Intensity-modulated X-ray Therapy Research Articles

Comparison of intensity modulated proton therapy beam configurations for treating thoracic esophageal cancer.

Specific proton-beam configurations are needed to spare organs at risk (OARs), including lungs, heart, and spinal cord, when treating esophageal squamous cell carcinoma (ESCC) in the thoracic region. This study aimed to propose new intensity-modulated proton therapy (IMPT) beam configurations and to demonstrate the benefit of IMPT compared with intensity-modulated x-ray therapy (IMXT) for treating ESCC. IMPT plans with three different beam angle configurations were generated on CT datasets of 25 ESCC patients that were treated with IMXT. The IMPT beam designs were two commonly-used beam configurations (anteroposterior and posterior oblique) and a recently proposed beam configuration (anterosuperior with posteroinferior). The target doses were 50-54Gy(RBE) and 60-64Gy(RBE) to the low-risk and high-risk target volumes, respectively. Robust optimization was applied for the IMPT plans. The differences in the dose-volume parameters between the IMXT and IMPT plans were compared. With target coverage comparable to standard IMXT, IMPT had significantly lower mean doses to the OARs. IMPT with an anteroposterior opposing beam generated the lowest lung dose (mean=7.1Gy(RBE), V20=14.1%) and the anterosuperior with posteroinferior beam resulted in the lowest heart dose (mean=12.8Gy(RBE), V30=15.7%) and liver dose (mean=3.9Gy(RBE), V30=5.9%). For the subgroup of patients with an inferior tumor location (PTVs overlapping a part of the contoured heart), the novel beam demonstrated the optimal OARs sparing. Compared with IMXT, the IMPT plans significantly reduced the radiation dose to the surrounding organs when treating ESCC. IMPT beam configuration selection depends on the tumor location relative to the heart.

Analysis of acute-phase toxicities of intensity-modulated proton therapy using a model-based approach in pharyngeal cancer patients

Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.

Potential benefits of adaptive intensity-modulated proton therapy in nasopharyngeal carcinomas.

PurposeTo investigate potential advantages of adaptive intensity‐modulated proton beam therapy (A‐IMPT) by comparing it to adaptive intensity‐modulated X‐ray therapy (A‐IMXT) for nasopharyngeal carcinomas (NPC).MethodsTen patients with NPC treated with A‐IMXT (step and shoot approach) and concomitant chemotherapy between 2014 and 2016 were selected. In the actual treatment, 46 Gy in 23 fractions (46Gy/23Fx.) was prescribed using the initial plan and 24Gy/12Fx was prescribed using an adapted plan thereafter. New treatment planning of A‐IMPT was made for the same patients using equivalent dose fractionation schedule and dose constraints. The dose volume statistics based on deformable images and dose accumulation was used in the comparison of A‐IMXT with A‐IMPT.ResultsThe means of the Dmean of the right parotid gland (P < 0.001), right TM joint (P < 0.001), left TM joint (P < 0.001), oral cavity (P < 0.001), supraglottic larynx (P = 0.001), glottic larynx (P < 0.001), , middle PCM (P = 0.0371), interior PCM (P < 0.001), cricopharyngeal muscle (P = 0.03643), and thyroid gland (P = 0.00216), in A‐IMPT are lower than those of A‐IMXT, with statistical significance. The means of, D0.03cc, and Dmean of each sub portion of auditory apparatus and D30% for Eustachian tube and D0.5cc for mastoid volume in A‐IMPT are significantly lower than those of A‐IMXT. The mean doses to the oral cavity, supraglottic larynx, and glottic larynx were all reduced by more than 20 Gy (RBE = 1.1).ConclusionsAn adaptive approach is suggested to enhance the potential benefit of IMPT compared to IMXT to reduce adverse effects for patients with NPC.

Normal Tissue Complication Probability for Hematologic and Gastrointestinal Toxicity in Postoperative Whole Pelvic Radiotherapy for Gynecologic Malignancies using Intensity Modulated Proton Therapy with Robust Optimization

Hematologic toxicity (HT) and gastrointestinal toxicity (GI) are often observed in the postoperative whole pelvic radiotherapy (WPRT) for gynecologic malignancies since the irradiation field contains large volume of the bone marrow (BM) and bowel bag (BB). Although proton beam therapy with single field uniform dose optimization has a potential of the risk reduction of HT compared with intensity modulated X-ray therapy (IMXT), the risk reduction of GI has not been previously described. Thus, the aim of this in silico study was to evaluate the risk of HT and GI using intensity modulated proton therapy with robust optimization (robust IMPT). This dosimetric planning study included 9 patients who had previously undergone hysterectomy and WPRT at our institution from 2008 to 2020. For robust IMPT planning, we used two posterior oblique fields and a 3.5% beam specific margin from the distal and proximal edges of clinical target volume (CTV) in water equivalent space to discern the range uncertainty. The prescribed dose was 45 GyE in 25 fractions for 99% of the CTV (CTV D99). We evaluated CTV coverage using following indicators, CTV D99, conformity index (CI), homogeneity index (HI); dose volume statistics of BM received 10 and 20 GyE (BM V10 and BM V20), and BB received 40 GyE (BB V40); the planning robustness for CTV by shifting each 5 mm for six axes; and the risk of HT and GI using the Lyman-Kutcher-Burman normal tissue complication probability (LKB-NTCP) model. The parameters of LKB-NTCP model were determined to calculate the risk of grade ≥ 3 acute HT and chronic GI such as obstruction or perforation. We performed the comparative evaluation of NTCP value for HT and GI between robust IMPT and IMXT prescribed 45 GyE in 25 fractions for 95% of the planning target volume with 7-fields step and shoot technique. The Wilcoxon signed rank test was used for all statistical comparisons. In the LKB-NTCP modeling analysis, the NTCP values for robust IMPT were significantly lower than IMXT (HT: 0.06±0.02 for robust IMPT and 0.19±0.03 for IMXT, p<0.05, and GI: 0.01±0.004 for robust IMPT and 0.03±0.01 for IMXT, p<0.05, respectively). Moreover, robust IMPT was excellent CTV coverage; the mean and standard deviation of CTV D99, CI, and HI was 45.63±0.21 GyE, 1.00±0.001, and 0.03±0.01, respectively. The dose volume statistics for BM V10, BM V20 and BB V40 were 61.41±4.47%, 53.12±4.75%, and 17.77±3.45%, respectively. Changes in the mean value of CTV D99 in the shifted plan were within 2%, except for the anterior shift plan (left: -1.05%, right: -0.91%, superior: -0.97%, inferior: -1.17%, anterior: -2.59%, and posterior: -0.10%). Robust IMPT for WPRT reduced the risk of HT and GI without compromising CTV coverage, compared with IMXT. These results indicate that robust IMPT has a clinical advantage in reducing the risk of HT and GI in the treatment of gynecologic malignances.

Intensity-Modulated Proton Therapy with Dose Painting based on Hypoxia Imaging for Nasopharyngeal Cancer

In precision medicine, reducing recurrence rates and toxicities is necessary for nasopharyngeal cancer (NPC) patients. Hypoxia is a well-known risk factor for radioresistance. Radiation dose escalation (DE) to hypoxic regions is one strategy, especially for locally advanced cases in which tumor control may be unsuccessful. Radiation dose reduction is also a valuable approach. A clinical trial of dose de-escalation (DDE) for oropharyngeal cancer based on hypoxia status was recently reported. DDE may also be applicable for NPC patients with good prognostic characteristics. The purpose of this study was to investigate the feasibility of hypoxia-based dose painting for intensity-modulated proton therapy (IMPT) and intensity-modulated X-ray therapy (IMXT) with constraints on doses to organs at risk (OARs) and normal tissue complication probabilities (NTCPs) in DE and DDE scenarios. DE and DDE treatment plans for IMPT and IMXT were generated for ten NPC patients who underwent 18F-fluoromisonidazole (FMISO)-PET before definitive radiotherapy. In the DE scenario, 70 Gy was prescribed to the tumor in a standard manner, with DE to 84 Gy to FMISO-PET-positive (hypoxic) regions. In the DDE scenario, 70 Gy was prescribed to the hypoxic region, with DDE to 60 Gy to non-hypoxic regions. Prescribed doses to high- and low-risk areas were 63 and 56 Gy, respectively, in the DE scenario and 54 and 48 Gy, respectively, in the DDE scenario. The constraints for doses to OARs were a parotid gland mean dose (Dmean) <26 Gy and an oral cavity Dmean <39 Gy. The criterion for NTCP was probability ≤50% for all five toxicities: salivary flow reduction, xerostomia, dysphagia, tube feeding dependence and dysgeusia. The determined doses to hypoxic and non-hypoxic target volumes were prescribed in all IMPT and IMXT plans in the DE and DDE scenarios. The numbers of patients who satisfied the parotid gland, oral cavity and NTCP criteria were 7, 10 and 10, respectively, for IMPT and 0, 1 and 0, respectively, for IMXT in the DE scenario and 10, 10 and 10, respectively, for IMPT and 1, 2 and 5, respectively, for IMXT in the DDE scenario. Dmean for the contralateral parotid gland was 25.2±3.0 for IMPT and 36.3±3.4 for IMXT (p=0.0003) in the DE scenario and 21.4±2.6 for IMPT and 30.9±3.0 for IMXT (p=0.0003) in the DDE scenario. Dmean for the oral cavity was 28.8±7.3 for IMPT and 49.3±4.9 for IMXT (p=0.0003) in the DE scenario and 24.5±6.2 for IMPT and 41.3±4.3 for IMXT (p=0.0003) in the DDE scenario. For all toxicities, NTCPs were lower for IMPT than for IMXT for all patients. ΔNTCP, calculated as NTCPIMXT-NTCPIMPT, was more than 10% for 3 or more toxicities for 9 patients in the DE scenario and 8 patients in the DDE scenario. Compared with IMXT, IMPT satisfied parotid, oral cavity and NTCP criteria in more patients and reduced doses to OARs and NTCPs in both the DE and DDE scenarios. IMPT could be more useful than IMXT when conducting hypoxia-based dose painting while maintaining low toxicities.

