Maximum Point Dose Research Articles

Dosimetric parameters associated with the long-term oncological outcomes of Gamma Knife surgery for sellar and parasellar tumors in pediatric patients.

The authors aimed to investigate the dosimetric parameter and the minimally required dose associated with long-term control of sellar and parasellar tumors after Gamma Knife surgery (GKS) in children. A retrospective analysis was performed on pediatric patients younger than 19 years of age who were diagnosed with sellar and parasellar tumors and received GKS at the authors' institution from 1998 to 2019. Cox proportional hazards regression analyses were used to investigate the dosimetric parameters associated with treatment outcome. The Kaplan-Meier method was used to analyze tumor control rates after GKS. Overall, 37 patients with 40 sellar and parasellar tumors, including 22 craniopharyngiomas and 12 pituitary adenomas, had a mean follow-up of 85.8 months. The gross target volume was 0.05 cm3 to 15.28 cm3, and the mean marginal dose was 15.8 Gy (range 9.6-30.0 Gy). Ten patients experienced treatment failure at a mean of 28.0 ± 26.7 months. The actuarial 5- and 10-year tumor control rates were 79.0% and 69.8%, respectively. D98% was an independent predictive factor of tumor control (HR 0.846 [95% CI 0.749-0.956], p = 0.007), with a cutoff value of 11.5 Gy for the entire cohort and 10 Gy for the craniopharyngioma group. Visual deterioration occurred in 2 patients with the maximum point dose of 10.1 Gy and 10.6 Gy to the optic apparatus. In pediatric patients, D98% was a reliable index of the minimum required dose for long-term control of sellar and parasellar tumors after GKS. The optimal D98% value for each tumor diagnosis needs to be elucidated in the future.

Design, realization, and characterization of a novel diamond detector prototype for FLASH radiotherapy dosimetry.

PurposeFLASH radiotherapy (RT) is an emerging technique in which beams with ultra‐high dose rates (UH‐DR) and dose per pulse (UH‐DPP) are used. Commercially available active real‐time dosimeters have been shown to be unsuitable in such conditions, due to severe response nonlinearities. In the present study, a novel diamond‐based Schottky diode detector was specifically designed and realized to match the stringent requirements of FLASH‐RT.MethodsA systematic investigation of the main features affecting the diamond response in UH‐DPP conditions was carried out. Several diamond Schottky diode detector prototypes with different layouts were produced at Rome Tor Vergata University in cooperation with PTW‐Freiburg. Such devices were tested under electron UH‐DPP beams. The linearity of the prototypes was investigated up to DPPs of about 26 Gy/pulse and dose rates of approximately 1 kGy/s. In addition, percentage depth dose (PDD) measurements were performed in different irradiation conditions. Radiochromic films were used for reference dosimetry.ResultsThe response linearity of the diamond prototypes was shown to be strongly affected by the size of their active volume as well as by their series resistance. By properly tuning the design layout, the detector response was found to be linear up to at least 20 Gy/pulse, well into the UH‐DPP range conditions. PDD measurements were performed by three different linac applicators, characterized by DPP values at the point of maximum dose of 3.5, 17.2, and 20.6 Gy/pulse, respectively. The very good superimposition of three curves confirmed the diamond response linearity. It is worth mentioning that UH‐DPP irradiation conditions may lead to instantaneous detector currents as high as several mA, thus possibly exceeding the electrometer specifications. This issue was properly addressed in the case of the PTW UNIDOS electrometers.ConclusionsThe results of the present study clearly demonstrate the feasibility of a diamond detector for FLASH‐RT applications.

Hot Spot Not Hot Enough? Differences in Local Control for Non-Small Cell Lung Cancer Treated With Stereotactic Body Radiotherapy Based on Maximum Point Dose within the Planning Target Volume

<h3>Purpose/Objective(s)</h3> One of the defining characteristics of stereotactic body radiation therapy (SBRT) is the creation of a steep dose gradient, resulting in a higher dose centrally within the planning target volume (PTV) than at the periphery. However, there is no consensus regarding objectives for the maximum point dose delivered to the PTV. In this study, we investigated whether higher relative maximum doses within the PTV were associated with improved tumor control. <h3>Materials/Methods</h3> We performed a single-institution retrospective review of patients with early-stage, node-negative NSCLC who received curative-intent SBRT between 2005 and 2018. Patients with biopsy-proven NSCLC or presumed NSCLC based on radiographic findings were included. All patients underwent four-dimensional computed tomography (CT) for radiation planning and were treated with a free-breathing technique, utilizing an internal target volume (ITV) to account for tumor motion during the respiratory cycle. The PTV was defined as a 5-mm expansion from the ITV. We calculated the relative maximum dose to the PTV from a ratio of the maximum point dose delivered within the PTV to the prescription dose. We analyzed outcomes using the Kaplan-Meier method and used a log-rank test to assess prognostic impact. <h3>Results</h3> The study population consisted of 175 patients and 186 individual lung nodules with a median follow-up time of 2.6 (range, 0.1 – 12) years for all patients and 3.5 (range, 0.2 – 8.4) years for living patients. The median age was 70.2 (range, 43 – 90) years, and the median maximum tumor diameter was 1.9 (range, 0.7 – 5.6) cm. Most tumors were peripheral with only 9.7% (n=18) centrally located. The median prescription dose was 50 (range, 48 – 62.5) Gy in 5 (range, 4-10) fractions. The median relative maximum dose delivered to the PTV was 110%. Among the entire cohort, the 3-year rates (95% CI) of local control (LC), cause-specific survival, and overall survival were 81.0% (73.8% – 86.5%), 72.4% (64.5 – 79.1%), and 48.3% (40.7% – 55.9%), respectively. The 3-year rate of LC was superior among patients treated with a maximum point dose ≥ 110% vs. < 110% (86% vs. 74%, p=0.03). The difference in 3-year LC was more pronounced between a maximum point dose ≥ 120% vs. < 120% (94% vs. 79%, p = 0.05). The maximum point dose was significant for LC on multivariate analysis (p = 0.03). <h3>Conclusion</h3> Patients with early-stage NSCLC treated with SBRT with a relative maximum dose in the PTV of at least 110% demonstrated improved local control. Thus, more homogeneous SBRT plans may compromise the ablative treatment. Further studies should clarify specific objectives for the maximum point dose delivered to the PTV.

3D dose delivery QA using couch and gantry mounted cameras

While 2D planar radiation therapy quality assurance techniques suffice for linac verification, a full 3D dosimetry measurement is ideal for robust treatment plan verification. In this study, an optical 3D dose reconstruction technique based on radioluminescence imaging is presented, using two orthogonal views provided by gantry and couch mounted cameras. Both small field and multi-target beam apertures were tested, mimicking typical 3D radiosurgery plans. Pass rates >94% for 3D gamma with 2%/2mm were achieved in all cases. Slice images were used for gamma analysis in each of transverse, sagittal and coronal planes, through the point of maximum dose. This proposed system can enable real-time imaging of beam delivery dynamics in a cylindrical water-equivalent phantom with high spatial resolution 3D reconstruction of the dose distribution, and verification of each beamlet used.

Tangential Volumetric Modulated Arc Therapy for Locally Advanced Breast Cancer

Cardiovascular toxicity from breast radiation therapy (RT) is a concern to patients and providers. Herein, we present a cardiac-sparing strategy using tangential volumetric modulated arc therapy (tVMAT) in comparison with standard 3-dimensional conformal RT. Ten patients with left-sided breast cancer previously treated with adjuvant RT covering the breast, as well as the axillary and supraclavicular nodal regions, were selected for the study. For each patient, 2 plans were created: a dual-isocenter 3-field 3-dimensional conformal RT plan and a monoisocentric tVMAT plan. The prescription for both techniques was 50 Gy in 25 fractions to the breast and nodal target volumes. Compared with 3-dimensional conformal RT, tVMAT provided more uniform coverage to the breast and regional lymph nodes (mean conformity index: 1.42 for tVMAT vs 2.42 for 3-dimensional conformal RT; P < .01), and the maximum point dose for tVMAT was lower on average (112.8% for tVMAT vs 121.5% for 3-dimensional conformal RT; P < .001). Coverage to the lymph nodes was superior for tVMAT (average minimum coverage to 95% of entire nodal target volumes: 99.5% of prescribed dose for tVMAT vs 94.9% for 3-dimensional conformal RT; P < .001). Organ-at-risk sparing was improved with tVMAT, with a lower average V20Gy for the left lung (15.0% for tVMAT vs 24.6% for 3-dimensional conformal RT; P < .01) and lower mean heart dose (156 cGy for tVMAT vs 200 cGy for 3-dimensional conformal RT; P < .01). Tangential volumetric modulated arc therapy is a promising technique for the treatment of intact breast and regional lymphatics, and it may improve target coverage and organ-at-risk avoidance compared with 3-dimensional conformal techniques.

Risk factors for primary site necrosis after definitive concurrent chemoradiotherapy in head and neck cancer.

