Normal Tissue Constraints Research Articles

Hemiablative Focal Low Dose Rate Brachytherapy: A Phase II Trial Protocol.

BackgroundThe objective of focal brachytherapy (BT) is to provide effective prostate cancer control for low-risk disease but with reduced genitourinary, gastrointestinal and sexual side effects in a cost-effective way.ObjectiveThe aim of this study is to describe a phase II study examining technical and dosimetric feasibility and toxicity, quality of life changes, and local control with post-treatment biopsy outcomes in men with early stage low volume prostate cancer treated with focal iodine-125 seed BT.MethodsThe study design is a prospective, multicenter trial with a planned sample size of 20 patients including men with a minimum age of 60 years, a life expectancy estimated to be greater than 10 years, with low or low-tier intermediate risk prostate cancer, unilateral disease on the biopsy, and a Gleason score of ≤3+4 and <25% cores involved. The investigations specific for the study are multi-parametric magnetic resonance imaging (Mp-MRI) baseline, at 20 and 36 months to rule out high grade disease and a transperineal mapping biopsy (baseline and at 36 months) for more accurate patient selection. The hemigland region will receive 144 Gy. Standard normal tissue constraints will be considered as for a whole gland (WG) implant. Dosimetric parameters will be evaluated at day 30 after the implant. Toxicity and quality of life will be evaluated with international validated questionnaires focusing on urinary, rectal, sexual domain, and general health-related quality of life. The patients will complete this assessment at baseline and then approximately every 6 months after the implant up to 10 years.ResultsTo date, one patient is involved in the trial. He underwent the pre-implant investigations which found bilateral disease. Therefore, a standard seed implant was performed. If the results from this trial provide evidence that the treatment is safe, feasible, and improves toxicity, funding will be sought to conduct a large, multicenter, randomized controlled trial (RCT).ConclusionsThis protocol is designed to show feasibility in delivering hemigland focal therapy with seed BT. It may answer crucial questions and obtain data which will enable downstream decisions on focal low dose rate (LDR) prostate BT.ClinicalTrialClinicaltrial.gov NCT02643511; https://www.clinicaltrials.gov/ct2/show/NCT02643511 (Archived by Webcite at http://www.webcitation.org/6ghLCzIhY)

SU‐F‐T‐395: Evaluation of Best Dosimetry Achievable with VMAT and IMRT Treatment Techniques Targeting Borderline Resectable Pancreatic Cancer

Purpose:To determine from retrospective study the most appropriate technique for targeting small borderline operable pancreatic cancer surrounding blood vessels by evaluating the dosimetry and normal tissue sparing achievable using Volumetric Modulated Arc Therapy (VMAT) and Intensity Modulated Radiation Therapy (IMRT).Methods:Treatment plans from ten patients who have undergone treatment with a prescribed dose of 4950 cGy, at 275 cGy per fraction, were analyzed. All plans were replanned using Eclipse TPS (Varian Medical Systems, Palo Alto, CA) with complementary VMAT or IMRT techniques to obtain paired data sets for comparison. The coverage to at least 95% of the planned target volume (PTV) was normalized to receive 100% of the prescription dose. The normal tissue constraints followed the quantitative analysis of normal tissue effects in the clinic (QUANTEC) guidelines and the organs at risks (OARs) were liver, kidneys, spinal cord and bowel. The plan evaluation was based on conformity index (CI), homogeneity index (HI), uniformity index (UI), DVH parameters, and student's‐t statistics (2 tails).Results:The VMAT technique delivered less maximum dose to the right kidney, left kidney, total kidney, liver, spinal cord, and bowel by 9.3%, 5.9%, 6.7%, 3.9%, 15.1%, 3.9%, and 4.3%, respectively. The averaged V15 for the total kidney was 10.21% for IMRT and 7.29% for VMAT. The averaged V20 for the bowel was 19.89% for IMRT and 14.06% for VMAT. On average, the CI for IMRT was 1.20 and 1.16 for VMAT (p = 0.20). The HI was 0.08 for both techniques (p = 0.91) and UI was 1.05 and 1.06 for IMRT and VMAT respectively (p = 0.59).Conclusion:Both techniques achieve adequate PTV coverage. Although VMAT techniques show better normal tissue sparing from excessive dose, no significant differences were observed. Slight discrepancies may rise from different versions of calculation algorithms.

