NTCP Values Research Articles

Quantify the Effect of Air Gap Errors on Skin Dose for Breast Cancer Radiotherapy.

Purpose: Determining the impact of air gap errors on the skin dose in postoperative breast cancer radiotherapy under dynamic intensity-modulated radiation therapy (IMRT) techniques. Methods: This was a retrospective study that involved 55 patients who underwent postoperative radiotherapy following modified radical mastectomy. All plans employed tangential IMRT, with a prescription dose of 50 Gy, and bolus added solely to the chest wall. Simulated air gap depth errors of 2 mm, 3 mm, and 5 mm were introduced at depression or inframammary fold areas on the skin, resulting in the creation of air gaps named Air2, Air3, and Air5. Utilizing a multivariable GEE, the average dose (Dmean) of the local skin was determined to evaluate its relationship with air gap volume and the lateral beam's average angle (AALB). Additionally, an analysis was conducted on the impact of gaps on local skin. Results: When simulating an air gap depth error of 2 mm, the average Dmean in plan2 increased by 0.46 Gy compared to the initial plan (planO) (p < .001). For the 3-mm air gap, the average Dmean of plan3 was 0.51 Gy higher than that of planO (p < .001). When simulating the air gap as 5 mm, the average Dmean of plan5 significantly increased by 0.59 Gy compared to planO (p < .001). The TCP results showed a similar trend to those of Dmean. As the depth of air gap error increases, NTCP values also gradually rise. The linear regression of the multivariable GEE equation indicates that the volume of air gaps and the AALB are strong predictors of Dmean. Conclusion: With small irregular air gap errors simulated in 55 patients, the values of skin's Dmean, TCP, and NTCP increased. A multivariable linear GEE regression model may effectively explain the impact of air gap volume and AALB on the local skin.

Technical note: Evaluation of deep learning based synthetic CTs clinical readiness for dose and NTCP driven head and neck adaptive proton therapy.

Adaptive proton therapy workflows rely on accurate imaging throughout the treatment course. Our centre currently utilizes weekly repeat CTs (rCTs) for treatment monitoring and plan adaptations. However, deep learning-based methods have recently shown to successfully correct CBCT images, which suffer from severe imaging artifacts, and generate high quality synthetic CT (sCT) images which enable CBCT-based proton dose calculations. To compare daily CBCT-based sCT images to planning CTs (pCT) and rCTs of head and neck (HN) cancer patients to investigate the dosimetric accuracy of CBCT-based sCTs in a scenario mimicking actual clinical practice. Data of 56 HN cancer patients, previously treated with proton therapy was used to generate 1.962 sCT images, using a previously developed and trained deep convolutional neural network. Clinical IMPT treatment plans were recalculated on the pCT, weekly rCTs and daily sCTs. The dosimetric accuracy of sCTs was compared to same day rCTs and the initial planning CT. As a reference, rCTs were also compared to pCTs. The dose difference between sCTs and rCTs/pCT was quantified by calculating the D98 difference for target volumes and Dmean difference for organs-at-risk. To investigate the clinical relevancy of possible dose differences, NTCP values were calculated for dysphagia and xerostomia. For target volumes, only minor dose differences were found for sCT versus rCT and sCT versus pCT, with dose differences mostly within ±1.5%. Larger dose differences were observed in OARs, where a general shift towards positive differences was found, with the largest difference in the left parotid gland. Delta NTCP values for grade 2 dysphagia and xerostomia were within ±2.5% for 90% of the sCTs. Target doses showed high similarity between rCTs and sCTs. Further investigations are required to identify the origin of the dose differences at OAR levels and its relevance in clinical decision making.

Partitioning of discrete proton arcs into interlaced subplans can bring proton arc advances to existing proton facilities.