To identify risk factors of primary site necrosis (PSN) after definitive concurrent chemoradiation therapy (CCRT) in patients with nonoral cavity head and neck cancer (HNC). We retrospectively reviewed the records of 256 patients treated with CCRT for HNC during 2010-2018. Patient-related (age, sex, history of smoking, hypertension, diabetes mellitus, serum hemoglobin and albumin), tumor-related (tumor site, American Joint Committee on Cancer stage), and treatment-related (induction chemotherapy, maximum point dose and mean dose of planning target volume [PTV] of primary site, absolute volumes of the PTV receiving >50-75 Gy [V50-V75]) variables were analyzed. Critical dosimetric parameters of PSN were identified using receiver operating characteristic (ROC) curve analysis. Univariate and multivariate Cox regression analyses were used to select the significant variables for PSN development. After median follow-up of 44 months (range, 5-127), 7 patients (2.7%) developed PSN with a median time to event of 10 months (range, 3-12). V70 ⩾79.8 mL was the most critical dosimetric parameter for PSN (area under the ROC curve 0.873, sensitivity 0.857, specificity 0.747). In univariate analyses, pretreatment serum hemoglobin <11.0 g/dL and V70 ⩾79.8 mL were significantly associated with higher risk of PSN occurrence. V70 ⩾79.8 mL (hazard ratio 5.960, 95% confidence interval 1.289-27.548; p = 0.022) remained significant predictors of PSN in multivariate analyses. V70 ⩾79.8 mL is significantly related to the risk of developing PSN. These findings offer valuable clues for clinicians to minimize PSN incidence in HNC treated with curative CCRT.

Clinical Workflow for Planning and Treating Palliative Patients on Diagnostic Images

Care coordination for inpatients requiring palliative radiotherapy remains a challenge. One such challenge is timely CT simulation. Previously published data demonstrate that rapid radiotherapy delivery is associated with improved patient satisfaction and reduced duration of hospitalization. The purpose of this study was to assess the feasibility of eliminating RT simulation from the current clinical workflow for palliative patients by using diagnostic images as the primary image dataset.A cohort of 11 previously treated palliative patients were identified. Treatment sites evaluated included spine (4), sacrum (2), shoulder (1), lung (1), humerus (1), pelvis (1) and whole brain (1). Diagnostic CT images on a curved couch without RT immobilization were used to generate diagnostic plans. The diagnostic plans were copied and recalculated on corresponding simulation CT images, which were the clinically used datasets for planning and treatment. For the whole brain patient who only had a diagnostic MRI, a synthetic CT scan was generated with brain, muscle, adipose and bone overridden following ICRU 44. Anatomic surrogates were aligned to couch indexing notches to avoid large shift during patient setup. The quality of diagnostic imaging based treatment plans were compared against traditional CT simulation based plans by a group of physicians.All diagnostic plans, except the shoulder, were clinically acceptable. Minor dose distribution deviation from the previously approved clinical plans were noted, but were not clinically significant, as illustrated in the table. The average change in maximum point dose was 0.1 Gy, ranged between -0.8 Gy and 0.5 Gy. Change in PTV D95 and V95 ranged from -1.3% to 0.5%, and from 0% to 2.8%, respectively. The rejected shoulder case was secondary to a limited field of view (FOV) on the diagnostic images. However, a limited FOV may be corrected through estimation of missing tissue or more appropriate diagnostic image selection. The impact from CT calibration and anatomy change on different couches was negligible.A clinical workflow to generate treatment plans on diagnostic imaging was developed. This workflow eliminates the need for formal CT simulation, allowing for expedited radiotherapy. Diagnostic imaging based treatment plans were deemed to be clinically acceptable after careful quality and dosimetric assessment against traditional CT simulation based treatment plans. Limitations of the new workflow were identified and iterative improvements are currently underway.

Phase I Trial of Dose-Escalated Five-Fraction Stereotactic Ablative Radiotherapy for Early-Stage Lung Squamous Cell Carcinoma