SU‐F‐T‐150: Comparing Normal Tissue Irradiated Volumes for Proton Vs. Photon Treatment Plans On Lung Patients

Purpose:The aim of this work is to compare the “irradiated volume” (IRV) of normal tissues receiving 5, 20, 50, 80 and 90% or higher of the prescription dose with passively scattered proton therapy (PSPT) vs. IMRT of lung cancer patients. The overall goal of this research is to understand the factors affecting outcomes of a randomized PSPT vs. IMRT lung trial.Methods:Thirteen lung cancer patients, selected randomly, were analyzed. Each patient had PSPT and IMRT 74 Gy (RBE) plans meeting the same normal tissue constraints generated. IRVs were created for pairs of IMRT and PSPT plans on each patient. The volume of iGTV, (respiratory motion‐incorporated GTV) was subtracted from each IRV to create normal tissue irradiated volume IRVNT. The average of IRVNT DVHs over all patients was also calculated for both modalities and inter‐compared as were the selected dose‐volume indices. Probability (p value) curves were calculated based on the Wilcoxon matched‐paired signed‐rank test to determine the dose regions where the statistically significant differences existed.Results:As expected, the average 5, 20 and 50% IRVNT's for PSPT was found to be significantly smaller than for IMRT (p &lt; 0.001, 0.01, and 0.001 respectively). However, the average 90% IRVNT for PSPT was greater than for IMRT (p = 0.003) presumably due to larger penumbra of protons and the long range of protons in lower density media. The 80% IRVNT for PSPT was also larger but not statistically distinguishable (p = .224).Conclusion:PSPT modality has smaller irradiated volume at lower doses, but larger volume at high doses. A larger cohort of lung patients will be analyzed in the future and IRVNT of patients treated with PSPT and IMRT will be compared to determine if the irradiated volumes (the magnitude of “dose bath”) correlate with outcomes.

Clinical results of mean GTV dose optimized robotic guided SBRT for liver metastases.

BackgroundWe retrospectively evaluated the efficacy and toxicity of gross tumor volume (GTV) mean-dose-optimized and real-time motion-compensated robotic stereotactic body radiation therapy (SBRT) in the treatment of liver metastases.MethodsBetween March 2011 and July 2015, 52 patients were treated with SBRT for a total of 91 liver metastases (one to four metastases per patient) with a median GTV volume of 12 cc (min 1 cc, max 372 cc). The optimization of mean GTV dose was prioritized during treatment planning at the potential cost of planning target volume (PTV) coverage reduction while adhering to safe normal tissue constraints. The delivered median GTV biological effective dose (BED10) was 142.1 Gy10 (range, 60.2 Gy10 –165.3 Gy10) and the prescribed PTV BED10 ranged from 40.6 Gy10 to 112.5 Gy10 (median, 86.1 Gy10). We analyzed local control (LC), progression-free interval (PFI), overall survival (OS), and toxicity.ResultsMedian follow-up was 17 months (range, 2–49 months). The 2-year actuarial LC, PFI, and OS rates were 82.1, 17.7, and 45.0 %, and the median PFI and OS were 9 and 23 months, respectively. In univariate analysis histology (p < 0.001), PTV prescription BED10 (HR 0.95, CI 0.91–0.98, p = 0.002) and GTV mean BED10 (HR 0.975, CI 0.954–0.996, p = 0.011) were predictive for LC. Multivariate analysis showed that only extrahepatic disease status at time of treatment was a significant factor (p = 0.033 and p = 0.009, respectively) for PFI and OS. Acute nausea or fatigue grade 1 was observed in 24.1 % of the patients and only 1 patient (1.9 %) had a side effect of grade ≥ 2.ConclusionsRobotic real-time motion-compensated SBRT is a safe and effective treatment for one to four liver metastases. Reducing the PTV prescription dose and keeping a high mean GTV dose allowed the reduction of toxicity while maintaining a high local control probability for the treated lesions.

Bayesian randomized trial comparing intensity modulated radiation therapy versus passively scattered proton therapy for locally advanced non-small cell lung cancer.

8500Background: We assessed rates of and time to treatment failure (TF) [either grade ≥ 3 radiation pneumonitis (RP) or local recurrence (LR) within 12 months] in a Bayesian randomized trial of intensity-modulated radiotherapy (IMRT) vs. 3D proton therapy (3DPT), both with concurrent chemotherapy, for locally advanced non-small cell lung cancer (NSCLC). Methods: Assumptions for chosen sample size (n = 150) were that TF rate is log-normally distributed; IMRT will produce TF rates of 30% at 6 months (mos) and 40% at 12 mos; and 3DPT would reduce the TF rate by 10%. Pairs of IMRT and 3DPT plans were created for each patient. Patients were eligible for randomization only if both plans satisfied normal tissue constraints at the same radiation dose. Patients not eligible for randomization (NR) were treated with the modality producing the better plan. Patients denied coverage for protocol treatment were treated with the modality that was covered. Results: Of 255 enrolled patients, 149 were randomly allocated to ...

Protocol for the isotoxic intensity modulated radiotherapy (IMRT) in stage III non-small cell lung cancer (NSCLC): a feasibility study

IntroductionThe majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy, the non-surgical gold standard of care. As the alternative treatment options of sequential...

Two-arc volumetric modulated arc therapy to provide dosimetric advantages for pancreas stereotactic body radiotherapy.

445 Background: Stereotactic body radiation therapy(SBRT) is increasingly used in locally advanced pancreatic cancer (LAPC). SBRT can be delivered using 3D conformal, static intensity modulated radiotherapy (IMRT), and volumetric modulated arc therapy (VMAT) techniques. Prior data suggest advantages of using VMAT over IMRT for single-fraction pancreas SBRT. We performed the first dosimetric comparison of IMRT with one and two arc VMAT for 5-fraction pancreas SBRT, a more commonly used regimen. Methods: We generated 5-fraction SBRT plans for 12 LAPC patients who were previously treated at our institution with standard fractionation. The prescription dose was 33 Gy delivered in 6.6 Gy fractions. Assuming breath hold, 3 plans were generated for each patient: 9-beam static IMRT, 1-arc VMAT (VMAT1), and 2-arc VMAT (VMAT2) targeting the primary tumor. Target coverage and normal tissue doses were compared between the delivery techniques. Results: Each plan met target coverage planning goals. More VMAT2 plans (100%) were able to meet all normal tissue constraints than VMAT1 (83.3%) or IMRT (75%). Duodenal dose was most lowest for VMAT2 compared to VMAT1 and IMRT for mean dose (8.66 vs. 9.00 vs. 8.99 Gy); D4% (25.9 vs. 26.6 vs. 26.3 Gy); V10Gy (38.02 vs. 39.33 vs. 40.11%), V15Gy (23.98 vs. 25.88 vs. 25.97%), V20Gy (12.73 vs. 13.84 vs. 14.95%), and V25Gy (5.96 vs. 6.85 vs. 6.78%)(all p &lt; 0.05). The tumors closest to the duodenum had statistically significantly improved V30Gy for VMAT2 compared to VMAT1 and IMRT (both p &lt; 0.001). VMAT1 and VMAT2 reduced dose to the stomach, spinal cord, and liver compared to IMRT; kidney dose, however, was lowest using IMRT. VMAT2 plans had the highest conformity, but required the most monitor units to deliver. Delivery time was significantly longer with IMRT, compared to VMAT1 and VMAT2 (8.25 vs. 2.16 vs. 3.33 mins). Conclusions: These data suggest that VMAT2 should be strongly considered for 5-fraction pancreas SBRT because of superior normal tissue sparing, more conformal target volume coverage, and faster treatment delivery time (compared to IMRT). Further evaluation is needed to clarify whether the dosimetric advantages of VMAT2 are clinically significant.

The significance of PTV dose coverage on cancer control outcomes in early stage non-small cell lung cancer patients treated with highly ablative stereotactic body radiation therapy.

We evaluated whether patients with early-stage non-small-cell lung cancers (NSCLCs) treated with stereotactic body radiation therapy (SBRT) without full prescription dose coverage of the planning target volume (PTV) had inferior outcomes. The SBRT regimen was 54 Gy in three fractions. Dosimetric constraints were as per the Radiation Therapy Oncology Group 0236 guidelines. All patients underwent four-dimensional CT (4D-CT) simulation. The internal target volume (ITV) was defined using 4D-CT, and the PTV was defined as a 6-mm longitudinal and a 3-mm axial expansion from the ITV. If normal tissue constraints were beyond tolerance, ITV-based dosing was employed where priority was made for full ITV coverage at the expense of PTV coverage. Patients with and without full PTV dose coverage were compared, and control rates were estimated using Kaplan-Meier analysis. 120 NSCLC cases were evaluated with 81% having adequate PTV dose coverage. ITV and PTV were significantly larger in the cohort with inadequate PTV dose coverage (p = 0.0085 and p = 0.0038, respectively), and the mean ITV and PTV doses were higher in patients with adequate PTV dose coverage (p = 0.002 and p < 0.0001, respectively). The 3-year local control rate was 100% for both cohorts. There was no difference in 3-year regional control (p = 0.36), disease-specific survival (p = 0.79) or overall survival (p = 0.73). When delivering a highly ablative SBRT regimen for early-stage NSCLC, full-dose coverage of the ITV is sufficient for local control. Our data are among the first to evaluate the utility of PTV margins in a highly ablative SBRT regimen and suggest that when dosing constraints cannot be met, full tumouricidal dose coverage of the ITV is sufficient for local control.

Validation of RTOG 0813 Normal Tissue Constraints for Stereotactic Body Radiation in Central Lung Tumors

Validation of RTOG 0813 Normal Tissue Constraints for Stereotactic Body Radiation in Central Lung Tumors

Adaptive planning using positron emission tomography for locally advanced lung cancer: A feasibility study

PurposeTo evaluate the feasibility of adaptive planning using positron emission tomography–computed tomography (PET-CT) in locally advanced non-small cell lung cancer. Methods and materialsPatients with locally advanced non-small cell lung cancer receiving definitive radiation therapy (RT) were eligible. Initial planning PET-CT was performed and a conventional RT plan (2 Gy/fraction to 60 Gy) was designed. A second planning PET-CT was obtained at ~50 Gy. Dose escalation to ~70 Gy for residual fludeoxyglucose-avid disease was pursued at the discretion of the treating oncologists. The primary endpoint was feasibility of adaptive planning using interim PET-CT. Normal tissue dose-volume parameters were calculated for both adaptive and simulated nonadaptive plans. ResultsFrom 2012 to 2014, 33 eligible patients were enrolled and underwent planning PET-CT, 3 of which were found to have new distant metastases. Of 30 patients who initiated RT, interim PET-CT was obtained in 29. This showed complete response in 2 patients, partial response/stable disease in 24, and new distant metastases in 3. Selective dose escalation was performed in 17 patients. For those receiving a boost, the median gross tumor volumes pre-RT and at ~50 Gy were 78 mL and 29 mL, respectively (P = .01). Reasons for no dose escalation were normal tissue constraints (n = 3), poorly defined residual disease (n = 2), acute toxicity (n = 1), and refusal of further therapy (n = 1). Adaptive planning compared with a simulated nonadaptive approach allowed for significant dose reductions to the lungs, heart, and esophagus (all P < .01). ConclusionsAdaptive planning using PET-CT was feasible and allows for significant dose reductions to normal tissues compared with traditional planning techniques.

Rates of unacceptable variation (UV) of normal tissue constraints in patients undergoing chest wall/breast and regional nodal irradiation (RNI) in a routine clinical practice.

