Dataset Information

Robust Intensity Modulated Proton Therapy (IMPT) Increases Estimated Clinical Benefit in Head and Neck Cancer Patients.

ABSTRACT:

Purpose

To compare the clinical benefit of robust optimized Intensity Modulated Proton Therapy (minimax IMPT) with current photon Intensity Modulated Radiation Therapy (IMRT) and PTV-based IMPT for head and neck cancer (HNC) patients. The clinical benefit is quantified in terms of both Normal Tissue Complication Probability (NTCP) and target coverage in the case of setup and range errors.

Methods and materials

For 10 HNC patients, PTV-based IMRT (7 fields), minimax and PTV-based IMPT (2, 3, 4, 5 and 7 fields) plans were tested on robustness. Robust optimized plans differed from PTV-based plans in that they target the CTV and penalize possible error scenarios, instead of using the static isotropic CTV-PTV margin. Perturbed dose distributions of all plans were acquired by simulating in total 8060 setup (±3.5 mm) and range error (±3%) combinations. NTCP models for xerostomia and dysphagia were used to predict the clinical benefit of IMPT versus IMRT.

Results

The robustness criterion was met in the IMRT and minimax IMPT plans in all error scenarios, but this was only the case in 1 of 40 PTV-based IMPT plans. Seven (out of 10) patients had relatively large NTCP reductions in minimax IMPT plans compared to IMRT. For these patients, xerostomia and dysphagia NTCP values were reduced by 17.0% (95% CI; 13.0-21.1) and 8.1% (95% CI; 4.9-11.2) on average with minimax IMPT. Increasing the number of fields did not contribute to plan robustness, but improved organ sparing.

Conclusions

The estimated clinical benefit in terms of NTCP of robust optimized (minimax) IMPT is greater than that of IMRT and PTV-based IMPT in HNC patients. Furthermore, the target coverage of minimax IMPT plans in the presence of errors was comparable to IMRT plans.

SUBMITTER: van Dijk LV

PROVIDER: S-EPMC4816406 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Robust Intensity Modulated Proton Therapy (IMPT) Increases Estimated Clinical Benefit in Head and Neck Cancer Patients.

van Dijk Lisanne V LV Steenbakkers Roel J H M RJ ten Haken Bennie B van der Laan Hans Paul HP van 't Veld Aart A AA Langendijk Johannes A JA Korevaar Erik W EW

PloS one 20160331 3

<h4>Purpose</h4>To compare the clinical benefit of robust optimized Intensity Modulated Proton Therapy (minimax IMPT) with current photon Intensity Modulated Radiation Therapy (IMRT) and PTV-based IMPT for head and neck cancer (HNC) patients. The clinical benefit is quantified in terms of both Normal Tissue Complication Probability (NTCP) and target coverage in the case of setup and range errors.<h4>Methods and materials</h4>For 10 HNC patients, PTV-based IMRT (7 fields), minimax and PTV-based I ...[more]

PMID: 27030987

Similar Datasets

Project description:Intensity-modulated proton therapy (IMPT) is highly sensitive to uncertainties in beam range and patient setup. Conventionally, these uncertainties are dealt using geometrically expanded planning target volume (PTV). In this paper, the authors evaluated a robust optimization method that deals with the uncertainties directly during the spot weight optimization to ensure clinical target volume (CTV) coverage without using PTV. The authors compared the two methods for a population of head and neck (H&N) cancer patients.Two sets of IMPT plans were generated for 14 H&N cases, one being PTV-based conventionally optimized and the other CTV-based robustly optimized. For the PTV-based conventionally optimized plans, the uncertainties are accounted for by expanding CTV to PTV via margins and delivering the prescribed dose to PTV. For the CTV-based robustly optimized plans, spot weight optimization was guided to reduce the discrepancy in doses under extreme setup and range uncertainties directly, while delivering the prescribed dose to CTV rather than PTV. For each of these plans, the authors calculated dose distributions under various uncertainty settings. The root-mean-square dose (RMSD) for each voxel was computed and the area under the RMSD-volume histogram curves (AUC) was used to relatively compare plan robustness. Data derived from the dose volume histogram in the worst-case and nominal doses were used to evaluate the plan optimality. Then the plan evaluation metrics were averaged over the 14 cases and were compared with two-sided paired t tests.CTV-based robust optimization led to more robust (i.e., smaller AUCs) plans for both targets and organs. Under the worst-case scenario and the nominal scenario, CTV-based robustly optimized plans showed better target coverage (i.e., greater D95%), improved dose homogeneity (i.e., smaller D5% - D95%), and lower or equivalent dose to organs at risk.CTV-based robust optimization provided significantly more robust dose distributions to targets and organs than PTV-based conventional optimization in H&N using IMPT. Eliminating the use of PTV and planning directly based on CTV provided better or equivalent normal tissue sparing.

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.

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.