Probabilistic dose distribution from interfractional motion in carbon ion radiation therapy for prostate cancer shows rectum sparing with moderate target coverage degradation.

PurposeThis observational study investigates the influence of interfractional motion on clinical target volume (CTV) coverage, planning target volume (PTV) margins, and rectum tissue sparing in carbon ion radiation therapy (CIRT). It reports dose coverage to target structures and organs at risk in the presence of interfractional motion, investigates rectal tissue sparing, and provides recommendations for lowering the rate of toxicity. We also propose probabilistic DVH based on cone-beam computed tomography (CBCT) table shifts from photon therapy for consideration in bone-matching CIRT treatment planning to represent probable dose to our CIRT patient population.MethodsAt Gunma University Hospital intensity-modulated x-ray therapy (IMXT, aka IMRT) prostate cancer patients are positioned on a table which is shifted twice based on CBCT to align bones and then align prostate tissue to isocenter. These shifts thereby contain interfractional motion. A total of 1306 such table shifts from 85 patients were collected. Normal probability distributions were fit to the difference between bone-matching and prostate-matching CBCT-to-planning CT table shifts (i.e. interfractional motion). Between 2011 and 2016 CIRT prostate patients were treated with three beams to PTV1 (lateral-opposing and anterior) one per day for 9 fractions and two beams for a boost PTV2 (lateral-opposing) one per day for 7 fractions for a prescribed total of 57.6 Gy(RBE) as follows: PTV1 extends the prostate contour by 10/10, 5/10, 6/6 mm in the right/left, posterior/anterior, and superior/inferior directions, respectively, and the proximal seminal vesicles contour by 5 mm superiorly and inferiorly, 3 mm right and left. PTV2 reduces PTV1 posteriorly along a straight line to exclude the rectum and reduces the superior and inferior margins by 6 mm. Probable interfractional motion for 40 patients was simulated using each patient’s own beam data as follows: The previously fit normal probability distributions were randomly sampled 2000 times per patient, and the five beams were shifted and summed with the same relative weighting as in the 16-fraction regimen. The resulting dose distribution was then scaled back down by 16/2000 to match the prescribed number of fractions. We then analyzed the resulting doses to contoured structures.ResultsProbable dose to rectum is substantially less than planned: For example, mean+-standard deviation D2% for planned and probable DVH is 51+-1.9 and 45+-2.4, respectively. Cumulative DVH show mean CTV fraction receiving a given probable dose is less than the mean fraction receiving the corresponding planned dose for doses larger than 52 Gy(RBE), up to 19% less at 57.4 Gy(RBE). Our PTV1 margins generally cover 95% of interfractional motion but seminal vesicles and inferior prostate receive less dose than planned due to insufficient PTV2 margins.ConclusionAssuming rigidly shifting interfractional motion around the prostate region and neglecting minor changes in soft tissue stopping power, interfractional motion resulted in target underdosing but better tissue sparing in all cases. Given our low rates of relapse and recurrence, it appears less curative dose is needed than previously thought or else current planning target margins may be excessive: Planning target volumes should be reconsidered with the adoption of dose verification methods. Our probable dose distributions quantify expected dose for future dose verification studies.

Introduction to passive electron intensity modulation.

This work introduces a new technology for electron intensity modulation, which uses small area island blocks within the collimating aperture and small area island apertures in the collimating insert. Due to multiple Coulomb scattering, electrons contribute dose under island blocks and lateral to island apertures. By selecting appropriate lateral positions and diameters of a set of island blocks and island apertures, for example, a hexagonal grid with variable diameter circular island blocks, intensity modulated beams can be produced for appropriate air gaps between the intensity modulator (position of collimating insert) and the patient. Such a passive radiotherapy intensity modulator for electrons (PRIME) is analogous to using physical attenuators (metal compensators) for intensity modulated x‐ray therapy (IMXT). For hexagonal spacing, the relationship between block (aperture) separation (r) and diameter (d) and the local intensity reduction factor (IRF) is discussed. The PRIME principle is illustrated using pencil beam calculations for select beam geometries in water with half beams modulated by 70%–95% and for one head and neck field of a patient treated with bolus electron conformal therapy. Proof of principle is further illustrated by showing agreement between measurement and calculation for a prototype PRIME. Potential utilization of PRIME for bolus electron conformal therapy, segmented‐field electron conformal therapy, modulated electron radiation therapy, and variable surface geometries is discussed. Further research and development of technology for the various applications is discussed. In summary, this paper introduces a practical, new technology for electron intensity modulation in the clinic, demonstrates proof of principle, discusses potential clinical applications, and suggests areas of further research and development.

SU‐F‐T‐87: Comparison of Advanced Radiotherapy Techniques for Post‐ Mastectomy Breast Cancer Patients

Purpose:To determine if bolus electron conformal therapy (Bolus‐ECT) combined with intensity modulated x‐ray therapy (IMXT) and flattening filter free volumetric modulated arc therapy (FFF‐VMAT (6x and 10x)) can maintain equal or better dose coverage than standard volumetric modulated arc therapy (Std‐VMAT) while reducing doses to organs at risk (OARs).Methods:Bolus‐ECT with IMXT, FFF‐VMAT, and Std‐VMAT treatment plans were produced for ten post‐mastectomy radiotherapy (PMRT) patients previously treated at our clinic. The treatment plans were created on commercially available treatment planning system (TPS) and all completed treatment plans were reviewed and approved by a radiation oncologist. The plans were evaluated based on planning target volume (PTV) coverage, tumor control probability (TCP), dose homogeneity index (DHI), conformity index (CI), and dose to organs at risk (OAR).Results:All techniques produced clinically acceptable PMRT plans. Overall, Bolus‐ECT with IMXT exhibited higher maximum dose compared to all VMAT techniques. Bolus‐ECT with IMXT and FFF‐VMAT10x had slightly improved TCP over FFF‐VMAT6x and Std‐VMAT. However, all VMAT techniques showed improved CI and DHI over Bolus‐ECT with IMXT. All techniques showed very similar mean lung dose. Bolus‐ECT with IMXT exhibited a reduced mean heart dose over Std‐VMAT. Both FFF‐VMAT techniques had higher mean heart dose compared to Std‐VMAT. In addition, Bolus‐ECT with IMXT was able to reduce mean dose to the contralateral breast compared to Std‐VMAT and both FFF‐VMAT techniques had comparable but slightly reduced dose compared to Std‐VMAT.Conclusion:This work has shown that Bolus‐ECT with IMXT produces clinically acceptable plans while reducing OAR doses. Both FFF‐VMAT techniques are comparable to Std‐VMAT with slight improvements. Even though all VMAT techniques produce more homogenous and conformal dose distributions, Bolus‐ECT with IMXT is a viable option for treating post‐mastectomy patients possibly leading to reduced risks of normal tissue complications.

SU‐F‐T‐202: An Evaluation Method of Lifetime Attributable Risk for Comparing Between Proton Beam Therapy and Intensity Modulated X‐Ray Therapy for Pediatric Cancer Patients by Averaging Four Dose‐Response Models for Carcinoma Induction

Purpose:To examine how much lifetime attributable risk (LAR) as an in silico surrogate marker of radiation‐induced secondary cancer would be lowered by using proton beam therapy (PBT) in place of intensity modulated x‐ray therapy (IMXT) in pediatric patients.Methods:From 242 pediatric patients with cancers who were treated with PBT, 26 patients were selected by random sampling after stratification into four categories: a) brain, head, and neck, b) thoracic, c) abdominal, and d) whole craniospinal (WCNS) irradiation. IMXT was re‐planned using the same computed tomography and region of interest. Using dose volume histogram (DVH) of PBT and IMXT, the LAR of Schneider et al. was calculated for the same patient. The published four dose‐response models for carcinoma induction: i) full model, ii) bell‐shaped model, iii) plateau model, and ix) linear model were tested for organs at risk. In the case that more than one dose‐response model was available, the LAR for this patient was calculated by averaging LAR for each dose‐response model.Results:Calculation of the LARs of PBT and IMXT based on DVH was feasible for all patients. The mean±standard deviation of the cumulative LAR difference between PBT and IMXT for the four categories was a) 0.77±0.44% (n=7, p=0.0037), b) 23.1±17.2%,(n=8, p=0.0067), c) 16.4±19.8% (n=8, p=0.0525), and d) 49.9±21.2% (n=3, p=0.0275, one tailed t‐test), respectively. The LAR was significantly lower by PBT than IMXT for the the brain, head, and neck region, thoracic region, and whole craniospinal irradiation.Conclusion:In pediatric patients who had undergone PBT, the LAR of PBT was significantly lower than the LAR of IMXT estimated by in silico modeling. This method was suggested to be useful as an in silico surrogate marker of secondary cancer induced by different radiotherapy techniques.This research was supported by the Translational Research Network Program, JSPS KAKENHI Grant No. 15H04768 and the Global Institution for Collaborative Research and Education (GI‐CoRE), Hokkaido University, founded by the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan.

Phase I/II Trial Evaluating Carbon Ion Radiotherapy for Salvaging Treatment of Locally Recurrent Nasopharyngeal Carcinoma.

Background: Radiation therapy is the mainstay strategy for the treatment of nasopharyngeal cancer (NPC). Intensity-modulated X-ray therapy (IMXT) alone is the current standard for stage I and II NPC. For stage III and IV A/B diseases, concurrent chemotherapy should be provided in addition to IMXT. However, optimal treatment for locally recurrent NPC after previous definitive dose of radiotherapy is lacking. Various techniques including brachytherapy, IMXT, stereotactic radiosurgery or radiotherapy (SRS or SBRT) have been used in the management of locally recurrent NPC. Due to the inherent limitation of these techniques, i.e., limited range of irradiation or over-irradiation to surrounding normal tissues, moderate efficacy has been observed at the cost of severe toxicities. Carbon ion radiotherapy (CIRT) offers potential physical and biological advantages over photon and proton radiotherapy. Due to the inverted dose profile of particle beams and their greater energy deposition within the Bragg peak, precise dose delivery to the target volume(s) without exposing the surrounding organs at risk to extra doses is possible. In addition, CIRT provides an increased relative biological effectiveness (RBE) as compared to photon and proton radiotherapy. Such advantages may translate to improved outcomes after irradiation in terms of disease control in radio-resistant and previously treated, recurrent malignancies. It is therefore reasonable to postulate that recurrent NPC after high-dose radiotherapy could be more resistant to re-irradiation using photons. Reports on the treatment of radio-resistant malignancies in the head and neck region such as melanoma, sarcoma, and adenoid cystic carcinoma (ACC) have demonstrated superior local control rates from CIRT as compared to photon irradiation. Thus patients with recurrent NPC are likely to benefit from the enhanced biological effectiveness of carbon ions. As effective retreatment strategy is lacking for locally recurrent NPC, carbon ion radiation therapy offers an ideal alternate to conventional X-ray irradiation.Methods and Design: The recommended dose of re-irradiation using CIRT for locally recurrent NPC will be determined in the dose-escalating phase (Phase I) of the study. Efficacy in terms of local progression-free survival (LPFS) and overall survival (OS) will be studied in the second phase of the study. Increasing doses of CIRT using raster scanning technology from 55GyE (22×2.5 GyE) to 65 GyE (26× 2.5 GyE) will be delivered in the Phase I part of the study. The primary endpoint of the Phase I part of the study is acute and sub-acute toxicities; the primary endpoint in the Phase II part is local progression-free survival and overall survival. Using the historical 2-year OS rate of 50% in locally recurrent NPC patients treated with photon or proton, we hypothesize that CIRT can improve the 2-year OS rate to 70%.Discussion: The utilization of conventional radiation techniques including IMXT, brachytherapy, or stereotactic radiation therapy provides moderate efficacy in the treatment of locally recurrent NPC due to the limitations in dose distribution and biological effectiveness. Improved outcome in terms of treatment-induced toxicity, LC, LPFS, and OS are expected using CIRT due to the physical and biological characteristics of carbon ion beam. However, the recommended dose of CIRT used in re-irradiation for the local NPC focus remain to be determined. The recommended dose as well as the efficacy of CIRT in the treatment of locally recurrent NPC will be evaluated in the present trial.

SU‐E‐T‐503: Intensity Modulated Proton Therapy (IMPT) Versus Intensity Modulated X‐Ray Therapy (IMRT) for Patient with Hepatocellular Carcinoma: A Dosimetric Comparison

PurposeThis study compares the dosimetric parameters in treatment of unresectable hepatocellular carcinoma between intensity modulated proton therapy (IMPT) and intensity modulated x‐ray radiation therapy (IMRT). Methods and Materials: We studied four patients treated at our institution. All patients were simulated supine with 4D‐CT using a GE light speed simulator with a maximum slice thickness of 3mm. The average CT and an internal target volume to account for respiration motion were used for planning. Both IMRT and IMPT plans were created using Elekta's CMSXiO treatment planning system (TPS). The prescription dose was 58.05 CGE in 15 fractions. The IMRT plans had five beams with combination of co‐planar and non‐co‐planar. The IMPT plans had 2 to 3 beams. Dose comparison was performed based on the averaged results of the four patients.ResultsThe mean dose and V95% to PTV were 58.24CGE, 98.57% for IMPT, versus 57.34CGE and 96.68% for IMRT, respectively. The V10, V20, V30 and mean dose of the normal liver for IMPT were 23.10%, 18.61%, 13.75% and 9.78 CGE; and 47.19%, 37.55%, 22.73% and 17.12CGE for IMRT. The spinal cord didn't receive any dose in IMPT technique, but received a maximum of 18.77CGE for IMRT. The IMPT gave lower maximum dose to the stomach as compared to IMRT (19.26 vs 26.35CGE). V14 for left and right kidney was 0% and 2.32% for IMPT and 3.89% and 29.54% for IMRT. The mean dose, V35, V40 and V45 for small bowl were similar in both techniques, 0.74CGE, 6.27cc, 4.85cc and 3.53 cc for IMPT, 3.47CGE, 9.73cc, 7.61cc 5.35cc for IMRT.ConclusionBased on this study, IMPT plans gave less dose to the critical structures such as normal liver, kidney, stomach and spinal cord as compared to IMRT plans, potentially leading to less toxicity and providing better quality of life for patients.

Bone marrow sparing in intensity modulated proton therapy for cervical cancer: Efficacy and robustness under range and setup uncertainties

Background and purposeThis study evaluates the potential efficacy and robustness of functional bone marrow sparing (BMS) using intensity-modulated proton therapy (IMPT) for cervical cancer, with the goal of reducing hematologic toxicity. Material and methodsIMPT plans with prescription dose of 45Gy were generated for ten patients who have received BMS intensity-modulated X-ray therapy (IMRT). Functional bone marrow was identified by 18F-flourothymidine positron emission tomography. IMPT plans were designed to minimize the volume of functional bone marrow receiving 5–40Gy while maintaining similar target coverage and healthy organ sparing as IMRT. IMPT robustness was analyzed with ±3% range uncertainty errors and/or ±3mm translational setup errors in all three principal dimensions. ResultsIn the static scenario, the median dose volume reductions for functional bone marrow by IMPT were: 32% for V5Gy, 47% for V10Gy, 54% for V20Gy, and 57% for V40Gy, all with p<0.01 compared to IMRT. With assumed errors, even the worst-case reductions by IMPT were: 23% for V5Gy, 37% for V10Gy, 41% for V20Gy, and 39% for V40Gy, all with p<0.01. ConclusionsThe potential sparing of functional bone marrow by IMPT for cervical cancer is significant and robust under realistic systematic range uncertainties and clinically relevant setup errors.

3D calculation of radiation-induced second cancer risk including dose and tissue response heterogeneities.

Tools for comparing relative induced second cancer risk, to inform choice of radiotherapy treatment plan, are becoming increasingly necessary as the availability of new treatment modalities expands. Uncertainties, in both radiobiological models and model parameters, limit the confidence of such calculations. The aim of this study was to develop and demonstrate a software tool to produce a malignant induction probability (MIP) calculation which incorporates patient-specific dose and allows for the varying responses of different tissue types to radiation. The tool has been used to calculate relative MIPs for four different treatment plans targeting a subtotally resected meningioma: 3D conformal radiotherapy (3DCFRT), volumetric modulated arc therapy (VMAT), intensity-modulated x-ray therapy (IMRT), and scanned protons. Two plausible MIP models, with considerably different dose-response relationships, were considered. A fractionated linear-quadratic induction and cell-kill model gave a mean relative cancer risk (normalized to 3DCFRT) of 113% for VMAT, 16% for protons, and 52% for IMRT. For a linear no-threshold model, these figures were 105%, 42%, and 78%, respectively. The relative MIP between plans was shown to be significantly more robust to radiobiological parameter uncertainties compared to absolute MIP. Both models resulted in the same ranking of modalities, in terms of MIP, for this clinical case. The results demonstrate that relative MIP is a useful metric with which treatment plans can be ranked, regardless of parameter- and model-based uncertainties. With further validation, this metric could be used to discriminate between plans that are equivalent with respect to other planning priorities.

Proton therapy in adjuvant treatment of gastric cancer: Planning comparison with advanced x-ray therapy and feasibility report

Background. Adjuvant chemoradiotherapy improves both overall- and relapse-free survival in patients with resected gastric cancer. However, this comes at the cost of increased treatment-related toxicity. Proton therapy (PT) has distinct dosimetric characteristics that may reduce dose to normal tissues, improving the therapeutic ratio. The purpose of this treatment planning study is to compare PT and intensity-modulated x-ray therapy (IMXT) in gastric cancer with regards to normal tissue sparing.Material and methods. The patient population consisted of resected gastric cancer patients treated at a single institution between 2008 and 2013. Patients who had undergone 4D CT simulation were replanned to the originally delivered doses (45–54 Gy in 25–30 daily fractions) using six-field photon IMXT and 2–3-field PT (double scattering-uniform scanning techniques).Results. Thirteen patients were eligible for the planning comparison. IMXT provided slightly higher homogeneity indices (median values 0.04 ± 0.01 vs. 0.07 ± 0.01, p = 0.03). PT resulted in significantly (p < 0.05) lower intermediate-low doses for all the normal tissues examined (small bowel V15 82 ml vs. 133 ml, liver mean doses Gy 11.9 vs. 14.4 Gy, left/right kidney mean doses 5/0.9 Gy vs. 7.8/3.1 Gy, heart mean doses 7.4 Gy vs. 9.5 Gy). The total energy deposited outside the target volume was significantly lower with PT (median integral dose 90.1 J vs. 129 J). Four patients were treated with PT: treatment was feasible and verifications scans showed that target coverage was robust.Conclusion. PT can contribute to normal tissue sparing in the adjuvant treatment of gastric cancer, with a potential benefit in terms of compliance to treatment, acute and late toxicities.

Proton versus photon radiation therapy for patients with high‐risk neuroblastoma: The need for a customized approach

Proton therapy for treatment for high-risk neuroblastoma may offer sparing of organs at risk (OAR) when compared to intensity-modulated X-ray therapy (IMXT). Double-scattered proton plans and IMXT plans delivering 2,160 cGy to the primary tumor site and other residual disease were developed for 13 consecutive HR-NBL patients. Radiation doses to target volumes and OAR were calculated to determine the optimal modality for each. All patients received radiation (5/13 ≥ 2 sites). No patient has experienced local recurrence or clinical organ toxicity. Coverage was excellent using both protons and IMXT: median % dose delivered to 95% clinical target volume was 99% and 100%, respectively. For nine patients with lateralized disease, proton therapy offered sparing of the contralateral kidney both with regard to median dose and dose to 20% (median <1 cGy vs. 362 cGy, P = 0.01; median 100 cGy vs. 634 cGy, P = 0.02, respectively). Proton therapy did not reduce ipsilateral kidney dose, and for 2 select patients with lateralized disease IMXT improved overall bilateral renal sparing. Proton therapy improved median bowel (median 33 cGy vs. 590 cGy, P = 0.01), total body (median <1 cGy vs. 30 cGy, P = 0.15), and liver dose (median <1 cGy vs. 529, P < 0.001). When chest RT was required, proton therapy decreased median heart dose and mean lung dose. For most patients (11/13), proton therapy offered the optimal combination of target coverage and organ sparing, and is a feasible treatment for HR-NBL. We recommend a customized approach with careful evaluation of renal dosimetry; IMXT may be preferred for select patients.

Delivery confirmation of bolus electron conformal therapy combined with intensity modulated x-ray therapy

The purpose of this study was to demonstrate that a bolus electron conformal therapy (ECT) dose plan and a mixed beam plan, composed of an intensity modulated x-ray therapy (IMXT) dose plan optimized on top of the bolus ECT plan, can be accurately delivered. Calculated dose distributions were compared with measured dose distributions for parotid and chest wall (CW) bolus ECT and mixed beam plans, each simulated in a cylindrical polystyrene phantom that allowed film dose measurements. Bolus ECT plans were created for both parotid and CW PTVs (planning target volumes) using 20 and 16 MeV beams, respectively, whose 90% dose surface conformed to the PTV. Mixed beam plans consisted of an IMXT dose plan optimized on top of the bolus ECT dose plan. The bolus ECT, IMXT, and mixed beam dose distributions were measured using radiographic films in five transverse and one sagittal planes for a total of 36 measurement conditions. Corrections for film dose response, effects of edge-on photon irradiation, and effects of irregular phantom optical properties on the Cerenkov component of the film signal resulted in high precision measurements. Data set consistency was verified by agreement of depth dose at the intersections of the sagittal plane with the five measured transverse planes. For these same depth doses, results for the mixed beam plan agreed with the sum of the individual depth doses for the bolus ECT and IMXT plans. The six mean measured planar dose distributions were compared with those calculated by the treatment planning system for all modalities. Dose agreement was assessed using the 4% dose difference and 0.2 cm distance to agreement. For the combined high-dose region and low-dose region, pass rates for the parotid and CW plans were 98.7% and 96.2%, respectively, for the bolus ECT plans and 97.9% and 97.4%, respectively, for the mixed beam plans. For the high-dose gradient region, pass rates for the parotid and CW plans were 93.1% and 94.62%, respectively, for the bolus ECT plans and 89.2% and 95.1%, respectively, for the mixed beam plans. For all regions, pass rates for the parotid and CW plans were 98.8% and 97.3%, respectively, for the bolus ECT plans and 97.5% and 95.9%, respectively, for the mixed beam plans. For the IMXT component of the mixed beam plans, pass rates for the parotid and CW plans were 93.7% and 95.8%. Bolus ECT and mixed beam therapy dose delivery to the phantom were more accurate than IMXT delivery, adding confidence to the use of planning, fabrication, and delivery for bolus ECT tools either alone or as part of mixed beam therapy. The methodology reported in this work could serve as a basis for future standardization of the commissioning of bolus ECT or mixed beam therapy. When applying this technology to patients, it is recommended that an electron dose algorithm more accurate than the pencil beam algorithm, e.g., a Monte Carlo algorithm or analytical transport such as the pencil beam redefinition algorithm, be used for planning to ensure the desired accuracy.