67 Background: TheNSABP B51/RTOG 1304 clinical trial defines dose-volume constraints for targets/normal tissue receiving RNI. We sought to evaluate UV rate in normal tissue based on the NSABP B51/RTOG 1304 protocol in patients receiving chestwall/breast (CW/B) and RNI in daily practice. Methods: Treatment records of CW/B+RNI patients from 2/2012-5/2015 were studied for: CW or B radiotherapy (RT), RT type (intensity modulated [IMRT] or 3D conformal [3DCRT]), internal mammary node (IMN) inclusion, primary site boost, and nodal boost. No case is enrolled on B51/1304. Dose volume histogram (DVH) was analyzed for the rate of ≥ 1 UV for the following normal tissue constraints: Heart mean dose ≤ 5 Gy; ipsilateral lung (IL): V20 ≤ 35%, V10 ≤ 60%, V5 ≤ 70%; contralateral lung (CL) V5 ≤ 15%; contralateral breast (CB) V4.1 ≤ 5%. Logistic regression is used to test the association between UV and key variables. Results: 203 consecutive cases received CW/B+RNI (105 left, 98 right). RT was to CW in 170 (84%), B in 33 (16%), primary site boost 133 (66%), and IMN 170 (84%). 38 (19%) received IMRT and 14 (6.9%) had a nodal boost. 46 patients (22.6%) had ≥ 1 UV. 19 patients (9.4%) had ≥ 2 UV, all in IMRT patients. 2 patients (1.0%) had a heart UV at 5.2 Gy and 5.6 Gy. The most common UV was CB (n = 32, 15.7%) and IL V5 (n = 22, 10.8%). Higher UV rates are associated with use of IMRT (vs. 3DCRT): 86.8% vs. 7.9%, OR = 77.2 (95% CI 25.7-231.4, p &lt; 0.0001); IMN irradiation: OR = 11.5 (95% CI 1.5-86.8, p = 0.02); and use of nodal boost: OR = 7.4 (95% CI 2.3-23.4, p = 0.001). The most common UVs in IMRT cases are CB (n = 27, 71%), IL V5 (n = 19, 50%), CL V5 (n = 14, 37%) and for 3DCRT are IL V20 (n = 5, 3%), CB (n = 5, 3%) and IL V5 (n = 3, 1.8%). On multivariate analysis, use of IMRT (OR = 64.7, 95% CI 20.8-201.5, p &lt; 0.001) and use of nodal boost (OR = 5.5, 95% CI 1.1-27.1, p = 0.04) but not IMN irradiation (OR = 2.7, 95% CI 0.3-22.0, p = 0.35) were independently associated with higher UV rate. Conclusions: The rate of UV per B51/1304 criteria with 3DCRT in routine clinical practice is low (7.9%). Women treated with IMRT had a significantly higher overall UV rate and clinicians should be aware of this as they initiate treatment planning for RNI.

TU-AB-201-06: Evaluation of Electromagnetically Guided High- Dose Rate Brachytherapy for Ablative Treatment of Lung Metastases

Purpose: The advent of electromagnetic navigation bronchoscopy has enabled minimally invasive access to peripheral lung tumors previously inaccessible by optical bronchoscopes. As an adjunct to Stereotactic Ablative Radiosurgery (SABR), implantation of HDR catheters can provide focal treatments for multiple metastases and sites of retreatments. The authors evaluate a procedure to deliver ablative doses via Electromagnetically-Guided HDR (EMG-HDR) to lung metastases, quantify the resulting dosimetry, and assess its role in the comprehensive treatment of lung cancer. Methods: A retrospective study was conducted on ten patients, who, from 2009 to 2011, received a hypo-fractionated SABR regimen with 6MV VMAT to lesions in various lobes ranging from 1.5 to 20 cc in volume. A CT visible pathway was delineated for EM guided placement of an HDR applicator (catheter) and dwell times were optimized to ensure at least 98% prescription dose coverage of the GTV. Normal tissue doses were calculated using inhomogeneity corrections via a grid-based Boltzmann solver (Acuros_BV_1.5.0). Results: With EMG-HDR, an average of 83% (+/−9% standard deviation) of each patient's GTV received over 200% of the prescription dose, as compared to SABR where the patients received an average maximum dose of 125% (+/−5%). EMG-HDR enabled a 59% (+/−12%) decrease in the aorta maximum dose, a 63% (+/−26%) decrease in the spinal cord max dose, and 57% (+/−23%) and 70% (+/−17%) decreases in the volume of the body receiving over 50% and 25% of the prescription dose, respectively. Conclusion: EMG-HDR enables delivery of higher ablative doses to the GTV, while concurrently reducing surrounding normal tissue doses. The single catheter approach shown here is limited to targets smaller than 20 cc. As such, the technique enables ablation of small lesions and a potentially safe and effective retreatment option in situations where external beam utility is limited by normal tissue constraints.

Optimized Construction of Multi-Channel Brachytherapy Cylinder Applicators

The purpose of this work is to identify an optimal construction for rigid multi-channel brachytherapy cylinder applicators, such that the clinical user can maximize lateral dose coverage while minimizing surface and normal tissue doses. Cylindrical multi-channel applicators are commonly used in HDR gynecological brachytherapy to treat the post-hysterectomy vaginal cuff. Literature suggests that adjuvant vaginal brachytherapy has high efficacy and low morbidity for intermediate-risk endometrial cancer [1]. Commercial vaginal cylinders may not have fully considered dosimetric consequences of the cylinder’s construction. Therefore we seek to provide manufacturers with guidance on the optimal radial offsets for peripheral channels within multi-channel cylinder applicators. Commercial multi-channel applicators typically consist of a cylindrical obturator with various diameter build-up caps. The obturator contains one central channel and two or more peripheral channels positioned at a fixed radial distance from the central channel. The radial distance from the central channel to peripheral channels affects the radioactive loading/weighting and usability of peripheral channels. For example, peripheral channels that are located very close to the patient surface cannot be loaded without quickly exceeding a mucosal surface dose limit (e.g. 200%). An ideal radial offset for peripheral channels can maximize asymmetric peripheral dose coverage of the target while maintaining surface dose <200% of prescription dose. This work simulated a multichannel cylinder consisting of a central channel and two lateral channels. A point source approximation was used. Initially, three Ir-192 VS200 sources were simulated for a vaginal cuff treatment, one source in each channel. Optimal dwell times were determined using the methods of Deufel and Furutani [2] to achieve 100% prescription dose 5 mm apically and 5 mm posteriorly from the cylinder surface, with mucosal surface dose <200%. (See Fig1 (a)) The radial distance of peripheral channels was varied from 0 to Rapplicator. The optimal radial distance, dlat, is the distance where lateral 100% dose coverage is maximum. This method was then extended to a vaginal cuff plus vault treatment for a cylinder with 6.5cm treatment length (Fig1 (b)). Dose optimization points were placed at the apex, along the cylinder surface and posterior 5mm along the treatment length to produce a homogenous dose. Results were obtained for cylinders with 3.0, 3.5, and 4.0 cm diameters. A comparison of point and line source results was also performed. Fig 1(c) demonstrates the lateral coverage as a function of dlat for a 3.5 cm diameter cylinder. The optimal lateral channel position is located at 2.8 mm, 4.1 mm and 5.2 mm away from the central channel for the cylinder in diameters of 3, 3.5 and 4cm and provides maximal lateral coverage of 5.7 mm, 6.3 mm and 7 mm from the applicator surface, respectively. Doses 5mm apically, 5mm posteriorly, and at the lateral surface are shown in Fig 1(d). The optimal radial distance for peripheral channels increases and maximum lateral coverage distance increases as cylinder diameter increases. Figs 1(e) and (f) provides results for cuff plus vault treatment. Compared to three-source loading, cuff plus vault treatment with more inferior loading can push dose more laterally (e.g. 7.4 mm vs. 4.1 mm for the 3.5cm applicator) This work proposes a method for optimized construction geometry of multi-channel vaginal cylinders. Manufacturers may use results to construct an applicator that provides maximum lateral coverage while maintaining normal tissue constraints. Furthermore, this work shows that a library of Atlas plans for vaginal cuff treatment may be efficiently and optimally generated using the methods of Deufel and Furutani.

A phase 1 trial of preoperative partial breast radiation therapy: Patient selection, target delineation, and dose delivery

PurposeDiffusion of accelerated partial breast irradiation into clinical practice is limited by the need for specialized equipment and training. The accessible external beam technique yields unacceptable complication rates, likely from large postoperative target volumes. We designed a phase 1 trial evaluating preoperative radiation therapy to the intact tumor using widely available technology. Methods and materialsPatients received 15, 18, or 21 Gy in a single fraction to the breast tumor plus margin. Magnetic resonance imaging (MRI) was used in conjunction with standard computed tomography (CT)-based planning to identify contrast enhancing tumor. Skin markers and an intratumor biopsy marker were used for verification during treatment. ResultsMRI imaging was critical for target delineation because not all breast tumors were reliably identified on CT scan. Breast shape differences were consistently seen between CT and MRI but did not impede image registration or tumor identification. Target volumes were markedly smaller than historical postoperative volumes, and normal tissue constraints were easily met. A biopsy marker within the breast proved sufficient for setup localization. ConclusionsThis single fraction linear accelerator–based partial breast irradiation approach can be easily incorporated at most treatment centers. In vivo targeting may improve accuracy and can reduce the dose to normal tissues.

Changes in Gross Tumor Volume and Organ Motion Analysis During Neoadjuvant Radiochemotherapy in Patients With Locally Advanced Pancreatic Cancer Using an In-House Analysis System.

During radiation treatment, movement of the target and organs at risks as well as tumor response can significantly influence dose distribution. This is highly relevant in patients with pancreatic cancer, where organs at risk lie in close proximity to the target. Data sets of 10 patients with locally advanced pancreatic cancer were evaluated. Gross tumor volume deformation was analyzed. Dose changes to organs at risk were determined with focus on kidneys both without adaptive radiotherapy compensation and with replanning based on weekly acquired computed tomography scans. During irradiation, gross tumor volume changes between 0% and 26% and moves within a radius of 5 to 16 mm. Required maximal dose to organs at risk for kidneys can be met with the current practice of matching computed tomography scans during treatment and adjusting patient position accordingly. Comparison of the mean doses and V15, V20 volumes demonstrated that weekly replanning could bring a significant dose sparing of the left kidney. Manual matching with focus on bony structures can lead to overall acceptable positioning of patients during treatment. Thus, tolerance doses of organs at risk, such as the kidneys, can be met. With adequate margins, normal tissue constraints to organs at risk can be kept as well. Adaptive radiotherapy approaches (in this case with weekly rescanning) reduced dose to organs at risk, which may be especially important for hypofractionated approaches.

Dosimetric Comparison of Volumetric Modulated Arc Therapy, Tomotherapy and Intensity Modulated Radiation Therapy for Radiation Dose Escalation of Hepatic Malignancies

Previously, radiation therapy has had a limited role in the management of hepatic malignancies due to the risk of radiation induced liver disease (RILD). However, recent advancements have allowed for dose escalation within the tumour volume while sparing normal tissues. These techniques have been employed, although comparisons regarding dosimetric integrity and the feasibility of dose escalation using normal tissue complication probability (NTCP) models have yet to be established. The aim of this study is to provide a dosimetric comparison of intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), and Tomotherapy (HT) with regards to dose escalation for primary and metastatic hepatic malignancies. Seventeen clinically delivered IMRT plans and two clinically delivered VMAT plans for patients treated for liver cancer were retrospectively reviewed. Each data set was optimized using two alternate delivery techniques, providing each patient with an IMRT, VMAT and HT plan. The gross tumour volume (GTV) was defined by the original treating oncologist, no clinical target volume (CTV) was included and planning target volumes (PTV) were 3mm expansions. The dose prescription was escalated until an NTCP of 5% was exceeded or until dose-volume constraints of all other normal tissues, normalized to 2Gy equivalent biological effective dose (BED), was exceeded. All plans achieved intended normal tissue constraints, including dose to the normal liver. Mean doses for VMAT, HT and IMRT were 85.2±44.6Gy, 79.1±47Gy, and 72.4±41.5Gy, respectively. Analysis revealed statistical significance between escalation levels when comparing the three modalities to one another; VMAT vs. HT (p=<0.001), VMAT vs. IMRT (p<0.001), HT vs. IMRT (p=0.005). In four cases, dose escalations were limited by normal tissues, rather than 5% NTCP. A comparison between treatment times revealed significantly lower times for VMAT (149±42s) than HT (841±317s) (p<0.001). Analysis of monitor units (MU) for VMAT and IMRT depicted mean values of 1479±497MU and 1326±605MU, respectively (p=0.054). The utilization of partial arcs, coupled with the implementation of gating techniques allows VMAT to greatly reduce normal liver dose while achieving a high dose to the target volume. Overall, VMAT is superior in terms of dose escalation maximums and reduced treatment delivery time for hepatic cancer.

Is dose escalation achievable for esophageal carcinoma?

AimTo investigate the feasibility of dose escalation using rapid arc (RA) and Helical Tomotherapy (HT) for patients with upper, middle and distal esophageal carcinomas, even for large tumor volumes. BackgroundIn esophageal cancer, for patients with exclusive radio-chemotherapy, local disease control remains poor. Planning study with dose escalation was done for two sophisticated modulated radiotherapy techniques: Rapid arc against Tomotherapy. Materials and methodsSix patients treated with a RA simultaneous integrated boost (SIB) of 60Gy were re-planned for RA and HT techniques with a SIB dose escalated to 70Gy. Dose volume histogram statistics, conformity indices and homogeneity indices were analyzed. For a given set of normal tissue constraints, the capability of each treatment modality to increase the GTV dose to 70Gy was investigated. ResultsEither HT or VMAT may be used to escalate the dose delivered in esophageal tumors while maintaining the spinal cord, lung and heart doses within tolerance. Adequate target coverage was achieved by both techniques. Typically, HT achieved better lung sparing and PTV coverage than did RA. ConclusionsDose escalation for esophageal cancer becomes clinically feasible with the use of RA and HT. This promising result could be explored in a carefully controlled clinical study which considered normal tissue complications and tumor control as endpoints.

Reassessing dose constraints of organs at risk in children with abdominal neuroblastoma treated with definitive radiation therapy: a correlation with late toxicity.

In children treated with definitive radiation therapy (RT) for abdominal neuroblastoma, normal tissue constraints for organs at risk (OARs) are not well-standardized or evidence-based. In this study, we analyze dosimetric data of principal abdominal OARs, reassess existing RT planning constraints, and examine corresponding acute and late toxicity to OARs. The treatment plans of 30 consecutive children who underwent definitive RT for high-risk abdominal neuroblastoma were reviewed. Dose-volume histogram (DVH) statistics were recorded for the ipsilateral kidney (if unresected), contralateral kidney, and liver. DVH data were analyzed to determine if OAR constraints from recent protocols were met and correlated with the development of toxicity. The median follow-up period was 53.0 months. Ten, thirteen, and ten percent of patients' RT plans did not meet OAR DVH constraints for the liver, ipsilateral kidney, and contralateral kidney, respectively. Of the three patients whose plans did not achieve ipsilateral kidney DVH constraint(s), two developed evidence of late ipsilateral kidney hypoplasia, but maintained normal laboratory kidney function. No patient experienced late toxicity of the contralateral kidney nor developed RT-related late hepatic complications. In children treated for abdominal neuroblastoma, the risk of developing clinically significant RT-related late toxicity of the kidney and liver is not appreciable, even when current DVH parameters for OARs are not achieved in planning. Toxicity outcomes did not necessarily correlate with present-day OAR dose constraints. Currently utilized DVH constraints are highly variable, and must be further studied and supported by toxicity outcomes to more accurately characterize risk of complications.

Clinical Implementation of Intensity Modulated Proton Therapy for Thoracic Malignancies

Intensity modulated proton therapy (IMPT) can improve dose conformality and better spare normal tissue over passive scattering techniques, but range uncertainties complicate its use, particularly for moving targets. We report our early experience with IMPT for thoracic malignancies in terms of motion analysis and management, plan optimization and robustness, and quality assurance. Thirty-four consecutive patients with lung/mediastinal cancers received IMPT to a median 66 Gy(relative biological equivalence [RBE]). All patients were able to undergo definitive radiation therapy. IMPT was used when the treating physician judged that IMPT conferred a dosimetric advantage; all patients had minimal tumor motion (<5 mm) and underwent individualized tumor-motion dose-uncertainty analysis and 4-dimensional (4D) computed tomographic (CT)-based treatment simulation and motion analysis. Plan robustness was optimized by using a worst-case scenario method. All patients had 4D CT repeated simulation during treatment. IMPT produced lower mean lung dose (MLD), lung V5 and V20, heart V40, and esophageal V60 than did IMRT (P<.05) and lower MLD, lung V20, and esophageal V60 than did passive scattering proton therapy (PSPT) (P<.05). D5 to the gross tumor volume and clinical target volume was higher with IMPT than with intensity modulated radiation therapy or PSPT (P<.05). All cases were analyzed for beam-angle-specific motion, water-equivalent thickness, and robustness. Beam angles were chosen to minimize the effect of respiratory motion and avoid previously treated regions, and the maximum deviation from the nominal dose-volume histogram values was kept at <5% for the target dose and met the normal tissue constraints under a worst-case scenario. Patient-specific quality assurance measurements showed that a median 99% (range, 95% to 100%) of the pixels met the 3% dose/3 mm distance criteria for the γ index. Adaptive replanning was used for 9 patients (26.5%). IMPT using 4D CT-based planning, motion management, and optimization was implemented successfully and met our quality assurance parameters for treating challenging thoracic cancers.

Clinical Implementation of Intensity Modulated Proton Therapy in Thoracic Malignancies

Clinical Implementation of Intensity Modulated Proton Therapy in Thoracic Malignancies