Proton arcs have shown potential to reduce the dose to organs at risks (OARs) by delivering the protons from many different directions. While most previous studies have been focused on dynamic arcs (delivery during rotation), an alternative approach is discrete arcs, where step-and-shoot delivery is used over a large number of beam directions. The major advantage of discrete arcs is that they can be delivered at existing proton facilities. However, this advantage comes at the expense of longer treatment times. To exploit the dosimetric advantages of proton arcs, while achieving reasonable delivery times, we propose a partitioning approach where discrete arc plans are split into subplans to be delivered over different fractions in the treatment course. For three oropharyngeal cancer patients, four different arc plans have been created and compared to the corresponding clinical IMPT plan. The treatment plans are all planned to be delivered in 35 fractions, but with different delivery approaches over the fractions. The first arc plan (1×30) has 30 directions to be delivered every fraction, while the others are partitioned into subplans with 10 and 6 beam directions, each to be delivered every third (3×10), fifth fraction (5×6), or seventh fraction (7×10). All plans are assessed with respect to delivery time, target robustness over the treatment course, doses to OARs and NTCP for dysphagia and xerostomia. The delivery time (including an additional delay of 30 s between the discrete directions to simulate manual interaction with the treatment control system) is reduced from on average 25.2min for the 1×30 plan to 9.2min for the 3×10 and 7×10 plans and 5.7min for the 5×6 plans. The delivery time for the IMPT plan is 7.9min. When accounting for the combination of delivery time, target robustness, OAR sparing, and NTCP reduction, the plans with 10 directions in each fraction are the preferred choice. Both the 3×10 and 7×10 plans show improved target robustness compared to the 1×30 plans, while keeping OAR doses and NTCP values at almost as low levels as for the 1×30 plans. For all patients the NTCP values for dysphagia are lower for the partitioned plans with 10 directions compared to the IMPT plans. NTCP reduction for xerostomia compared to IMPT is seen in two of the three patients. The best results are seen for the first patient, where the NTCP reductions for the 7×10 plan are 1.6 p.p. (grade 2 xerostomia) and 1.5 p.p. (grade 2 dysphagia). The corresponding NTCP reductions for the 1×30 plan are 2.7 p.p. (xerostomia, grade 2) and 2.0 p.p. (dysphagia, grade 2). Discrete proton arcs can be implemented at any proton facility with reasonable treatment times using a partitioning approach. The technique also makes the proton arc treatments more robust to changes in the patient anatomy.

Dose mimicking based strategies for online adaptive proton therapy of head and neck cancer

Objective. To compare a not adapted (NA) robust planning strategy with three fully automated online adaptive proton therapy (OAPT) workflows based on the same optimization method: dose mimicking (DM). The added clinical value and limitations of the OAPT methods are investigated for head and neck cancer (HNC) patients. Approach. The three OAPT strategies aimed at compensating for inter-fractional anatomical changes by mimiking different dose distributions on corrected cone beam CT images (corrCBCTs). Order by complexity, the OAPTs were: (1) online adaptive dose restoration (OADR) where the approved clinical dose on the planning-CT (pCT) was mimicked, (2) online adaptation using DM of the deformed clinical dose from the pCT to corrCBCTs (OADEF), and (3) online adaptation applying DM to a predicted dose on corrCBCTs (OAML). Adaptation was only applied in fractions where the target coverage criteria were not met (D98% < 95% of the prescribed dose). For 10 HNC patients, the accumulated dose distributions over the 35 fractions were calculated for NA, OADR, OADEF, and OAML. Main results. Higher target coverage was observed for all OAPT strategies compared to no adaptation. OADEF and OAML outperformed both NA and OADR and were comparable in terms of target coverage to initial clinical plans. However, only OAML provided comparable NTCP values to those from the clinical dose without statistically significant differences. When the NA initial plan was evaluated on corrCBCTs, 51% of fractions needed adaptation. The adaptation rate decreased significantly to 25% when the last adapted plan with OADR was selected for delivery, to 16% with OADEF, and to 21% with OAML. The reduction was even greater when the best plan among previously generated adapted plans (instead of the last one) was selected. Significance. The implemented OAPT strategies provided superior target coverage compared to no adaptation, higher OAR sparing, and fewer required adaptations.

Radiobiological and dosimetric comparison of 60Co versus 192Ir high-dose-rate intracavitary-interstitial brachytherapy for cervical cancer

