Dataset Information

Impact of RBE variations on risk estimates of temporal lobe necrosis in patients treated with intensity-modulated proton therapy for head and neck cancer.

ABSTRACT:

Background

Temporal lobe necrosis (TLN) is a potential late effect after radiotherapy for skull base head and neck cancer (HNC). Several photon-derived dose constraints and normal tissue complication probability (NTCP) models have been proposed, however variation in relative biological effectiveness (RBE) may challenge the applicability of these dose constraints and models in proton therapy. The purpose of this study was therefore to investigate the influence of RBE variations on risk estimates of TLN after Intensity-Modulated Proton Therapy for HNC.

Material and methods

Seventy-five temporal lobes from 45 previously treated patients were included in the analysis. Sixteen temporal lobes had radiation associated Magnetic Resonance image changes (TLIC) suspected to be early signs of TLN. Fixed (RWD_Fix) and variable RBE-weighed doses (RWD_Var) were calculated using RBE = 1.1 and two RBE models, respectively. RWD_Fix and RWD_Var for temporal lobes were compared using Friedman's test. Based on RWD_Fix, six NTCP models were fitted and internally validated through bootstrapping. Estimated probabilities from RWD_Fix and RWD_Var were compared using paired Wilcoxon test. Seven dose constraints were evaluated separately for RWD_Fix and RWD_Var by calculating the observed proportion of TLIC in temporal lobes meeting the specific dose constraints.

Results

RWD_Var were significantly higher than RWD_Fix (p < 0.01). NTCP model performance was good (AUC:0.79-0.84). The median difference in estimated probability between RWD_Fix and RWD_Var ranged between 5.3% and 20.0% points (p < 0.01), with V_60GyRBE and D_Max at the smallest and largest differences, respectively. The proportion of TLIC was higher for RWD_Fix (4.0%-13.1%) versus RWD_Var (1.3%-5.3%). For V_65GyRBE ≤ 0.03 cc the proportion of TLIC was less than 5% for both RWD_Fix and RWD_Var.

Conclusion

NTCP estimates were significantly influenced by RBE variations. D_max as model predictor resulted in the largest deviations in risk estimates between RWD_Fix and RWD_Var. V_65GyRBE ≤ 0.03 cc was the most consistent dose constraint for RWD_Fix and RWD_Var.

SUBMITTER: Engeseth GM

PROVIDER: S-EPMC9969227 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Impact of RBE variations on risk estimates of temporal lobe necrosis in patients treated with intensity-modulated proton therapy for head and neck cancer.

Engeseth Grete May GM Hysing Liv Bolstad LB Yepes Pablo P Pettersen Helge Egil Seime HES Mohan Radhe R Fuller Clifton Dave CD Stokkevåg Camilla Hanquist CH Wu Richard R Zhang Xiaodong X Frank Steven Jay SJ Gunn Gary Brandon GB

Acta oncologica (Stockholm, Sweden) 20210917 2

<h4>Background</h4>Temporal lobe necrosis (TLN) is a potential late effect after radiotherapy for skull base head and neck cancer (HNC). Several photon-derived dose constraints and normal tissue complication probability (NTCP) models have been proposed, however variation in relative biological effectiveness (RBE) may challenge the applicability of these dose constraints and models in proton therapy. The purpose of this study was therefore to investigate the influence of RBE variations on risk es ...[more]

PMID: 34534047

Similar Datasets

Project description:PurposeEmpirical relative biological effectiveness (RBE) models have been used to estimate the biological dose in proton therapy but do not adequately capture the factors influencing RBE values for treatment planning. We reformulate the McNamara RBE model such that it can be added as a linear biological dose fidelity term within our previously developed sensitivity-regularized and heterogeneity-weighted beam orientation optimization (SHBOO) framework.MethodsBased on our SHBOO framework, we formulated the biological optimization problem to minimize total McNamara RBE dose to OARs. We solve this problem using two optimization algorithms: FISTA (McNam-FISTA) and Chambolle-Pock (McNam-CP). We compare their performances with a physical dose optimizer assuming RBE = 1.1 in all structures (PHYS-FISTA) and an LET-weighted dose model (LET-FISTA). Three head and neck patients were planned with the four techniques and compared on dosimetry and robustness.ResultsCompared to Phys-FISTA, McNam-CP was able to match CTV [HI, Dmax, D95%, D98%] by [0.00, 0.05%, 1.4%, 0.8%]. McNam-FISTA and McNam-CP were able to significantly improve overall OAR [Dmean, Dmax] by an average of [36.1%,26.4%] and [29.6%, 20.3%], respectively. Regarding CTV robustness, worst [Dmax, V95%, D95%, D98%] improvement of [-6.6%, 6.2%, 6.0%, 4.8%] was reported for McNam-FISTA and [2.7%, 2.7%, 5.3%, -4.3%] for McNam-CP under combinations of range and setup uncertainties. For OARs, worst [Dmax, Dmean] were improved by McNam-FISTA and McNam-CP by an average of [25.0%, 19.2%] and [29.5%, 36.5%], respectively. McNam-FISTA considerably improved dosimetry and CTV robustness compared to LET-FISTA, which achieved better worst-case OAR doses.ConclusionThe four optimization techniques deliver comparable biological doses for the head and neck cases. Besides modest CTV coverage and robustness improvement, OAR biological dose and robustness were substantially improved with both McNam-FISTA and McNam-CP, showing potential benefit for directly incorporating McNamara RBE in proton treatment planning.

Project description:BackgroundTo investigate the frequency of temporal lobe necrosis (TLN) soon after radiotherapy (RT) and identify differences among patients with various types of head and neck cancer (HNC) and between different RT methods.MethodsWe retrospectively reviewed 483 patients with HNC who had completed RT in our hospital after January, 2015. These patients were followed-up at the radio-oncology department and received contrast-enhanced magnetic resonance imaging (MRI) or computed tomography (CT) to identify metastases or recurrence of cancer at regular intervals. Meanwhile, the occurrence of TLN, graded according to the Common Terminology Criteria for Adverse Events V5.0, was recorded. We categorized the patients into nasopharyngeal carcinoma (NPC) and non-NPC groups and compared the cumulative occurrence of TLN between the groups using Kaplan-Meier and Cox regression analyses. We further compared the cumulative occurrence of TLN between proton beam therapy (PBT) and volumetric modulated arc therapy (VMAT) in patients with any HNC, NPC, and non-NPC HNC.ResultsCompared with the non-NPC group, the NPC group had a higher frequency of TLN (5.6% vs. 0.4%, p < 0.01) and were more commonly associated with TLN in the Kaplan-Meier analysis (p < 0.01) and the Cox regression model after covariates were adjusted for (adjusted hazard ratio: 13.35, 95% confidence interval: 1.37-130.61) during the follow-up period. Furthermore, the frequency of TLN was similar between patients receiving PBT and those receiving VMAT (PBT vs. VMAT: 4.7% vs. 6.3%, p = 0.76). Kaplan-Meier analysis revealed that the accumulated risks of TLN were similar between PBT and VMAT in patients with any HNC (p = 0.44), NPC (p = 0.84), and non-NPC HNC (p = 0.70).ConclusionOur study demonstrated that patients with NPC are susceptible to TLN during the early period after RT. In addition, PBT may be associated with an equivalent risk of TLN when compared with VMAT in patients with NPC or other HNCs.