Adjuvant Radiation for Bladder Cancer: A Dosimetry Study

Adjuvant Radiation for Bladder Cancer: A Dosimetry Study

Comparison of Scanning Beam Proton Therapy (SBPT) to Intensity Modulated X-ray Therapy (IMRT) for Postoperative Salvage Treatment of Prostate Cancer Patients

To determine if significant normal tissue sparing without sacrificing target coverage can be achieved using scanning beam proton therapy (SBPT) compared to intensity modulated x-ray therapy (IMRT) for prostate cancer patients treated for salvage after prostatectomy.

The energy margin strategy for reducing dose variation due to setup uncertainty in intensity modulated proton therapy (IMPT) delivered with distal edge tracking (DET)

Intensity‐modulated proton therapy (IMPT) can produce plans with similar target dose conformity but lower normal tissue dose than intensity‐modulated X‐ray therapy (IMXT). However, due to the finite range of proton beams in tissue, proton therapy treatment plans are usually more sensitive to setup uncertainties than X‐ray therapy plans. In this work, the energy margin (EM) concept, which was initially developed for passive scattering proton therapy, was generalized to apply to IMPT treatment planning. The effectiveness of the EM method was evaluated on five head‐and‐neck cancer patients with distal edge tracking (DET) treatment plans by comparing the original plans (ORG) without an EM to those with an EM. Three beam arrangements were considered: 24 beams delivered over a 360° arc, 12 beams delivered over a 180° arc, and 12 beams delivered over two 90° fan angles. Setup uncertainty was modeled by sampling rigid translational shifts from a Gaussian distribution with a mean of 0 mm and standard deviation of 2 mm in all directions. Delivered dose distributions for all 30 fractions were recalculated using the Geant4 Monte Carlo code. Normalized total dose (NTD) for both the CTV and a ring structure surrounding the PTV were recorded. The plan quality comparison revealed that EM plans had the same CTV coverage but higher dose to the normal tissue than ORG plans. After the simulated delivery, ORG plans resulted in more than 3% underdosage to 5% of the CTV volume in all three beam arrangements, whereas the EM plans did not. Both ORG and EM plans did not produce more than 5% overdose to D2% of the ring structure. The use of an EM for IMPT treatment planning can substantially reduce sensitivity of the resulting dose distributions to setup uncertainty.PACS number: 87.55.K‐

A treatment planning comparison between proton beam therapy and intensity-modulated x-ray therapy for recurrent nasopharyngeal carcinoma

A comparative treatment planning study was undertaken between proton beam therapy (PBT) and intensity-modulated x-ray therapy (IMXT) for patients with recurrent nasopharyngeal carcinoma (NPC), to assess the potential benefits and limitations of the two treatment modalities. We retrospectively analyzed seven patients with recurrent NPC treated at our proton center with PBT from 2004 to 2007. Eclipse proton treatment planning system and Eclipse inverse treatment planning system for IMXT were employed. For each patient, the IMXT plan was optimized with nine evenly spaced coplanar fields. Three coplanar beams and passive scattering mode were used for PBT. The dose prescription in cobalt Gray equivalent (CGE) for gross tumor volume (GTV) was 66CGE and for planning target volume (PTV), 62.7CGE. Dose-volume histograms (DVH) were used to evaluate the difference in dosimetric distributions for the target volume and the organs at risk (OARs). Optimal target volume coverage and similar target conformation were achieved in both PBT and IMXT. Median conformity index was 0.72 and 0.75 (p=0.15) and median inhomogeneity coefficient was 0.14 and 0.10 (p=0.08) for PBT and IMXT, respectively. Dose to OARs was significantly lower in PBT plans than IMXT. Median maximal dose to the brainstem was 27.89CGE(cobalt Gray equivalent) and 42.45Gy (p< 0.01), and the dose to 5% of the brainstem(D5) was 12.83CGE and 19.47Gy (p< 0.001 ), for PBT and IMXT, respectively. Median maximal dose to the spinal cord was 8.38CGE and 22.91Gy (p< 0.004), and the dose to 5% of the spinal cord was 2.18CGE and 13.62Gy (p< 0.001), for PBT and IMXT, respectively. The use of PBT, when compared with IMXT, resulted in similar levels of tumor conformation. PBT, however, exposed the OARs to a significantly lower dose, effectively sparing the brainstem, spinal cord, optic nerve and chiasm, temporal lobes and parotid glands. The superior dose distributions possible with PBT should translate into reduced morbidity and improved quality of life.