BackgroundHigh-dose-rate (HDR) intracavitary-interstitial brachytherapy (IC-ISBT) is an effective treatment for bulky, middle, and advanced cervical cancer. In this study, we compared the differences between 60Co and 192Ir HDR IC-ISBT plans in terms of radiobiological and dosimetric parameters, providing a reference for clinical workers in brachytherapy.MethodsA total of 30 patients with cervical cancer receiving HDR IC-ISBT were included in this study, and IC-ISBT plans for each individual were designed with both 60Co and 192Ir at a prescribed dose of CTV D90 = 6 Gy while keeping the dose to OARs as low as possible. Physical dose and dose–volume parameters of CTV and OARs were extracted from TPS. The EQD2, EUBED, EUD, TCP, and NTCP were calculated using corresponding formulas. The differences between the 60Co and 192Ir IC-ISBT plans were compared using the paired t-test.ResultsIn each patient's 60Co and 192Ir IC-ISBT plan, the average physical dose and EQD2 of 60Co were lower than those of 192Ir, and there were statistically significant differences in D2cc and D1cc for the OARs (p < 0.05); there were statistically significant differences in D0.1 cc for the bladder (p < 0.05) and no significant differences in D0.1 cc for the rectum or intestines (p > 0.05). The EUBED ratio (60Co/192Ir) at the CTV was mostly close to 1 when neither 60Co or 192Ir passed their half-lives or when both passed two half-lives, and the difference between them was not significant; at the OARs, the mean value of 60Co was lower than that of 192Ir. There was no statistical difference between 60Co and 192Ir in the EUD (93.93 versus 93.92 Gy, p > 0.05) and TCP (97.07% versus 97.08%, p > 0.05) of the tumors. The mean NTCP value of 60Co was lower than that of 192Ir.ConclusionsConsidering the CTV and OARs, the dosimetric parameters of 60Co and 192Ir are comparable. Compared with 192Ir, the use of 60Co for HDR IC-ISBT can ensure a similar tumor control probability while providing better protection to the OARs. In addition, 60Co has obvious economic advantages and can be promoted as a good alternative to 192Ir.

A dosemetric and radiobiological impact of VMAT and 3DCRT on lumbosacral plexuses, an underestimated organ at risk in cervical cancer patients.

BackgroundThe purpose of this study was to evaluate dosimetric and radiobiological difference between volumetric modulated arc therapy (VMAT) and 3-dimensional conformal radiotherapy (3DCRT) in organ at risk (OAR) lumbosacral plexus (LSP) in cervical cancer patients.Materials and methods30 patients of cervical cancer who were treated using 3DCRT or VMAT along with chemotherapy followed by brachytherapy were enrolled. LSP was delineated retrospectively. Dosimetric and radiobiological difference was evaluated. Patients were followed for radiation induced lumbosacral plexopathy (RILSP).ResultsMedian follow-up was 12 months (3–16 months). 53.3% of patients were treated by 3DCRT and 46.7% by VMAT. The mean (±SD) LSP volume: 119.03 ± 15 cm3. The mean volume percentages (%) of the LSP: V5, V10, V20, V30, V40, V50, V55, and V60 were 100%, 99.8%, 99.2%, 94.3%, 84.03%, 59.7%, 0%, 0%, respectively. All patients received doses to the LSP in excess of 50 Gy, one patient received 55 Gy. A statistically significant difference was observed in the median value of V20, V30, V40, V50, D50, P2, P4, P7, P8, P9, and P10 across two different techniques of radiotherapy — VMAT and 3DCRT. None of the patients presented with RILSP. NTCP value was less in VMAT plans compared to 3DCRT, which is also statistically significant.ConclusionRILSP is a rare and often refractory complication of pelvic radiotherapy. Advance radiotherapy technique with proper OAR delineation and constraint can prevent the occurrence of RILSP. VMAT has potential benefits for the probability of dose reduction in LSP. Further studies are required focusing on dose distribution in LSP–OAR and radiotherapy modality.

A Decision Support Tool to Optimize Selection of Head and Neck Cancer Patients for Proton Therapy.

Simple SummaryA decision support tool was developed to select head and neck cancer patients for proton therapy. The tool uses delineation data to predict expected toxicity risk reduction with proton therapy and can be used before a treatment plan is created. The positive predictive value of the tool is >90%. This tool significantly reduces delays in commencing treatment and avoid redundant photon vs. proton treatment plan comparison.Selection of head and neck cancer (HNC) patients for proton therapy (PT) using plan comparison (VMAT vs. IMPT) for each patient is labor-intensive. Our aim was to develop a decision support tool to identify patients with high probability to qualify for PT, at a very early stage (immediately after delineation) to avoid delay in treatment initiation. A total of 151 HNC patients were included, of which 106 (70%) patients qualified for PT. Linear regression models for individual OARs were created to predict the Dmean to the OARs for VMAT and IMPT plans. The predictors were OAR volume percentages overlapping with target volumes. Then, actual and predicted plan comparison decisions were compared. Actual and predicted OAR Dmean (VMAT R2 = 0.953, IMPT R2 = 0.975) and NTCP values (VMAT R2 = 0.986, IMPT R2 = 0.992) were highly correlated. The sensitivity, specificity, PPV and NPV of the decision support tool were 64%, 87%, 92% and 51%, respectively. The expected toxicity reduction with IMPT can be predicted using only the delineation data. The probability of qualifying for PT is >90% when the tool indicates a positive outcome for PT. This tool will contribute significantly to a more effective selection of HNC patients for PT at a much earlier stage, reducing treatment delay.

Mathematical Modeling of Uniform and Nonuniform Malignian and Normal Tissues Irradiation. Mathematical Analysis of the Tumour Grid Irradiation

Purpose: On base created mathematical model (MM) modified Veybull distribution, intended for NTCP calculation, depending on irradiated volume V and uniform irradiation dose D, to develop the MM, which allows to realize transition from nonuniform dose in tissue to the equivalent, uniform identical dose. To research the hypothesis, under what condition lumpy sharing dose in system tumors+normal tissues will be more efficient, than uniform dose.&#x0D; Material and Methods: Lumpy sharing dose are described as a differential histogram dose-volume (DDVH). The MM for calculation transition lumpy distribution of the absence of the beam complication probability (ACPr) in tissue is designed. It was used for MM conclusion, which allows to calculate transition values of the Adequate Dose (AD) of the uniform irradiation tissues, which use brings about ACPr in tissues. &#x0D; Results: On base of the suggestions and proved affirmation MMs are received, which allow for lumpy distribution of local NTCP values, presented as a DHDV, to calculate transition values ACPr, as well as select from it MM for reduction of the lumpy sharing dose. On base created MM question was explored, in what case tumors and normal tissue through a grid irradiation will be more effective than uniform irradiation.&#x0D; Conclusion: The transition from lumpy sharing doses in tissues to equivalent uniform dose present the significant interest for the RT planning efficiency. Their study is necessary, where the radiation of biosubjects is influenced.

Moving organ toxicity management in radiation therapy with simple fuzzy logic

The aim of present work is to estimate and manage real time toxicity of moving organ bladder in deciding level of damage using a simple fuzzy logic method. The target and bladder inter-treatment motions are considered in radiation therapy of prostate cancer in the present study. Materials and methods: The prostate target and nearby critical structures like bladder varies due to physiological behaviour during the course of radiation therapy treatment. The total displacement errors of prostate target shift ranging from 0-5 mm s.d. was considered in this study while maintain tumor dose conformity. The Mamdani-type Fuzzy Inference System (FIS) was applied for determine biological acceptable margin using TCP and NTCP parameters. The bladder volume variations with weekly analysis of cone beam CT (CBCT) were considered. Using irradiated volume-risk relationship in planning, the overlapped risk volumes were estimated. Fuzzy rules and membership function were used basis on setup errors, asymmetrical nature of organ motion and limitations of normal tissue toxicity in margin formulations. Results and discussion: The prostate target motion management was in a good consistent with conventional margin formulations at 5 mm s.d. displacement error range to maintain conformity index (CI) of target. With application of conventional margins of target volume, the sub-volumes of critical organs such as bladder and corresponding its NTCP values were fuzzified using inter treatment volume variations of critical organs. The risk factor (RF) of critical organs were qualitatively assessed with for each fractional volume of irradiated to total volume and relevant NTCP values. Conclusion: A simple fuzzy logic may be suitable to estimate critical moving organs toxicity like bladder biologically. Using proposed simple and fast method, there is interplay between volume-risk relationship and NTCP of OARs to management of normal-tissue risk level of radiation therapy.

Myths, facts and scope of spinal cord tolerance dose revision in Intensity modulated SIB treatment of locally advanced head and neck cancer: A dosimetrical and radiobiological demonstration

PurposeTo explore the possibility of revising the spinal cord tolerance dose in Simultaneously Integrated Boost (SIB) intensity modulated treatment plan of locally advanced head and neck (H&N) cancer and assessment of achieved planning gain due to the revision. In SIB regimen, the Organ at Risk (OARs) tolerance dose is equally distributed throughout the treatment. Clinicians have usually considered the spinal cord tolerance to be the same as in conventional technique. However, in SIB fractionation regimen with intensity modulation treatment, the spinal cord may receive a physical dose of 45Gy, with much lesser dose per fraction than 2Gy per fraction. So when the dose of spinal cord is distributed throughout the treatment, the tolerance dose limit of physical dose can be considered higher than the usual conventional dose limits. In this study, an attempt has been made to explore the possibilities of dose escalation and treatment planning benefits while exploiting this “Window of Opportunity (WoO)” of increase in spinal cord and Planning Risk Volume (PRV) spinal cord tolerance dose. Material and methodsA total of 12 patients CT data set along with approved structure set of H&N cancer used for treatment planning in. Three independent SIB VMAT plans named as SPC, SPR and SPDE were generated for the 12 patients. First plan (SPC) was generated by considering standard spinal cord tissue constraint of maximum dose of 45Gy and PRV spinal cord maximum dose 50Gy as per QUANTEC summary and second plan (SPR) was generated considering spinal cord tissue constraint of maximum dose 52.50Gy and PRV spinal cord maximum dose 56.35Gy while optimization and dose calculation. The objectives for rest of the Organ at Risk (OAR) were kept same in both the plans during optimization and dose calculation. The SPC plan was copied for creation of third plan (SPDE) in which dose was escalated by increasing dose per fraction for target volumes such that dose to spinal cord reached a maximum dose of 52.50Gy and PRV spinal cord maximum dose of 56.35Gy. In this plan there have been changes to only dose per fraction, however dose optimization and dose calculation have not been performed. Radiobiological parameters TCP and NTCP were also calculated by using indigenously developed software. ResultsConsidering the increase of spinal cord tolerance dose as “window of opportunity”, a sufficient escalation in physical dose, Biological Effective Dose (BED) and Tumor Control Probability (TCP) was observed for all target volumes with acceptable level of NTCP values. ConclusionSufficient dose escalation and increased in TCP for target volumes or effective planning benefits can be achieved by revising the spinal cord tolerance dose in intensity modulated SIB treatment of locally advanced H&N cancers.

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.

Dosimetric Impact of the Positional Imaging Frequency for Hypofractionated Prostate Radiotherapy - A Voxel-by-Voxel Analysis.

BackgroundTo investigate deviations between planned and applied treatment doses for hypofractionated prostate radiotherapy and to quantify dosimetric accuracy in dependence of the image guidance frequency.MethodsDaily diagnostic in-room CTs were carried out in 10 patients in treatment position as image guidance for hypofractionated prostate radiotherapy. Fraction doses were mapped to the planning CTs and recalculated, and applied doses were accumulated voxel-wise using deformable registration. Non-daily imaging schedules were simulated by deriving position correction vectors from individual scans and used to rigidly register the following scans until the next repositioning before dose recalculation and accumulation. Planned and applied doses were compared regarding dose-volume indices and TCP and NTCP values in dependence of the imaging and repositioning frequency.ResultsDaily image-guided repositioning was associated with only negligible deviations of analyzed dose-volume parameters and conformity/homogeneity indices for the prostate, bladder and rectum. Average CTV T did not significantly deviate from the plan values, and rectum NTCPs were highly comparable, while bladder NTCPs were reduced. For non-daily image-guided repositioning, there were significant deviations in the high-dose range from the planned values. Similarly, CTV dose conformity and homogeneity were reduced. While TCPs and rectal NTCPs did not significantly deteriorate for non-daily repositioning, bladder NTCPs appeared falsely diminished in dependence of the imaging frequency.ConclusionUsing voxel-by-voxel dose accumulation, we showed for the first time that daily image-guided repositioning resulted in only negligible dosimetric deviations for hypofractionated prostate radiotherapy. Regarding dosimetric aberrations for non-daily imaging, daily imaging is required to adequately deliver treatment.

Clinical implication in the use of the AAA algorithm versus the AXB in nasopharyngeal carcinomas by comparison of TCP and NTCP values

PurposeRetrospective analysis of volumetric modulated arc therapy treatment plans to investigate qualitative, possible, clinical consequences of the use of AAA versus AXB in nasopharyngeal cancer (NPC) cases.MethodsThe dose distribution of 26 treatment plans, produced using RapidArc technique and AAA algorithm, were recalculated using AXB and the same number of monitor units provided by AAA and clinically delivered to each patient. The potential clinical effect of dosimetric differences in the planning target volume (PTV) and in organs at risk (OAR) were evaluated by comparing TCP and NTCP values. The Wilcoxon Signed Rank test was used for statistical comparison of all results obtained from the use of the two algorithms.ResultsThe poorer coverage of the PTV, with higher prescribed dose, was reflected in the TCP, which was significantly lower when AXB was used, the median value was 81.55% (range: 74.90, 88.60%) and 84.10% (range: 77.70, 89.90%) for AAA (p < 0.001). OAR mean dose was lower in the AXB recalculated plan than the AAA plan and the difference was statistically significant for all the structures. The NTCP for developing mandible necrosis showed the largest median percentage difference between AAA and AXB (56.6%), the NTCP of risk for larynx edema of Grade ≥ 2 followed with 12.2%.ConclusionsDifferences in dose distribution of NPC treatment plans recalculated with AXB are of clinical significance in those situations where the PTV and OAR involve air or bone, media in which AXB has been shown to more accurately represent the true dose distribution. The availability of AXB algorithm could improve patient dose estimation, increasing the data consistency of clinical trials.