Project description:Owing to its physical properties, intensity-modulated proton therapy (IMPT) used for patients with oropharyngeal carcinoma has the ability to reduce the dose to organs at risk compared to intensity-modulated radiotherapy (IMRT) while maintaining adequate tumor coverage. Our aim was to compare the clinical outcomes of these two treatment modalities.We performed a 1:2 matching of IMPT to IMRT patients. Our study cohort consisted of IMPT patients from a prospective quality of life study and consecutive IMRT patients treated at a single institution during the period 2010-2014. Patients were matched on unilateral/bilateral treatment, disease site, human papillomavirus status, T and N status, smoking status, and receipt of concomitant chemotherapy. Survival analyzes were performed using a Cox model and binary toxicity endpoints using a logistic regression analysis.Fifty IMPT and 100 IMRT patients were included. The median follow-up time was 32months. There were no imbalances in patient/tumor characteristics except for age (mean age 56.8years for IMRT patients and 61.1years for IMPT patients, p-value=0.010). Statistically significant differences were not observed in overall survival (hazard ratio (HR)=0.55; 95% confidence interval (CI): 0.12-2.50, p-value=0.44) or in progression-free survival (HR=1.02; 95% CI: 0.41-2.54; p-value=0.96). The age-adjusted odds ratio (OR) for the presence of a gastrostomy (G)-tube during treatment for IMPT vs IMRT were OR=0.53; 95% CI: 0.24-1.15; p-value=0.11 and OR=0.43; 95% CI: 0.16-1.17; p-value=0.10 at 3months after treatment. When considering the pre-planned composite endpoint of grade 3 weight loss or G-tube presence, the ORs were OR=0.44; 95% CI: 0.19-1.0; p-value=0.05 at 3months after treatment and OR=0.23; 95% CI: 0.07-0.73; p-value=0.01 at 1year after treatment.Our results suggest that IMPT is associated with reduced rates of feeding tube dependency and severe weight loss without jeopardizing outcome. Prospective multicenter randomized trials are needed to validate such findings.

Project description:PurposeTo design and commission a head and neck (H&N) anthropomorphic phantom that the Imaging and Radiation Oncology Core Houston (IROC-H) can use to verify the quality of intensity-modulated proton therapy H&N treatments for institutions participating in National Cancer Institute-sponsored clinical trials.Materials and methodsThe phantom design was based on a generalized oropharyngeal tumor, including critical H&N structures (parotid glands and spinal cord). Radiochromic film and thermoluminescent dosimeter (TLD)-100 capsules were embedded in the phantom and used to evaluate dose delivery. A spot-scanning treatment plan with typical clinical constraints for H&N cancer was created by using the Eclipse analytic algorithm. The treatment plan was approved by a radiation oncologist and the phantom was irradiated 4 times. The measured dose distribution using a ±7%/4 mm gamma analysis (85% of pixels passing) and point doses were compared with the treatment planning system calculations. The prescribed target dose was 6 Gy (RBE) with 646.2 cGy (RBE) and 648.6 cGy (RBE) planned to the superior and inferior TLD, respectively.ResultsFor point dosimetry, the average measured-to-calculated dose ratios were 0.984 and 0.986 for the superior and inferior target TLD, respectively. Dose values for the superior and inferior target TLDs were 636.1 cGy and 639.6 cGy, respectively. For the relative dose comparison, the pixel passing rates for the axial and sagittal films, respectively, were 95.5% and 94.2% for trial 1, 97.3% and 93.2% for trial 2, 93.4% and 90.0% for trial 3, and 96.2% and 92.7% for trial 4.ConclusionThe anthropomorphic H&N phantom was successfully designed so that TLD measured-to-calculated ratios were within IROC-H's 7% acceptance criteria, 1.6% and 1.4% lower than expected for the superior and inferior target TLDs, respectively. All trials passed the 85% pixel passing criteria established at IROC-H for the relative dose comparison performed when using a gamma index of ±7%/4 mm.

Project description:PurposeRadiation therapy (RT) improves control of Hodgkin lymphoma (HL), but patients who undergo RT are at risk for late effects, including cardiovascular disease and second cancers, because of radiation doses to organs at risk (OARs). Proton therapy (PT) can reduce OAR doses compared with conventional photon RT. However, access to PT is currently limited, so referrals must be appropriately selective. We aimed to identify subgroups of patients with HL who could benefit the most dosimetrically from RT with PT based on the prechemotherapy disease characteristics.Methods and materialsNormal tissue radiation doses were calculated for 21 patients with HL who were treated with deep-inspiration breath-hold pencil-beam scanning (PBS) PT and compared with doses from 3-dimensional conformal (3D-CRT) and partial arc volumetric modulated (PartArc) photon RT. Prechemotherapy disease characteristics associated with significant dosimetric benefits from PBS compared with photon RT were identified.ResultsTreatment with PBS was well tolerated and provided with good local control. PBS provided dosimetric advantages for patients whose clinical treatment volume extended below the seventh thoracic level and for female patients with axillary disease. In addition, an increasing dosimetric benefit for some OARs was observed for increasing target volume. PBS significantly reduced the mean dose to the heart, breast, lungs, spinal cord, and esophagus. Dose homogeneity and conformity within the target volume were also superior with PBS, but some high-dose measures and hot spots were increased with PBS compared with partial arc volumetric modulated photon RT.ConclusionsPBS gives good target coverage and local control while providing reductions in radiation dose to OARs for individuals who receive RT for HL compared with advanced photon RT. Our findings highlight groups of patients who would be expected to gain more dosimetric benefit from PBS. These findings facilitate the selection of patients who should be considered a priority for PT.

Dataset Information

Robust Intensity Modulated Proton Therapy (IMPT) Increases Estimated Clinical Benefit in Head and Neck Cancer Patients.

Purpose

Methods and materials

Results

Conclusions

Publications

Robust Intensity Modulated Proton Therapy (IMPT) Increases Estimated Clinical Benefit in Head and Neck Cancer Patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets