Percentage Of Maximum Dose Research Articles

M199. COPY NUMBER VARIANCE (CNV) ANALYSIS TO DETERMINE OPTIMAL ANTIPSYCHOTIC DOSAGE IN SCHIZOPHRENIA: A PILOT STUDY

BackgroundThe relationship between genetic polymorphisms of antipsychotic drug-metabolizing agents and drug response has been thoroughly investigated and analyzed. However, from a pharmacokinetic standpoint, few studies have explored the relationship between Copy number variants (CNV) and antipsychotic dosage. The aim of the present study is to test the association between antipsychotic dosage and CNV in schizophrenia (SCZ) patients.MethodsThe current dosage of antipsychotic medications was collected from 263 schizophrenia patients. The dosage was standardized using three different methods: chlorpromazine equivalent(CPZe), defined daily dose (DDD), and percentage of maximum dose (PM %). The patients were then genotyped using the Illumina HumanOmni2.5–8 BeadChip Kit.ResultsThe CNV analysis did not show that CNVs are associated with dosage variation for CPZe, PM %, and DDD.DiscussionIn this pilot sample, we investigated for the first time CNVs and standardized antipsychotic dosage. The relationship between CNV and optimal antipsychotic dosage has far reaching clinical implications. Further analysis is required that utilitze large prescription databases to build on the results presented in this pilot study.

SU‐F‐T‐635: Lung SBRT: Dosimetric and Treatment Time Comparison of Volumetric‐Modulated Arc Therapy and Three‐Dimensional Conformal Radiotherapy in Clinically Treated Cases

Purpose:To compare three‐dimensional conformal radiotherapy (3D CRT) and volumetric‐modulated arc therapy (VMAT) in lung stereotactic body radiation therapy (SBRT)Methods:A retrospective study of clinically treated lung SBRT cases treated between 2010 and 2015 at our hospital was performed. All treatment modalities were included in this evaluation (VMAT, 3D CRT, static IMRT, and dynamic conformal arc therapy). However, the majority of treatment modalities were either VMAT or 3D CRT. Treatment times of patients and dosimetric plan quality metrics were compared. Treatment times were calculated based on the time the therapist opened and closed the patient's treatment plan. This treatment time closely approximates the utilization time of the treatment room. The dosimetric plan quality metrics evaluated include ICRU conformity index, the volume of 105% prescribed dose outside PTV, the ratio of volume of 50% prescribed dose to the volume of PTV, the percentage of maximum dose at 2 cm away from PTV to the prescribed dose, and the V20 (percentage of lung volume receiving 20 Gy or more).Results:Treatment time comparisons show that on average VMAT has shorter treatment times than 3D CRT. Dose conformity, defined by the ICRU conformity index, and high dose spillage, defined by the volume of 105% dose outside the PTV, is reduced when using VMAT compared to 3D CRT. V20 and intermediate dose spillage/fall‐off metrics of VMAT and 3D are not significantly different.Conclusion:Clinically treated lung SBRT cases indicate VMAT is superior to 3D with regard to shorter treatment times, plan dose conformity, and plan high dose spillage.

Genome-wide association analysis to predict optimal antipsychotic dosage in schizophrenia: a pilot study.

In recent years, several studies have investigated genetic polymorphisms of antipsychotic drug-metabolizing enzymes and receptors. However, most studies focused on drug response and very few have investigated the genetic influence on antipsychotic dosage. The aim of the present study is to test the association between antipsychotic dosages at genome-wide level. The current dosage of antipsychotic medications was collected from 79 schizophrenia patients. The dosage was standardized using three different methods: chlorpromazine equivalent (CPZe), defined daily dose (DDD), and percentage of maximum dose (PM%). The patients were then genotyped using the Illumina HumanOmni2.5-8 BeadChip Kit. All markers were screened for significance using linear regression, and the p values were visualized using a Manhattan plot. The genome-wide analysis showed that the top Single-Nucleotide Polymorphisms (SNPs) associated with dosage variation were rs981975 on chromosome 14 for CPZe, rs4470690 on chromosome 4 for PM%, and rs79323383 on chromosome 8 for DDD. However, no genome-wide significantly associated SNPs were identified. In this pilot sample, we found promising trends for pharmacodynamic targets associated with antipsychotic dosage. Therefore, studies combining large prescription databases may identify genetic predictors to adjust the dose of antipsychotic medication.

USEFULNESS OF SIMPLE SHIELDING TECHNIQUE USING MULTILEAF COLLIMATOR IN BREAST RADIATION THERAPY

This study was designed to assess whether the conventional tangential technique, using a multileaf collimator (MLC), allows a reduced dose to the organs at risk (OAR) in breast radiation therapy. A total of forty right and left 20 for each breast cancer patients that underwent radiation therapy after breast conserving surgery were included in this study. For each patient, the planning target volume (PTV) and OAR (heart, left anterior descending artery (LAD), liver and lung) were defined and dose distribution were produced for conventional tangential beams using 6 MV photons. The treatment plans were made using the following two techniques for all patients. For the first plan (P1), MLC was designed to shield as much of OAR as possible without compromising the coverage of PTV. In the second plan (P2), the treatment plan was created without using MLC. Dose-volume histograms for OARs were calculated for all plans. For left breast cancer, the percentage of maximum dose (Dmax%) and mean dose (Dmean%) of OARs (heart and LAD) were calculated, and for right breast cancer, the percentage of the mean dose (Dmean%) of the liver was calculated. The Dmean% of the lung was calculated in all patients. The mean values of Dmax% of the heart (86.9±19.5% range, 35.1-100.6%) in P1 were significantly lower than in P2 (98.3±3.4% range, 91.7-105.2%) (p=0.001). The mean values of Dmax% of LAD (78.4±22.5% range, 26.5-99.7%) in P1 was significantly lower than in P2 (93.3±8.1% range, 67.9-102.1%) (p<0.001). In P1, the mean values of Dmean% of the liver (4.8±2.0%) were significantly lower than in P2 (6.2±2.5%) (p<0.001). The mean values of Dmean% of the lung were significantly lower in P1 (9.3±2.3%) than in P2 (9.7±2.4%) (p<0.001). P1, by using MLC, allows a significantly reduced dose to OAR compared with P2. We can suggest that it is reasonable to routinely use MLC in the conventional tangential technique for breast radiation therapy considering the primary tumor location.

SU-E-T-703: Brain Dose From Gamma Knife Depends Primarily On the Treated Volume and Not On the Number, Shape Or Location of the Lesions

Purpose: To assess the hypothesis that the volume of brain parenchyma that receives a certain dose level in Gamma‐Knife is dependent on the treated volume and not on the number, shape or location of the lesions. This would help a physician validate the suitability of GammaKnife based stereotactic radiosurgery (GKSR) prior to treatment. Methods: Simulation studies were performed to establish the hypothesis for an oblong, a spherical lesion of various sizes and multiple spherical lesions. A similar study was performed on forty patients who underwent GKSR with mean age 54 (range 7–80), mean number of lesions 2.5 (range 1–6) and mean lesion volume at presentation 4.4cc (range 0.02cc–22.2cc). Following recommendations of QUANTEC, V12 of brain (VB12) was measured and a power‐law based relation is proposed here for estimating VB12 from the volume of target treated to 50% of maximum dose (VT50%). Results: In the simulation study, the volume of brain irradiated by 50% (VB50%), 10% (VB10%) and 1% (VB1%) of maximum dose was found to have linear, linear and exponentially increasing dependence on VT50%, respectively. In the retrospective study on forty GKSR patients, a similar relationship was found to predict the brain dose with a Spearman correlation coefficient >0.9 and the corresponding p‐value from Students T‐test <1*10‐4 for all the above 3 dependences. The relationships between clinical VT50% and the number and aspect ratio of lesions were statistically insignificant. The measured VB12 of brain agrees with the calculated value of VB12 to within 1.7%. Conclusion: The simulation and the retrospective clinical studies indicate that the volume of brain irradiated by a percentage of maximum dose is dependent on the treated volume and not on the number, shape or location of the lesions.

A plea for the GTV median dose reporting in SBRT/can the ICRU 83 reporting way be applied to SBRT plans?

Purpose Plan comparison is difficult with various prescriptions (80% of maximum dose, on the 70% or 50%). In 2010 the AAPM TG 101 suggests to report SBRT with prescription ICRU reference point or isodose covering PTV to a particular percentage. At the same time ICRU report 83 for IMRT was published, the ICRU point is abandoned and prescription is based on median target dose. Can we conciliate these 2 reports? Methods Theoretical plans with Cyberknife for spherical GTV of from 2 to 60 mm were created with prescription of 10 Gy with based on % of maximum dose perfectly adjusted to cover 95% of PTV. GTV median doses were collected. Plans with a shift equal to the PTV margin, in the direction of the minimum observed in the dose distribution, were created and the GTV D50% were again collected. Three different clinical situations: brain metastases, prostate and lung lesion were assessed with different percentage of maximum dose used for prescription and again applying a shift. Results The GTV median dose is little sensitive to the minimum in the PTV, and thus remains almost constant in all cases i.e. when we imagine a systematic error equal to the PTV margin. With the 6 mm PTV and a prescription isodose of 54%, i.e. with a fall-off of 20%/mm at the edge of the PTV, the GTV median dose is 14.77 Gy and 14.75 Gy with the shift. For the particular case of lung where the PTV includes a low density region, using Monte-Carlo calculation, the GTV median dose is also stable. Conclusions The GTV median dose appears to be a convenient way to describe the dose distribution delivered, whatever the % of maximum dose used for prescription. For a better understanding of the dose distributions, every team should report PTV D98%, PTV D95%, PTV D2% and GTV median dose like ICRU report 83 recommends for IMRT, in order to compare clinical studies.