Dosimetric Impact of Interfractional Variations for Post-prostatectomy Radiotherapy to the Prostatic Fossa-Relevance for the Frequency of Position Verification Imaging and Treatment Adaptation.

Background and purpose: To analyze divergences between the planned and applied treatment doses for post-prostatectomy radiotherapy to the prostatic fossa on a voxel-by-voxel basis based on interfractional anatomic variations and imaging frequency.Materials and methods: For 10 patients receiving intensity-modulated postoperative radiotherapy to the prostatic fossa, position verification was carried out by daily in-room CT imaging in treatment position (340 fraction CTs). Applied fraction doses were recalculated on daily CT scans, and treatment doses were accumulated on a voxel-by-voxel basis after deformable image registration. To simulate weekly imaging, derived weekly position correction vectors were used to rigidly register all daily scans of the respective treatment week onto the planning CT before dose accumulation. Detailed dose statistics of the prescribed and applied treatment doses were compared in relation to the frequency of position verification imaging. Derived NTCP and Pinjury values were calculated for the rectum and bladder.Results: Despite a large variability in the pelvic anatomy, daily CT-based patient repositioning resulted in largely negligible deviations of the analyzed dose-volume, conformity, and uniformity parameters from the planned doses for post-prostatectomy radiotherapy, and only the bladder exhibited significant increases in the accumulated mean and median doses. Derived NTCP for the applied doses to the rectum and bladder and Pinjury values did not significantly deviate from the treatment plan. In contrast, weekly CT-based repositioning resulted in significant decreases of the PTV coverage and dose conformity as well as large deviations of the applied doses to the rectum and bladder from the planned doses. Consecutively, NTCP for the rectum and Pinjury were found falsely reduced for weekly patient repositioning.Conclusions: Our data indicate for the first time in a voxel-by-voxel analysis that daily imaging is required for reliable adaptive delivery of intensity-modulated radiotherapy to the prostatic fossa. This work will help guiding adaptive treatment strategies for post-prostatectomy radiotherapy.

Dosimetric Impact of Interfractional Variations in Prostate Cancer Radiotherapy-Implications for Imaging Frequency and Treatment Adaptation.

Background and purpose: To analyze deviations of the applied from the planned doses on a voxel-by-voxel basis for definitive prostate cancer radiotherapy depending on anatomic variations and imaging frequency.Materials and methods: Daily in-room CT imaging was performed in treatment position for 10 patients with prostate cancer undergoing intensity-modulated radiotherapy (340 fraction CTs). Applied fraction doses were recalculated on daily images, and voxel-wise dose accumulation was performed using a deformable registration algorithm. For weekly imaging, weekly position correction vectors were derived and used to rigidly register daily scans of that week to the planning CT scan prior to dose accumulation. Applied and prescribed doses were compared in dependence of the imaging frequency, and derived TCP and NTCP values were calculated.Results: Daily CT-based repositioning resulted in non-significant deviations of all analyzed dose-volume, conformity and uniformity parameters to the CTV, bladder and rectum irrespective of anatomic changes. Derived average TCP values were comparable, and NTCP values for the applied doses to the bladder and rectum did not significantly deviate from the planned values. For weekly imaging, the applied D2 to the CTV, rectum and bladder significantly varied from the planned doses, and the CTV conformity index and D98 decreased. While TCP values were comparable, the NTCP for the bladder erroneously appeared reduced for weekly repositioning.Conclusions: Based on daily diagnostic quality CT imaging and voxel-wise dose accumulation, we demonstrated for the first time that daily, but not weekly imaging resulted in only negligible deviations of the applied from the planned doses for prostate intensity-modulated radiotherapy. Therefore, weekly imaging may not be adequately reliable for adaptive treatment delivery techniques for prostate. This work will contribute to devising adaptive re-planning strategies for prostate radiotherapy.

Predicting Optimal IMRT Dose Objectives by Relating TCP and NTCP to Target Dose Heterogeneity

There is growing interest in relaxing homogeneity constraints in IMRT treatments for solid tumors that do not contain normal tissue. Knowledge-based dose predictions can improve plan quality, but depend on historical data typically incorporating homogeneity constraints. An analytical TCP and NTCP model could be used to estimate optimal target dose heterogeneity prior to plan optimization by assuming basic properties of the dose distribution, thereby improving prospective plan quality. We derived and validated an analytical model of TCP and NTCP based on the properties of co-planar VMAT including target dose heterogeneity, beam penumbra, and dose spillage outside of the target. We derived the TCP/NTCP model with input parameters including tumor size, tumor edge dose (prescription dose), tumor center dose, fractionation, and estimates of standard radio-biological parameters such as tumor clonogen density, radio-sensitivity mean and variance, and Lyman-Kutcher-Burman (LKB) NTCP model parameters. To validate the model, we created a virtual phantom incorporating a spherical tumor with 2 cm diameter and produced a series of VMAT plans in a treatment planning system with varying central target dose between 108% and 262% of the prescription while minimizing dose spillage outside of the target. Differential DVHs were exported and used to estimate TCP and NTCP using the Marsden and LKB models assuming a radio-resistant tumor prescribed 60 Gy in 30 fractions completely surrounded by a single cylindrical parallel organ. The TCP and NTCP were also calculated for these test cases using the analytical model, and compared to the values calculated using the treatment planning system data. The target heterogeneity and corresponding TCP and NTCP values estimated by the analytical model and planning system based approaches are summarized in Table 1. The errors in the TCP and NTCP estimates of the model were within 0.04 and 0.01, respectively, for all plans, despite not requiring a dose calculation. The analysis also demonstrated a steady increase in TCP with increased central target dose, and a transient decrease in NTCP. A central target dose of 111% minimized NTCP, and a central target dose of 124% maximized TCP while providing the same or lower NTCP as a homogeneous target dose. We have derived an analytical model of TCP and NTCP based on simple tumor and dose characteristics that can be applied immediately following contouring to estimate optimal target dose heterogeneity. This tool can be used to improve the dose objectives used in prospective clinical trials. We will present results following model validation in multiple clinical scenarios and demonstrate patient use cases.Abstract 3822; Table 1Central Target Dose (% of Rx)TCPNTCPPinnacleModelPinnacleModel1080.680.640.0500.0481110.720.680.0490.0471240.800.790.0500.0471610.920.930.0530.0522050.960.970.0590.0592340.980.980.0570.0632490.990.980.0580.0642621.000.980.0560.065 Open table in a new tab

Multicriteria optimization: Site-specific class solutions for VMAT plans

Multicriteria optimization (MCO), a novel commercially available optimization method for IMRT and VMAT has the potential to improve treatment planning techniques and workflows. MCO allows planners and physicians to assess in real time the impact and tradeoffs between all clinical goals and organ constraints. We investigate the feasibility of a universal set of objectives and constraints for VMAT plans in different anatomical sites and the impact of involving the Physician in the navigation of the generated Pareto plans. We randomly selected 20 prostate only, 14 whole pelvis, 10 advanced lung, 15 pancreas, and 7 head and neck plans planned with a VMAT technique. Using the clinically delivered isocenter and beam set-up, we retrospectively generated MCO plans with a universal set of constraints and objectives for each anatomical site. The MCO plan scores were compared with clinical plans or an independent plan generated with DMPO. For prostate only plans the TCP values for the clinical and MCO plans were similar and the rectum NTCP values and overall P+ were slightly better for the MCO plans. For whole pelvis, the resulting MCO plans were comparable in all the dosimetric measures to the clinical plans. For lung, the MCO dosimetric comparison also yielded comparable plans but when evaluating individual patients, there were 5 patients for which MCO plans had a clear advantage in reducing dose to lung and/or esophagus while improving/maintaining target coverage, 4 patients with comparable plans and 1 patient where MCO was worse. Allowing the physician to navigate independently produced a different selection of dosimetric trade-offs. Comparable MCO plans were also obtained for pancreas and head and neck. Based on our experience with many anatomical sites and a large number of patient plans, we have found that VMAT MCO plans are comparable to the clinical plans and can be produced with a universal set of objectives and constraints, even for a wide range of geometries and anatomies.

Evaluation of various common prostate IMRT techniques based on estimated tumor control and normal tissue complication probabilities in correlation with patients anatomical parameters derived from the CT scans

Abstract Background: The relationship between the prostate IMRT techniques and patients anatomical parameters has been rarely investigated. Objective: to evaluate various prostate IMRT techniques based on tumor control and normal tissue complication probability (TCP and NTCP) values and also the correlation of such techniques with patients anatomical parameters. Methods: Four IMRT techniques (9, 7 and 5 fields and also automatic) were planned on the CT scans of 63 prostate cancer patients. The sum of distances between the organs at risk (OARs) and target tissue and also their average joint volumes were measured and assumed as anatomical parameters. Selected dosimetric and radiobiological parameters (TCP and NTCP) values were compared among various techniques and the correlation with the above anatomical parameters were assessed using Pearsons’ correlation. Results: High correlations were found between the dosimetric/radiobiological parameters of OARs with the joint volumes and with the distances between the OARs and target tissue in all the techniques. The TCP and complication free tumor control probability (P+) values were decreased with increasing the joint volume and decreasing the distances between the OARs and target tissue (as poly-nominal functions). The NTCP values were increased with increasing the joint volumes and decreasing the distances (3-degree poly-nominal functions). For the low percent joint volumes (&lt;20%) and high distances (&gt;7 cm), The TCP, NTCP and P+ showed no statistical differences between various techniques (P-value&gt;0.07). However, 9 and 7 fields techniques indicated better radiobiological results (P-value&lt;0.05) in almost other ranges (&gt;20% joint volumes and &lt;7 cm distances). Conclusion: Based on our results, it would be possible to compare radiobiological effects of various common IMRT techniques and choose the best one regarding to patients anatomical parameters derived from the CT scans.

Comparison between artificial neural network and radiobiological modeling for prediction of thyroid gland complications of after radiotherapy

Introduction: Hypothyroidism is one of the frequent side effects of radiotherapy of head and neck cancers, breast cancer, and Hodgkin's lymphoma. It is recommended to estimate the normal tissue complication probability of thyroid gland using radiobiological modeling during treatment planning. Moreover, the use of artificial neural network is also proposed as a new method for this aim. The purpose of this study is to compare the results of the radiobiological modeling with the artificial neural network. Materials and Methods: Thyroid dose-volume histograms from a dataset of 44 consecutive patients treated with 3D- CRT for head-and-neck cancers and breast cancer were extracted. Dose-volumetric and radiobiological parameters of thyroid gland including the minimum dose, the maximum dose, the mean dose, TD50, EUD, m, n, and NTCP values calculated by LKB model were used as the input variables of the artificial neural network (ANN) method. The results of each method were then compared with each other. Evaluation of the two methods was estimated using the root- mean-square error (RMSE) and the coefficient of determination (R2). Results: The values for simulation results were RMSE = 0.008 and R2 = 0.99. Using error estimation criteria, results obtained by the ANN method showed the potential prediction of this method for complications of thyroid gland as same as the radiobiological modeling method. Conclusion: Artificial neural network (ANN) can be used in modeling and patients could hopefully benefit from its individualized estimation of normal tissue complications in the clinic.

OA128] Influence of SBRT fractionation on the behavior of TCP and NTCP for prosatet cancer

Purpose Traditionally, radiation treatment dosimetric plans are evaluated by degree of PTV coverage by prescribed dose and the fulfillment of QUANTEC limitations on OARs. In the case of hypofractionated SBRT irradiation plans should be optimized with respect to optimal fractionation and total delivered dose. In this case one could use macroscopic radiobiological criteria, namely TCP and NTCP. The aim of the work is to optimize prostate cancer SBRT treatment basing on TCP/NTCP criteria in the range of total doses from 33.5 Gy to 38 Gy delivered in 4 or 5 fractions. Methods SBRT treatment plans based on VMAT dose delivery technique (4 full arcs) were made in Elekta MONACO planning system v. 5.10. Five patients with T1 and T2 prostate cancer were planned to total doses from 33.5 Gy to 38 Gy in four or five fractions. Differential DVHs were used for simulation of TCP values using Niemierko model and Stavrev-Niemerko model assuming that for prostate cancer α β = 1.5 ± 0.5 Gy. For calculation of NTCP the models of Niemierko and Kallman were used. All plans were compared basing on UTCP = TCP 1 - NTCP . NTCP values were calculated for the forward wall of rectum as the most irradiated OAR. Thus, using all TCP and NTCP models four variants are possible for each total dose of irradiation and fractionation. Results All plans were planned to the best of the medical physicist experience resulting in 98% of PTV covered by 98% of prescribed dose, and 100% of CTV covered by 99% of dose. CI and HI were equal to 0.99. For all five patients the best plans resulted in UTCP values 0.97–0.98 that were obtained for two variants of irradiation: 33.5 Gy in 4 fractions or 36 Gy in 5 fractions. Further increase of dose for both fractionations resulted in significant damage of the OAR. For all plans TCP values were larger than 0.97 tending to unit with increase of total dose as expected. Conclusion Simulation of TCP/NTCP values of the different VMAT irradiation plans was carried out using different models. The results allowed to find the optimal plan with respect to fractionation and dose per fraction.