Monte Carlo transport code along with a model of the range and intensity modulation device. Several design parameters were investigated and optimized, culminating in the ability to create topotherapy treatment plans using distal-edge tracking on both phantom and patient datasets.Beam transport calculations show that a pair of electromagnetic quadrupoles can be used to create a divergent fan beam of 200 MeV protons over a distance of 2.1 m. The quadrupole lengths were 30 and 48 cm, respectively, with transverse field gradients less than 20 T/m, which is within the range of water-cooled magnets for the quadrupole radii used. MCNPX simulations of topotherapy treatment plans suggest that, when using the distal edge tracking delivery method, many delivery angles are more important than insisting on narrow beam channel widths in order to obtain conformal target coverage. Overall, the sharp distal falloff of a proton depth-dose distribution was found to provide sufficient control over the dose distribution to meet objectives, even with coarse lateral resolution and channel widths as large as 2 cm. Treatment plans on both phantom and patient data show that dose conformity suffers when treatments are delivered from less than approximately ten angles. Treatment time for a sample prostate delivery is estimated to be on the order of 10 min, and neutron production is estimated to be comparable to that found for existing collimated systems.Fan beam proton therapy is a method of delivering intensity modulated proton therapy which may be employed as an alternative to magnetic scanning systems. A fan beam of protons can be created by a set of quadrupole magnets and modified by a dual-purpose range and intensity modulator. This can be used to deliver inversely planned treatments, with spot intensities optimized to meet user defined dose objectives. Additionally, the ability of a fan beam delivery system to effectively treat multiple beam spots simultaneously may provide advantages as compared to spot scanning deliveries.
| S-EPMC3799727 | biostudies-other
Project description:To investigate the feasibility and potential clinical benefit of linear energy transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT).A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose-volume and LET-volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs.The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation.We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in identifying the clinically optimal solution.
| S-EPMC4520412 | biostudies-literature
Project description:Intensity modulated proton therapy (IMPT) is highly sensitive to range uncertainties and uncertainties caused by setup variation. The conventional inverse treatment planning of IMPT optimized based on the planning target volume (PTV) is not often sufficient to ensure robustness of treatment plans. In this paper, a method that takes the uncertainties into account during plan optimization is used to mitigate the influence of uncertainties in IMPT.The authors use the so-called "worst-case robust optimization" to render IMPT plans robust in the face of uncertainties. For each iteration, nine different dose distributions are computed-one each for ± setup uncertainties along anteroposterior (A-P), lateral (R-L) and superior-inferior (S-I) directions, for ± range uncertainty, and the nominal dose distribution. The worst-case dose distribution is obtained by assigning the lowest dose among the nine doses to each voxel in the clinical target volume (CTV) and the highest dose to each voxel outside the CTV. Conceptually, the use of worst-case dose distribution is similar to the dose distribution achieved based on the use of PTV in traditional planning. The objective function value for a given iteration is computed using this worst-case dose distribution. The objective function used has been extended to further constrain the target dose inhomogeneity.The worst-case robust optimization method is applied to a lung case, a skull base case, and a prostate case. Compared with IMPT plans optimized using conventional methods based on the PTV, our method yields plans that are considerably less sensitive to range and setup uncertainties. An interesting finding of the work presented here is that, in addition to reducing sensitivity to uncertainties, robust optimization also leads to improved optimality of treatment plans compared to the PTV-based optimization. This is reflected in reduction in plan scores and in the lower normal tissue doses for the same coverage of the target volume when subjected to uncertainties.The authors find that the worst-case robust optimization provides robust target coverage without sacrificing, and possibly even improving, the sparing of normal tissues. Our results demonstrate the importance of robust optimization. The authors assert that all IMPT plans should be robustly optimized.
| S-EPMC3281975 | biostudies-other
Project description:PURPOSE:To conduct phase 1 and 2 trials with photon intensity modulated radiation therapy and intensity modulated proton therapy (IMPT) arms to selectively escalate the retroperitoneal sarcoma preoperative radiation dose to tumor volume (clinical target volume [CTV] 2) that is judged to be at a high risk for positive margins and aim to reduce local recurrence. We report on the IMPT study arm in phase 1. METHODS AND MATERIALS:Patients aged ?18 years with primary or locally recurrent retroperitoneal sarcoma were treated with preoperative IMPT, 50.4 GyRBE in 28 fractions, to CTV1 (gross tumor volume and adjacent tissues at risk of subclinical disease) with a simultaneous integrated boost to CTV2 to doses of 60.2, 61.6, and 63.0 GyRBE in 28 fractions of 2.15, 2.20, and 2.25 GyRBE, respectively. The primary objective of the phase 1 study was to determine the maximum tolerated dose to CTV2, which will be further tested in the phase 2 study. RESULTS:Eleven patients showed increasing IMPT dose levels without acute dose limiting toxicities that prevented dose escalation to maximum tolerated dose. Acute toxicity was generally mild with no radiation interruptions. No unexpected perioperative morbidity was noted. Eight months postoperatively, one patient developed hydronephrosis that was treated by stent with ureter dissected off tumor and received 57.5 GyRBE. Retained ureter(s) was (were) subsequently constrained to 50.4 GyRBE without further problem. With an 18-month median follow-up, there were no local recurrences. CONCLUSIONS:IMPT dose escalation to CTV2 to 63 GyRBE was achieved without acute dose limiting toxicities. The phase 2 study of IMPT will accrue patients to that dose. Parallel intensity modulated radiation therapy phase 1 arm is currently accruing at the initial dose level. Ureters that undergo a high dose radiation and/or surgery are at risk for late hydro-ureter. Future studies will constrain retained ureters to 50.4 GyRBE to avoid ureteral stricture.
| S-EPMC5514168 | biostudies-literature
Project description:PurposeWe compared work outcomes in patients with oropharyngeal cancer (OPC), randomized to intensity-modulated proton (IMPT) versus intensity-modulated photon therapy (IMRT) for chemoradiation therapy (CRT).Patients and methodsIn 147 patients with stage II-IVB squamous cell OPC participating in patient-reported outcomes assessments, a prespecified secondary aim of a randomized phase II/III trial of IMPT (n = 69) versus IMRT (n = 78), we compared absenteeism, presenteeism (i.e., the extent to which an employee is not fully functional at work), and work productivity losses. We used the work productivity and activity impairment questionnaire at baseline (pre-CRT), at the end of CRT, and at 6 months, 1 year, and 2 years. A one-sided Cochran-Armitage test was used to analyze within-arm temporal trends, and a χ2 test was used to compare between-arm differences. Among working patients, at each follow-up point, a 1-sided Wilcoxon rank-sum test was used to compare work-productivity scores.ResultsPatient characteristics in IMPT versus IMRT arms were similar. In the IMPT arm, within-arm analysis demonstrated that an increasing proportion of patients resumed working after IMPT, from 60% (40 of 67) pre-CRT and 71% (30 of 42) at 1 year to 78% (18 of 23) at 2 years (P = 0.025). In the IMRT arm, the proportion remained stable, with 57% (43 of 76) pre-CRT, 54% (21 of 39) at 1 year, and 52% (13 of 25) working at 2 years (P = 0.47). By 2 years after CRT, the between-arm difference between patients who had IMPT and those who had IMRT trended toward significance (P = 0.06). Regardless of treatment arm, among working patients, the most severe work impairments occurred from treatment initiation to the end of CRT, with significant recovery from absenteeism, presenteeism, and productivity impairments by the 2-year follow-up (P < 0.001 for all). Higher magnitudes of recovery from absenteeism (at 1 year, P = 0.05; and at 2 years, P = 0.04) and composite work impairment scores (at 1 year, P = 0.04; and at 2 years, P = 0.04) were seen in patients treated with IMPT versus those treated with IMRT.ConclusionIn patients with OPC receiving curative CRT, patients randomized to IMPT demonstrated increasing work and productivity recovery trends. Studies are needed to identify mechanisms underlying head and neck CRT treatment causing work disability and impairment.
| S-EPMC8270077 | biostudies-literature
Project description:To report the early clinical outcomes of combining intensity-modulated radiation therapy (IMRT) and intensity-modulated proton therapy (IMPT) in comparison with IMRT alone in treating oropharynx cancer (OPC) patients. The medical records of 148 OPC patients who underwent definitive radiotherapy (RT) with concurrent systemic therapy, from January 2016 till December 2019 at Samsung Medical Center, were retrospectively reviewed. During the 5.5 weeks' RT course, the initial 16 (or 18) fractions were delivered by IMRT in all patients, and the subsequent 12 (or 10) fractions were either by IMRT in 81 patients (IMRT only) or by IMPT in 67 (IMRT/IMPT combination), respectively, based on comparison of adaptive re-plan profiles and availability of equipment. Propensity-score matching (PSM) was done on 76 patients (38 from each group) for comparative analyses. With the median follow-up of 24.7 months, there was no significant difference in overall survival and progression free survival between groups, both before and after PSM. Before PSM, the IMRT/IMPT combination group experienced grade ≥ 3 acute toxicities less frequently: mucositis in 37.0% and 13.4% (p < 0.001); and analgesic quantification algorithm (AQA) in 37.0% and 19.4% (p = 0.019), respectively. The same trends were observed after PSM: mucositis in 39.5% and 15.8% (p = 0.021); and AQA in 47.4% and 21.1% (p = 0.016), respectively. In multivariate logistic regression, grade ≥ 3 mucositis was significantly less frequent in the IMRT/IMPT combination group, both before and after PSM (p = 0.027 and 0.024, respectively). AQA score ≥ 3 was also less frequent in the IMRT/IMPT combination group, both before and after PSM (p = 0.085 and 0.018, respectively). In treating the OPC patients, with comparable early oncologic outcomes, more favorable acute toxicity profiles were achieved following IMRT/IMPT combination than IMRT alone.
| S-EPMC8037748 | biostudies-literature
Project description:We compared mandibular doses and osteoradionecrosis in patients with oropharyngeal cancer after intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT).We identified 584 patients who received definitive radiotherapy for oropharyngeal cancer from January 2011 through June 2014 at MD Anderson Cancer Center (534 IMRT and 50 IMPT). The dosimetric variables and osteoradionecrosis were compared with Chi-square test or Fisher's exact test.Median follow-up time for all patients (534 IMRT and IMPT) was 33.8months (33.8months IMRT vs. 34.6months IMPT, P=0.854), and median time to osteoradionecrosis was 11.4months (range 6.74-16.1months). Mandibular doses were lower for patients treated with IMPT (minimum 0.8 vs. 7.3Gy; mean 25.6 vs. 41.2Gy; P<0.001), and osteoradionecrosis rates were lower as well: 2% IMPT (1 grade 1), 7.7% IMRT (12 grade 4, 5 grade 3, 1 grade 2 and 23 grade 1). Osteoradionecrosis location depended on the primary tumor site and high-dose field in the mandible.Osteoradionecrosis events were significantly associated with higher dose irradiation to mandibular. Use of IMPT minimized excess irradiation of the mandible and consequently reduced the risk of osteoradionecrosis for oropharyngeal cancer.
| S-EPMC5779856 | biostudies-literature
Project description:PURPOSE:To investigate the consequences of residual setup error on target dose distribution using various image registration strategies for breast cancer treated with intensity-modulated proton therapy (IMPT). MATERIALS AND METHODS:Among 11 post-lumpectomy patients who received IMPT, 44 dose distributions were computed. For each patient, the original plan (Plan-O) and three verification plans were calculated using different alignments: bony anatomy (VPlan-B), breast tissue (VPlan-T), and skin (VPlan-S). The target coverage were evaluated for each alignment technique. Additionally, 2 subvolumes-BreastNearSkin (1-cm rim of anterior CTV) and BreastNearCW (1-cm rim of posterior CTV)-were created to help localize CTV underdosing. Furthermore, we divided the setup error into the posture error and breast error. Patients with a large posture error and those with good posture setup but a large breast error were identified to evaluate the effect of posture error and breast error. RESULTS:For Plan-O, VPlan-B, VPlan-T, and VPlan-S, respectively, the median (interquartile range) breast CTV D95 was 95.7%(94.7-96.3%), 95.1% (93.9-95.7%), 95.2% (94.8-95.6%), and 95.2% (94.9-95.7%); BreastNearCW D95 was 96.9% (95.6-97.3%), 94.8% (93.5-97.0%), 95.6% (94.8-97.0%), 95.6% (94.8-97.1%); and BreastNearSkin D95 was 94.1% (92.7-94.4%), 93.6% (92.2-94.5%), 93.5% (92.4-94.5%), and 94.4% (92.2-94.5%) of the prescription dose. 4/11 patients had ?1% decrease in breast CTV D95, 1 of whom developed breast edema while the other 3 all had a?>?2o posture error. The CTV D95 variation was within 1% for the patients with good posture setup but >2o breast error. CONCLUSION:Acceptable target coverage was achieved with all three alignment strategies. Breast tissue and skin alignment maintained the breast target coverage marginally better than bony alignment, with which the posterior CTV along the chest wall is the predominant area affected by under-dosing. For target dose distribution, posture error appears more influential than breast error.
| S-EPMC7045466 | biostudies-literature
Project description:PurposeThe aim of the present study was to compare the dose distribution generated from photon volumetric modulated arc therapy (VMAT), intensity modulated proton therapy (IMPT), and intensity modulated carbon ion therapy (IMCIT) in the delivery of hypo-fractionated thoracic radiotherapy.Methods and materialsTen selected patients who underwent thoracic particle therapy between 2015 and 2016 were re-planned to receive a relative biological effectiveness (RBE) weighted dose of 60 Gy (i.e., GyE) in 15 fractions delivered with VMAT, IMPT, or IMCIT with the same optimization criteria. Treatment plans were then compared.ResultsThere were no significant differences in target volume dose coverage or dose conformity, except improved D95 was found with IMCIT compared with VMAT (p = 0.01), and IMCIT was significantly better than IMPT in all target volume dose parameters. Particle therapy led to more prominent lung sparing at low doses, and this result was most prominent with IMCIT (p < 0.05). Improved sparing of other thoracic organs at risk (OARs) was observed with particle therapy, and IMCIT further lowered the D1cc and D5cc for major blood vessels, as compared with IMPT (p = 0.01).ConclusionAlthough it was comparable to VMAT, IMCIT led to significantly better tumor target dose coverage and conformity than did IMPT. Particle therapy, compared with VMAT, improved thoracic OAR sparing. IMCIT, compared with IMPT, may further improve normal lung and major blood vessel sparing under limited respiratory motion.
| S-EPMC5558745 | biostudies-literature