We aimed to evaluate the safety of and maximum tolerated dose (MTD) for 5-fraction stereotactic ablative radiotherapy (SABR) for early-stage lung squamous cell carcinoma (SCC), for which local failure rates appears higher than that of early-stage adenocarcinomas.A single institution phase I study was conducted in pathologically confirmed early-stage lung SCC. The 3+3 design involved 4 dose levels of 11, 12, 13, and 14 Gy x 5 fractions delivered every other day (dose levels DL1, DL2, DL3, and DL4, respectively). The primary objective was to determine the MTD of 5-fraction SABR, which was defined as the dose associated with a 33% rate of dose-limiting toxicities, defined as grade ≥3 respiratory/mediastinal or cardiac events (or grade ≥4 gastrointestinal or chest wall events), with toxicities reported until data lock in October 2020. Target volume delineation and organ-at-risk (OAR) constraints were based on RTOG 0813, using OAR constraints expressed in percent of prescription as fixed constraints from the 11 Gy per fraction prescription for all DL. Institutional constraints for the chest wall were used (V30 < 30cm3, up to 70 cm3 acceptable; maximum point dose 52.5 Gy). Target coverage objectives included ≥95% of the planning target volume (PTV) to be covered by 100% of the prescription dose, and 100% of the internal target volume (ITV) to receive ≥110% of the prescription dose. For technically challenging cases, it was permitted to prescribe as low as 50 Gy (BED of 100 Gy10) to a small portion of the GTV, ITV (if used) and corresponding PTV adjacent to a critical OAR (split target volume prescription). SABR was delivered using free breathing, deep inspiration breathhold, or expiratory gating. Thus, ITVs were not used for all patients.From October 2017 to June 2020, 13 patients were enrolled: 3 in DL1, 3 in DL2, 4 in DL3, and 3 in DL4. Seven (IASLC definition) or 6 (RTOG) patients had central lesions, and the rest abutted the chest wall. All patients completed SABR per protocol without major deviations. At 18.4 months median follow-up (range, 2.4-25.6 months), no patient developed dose limiting toxicities. There were no grade 4-5 events and 1 grade 3 event (painful brachial plexopathy, which occurred in DL1 at 16 months post-SABR at the time of local progression). There were 7 instances of grade 2 toxicities. These included fatigue (n = 1, DL2), chest wall pain (n = 2, DL2 & DL4), cough (n = 1, DL3), dyspnea (n = 2, DL3 & DL4), nausea (n = 1, DL4), and wheezing (n = 1, DL4). Eight (62%) patients required utilization of "split target volume" prescriptions. The mean total dose to the GTV ranged from 60.9-62.2 Gy for DL1, 63.2-68.6 Gy for DL2, 67.3-78.8 Gy for DL3, and 75.5-82.2 Gy for DL4. The median GTV was 19.9 cc (range 5-57cc).5-fraction SABR for early-stage lung SCC up to 14 Gy x 5 fractions using a split target prescription for OAR adjacent tumor appears safe. Long term follow up will be needed to assess late toxicities and tumor control. (NCT03321747).

Quality Metric to Assess Adequacy of Hydrogel Rectal Spacer Placement for Prostate Radiotherapy and Association of Metric Score With Dosimetric and Gastrointestinal Toxicity Outcomes

<h3>Purpose/Objective(s)</h3> Hydrogel rectal spacer placement (HSP) has been shown to minimize rectal dose during prostate cancer radiotherapy, yet its potential benefit for modulating rectal toxicity could in large part depend upon the quality of prostate-rectal separation achieved from HSP. We therefore developed a practical quality metric to evaluate HSP, validating its association with rectal dose reduction, as well as physician- and patient-reported rectal toxicity using a prospective dataset of men treated with prostate stereotactic body radiotherapy (SBRT). <h3>Materials/Methods</h3> Using the axial T2-weighted MRI images from a small pilot cohort of men with HSP who had been treated at our institution with prostate SBRT, a hydrogel spacer quality metric was devised from prostate-rectal space thickness (PRST) measurements. A score of 0, 1, or 2 was assigned to a PRST of < 0.3 cm, 0.3-0.9 cm, or ≥1 cm, respectively; an overall spacer quality score (SQS) was computed from individual scores (total of 9) at rectal midline and 1 cm to the right and left, located at the level of the prostate base, midgland, and apex. This quality metric was then applied to MRI simulation scans of 43 men with low/intermediate risk prostate cancer who had been enrolled on a multi-institutional phase II study to assess safety and efficacy of HSP during prostate SBRT. Associations between SQS and rectal dosimetry, late gastrointestinal (GI) toxicity, and EPIC bowel quality of life were quantified in these men treated with 45 Gy in 5 fractions. <h3>Results</h3> Among this cohort, the majority had a SQS of 1 (n = 18; 42%) or 2 (n = 18; 42%). SQS was associated with maximum rectal point dose (rectal Dmax; <i>P</i> = 0.001), maximum dose to 1 cc of rectum (D1cc; <i>P</i> = 0.003), and volume of rectum receiving ≥100% of prescription dose (V45; <i>P</i> = 0.03). For those with SQSs of 0, 1 and 2, the median rectal Dmax (cGy) was 4683, 4600, and 3921, respectively. SQS was associated with incidence of late GI toxicity (<i>P</i> = 0.03) and highest late GI toxicity score (<i>P</i> = 0.02). Among the 20 men who developed late GI toxicity, 57%, 67% and 22% with Grade ≥1 had a SQS of 0, 1, and 2, respectively. Men with SQSs of 2 compared to 0-1 had 1.36 times lower odds of an increased rectal Dmax (95% CI: 1.14-1.63); and 1.20 times lower odds of an increased rectal D1cc (95% CI: 1.07-1.34). Men with SQSs of 2 versus 0-1 had 3.30 times lower odds of a higher late GI toxicity score (95% CI: 1.18-9.28). While evidence of a significant difference in baseline EPIC bowel summary score between SQSs was not observed (<i>P</i> = 0.07) as expected, men with SQSs of 2 compared to 0-1 had 3.52 times higher odds (95% CI: 0.91-13.64) of a superior bowel summary score 12 months from prostate SBRT. <h3>Conclusion</h3> We developed a reliable, easy to use, and informative metric for assessing HSP, which appears to be associated with rectal dosimetry and late GI toxicity in men treated with prostate SBRT.

Treatment Outcomes Following Proton Therapy for High Grade Spinal Cord Ependymoma in Children

There is limited information published on the outcome of children treated with radiation for high-grade ependymoma of the spinal cord. Thus, little evidence is available to inform decisions of target volume or prescription dose. Moreover, there is virtually no mature outcome data on proton therapy, despite theoretical advantages in normal tissue exposure. We therefore performed a bicentric retrospective study to better inform treatment of this rare tumor in children.Between 2008 and 2019, 14 consecutive pediatric patients with a non-metastatic grade II or III spinal ependymoma were treated with proton therapy at the University of Florida and Massachusetts General Hospital. The median age of the children at the time of radiation was 14 years old (range, 1.5-18 years). Five tumors arose within the cervical cord (C1-5, C1-2, C1-T1, C3-T1, C4-C6), 3 within the thoracic spine (C7-T4, T7-L1, T11-T12), and 6 within the lumbosacral spine (L3-L5, L3-L5, L4-S2, S2-S5, L2-L3, L2-L3). Six tumors were grade II histology and 8 were grade III. Prior to radiotherapy, 3 patients had undergone a subtotal resection while the other 11 had a gross total or near total resection. One patient received chemotherapy according to the International Society of Pediatric Oncology (SIOP) infant regimen and 1 patient received chemotherapy according to Children's Oncology Group (COG) ACNS0831. For radiation, the gross tumor volume (GTV) was defined by the gross disease and/or tumor bed at the time of radiation. The CTV was defined by the GTV + 5-10 mm. The CTV received 50.4 Gy (n = 8), 52.2 (n = 1), or 54 Gy (n = 5), with the latter undergoing boost to just the GTV following the initial 50.4 Gy to respect spinal cord tolerance. For the cohort, the median maximum point dose to the spinal cord was 52.4 Gy (range, 0-53.9 Gy). The median maximum dose to 0.1 cc of spinal cord was 51.3 Gy (range, 0-52.5 Gy). The median volume of cord receiving ≥50.4 Gy was 3.4 cc (range, 0-17.1 cc).With a median follow-up of 6.3 years (range, 1.5 - 14.8 years), no tumors have progressed and all patients are alive. Serious acute toxicity was limited to 1 case of grade 2 nausea. While most patients experienced neurologic sequela following surgery, only 1 patient developed additional neurologic deficits following radiation: An 18-year-old male who received 54 Gy following gross total resection of a lumbosacral tumor developed grade 2 erectile dysfunction. There were 2 cases of chronic musculoskeletal toxicity attributable to surgery and radiation in survivors. No patients have developed cardiac, pulmonary, or other visceral organ complications, nor has any patient developed a second malignancy.These outcomes suggest that radiation to a dose of 50-54 Gy can be safely delivered and plays a beneficial role in the multidisciplinary management of children with grade II/III spinal cord ependymoma. Proton therapy may reduce the late radiation effects and is not associated with unexpected spinal cord toxicity.

Unusual complications after MammoSite brachytherapy: out‐of‐field rib fracture and Mondor's disease

AbstractRecent reports have documented in‐field rib fractures as a rare complication of accelerated partial breast irradiation. Here, we report a case of an out‐of‐field rib fracture, with a maximum point dose of &lt;50% of the prescribed dose, and Mondor's disease in a 61‐year‐old woman after MammoSite brachytherapy. This is the first case in the literature in which rib fractures occurred out‐of‐field, without trauma or risk factors. It also highlights a rare clinical entity, Mondor's disease, of which its recognition is important for radiation oncologists given its potential for tumor recurrence.

A Volumetric Dosimetry Analysis of Vertebral Body Fracture Risk After Single Fraction Spine Stereotactic Body Radiation Therapy

PurposeVertebral compression fractures (VCF) are a common and severe complication of spine stereotactic body radiation therapy (SBRT). We sought to analyze how volumetric dosimetry and clinical factors were associated with the risk of VCF. Methods and MaterialsWe evaluated 173 spinal segments that underwent single fraction SBRT in 85 patients from a retrospective database. Vertebral bodies were contoured and dosimetric values were calculated. Competing risk models were used to evaluate the effect of clinical and dosimetry variables on the risk of VCF. ResultsOur primary endpoint was development of a post-SBRT VCF. New or progressive fractures were noted in 21/173 vertebrae (12.1%); the median time to fracture was 322 days. Median follow-up time was 426 days. Upon multivariable analysis, the percentages of vertebral body volume receiving >20 Gy and >24 Gy were significantly associated with increased risk of VCF (hazard ratio, 1.036, 1.104; P = .029, .044, respectively). No other patient or treatment factors were found to be significant on multivariable analysis. Sensitivity analysis revealed that the percentages of vertebral body volume receiving >20 Gy and >24 Gy required to obtain 90% sensitivity for predicting vertebral body fracture were 24% and 0%, respectively. ConclusionsVCF is a common complication after SBRT, with a crude incidence of 12.1%. Treatment plans that permit higher volumes receiving doses >20 Gy and >24 Gy to the vertebral body are associated with increased risk of VCF. To achieve 90% sensitivity for predicting VCF post-SBRT, the percentage of vertebral volume receiving >20 Gy should be <24% and maximum point dose should be <24 Gy. These results may help guide clinicians when evaluating spine SBRT treatment plans to minimize the risk of developing posttreatment VCF.

Estimating the tolerance of brachial plexus to hypofractionated stereotactic body radiotherapy: a modelling-based approach from clinical experience

BackgroundBrachial plexopathy is a potentially serious complication from stereotactic body radiation therapy (SBRT) that has not been widely studied. Therefore, we compared datasets from two different institutions and generated a brachial plexus dose–response model, to quantify what dose constraints would be needed to minimize the effect on normal tissue while still enabling potent therapy for the tumor.MethodsTwo published SBRT datasets were pooled and modeled from patients at Indiana University and the Richard L. Roudebush Veterans Administration Medical Center from 1998 to 2007, as well as the Karolinska Institute from 2008 to 2013. All patients in both studies were treated with SBRT for apically located lung tumors localized superior to the aortic arch. Toxicities were graded according to Common Terminology Criteria for Adverse Events, and a probit dose response model was created with maximum likelihood parameter fitting.ResultsThis analysis includes a total of 89 brachial plexus maximum point dose (Dmax) values from both institutions. Among the 14 patients who developed brachial plexopathy, the most common complications were grade 2, comprising 7 patients. The median follow-up was 30 months (range 6.1–72.2) in the Karolinska dataset, and the Indiana dataset had a median of 13 months (range 1–71). Both studies had a median range of 3 fractions, but in the Indiana dataset, 9 patients were treated in 4 fractions, and the paper did not differentiate between the two, so our analysis is considered to be in 3–4 fractions, one of the main limitations. The probit model showed that the risk of brachial plexopathy with Dmax of 26 Gy in 3–4 fractions is 10%, and 50% with Dmax of 70 Gy in 3–4 fractions.ConclusionsThis analysis is only a preliminary result because more details are needed as well as additional comprehensive datasets from a much broader cross-section of clinical practices. When more institutions join the QUANTEC and HyTEC methodology of reporting sufficient details to enable data pooling, our field will finally reach an improved understanding of human dose tolerance.

Dosimetric Impact of Physician Style Variations in Contouring CTV for Postoperative Prostate Cancer: A Deep Learning—Based Simulation Study

Inter-observer variation is a significant problem in clinical target volume (CTV) segmentation in postoperative settings, where there is no gross tumor present. In this scenario, the CTV is not an anatomically established structure, but one determined by the physician based on the clinical guideline used, the preferred trade-off between tumor control and toxicity, their experience and training background, and other factors. This results in high inter-observer variability between physicians. This variability has been considered an issue, but the absence of multiple physician CTV contours for each patient and the significant amount of time required for dose planning based on each physician CTV have made it impractical to study its dosimetric consequences. In this study, we analyze the impact that variations in physician style have on dose to organs-at-risk (OAR) by simulating the clinical workflow via deep learning. For a given patient previously treated by one physician, we use deep learning–based tools to simulate how other physicians would contour the CTV and how the corresponding dose distributions would look for other physicians. To simulate multiple physician styles, we use a previously developed in-house CTV segmentation model that can produce physician style–aware segmentations. The corresponding dose distribution is predicted using another in-house deep learning tool, which, can predict dose within 3% of the prescription dose, on average, on the test data. For every test patient, four different physician style CTVs are considered, and four different dose distributions are analyzed. OAR dose metrics are compared, showing that even though physician style variations result in organs getting different doses, all the important dose metrics except maximum dose point are within the clinically acceptable limit.

P05.14 Dosimetric Impact of Using the Acuros XB for Planning of SBRT of Centrally Located NSCLC

Stereotactic Body Radiation Treatment (SBRT) of lung cancer is applied to a heterogeneous density gradient. Dose modeling is highly dependent on the accuracy of the calculation algorithm. This study aims to assess the dosimetric implications calculated by Acuros External Beam (AXB) instead of the Anisotropic Analytical Algorithm (AAA) in SBRT of centrally located-Non small cell lung cancer (CL-NSCLC). Twelve IMRT plans for SBRT of CL-NSCLC were investigated retrospectively. The prescribed scheme was 50 Gy in 5 fractions every 2 days. The plans originally calculated by AAA aimed to cover 95% PTV by varying prescription isodose lines at 70 to 90%. These plans were recalculated by AXB (Dose to medium) and verified by the benchmark Monte Carlo (MC) method. Dosimetric parameters e.g. V20Gy Lungs, D95%(PTV), D98%(GTV), dose gradient (the ratio of 50% prescription isodose volume to the PTV, R50%), and doses to organs at risk (spinal cord, heart, esophagus, trachea, bronchus, and major vessels) were compared. AAA has generally overestimated the PTV dose compared to AXB and MC. The mean differences for D95%(PTV) and D98%(GTV) is 3.1% and 2.8% higher than that of AXB, respectively. The differences were significant with p-value<0.05. They were further verified by MC method, the results agreed with that of AXB. The agreement between AXB and MC in all PTV parameters were within 1.6% and the differences were not significant. No significant differences were also noted on V20Gy Lungs between the three algorithms but three cases were observed with maximum point dose to the lung tissue 1cm surrounding the PTV increased over 11% after the recalculation of AXB. Moreover, two cases were reported exceeding in heart dose and three cases were found degrading from none to minor deviation in dose gradient R50%. AXB has been investigated intensively and found to perform superiorly to AAA especially in calculating the rapid change in heterogeneous density gradient e.g. in regions of re-buildup in soft tissue after passed through lung/air. Although AXB and MC have two completely different way in solving Linear Boltzmann Transport Equation (LBTE), the agreement between AXB and MC was widely acceptable, AXB provides an accurate but faster alternative to MC method. In this study, a significant under-dosage in PTV and large dose difference in modeling tissue/air interface were observed after remodeled with AXB and MC. Since the PTV of SBRT for NSCLC is relatively small, the PTV missed in AAA may lead to a reduction in treatment outcome. Hence, AXB should be used in preference to AAA to model SBRT for centrally located NSCLC.

Initial Data Pooling for Radiation Dose-Volume Tolerance for Carotid Artery Blowout and Other Bleeding Events in Hypofractionated Head and Neck Retreatments

Dose-volume data for injury to carotid artery and other major vessels in stereotactic body radiation therapy (SBRT)/SABR head and neck reirradiation were reviewed, modeled, and summarized. A PubMed search of the English-language literature (stereotactic and carotid and radiation) in April 2018 found 238 major vessel maximum point doses in 6 articles that were pooled for logistic modeling. Two subsequent studies with dose-volume major vessel data were modeled separately for comparison. Attempts were made to separate carotid blowout syndrome from other bleeding events (BE) in the analysis, but we acknowledge that all except 1 data set has some element of BE interspersed. Prior radiation therapy (RT) dose was not uniformly reported per patient in the studies included, but a course on the order of conventionally fractionated 70 Gy was considered for the purposes of the analysis (with an approximately ≥6-month estimated interval between prior and subsequent treatment in most cases). Factors likely associated with reduced risk of BE include nonconsecutive daily treatment, lower extent of circumferential tumor involvement around the vessel, and no surgical manipulation before or after SBRT. Initial data pooling for reirradiation involving the carotid artery resulted in 3 preliminary models compared in this Hypofractionated Treatment Effects in the Clinic (HyTEC) report. More recent experiences with alternating fractionation schedules and additional risk-reduction strategies are also presented. Complications data for the most critical structures such as spinal cord and carotid artery are so limited that they cannot be viewed as strong conclusions of probability of risk, but rather, as a general guideline for consideration. There is a great need for better reporting standards as noted in the High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic introductory paper.

Impact of the Skull Size on the Normal Brain Radiation Dose During Gamma Knife Radiosurgery: Results of a Pilot Study.

The objective of the present study was evaluation of the interrelationships between changes in the skull size and variations in the normal brain radiation dose during Gamma Knife surgery (GKS). With use of systematic modeling within Leksell GammaPlan® (Elekta AB; Stockholm, Sweden) in each of 15 analyzed cases, the skull was "expanded" and "contracted" by variation of its measurement values from 0 to ±3 cm. The mean normal brain radiation dose was then computed for each variant of the adjusted skull size and compared with the original treatment plan. Variations in the maximum point dose delivered to selected critical anatomical structures were also investigated. With changes in the skull radius within ±3cm, the maximum absolute deviation in the mean normal brain radiation dose was 0.8%. As the skull radius increased, the mean normal brain radiation dose also increased linearly (confidence level >99%) with a positive slope of 0.2% per centimeter of radius length change. The maximum point dose deviations in all evaluated critical anatomical structures did not exceed 0.5%, with an overall trend toward a dose increase in parallel with an increase in the skull radius. The small skull size of pediatric patients may be associated with dosimetric advantages in terms of normal brain sparing during GKS.

Advanced dose calculation algorithm in superficial brachytherapy - the impact of tissue inhomogeneity on treatment plan dosimetry.

PurposeGiven tissue inhomogeneity and lack of backscatter media, superficial brachytherapy necessitates more accurate dosimetry than TG-43 formalism. However, the introduction of modern model-based dose calculation algorithms into clinical practice should be carefully evaluated. The aim of this work was to compare dose distributions calculated with TG-43 and advanced collapsed cone engine (ACE) algorithms for individual multi-catheter moulds, and investigate the impact of target size and the lack of bolus to differences between plans.Material and methodsEleven treatment plans for individual mould multi-catheter high-dose-rate brachytherapy (IMM HDR) were selected for retrospective analysis. All treatment plans were initially calculated with TG-43 formula and re-calculated using ACE algorithm. Plan re-calculation with ACE was repeated for each plan in order to assess the impact of bolus. To evaluate differences between TG-43 and ACE dose distributions, dose-volume histogram (DVH) parameters for each ROI were compared. Dmax (maximal point dose), D0.1cc, and D2cc were calculated for each risk’s organ (OARs) and for external contour. For clinical target volume (CTV), D98, D90, D50, CTV coverage (CTV-V100), and dose delivered to reference point were compared between the plans.ResultsA significantly lower values (p < 0.05) of CTV parameters were observed for treatment plans calculated with ACE algorithm comparing to TG-43. Further analysis showed that differences between CTV-V100 for ACE and TG-43 plans depended on CTV volume. Dosimetric parameters for OARs were significantly lower in ACE plans than those of TG-43. Only D2cc for external and D0.1cc for both eye lenses in ACE plans were insignificantly different comparing to TG-43 plans.ConclusionsResults show that differences between dosimetric parameters are statistically significant. However, their clinical relevance is still undetermined. Careful re-evaluation of the clinical results based on long-term research on TG-43 is necessary to safely introduce modern algorithms to clinical practice.

Development and Validation of a Nomogram for Predicting Radiation-Induced Temporal Lobe Injury in Nasopharyngeal Carcinoma.

BackgroundThe purpose was to develop and validate a nomogram for prediction on radiation-induced temporal lobe injury (TLI) in patients with nasopharyngeal carcinoma (NPC).MethodsThe prediction model was developed based on a primary cohort that consisted of 194 patients. The data was gathered from January 2008 to December 2010. Clinical factors associated with TLI and dose–volume histograms for 388 evaluable temporal lobes were analyzed. Multivariable logistic regression analysis was used to develop the predicting model, which was conducted by R software. The performance of the nomogram was assessed with calibration and discrimination. An external validation cohort contained 197 patients from January 2011 to December 2013.ResultsAmong the 391 patients, 77 patients had TLI. Prognostic factors contained in the nomogram were Dmax (the maximum point dose) of temporal lobe, D1cc (the maximum dose delivered to a volume of 1 ml), T stage, and neutrophil-to-lymphocyte ratios (NLRs). The Internal validation showed good discrimination, with a C-index of 0.847 [95%CI 0.800 to 0.893], and good calibration. Application of the nomogram in the external validation cohort still obtained good discrimination (C-index, 0.811 [95% CI, 0.751 to 0.870]) and acceptable calibration.ConclusionsThis study developed and validated a nomogram, which may be conveniently applied for the individualized prediction of TLI.

GEANT4 simulation study of over-response phenomenon of fiber x-ray sensor* *Project supported by the Natural Science Foundation of Heilongjiang Province, China (Grant No. ZD2019H003), the Joint Research Fund in Astronomy under Cooperative Agreement Between the National Natural Science Foundation of China and Chinese Academy of Sciences (Grant Nos. U1631239 and U1931206), the 111 Project, China (Grant No. B13015), and the

The purpose of this article is to explore the cause of the over-response phenomenon of fiber x-ray sensor. The sensor is based on a length of PMMA fiber, whose end is filled with the scintillation material Gd2O2S:Tb. The Monte Carlo simulation software GEANT4 uses the phase space file provided by the International Atomic Energy Agency (IAEA), by irradiating the fiber x-ray sensor in the water phantom, counting the fluorescence signal of the optical fiber x-ray sensor after propagation through the fiber. In addition, the number of Cerenkov photons propagating through the fiber is also counted. Comparing this article with previous research, we believe that one of the reasons for the over-response of the fiber x-ray sensor is the non-linear response of the deposition energy of the scintillator to the fluorescence. By establishing a region of interest and counting the x-rays in this region, the simulation results show that the counted number of x-rays that may affect the fiber x-ray sensor is the biggest in the area of interest at a water depth of 5 cm. This result is close to the maximum dose point of the experimental and simulated percentage depth dose (PDD) curve of fiber x-ray sensor. Therefore, the second reason of the over-response phenomenon is believed to be fact that the inorganic materials such as Gd2O2S:Tb have larger effective atomic numbers, so the fiber x-ray sensors will cause more collisions with x-ray in a low energy region of 0.1 MeV–1.5 MeV.