Project description:PurposeTo incorporate small non-rigid variations of head and neck patients into the robust evaluation of intensity-modulated proton therapy (IMPT) for the selection of robust treatment plans.MethodsA cohort of 20 nasopharynx cancer patients with weekly kilovoltage CT (kVCT) and 15 oropharynx cancer patients with weekly cone-beam CT (CBCT) were retrospectively included. Anatomical variations between week 0/week 1 of treatment were acquired using deformable image registration (DIR) for all 35 patients and then applied to the planning CT of four patients who have kVCT scanned each week to simulate potential small non-rigid variations (sNRVs). The robust evaluations were conducted on IMPT plans with: (1) different number of beam fields from 3-field to 5-field; (2) different beam angles. The robust evaluation before treatment, including the sNRVs and setup uncertainty, referred to as sNRV+R evaluation was compared with the conventional evaluation (without sNRVs) in terms of robustness consistency with the gold standard evaluation based on weekly CT.ResultsAmong four patients (490 scenarios), we observed a maximum difference in the sNRV+R evaluation to the nominal dose of: 9.37% dose degradation on D95 of clinical target volumes (CTVs), increase in mean dose (D mean$_{\text{mean}}$ ) of parotid 11.87 Gy, increase in max dose (D max$_{\text{max}}$ ) of brainstem 20.82 Gy. In contrast, in conventional evaluation, we observed a maximum difference to the nominal dose of: 7.58% dose degradation on D95 of the CTVs, increase in parotid D mean$_{\text{mean}}$ by 4.88 Gy, increase in brainstem D max$_{\text{max}}$ by 13.5 Gy. In the measurement of the robustness ranking consistency with the gold standard evaluation, the sNRV+R evaluation was better or equal to the conventional evaluation in 77% of cases, particularly, better on spinal cord, parotid glands, and low-risk CTV.ConclusionThis study demonstrated the additional dose discrepancy that sNRVs can make. The inclusion of sNRVs can be beneficial to robust evaluation, providing information on clinical uncertainties additional to the conventional rigid isocenter shift.

Project description:PurposeTo demonstrate temporal lobe necrosis (TLN) rate and clinical/dose-volume factors associated with TLN in radiation-naïve patients with head and neck cancer treated with proton therapy where the field of radiation involved the skull base.Materials and methodsMedical records and dosimetric data for radiation-naïve patients with head and neck cancer receiving proton therapy to the skull base were retrospectively reviewed. Patients with <3 months of follow-up, receiving <45 GyRBE or nonconventional fractionation, and/or no follow-up magnetic resonance imaging (MRI) were excluded. TLN was determined using MRI and graded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Clinical (gender, age, comorbidities, concurrent chemotherapy, smoking, radiation techniques) and dose-volume parameters were analyzed for TLN correlation. The receiver operating characteristic curve and area under the curve (AUC) were performed to determine the cutoff points of significant dose-volume parameters.ResultsBetween 2013 and 2019, 234 patients were included. The median follow-up time was 22.5 months (range = 3.2-69.3). Overall TLN rates of any grade, ≥ grade 2, and ≥ grade 3 were 5.6% (N = 13), 2.1%, and 0.9%, respectively. The estimated 2-year TLN rate was 4.6%, and the 2-year rate of any brain necrosis was 6.8%. The median time to TLN was 20.9 months from proton completion. Absolute volume receiving 40, 50, 60, and 70 GyRBE (absolute volume [aV]); mean and maximum dose received by the temporal lobe; and dose to the 0.5, 1, and 2 cm3 volume receiving the maximum dose (D0.5cm3, D1cm3, and D2cm3, respectively) of the temporal lobe were associated with greater TLN risk while clinical parameters showed no correlation. Among volume parameters, aV50 gave maximum AUC (0.921), and D2cm3 gave the highest AUC (0.935) among dose parameters. The 11-cm3 cutoff value for aV50 and 62 GyRBE for D2cm3 showed maximum specificity and sensitivity.ConclusionThe estimated 2-year TLN rate was 4.6% with a low rate of toxicities ≥grade 3; aV50 ≤11 cm3, D2cm3 ≤62 GyRBE and other cutoff values are suggested as constraints in proton therapy planning to minimize the risk of any grade TLN. Patients whose temporal lobe(s) unavoidably receive higher doses than these thresholds should be carefully followed with MRI after proton therapy.

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: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.

Dataset Information

Impact of RBE variations on risk estimates of temporal lobe necrosis in patients treated with intensity-modulated proton therapy for head and neck cancer.

Background

Material and methods

Results

Conclusion

Publications

Impact of RBE variations on risk estimates of temporal lobe necrosis in patients treated with intensity-modulated proton therapy for head and neck cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets