Mean Dose Ratio Research Articles

Parallel explorations in LA-NSCLC: Chemoradiation dose-response optimisation considering immunotherapy and cardiac toxicity sparing

Background and purposeChemoradiotherapy (CRT) for locally-advanced non-small cell lung cancer (LA-NSCLC) has undergone advances, including increased overall survival (OS) when combined with immune checkpoint blockade (ICB), and using cardiac-sparing techniques to reduce the radiotoxicity. This research investigated 1) how radiotherapy schedules can be optimised with CRT-ICB schemes, and 2) how cardiac-sparing might change the OS for concurrent CRT (cCRT). Methods and materialsSurvival data and dosimetric indices were sourced from published studies, with 2-year OS standardised and the hazard ratio of mean heart dose (MHD) against radiotoxicity tabulated in purpose. A published CRT dose–response model was selected, then modified with ICB and cardiac-sparing hypotheses. Models were maximum likelihood fitted, then visualised the prediction outcomes after bootstrapping. ResultsThe modelled 2-year OS rate of cCRT-ICB reached 71 % (95 % confidence intervals, CI 62 %, 84 %) and 66 % (95 % CI: 53 %, 81 %) for stage IIIA and IIIB/C, respectively, given 60 Gy in 2 Gy-per-fraction. 60 Gy in 30 fractions remained the best schedule for cCRT-ICB, whereas modest dose de-escalation to 55 Gy only reduced the OS in 2 %. Sequential CRT (sCRT)-ICB provided 6 % OS increases versus the best OS rate achieved by sCRT alone. Photon MHD-sparing achieved a 5–10 % increase in modelled 2-year OS, with protons providing a further roughly 5–10 % increase. ConclusionNeither dose-escalation nor de-escalation relative to 60 Gy in 30 fractions influenced the survival with cCRT-ICB, while 5 Gy dose de-escalation might benefit patients with heavily irradiated organs at risk. Cardiac-sparing improved OS, and protons provided advantages for tumours anatomically overlapped or lay below the heart.

Inter-fraction motion robustness in a prospective phase II trial on dose-escalated proton reirradiation for locally recurrent rectal cancer

Background and purposeIntensity modulated proton therapy (IMPT) enables generation of conformal dose plans with organ at risk (OAR) sparing potential. However, pelvic IMPT robustness is challenged by inter-fraction motion caused by constant anatomical variations. In this study, the dosimetric impact of inter-fraction motion on target coverage and dose to OAR was quantified in the prospective phase II study ReRad-II on dose-escalated proton reirradiation for locally recurrent rectal cancer (LRRC). Materials and methodsThe inter-fraction motion robustness was assessed for the initial twelve patients enrolled in the ReRad-II study. Patients with resectable LRRC were assessed for neoadjuvant IMPT (55 Gy(RBE)/44Fx) and unresectable recurrences for definitive IMPT (57.5–65 Gy(RBE)/ 46-52Fx). Target coverage and dose to OAR were assessed for robustly optimised three-field IMPT, on 12 plan computerized tomography (CT) scans (pCT) − and 47 repetitive control CT scans (cCTs) during the treatment. The target coverage and doses to OAR were re-calculated on each cCT and the mean dose ratio (pCT/cCT-ratio) and target coverage (V95%) was evaluated. ResultsThe target coverage was robust with a mean dose pCT/cCT-ratio of 1.00 (+/-1%). The V95% target coverage for every cCT were above the accepted worst-case scenario in the robust evaluation. Considerable variation in bladder-, bowel bag-, and bowel loop volume was observed. The OAR with the largest variation in ratio was the bladder (pCT/cCT-ratio: 1.3 (range: 0.5–4.7). ConclusionsIMPT for dose-escalated reirradiation of LRRC provided anatomically robust target coverage despite OAR changes. Inter-fraction motion resulted in OAR doses varying within clinically acceptable range.

IAEA/WHO postal dosimetry audit methodology for electron beams using radio photoluminescent dosimeters.

Independent dosimetry audits are an important intervention in radiotherapy for quality assurance. Electron beams, used for superficial radiotherapy treatments, must also be tested in dosimetry audits as part of a good quality assurance program to help prevent clinical errors. To establish a new service for IAEA/WHO postal dosimetry audits in electron beams using RPL dosimeters. A novel postal audit methodology employing a PMMA holder system for RPLDs was developed. The associated correction factors including holder dependence, energy dependence, dose response non-linearity, and fading were obtained and tested in a multi-center (n=12) pilot study. A measurement uncertainty budget was estimated and employed in analyzing the irradiated dosimeters. Holder and energy correction factors ranged from 1.004 to 1.010 and 1.019 to 1.059 respectively across the energy range. The non-linearity and fading correction models used for photon beams were tested in electron beams and did not significantly increase measurement uncertainty. The mean dose ratio±SD of the multi-center study was 1.001±0.011. The overall uncertainty budget was estimated as±1.42% (k=1). A methodology for IAEA/WHO postal dosimetry audits in electron beams was developed and validated in a multi-center study and is now made available to radiotherapy centers as a routine service.

Antifungal Choice during Intravenous to Oral Cyclosporine Switch Effects Bioavailability in Patients Who Underwent Allogeneic Hematopoietic Stem Cell Transplantation

Introduction: Cyclosporine is a key drug during hematopoietic stem cell transplantation for the prevention of Graft-versus-Host disease with the potential for involvement in drug-drug interactions. We conducted this study to evaluate the effects of antifungals on cyclosporine blood levels and biavailability values. Material and Methods: Patients who had allogeneic hematopoietic stem cell transplantation with normal kidney and liver function and no other drug-drug interactions that could affect cyclosporine blood levels were included in the study. Patients were categorized into moderate (fluconazole) and strong (voriconazole, posaconazole) CYP3A4 inhibitor antifungal users and non-azole (amphotericin B, caspofungin) users. We collected intravenous and oral cyclosporine blood concentrations and doses during cyclosporine administration route changes and evaluated the effects of them according to antifungal groups. Results: We included 94 patients. The moderate and strong CYP3A4 inhibitor user numbers were 54 and 22, respectively. 18 patients with non-azole antifungal prescriptions were included. ANOVA revealed that there was a statistically significant difference in blood corrected concentrations (p<0.0001). The mean oral dose to intravenous dose ratio was 1.44 and 1.53 for the strong and moderate CYP3A4 inhibitor groups, respectively. This ratio was 1.51 for non-azole antifungal users. The median cyclosporine concentrations were higher after switching to oral cyclosporine in three antifungal groups. The highest mean cyclosporine concentration was 378,45 ng/mL and was obtained from patients with strong CYP3A4 inhibitor antifungals. The lowest mean cyclosporine concentration was observed in patients who were prescribed non-azole antifungals, which was subtherapeutic at 165,95 ng/mL. Bioavailability values were 1.17, 0.97, and 0.9 for moderate inhibitor, strong inhibitor, and non-azole users, respectively. In our study, the general oral dose to intravenous dose ratio regardless of the antifungal choice was 1.50. Despite having the lowest dose ratio (1.44), the highest bioavailability (1.17) was achieved by strong CYP3A4 inhibitor users, and nine of them experienced supratherapeutic cyclosporine levels. After applying a 1.53 dose ratio, the highest mean dose ratio among groups, the number of patients with supratherapeutic cylosporine levels increased to twenty-two from six. Eight patients with non-azole antifungal prescriptions still experienced subtherapeutic cyclosporine blood levels after the initiation of a 1.51 mean dose ratio, which suggests non-azole users may need higher oral cyclosporine doses (Figure 1). Conclusion: Cyclosporine is a gold medicine during the allogeneic hematopoeitic stem cell trasnplantation process. Concomitant antifungal therapy affects cyclosporine blood levels during cyclosporine administration.Patients who are prescribed non-azole antifungals such as caspofungin and amphotericin B are at an increased risk of Graft-versus-Host disease due to the lack of therapeutic cyclosporine levels. Patients with azole antifungals may face cyclosporine toxicities during cyclosporine route change due to hepatic enzyme inhibitions. For patients with strong CYP3A4 inhibitor antifungals such as voriconazole and posaconazole, the oral dose to intravenous dose ratio should be adjusted carefully to avoid toxicity. Fluconazole, a moderate CYP3A4 inhibitor, causes a wide range of cyclosporine blood levels, which makes it hard to advise strict dose ratios. Because patient responses to enzyme inhibitors varied in our study, we advise taking precautions on an individual basis. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Impact of respiratory motion on lung dose during total marrow irradiation.

We evaluated the impact of respiratory motion on the lung dose during linac-based intensity-modulated total marrow irradiation (IMTMI) using two different approaches: (1) measurement of doses within the lungs of an anthropomorphic phantom using thermoluminescent detectors (TLDs) and (2) treatment delivery measurements using ArcCHECK where gamma passing rates (GPRs) and the mean lung doses were calculated and compared with and without motion. In the first approach, respiratory motions were simulated using a programmable motion platform by using typical published peak-to-peak motion amplitudes of 5, 8, and 12mm in the craniocaudal (CC) direction, denoted here as M1, M2, and M3, respectively, with 2mm in both anteroposterior (AP) and lateral (LAT) directions. TLDs were placed in five selected locations in the lungs of a RANDO phantom. Average TLD measurements obtained with motion were normalized to those obtained with static phantom delivery. The mean dose ratios were 1.01 (0.98-1.03), 1.04 (1.01-1.09), and 1.08 (1.04-1.12) for respiratory motions M1, M2, and M3, respectively. To determine the impact of directional respiratory motion, we repeated the experiment with 5-, 8-, and 12-mm motion in the CC direction only. The differences in average TLD doses were less than 1% when compared with the M1, M2, and M3 motions indicating a minimal impact from CC motion on lung dose during IMTMI. In the second experimental approach, we evaluated extreme respiratory motion 15 mm excursion in only the CC direction. We placed an ArcCHECK device on a commercial motion platform and delivered the clinical IMTMI plans of five patients. We compared, with and without motion, the dose volume histograms (DVHs) and mean lung dose calculated with the ArcCHECK-3DVH tool as well as GPR with 3%, 5%, and 10% dose agreements and a 3-mm constant distance to agreement (DTA). GPR differed by 11.1 ± 2.1%, 3.8 ± 1.5%, and 0.1 ± 0.2% with dose agreement criteria of 3%, 5%, and 10%, respectively. This indicates that respiratory motion impacts dose distribution in small and isolated parts of the lungs. More importantly, the impact of respiratory motion on the mean lung dose, a critical indicator for toxicity in IMTMI, was not statistically significant (p > 0.05) based on the Student's t-test. We conclude that most patients treated with IMTMI will have negligible dose uncertainty due to respiratory motion. This is particularly reassuring as lung toxicity is the main concern for future IMTMI dose escalation studies.

Comparison of Doses in Organs at Risk of Conventional and Three-Dimensional Treatment Planning in Hybrid Brachytherapy

INTRODUCTION: This retrospective study aims to evaluate the doses of organs at risk (OARs) calculated by conventional two-dimensional (2-D) and three-dimensional (3-D) treatment planning techniques in hybrid high dose rate (HDR) brachytherapy for cervical cancer. MATERIALS AND METHODS: Data of five patients treated with combination of intracavitary and interstitial brachytherapy were used. For each implant, computed tomography (CT) images were obtained, and the clinical target volume and OARs were contoured on CT images. In 3-D planning, the volumes of OARs were derived from dose-volume histogram (DVH) on a dose volume of 2 cc for bladder, rectum, and sigmoid. The OARs defined in replanning for 2-D treatment were the ICRU-38 bladder (bICRU) and rectum (rICRU) points. Paired T-tests were used to analyse the radiation doses of bladder and rectum obtained from both techniques. RESULTS: The mean point doses evaluated via bICRU) and rICRU were 89.34 GyEQD2 and 75.92 GyEQD2, respectively. Meanwhile, the mean volumetric doses of D2cc for bladder and rectum were 80.50 GyEQD2 and 69.08 GyEQD2, respectively. There is a significant difference in mean doses of ICRU point and D2cc volume for bladder (p&lt;0.05). However, there is no significant difference in mean doses of ICRU point and D2cc for rectum (p&gt;0.05). Overall, ICRU point doses overestimated volumetric D2cc doses with a mean dose ratio of 1.110 for bladder and 1.099 for rectum respectively. CONCLUSION: The bICRU in 2-D planning could not represent the bladder 2 cc used in 3-D planning, thus resulting in different total dose; whereas rICRU of 2-D planning was discovered to be similar with rectum 2 cc of 3-D planning and deemed reliable in total dose estimation

Dosing Patterns during Conversion to IPX066, Extended-Release Carbidopa-Levodopa (ER CD-LD), in Parkinson's Disease with Motor Fluctuations.

Background IPX066 is an extended-release (ER) oral formulation of carbidopa-levodopa (CD-LD). Following an initial peak at about one hour, plasma LD concentrations are maintained for about 4-5 hours. Objective To present dosing factors that may affect the successful conversion to ER CD-LD from other LD formulations. Methods Two-phase 3 studies of ER CD-LD vs. immediate-release (IR) CD-LD (ADVANCE-PD) and vs. CD-LD + entacapone (CLE; ASCEND-PD) in subjects with advanced PD included a 6-week, open-label conversion to ER CD-LD prior to treatment randomization. The “converted” daily LD dose ratio and dose frequency for ER CD-LD were compared to the prior LD treatment regimens at study entry. Results The average daily LD dose ratio at the end of dose conversion to ER CD-LD was approximately 2.1 for IR CD-LD and 2.8 for CLE. The final dose ratios tended to be slightly higher for participants taking lower LD doses at study entry but independent of dose frequency. ER CD-LD dose frequency increased with increasing LD dose and dose frequency at study entry. Participants on higher baseline LD doses ≥800 mg and dose frequencies ≥6 tended to have higher rates of discontinuation during conversion to ER CD-LD. Conclusions Converting participants from other LD formulations to ER CD-LD is based on their current LD regimen. For the most common daily doses (≤1250 mg) and dose frequencies (<7) of LD, final mean dose ratios were within tight ranges of 2.1 to 2.4 for IR CD-LD (ADVANCE-PD) and 2.4 to 2.8 for CLE (ASCEND-PD) and were generally independent of the LD dosing frequency at study entry. These trials are registered with NCT00974974, NCT01130493.

What Is the Optimal Radiation Technique for Esophageal Cancer? A Dosimetric Comparison of Four Techniques.

BackgroundEsophageal cancer treatment requires large radiation fields due to the deep location of the esophagus in the mediastinum and the high incidence of radial spread. There is no optimal radiation technique to ensure appropriate target coverage and minimal dose to all normal structures.MethodsFifteen consecutive cases of locally advanced esophageal cancer treated with radical chemoradiation (CRT) were analyzed. The total prescribed dose was 50.4 Gy in 28 fractions. A total of 60 plans were generated for analysis, including four different methods for each case. Method 1 consisted of a four-field conformal technique; method 2 was a two-plan technique (antero-posterior (AP), postero-anterior (PA), two posterior oblique fields (RPO and LPO)); method 3 was a three-field conformal technique (AP, LPO, RPO); and method 4 was a volumetric modulated arc radiotherapy (VMAT) technique. Dose ratios were calculated using the minimum, maximum, mean, and median doses of methods 2-4 over the dose of method 1. Ratios for the planning target volume (PTV) and to surrounding organs were analyzed.ResultsThe mean PTV dose ratio ranged from 0.994 to 1.048 (SD = 0.01) representing an adequate target coverage for all techniques based on an analysis of variance (ANOVA). For the lungs, method 2 had the lowest lung V20 with a ratio of 0.861 (SD = 0.12), whereas method 3 had the highest with 1.644 (SD = 0.14). For the heart, method 3 had the lowest heart V40 with a mean dose ratio of 0.807 (SD = 0.09), whereas method 2 had the highest with 1.160 (SD = 0.11). For the liver, method 2 had the lowest V30 with a mean ratio of 0.857 (SD = 0.1) whereas method 4 had the highest with 1.672 (SD = 0.48). For the spinal cord, method 3 had the lowest mean dose ratio of 0.559 (SD = 0.09) whereas method 2 had the highest with 1.094 (SD = 0.04).ConclusionThe four radiation techniques for esophageal cancer treatment were appropriate for target coverage. Method 2 had the most organ-sparing effect for the lungs and liver, and method 3 for the heart and spinal cord. VMAT did not add any significant sparing. A case-by-case decision should be made based on the patient’s comorbidities.

Digital breast tomosynthesis: Dose and image quality assessment

The aim of this work was to evaluate how different acquisition geometries and reconstruction parameters affect the performance of four digital breast tomosynthesis (DBT) systems (Senographe Essential – GE, Mammomat Inspiration – Siemens, Selenia Dimensions – Hologic and Amulet Innovality – Fujifilm) on the basis of a physical characterization.Average Glandular Dose (AGD) and image quality parameters such as in-plane/in-depth resolution, signal difference to noise ratio (SDNR) and artefact spread function (ASF) were examined.Measured AGD values resulted below EUREF limits for 2D imaging. A large variability was recorded among the investigated systems: the mean dose ratio DBT/2D ranged between 1.1 and 1.9.In-plane resolution was in the range: 2.2mm−1–3.8mm−1 in chest wall-nipple direction. A worse resolution was found for all devices in tube travel direction.In-depth resolution improved with increasing scan angle but was also affected by the choice of reconstruction and post-processing algorithms. The highest z-resolution was provided by Siemens (50°, FWHM=2.3mm) followed by GE (25°, FWHM=2.8mm), while the Fujifilm HR showed the lowest one, despite its wide scan angle (40°, FWHM=4.1mm).The ASF was dependent on scan angle: smaller range systems showed wider ASF curves; however a clear relationship was not found between scan angle and ASF, due to the different post processing and reconstruction algorithms.SDNR analysis, performed on Fujifilm system, demonstrated that pixel binning improves detectability for a fixed dose/projection.In conclusion, we provide a performance comparison among four DBT systems under a clinical acquisition mode.

Switch from abobotulinumtoxinA (Dysport®) to incobotulinumtoxinA (Xeomin®) botulinum toxin formulation: a review of 257 cases.

To explore the dose equivalence ratio and treatment costs for abobotulinumtoxinA and incobotulinumtoxinA for patients with focal dystonias. Patient chart review. Adult patients with blepharospasm (n = 19), cervical dystonia (n = 122), hemifacial spasm (n = 91) or segmental/generalized dystonia (n = 19) at a neurology outpatient clinic. Patients were switched from established abobotulinumtoxinA therapy to incobotulinumtoxinA at a ~4:1 unit ratio. Dose requirements, injection intervals, treatment efficacy, and adverse events were evaluated for a period of ≥ 1 year. Patients were switched from abobotulinumtoxinA to incobotulinumtoxinA with a mean dose ratio of 4.07 (standard deviation (SD) 0.50). After switching, incobotulinumtoxinA dose requirements remained stable; the mean (SD) dose ratio at the end of the review period (52-219 weeks after switching) was 3.89 (SD 0.58). Injection intervals also remained stable after switching. Adverse events were injection site pain (n = 45) and bruising (n = 4). Five patients (2.0%) discontinued incobotulinumtoxinA treatment: 4 stopped receiving injections, and 1 reverted to abobotulinumtoxinA. Switching to incobotulinumtoxinA reduced the mean toxin expenditure to 76.7% of the cost of abobotulinumtoxinA. For patients with conditions commonly treated in dystonia clinics, switching from abobotulinumtoxinA to incobotulinumtoxinA, given at equivalent doses (~4:1 unit ratio) at similar intervals, was effective, well tolerated and achieved cost savings.

Critical appraisal of serum phenytoin variation with patient characteristics in a North Indian population.

Phenytoin (PHT) is one of the frontrunner drugs used as monotherapy in the management of epilepsy. It is also one of the most common drugs causing adverse drug reactions (ADRs). The aim of this study was to study the relationship between serum PHT levels and the age, gender, dosage and genetic polymorphisms in a North Indian population. This knowledge will help in devising drug dosage schedules in various sub-groups of patients as well as in reducing its ADRs. A retrospective analysis of data of 6224 patients from 1998 to 2009 receiving PHT alone for greater than (>) 4 weeks was performed. Patients suspected of being non-compliant, being overdosed or having a hepatic or renal disorder were excluded from the study. Two thousand eight hundred and eighty-eight patients fulfilling the inclusion criteria were divided into three groups: children (1-18 years), adults (19-60 years) and elderly (>60 years). There was a male preponderance (80%) in all the groups. A significant difference was found in the mean dose between children and adults as well as between children and elderly (P = 0.00). Also, there was a significant difference in the mean concentration and dose ratio between children and adults (P = 0.00). However, a negative correlation was observed between the daily dose and dose ratio (r = -0.36, P = 0.00) that was highest (r = -0.58, P = 0.00) in the elderly. There was a significant gender difference in the mean dose in both children (P = 0.03) and adults (P = 0.00), whereas the mean concentration differed in adults only. Every fifth patient was an intermediate metabolizer (IM) (CYP2C9FNx011/FNx013) and showed higher steady state drug levels (>17 mg/L) compared with extensive metabolizers (EMs) (<12 mg/L). The genetic difference between IM and EM was more prevalent in the dose ratio at maintenance dose, with a mean ± SD of 4.041 ± 1.288 mg/L/mg/kg in nine patients carrying the CYP2C9FNx011/FNx013 genotype compared with 2.145 ± 0.817 mg/L/mg/kg in 26 patients carrying the CYP2C9FNx011/FNx011 genotype (P = 0.00). North Indian female children and male adults frequently attain a higher serum concentration with the same dose when compared to the other groups. Absence of poor metabolizers may be responsible for a lower number of cases exhibiting toxicity in our population; however, this needs elucidation in a larger number of patients.

Preservation of anemia control and weekly ESA dosage after conversion from PEG-Epoetin beta to darbepoetin alfa in adult hemodialysis patients: the TRANSFORM study.

IntroductionThere is scant real-world information on switching treatment for anemia associated with chronic kidney disease (CKD) from methoxy polyethylene glycol-epoetin beta (PEG-Epo) to darbepoetin alfa (DA). TRANSFORM was a multi-center, observational study designed to describe the time course of hemoglobin (Hb) concentration (primary outcome measure) and other parameters of clinical management of anemia in European hemodialysis patients in clinical practice before and after a switch from PEG-Epo to DA.MethodsEligible subjects were adult patients with CKD dialyzed at European dialysis centers for ≥26 weeks and treated with PEG-Epo for ≥14 weeks immediately prior to being switched to DA and no earlier than January 2011. Erythropoiesis-stimulating agent doses and Hb values were recorded for the 14-week pre-switch and 26-week post-switch periods.ResultsOf the 1,027 eligible patients enrolled at 42 hemodialysis centers in 7 European countries, 785 were included in analyses. Mean (95% confidence interval [CI]) Hb was generally stable: 11.19 (11.11, 11.26), 11.48 (11.40, 11.57), and 11.29 (11.20, 11.37) g/dL at month −1 pre-switch and months 3 and 6 post-switch, respectively. The geometric mean (95% CI) PEG-Epo dose at month −1 was 27.4 (26.0, 28.8) µg/week; DA dose was 29.4 (27.9, 30.9), 23.3 (21.9, 24.9), and 25.6 (24.1, 27.1) µg/week at months 1, 4, and 6, respectively. The geometric mean (95% CI) dose ratio at switching was 1.06 (1.01, 1.11). When stratifying by dose-ratio categories <0.8, 0.8–1.2, and >1.2 at switching, mean DA dose and Hb converged within narrow ranges by month 6 post-switch: 23.9–27.0 µg/week and 11.1–11.5 g/dL, respectively. Hb excursions <10 g/dL were less frequent post-switch versus pre-switch.ConclusionMean Hb values remained within a narrow range following switching from PEG-Epo to DA in this population of hemodialysis patients. Time trends of mean Hb and DA dose indicate that physicians titrated DA doses post-switch, to attain Hb concentrations comparable to those attained pre-switch with PEG-Epo.FundingAmgen (Europe) GmbH, Zug, Switzerland.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-014-0161-5) contains supplementary material, which is available to authorized users.

Dosimetric effect of small bowel oral contrast on conventional radiation therapy, linear accelerator–based intensity modulated radiation therapy, and helical tomotherapy plans for rectal cancer

PurposeThis study evaluated the dosimetric effect of small bowel oral contrast on conventional radiation therapy, linear accelerator--based intensity modulated radiation therapy (IMRT), and helical tomotherapy (HT) treatment plans. Methods and materialsThirteen patients with rectal cancer underwent computed tomography (CT) simulation with oral contrast (CCT) in preparation for chemoradiation therapy. The contrast in the small bowel was contoured, and a noncontrast CT scan (NCCT) was simulated by reassigning a CT number of 0 Hounsfield units to the contrast volume. Conventional, IMRT, and HT plans were generated with the CCT. The plan generated on the CCT was then recalculated on the NCCT, maintaining the same number of monitor units for each field, and the plans were not renormalized. Dosimetric parameters representing coverage of the planning target volume with 45 Gy (D98%, D95%, D50%, and D2%) and sparing of the bladder and peritoneal cavity (D50%, D30%, and D10%) were recorded. The ratio of dose calculated in the presence of contrast to dose with contrast edited out was recorded for each parameter. A paired Student t test was used for comparison of plans. ResultsFor conventional plans, there was <0.1% variance in the dose ratio for all volumes of interest. For IMRT plans, there was a 1% decrease in the mean dose ratio, and the range of dose ratios for all volumes was greater than that for HT or conventional plans. For HT plans, for all volumes of interest, the mean dose ratio was <0.2%, and the range for all patients was <1%. For all IMRT dosimetric parameters, the difference was in the order of 1% of the mean dose (P < .05). The dose difference was not statistically significant for the conventional or HT plans. ConclusionsThe use of CCT during CT simulation has no clinically significant effect on dose calculations for conventional, IMRT, and HT treatment plans and may not require replacement of the contrast with a CT number of 0 Hounsfield units.

Creating Guidelines for Reactive and Prophylactic Enteral Feeding in Definitive (Chemo) IMRT for Head-and-Neck Cancer

course were consistent within 5% and 1.5% of the planned mean doses for PTvs and CTvs, respectively. For the tighter margin plans, the cumulative mean dose ratios were consistent within 4.3% and 2.3% of the planned mean doses for CTV2 and CTV3, respectively. No significant changes in D95 and D90 for the CTV2/3 cumulative doses in both reference and tighter margin plans were observed. While interfraction anatomical changes introduced minor variations in delivered target doses, improved normal structure sparing was observed in plan_0margin. The averaged planned cord maximum doses in Plan_0margin was 7.6% lower, and the parotid mean doses were 18.9% lower than plan_Ref. Similar dose variations of the delivered dose were seen for the reference and tighter margin plans. The delivered maximum and mean doses for the cord were 20% and 10% higher than the planned doses; a 3.6% higher cumulative mean dose for the parotids was also observed for the delivered dose than the planned doses in both plans. Conclusions: The GPU-based image framework enables real-time dose verification, accumulation and documentation. By imposing tighter PTV margins for level 2 and 3 targets for HN Varian Medical Systems, Inc. F. Honoraria; Accuray Inc., Siemens Medical Solutions, Viewray Inc. M. Steinberg: None. D. Low: None. S. Lee: None.

Real-Time Assessment of Dosimetric Variations in Head-and-Neck Radiation Therapy

Real-Time Assessment of Dosimetric Variations in Head-and-Neck Radiation Therapy

Pre-treatment quality assurance for stereotactic cranial plans

Objective To report the Results of Quality Assurance (QA) dose planning for stereotactic cranial treatments delivered with Dynamic Conformal Arcs (DCA) or Volumetric Modulated Arc Therapy (VMAT) techniques. Material and methods A total of 26 dose plans, 19 patients with DCA from Iplan® (Brainlab) and 7 patients with VMAT from EclipseTM (Varian), were verified with different QA methods. Plans were delivered on a Novalis TX unit. Each treatment field was checked for absolute isocenter dose using a Lucy® 3D QA Phantom (Standard Imaging) and a Diamond chamber (PTW). GafchromicTM EBT3 film dosimetry (ISP) was selected to verify total dose plans in the 2D axial planes. A flatbed RGB scanner (Epson Expression 10,000 XL) was used to digitize the films and the RIT software to analyze the data (gamma criteria 1 mm and 3%). Relative dose analysis was performed normalized at isocenter. Same criteria were used for Portal dosimetry (PD) verifications of VMAT plans. Finally for DCA plans, manual independent Monitor Units Calculation (MUC) number was implemented. Results Absolute isocenter dose measurements: the mean dose ratio (measured/expected) was for DCA (total of 102 fields, dose range 0.3–6 Gy), and for VMAT treatments (a total of 22 treatment fields, and dose range 0.3–1.3 Gy) 1.014 (SD 0.017) and 1.034 (SD 0.031) respectively. Films: the mean gamma agreement index (GAI) was for DCA plans (3 patients) and VMAT plans (3 patients) 99.9% (SD 0.1%) and 93.0 (SD 3.9%) respectively. PD: for VMAT plans (22 fields) the mean GAI was 93.4% (SD 3.4%). MUC: the mean relative difference over 102 treatment fields was 0.02% (SD 1.64%). Conclusion DCA QA results were excellent. VMAT, chosen to better spare organ at risk with its modulation, showed worst results likely for this last feature. HybridArc will next be tested. To report the Results of Quality Assurance (QA) dose planning for stereotactic cranial treatments delivered with Dynamic Conformal Arcs (DCA) or Volumetric Modulated Arc Therapy (VMAT) techniques. A total of 26 dose plans, 19 patients with DCA from Iplan® (Brainlab) and 7 patients with VMAT from EclipseTM (Varian), were verified with different QA methods. Plans were delivered on a Novalis TX unit. Each treatment field was checked for absolute isocenter dose using a Lucy® 3D QA Phantom (Standard Imaging) and a Diamond chamber (PTW). GafchromicTM EBT3 film dosimetry (ISP) was selected to verify total dose plans in the 2D axial planes. A flatbed RGB scanner (Epson Expression 10,000 XL) was used to digitize the films and the RIT software to analyze the data (gamma criteria 1 mm and 3%). Relative dose analysis was performed normalized at isocenter. Same criteria were used for Portal dosimetry (PD) verifications of VMAT plans. Finally for DCA plans, manual independent Monitor Units Calculation (MUC) number was implemented. Absolute isocenter dose measurements: the mean dose ratio (measured/expected) was for DCA (total of 102 fields, dose range 0.3–6 Gy), and for VMAT treatments (a total of 22 treatment fields, and dose range 0.3–1.3 Gy) 1.014 (SD 0.017) and 1.034 (SD 0.031) respectively. Films: the mean gamma agreement index (GAI) was for DCA plans (3 patients) and VMAT plans (3 patients) 99.9% (SD 0.1%) and 93.0 (SD 3.9%) respectively. PD: for VMAT plans (22 fields) the mean GAI was 93.4% (SD 3.4%). MUC: the mean relative difference over 102 treatment fields was 0.02% (SD 1.64%). DCA QA results were excellent. VMAT, chosen to better spare organ at risk with its modulation, showed worst results likely for this last feature. HybridArc will next be tested.

SU-E-T-463: A Dosimetric Evaluation of CBCT Guided Intra-Fractional Adaptive Radiotherapy for VMAT

Purpose: To investigate the dosimetric advantages of an image guided replanning strategy utilizing on-board CBCTs for VMAT plans. An intensity corrected grey-scale based CBCT to planning CT deformable image registration algorithm, combined with an intra-fractional morphing aperture optimization algorithm (ICDIR-MAO), is dosimtrically evaluated for head and neck cancer patients. Methods: : Head and neck VMAT plans were retrospectively adapted using the ICDIR-MAO algorithm. Patient CBCT and CT images are deformably registered with an intensity corrected demons based deformable image registration algorithm. The deformation vector field is applied to the PTV on the structure set to obtain a deformed PTV. Digitally reconstructed radiographs of the original PTV and deformed PTV are created for each treatment angle. MLC positions are generated to contour both PTVs and a ratio of original vs. deformed MLC positions that outline the PTV beam's eye view contour is applied to each angle of the planned MLC sequence. The deformed image is then sliced up and reformatted back into dicom files, with the associated metadata. The deformation vector field is added to the structure set at every point and a new dicom structure set is created. The new mlc sequences are reformatted back into dicom plans. All three dicom files are imported back into eclipse, and dose is re-calculated on the deformed plan, deformed image set, and associated deformed structures. Results: The mean and maximum dose ratios for the OARS were lowered for all cases. The mean dose for the PTV70Gy, PTV60Gy, and PTV54Gy was the same or better for the deformed plans. The dosimetric improvement was proportional to the contour volume overlap between the deformed CT and the original CT. Conclusion: : ICDIR-MAO for adaptive VMAT replanning improves the dosimetric quality for head and neck patients. This research is supported by CPRIT Individual Investigator Award RP110329

The role of lung lobes in radiation pneumonitis and radiation-induced inflammation in the lung: a retrospective study

We examined the relative response to radiation of the upper lung lobes (UL) versus lower lung lobes (LL) of normal lung tissue using normalized [18F]-fluorodeoxyglucose (FDG) uptake per radiation dose received per lung voxel in patients treated with either photons or protons and tested for correlation of the radiation response with clinical pneumonitis. Seventy-five patients (photon (n = 51) or proton (n = 24)) treated for esophageal cancer from November 1, 2003 to May 15, 2011 who received restaging FDG-positron emission tomography (PET) imaging 1 to 3 months after chemoradiation were selected. UL and LL were contoured using the major fissure as the boundary, with the right middle lobe being included in the right UL structure. Pneumonitis toxicity was scored using the Common Terminology Criteria for Adverse Events, version 4.0 based on the consensus of 5 clinicians. LL had a higher mean dose (15.6 Gy vs. 10.4 Gy, p<0.001), higher mean standard uptake value (SUV) (0.78 vs. 0.56, p=0.001) and SUV in low dose regions (0.80 vs. 0.66 for 10 to 20 Gy, p=0.001), and lower mean dose response (0.015 vs. 0.019, p=0.003) compared to the UL. The mean dose ratio of UL vs. LL (p < 0.001), and SUV in the region of lung receiving 0-10 Gy (p=0.04), but not the dose response ratio of UL vs. LL (p=0.53) correlated with symptomatic pneumonitis. Upper lung lobes had a greater pulmonary metabolic radiation response than lower lung lobes. Greater dose to UL relative to LL and higher SUV in the low dose region (10-20 Gy) on post-treatment PET correlated with symptomatic pneumonitis.

Utilization and cost comparison of erythropoiesis-stimulating agents in inpatient and outpatient hospital settings

Objective:To compare utilization and associated costs of epoetin alfa (EPO) and darbepoetin alfa (DARB), two erythropoiesis-stimulating agents (ESAs), in patients with cancer undergoing chemotherapy and patients with chronic kidney disease (CKD) not on dialysis in inpatient and outpatient hospital settings.Methods:An analysis of medical claims recorded between January 2006 and December 2009 was conducted using the Premier Perspective Comparative Hospital database. Patients included were ≥18 years old with cancer and chemotherapy or with pre-dialysis CKD and with ≥1 claim for EPO or DARB during a hospital inpatient or outpatient treatment episode. Patients treated with both ESAs or who were receiving dialysis were excluded. Mean cumulative drug costs and dose ratios (units EPO: mcg DARB) were calculated using cumulative dose and April 2010 wholesale acquisition costs.Results:Cancer chemotherapy: 13,832 inpatient stays (EPO: 10,454; DARB: 3378) and 5590 outpatient treatment episodes (EPO: 2856; DARB: 2734) were identified. The inpatient and outpatient populations reported ESA dose ratios of 230:1 and 238:1 with DARB cost premiums of 42% (EPO: $948; DARB: $1348) and 38% (EPO: $3358; DARB: $4627), respectively. CKD: 148,746 hospital stays (EPO: 116,017; DARB: 32,729) and 11,012 outpatient treatment episodes (EPO: 6921; DARB 4091) were identified. The inpatient and outpatient populations reported ESA dose ratios of 251:1 and 257:1 with DARB cost premiums of 30% (EPO: $566; DARB: $738) and 27% (EPO: $2077; DARB: $2642), respectively.Limitations:The lack of randomization may have led to confounding by indication. In addition, statistical significance must be interpreted with caution in studies involving large samples.Conclusions:This study of 19,422 patients with cancer receiving chemotherapy and 159,758 patients with pre-dialysis CKD reported ESA dose ratios ranging from 230:1–257:1 (units EPO: mcg DARB) and associated cost premiums of 27–42% for DARB.

SU-E-T-487: TomoTherapy Plan Quality Metrics for Multiple Anatomical Sites

Purpose: TomoTherapy IMRT plans for various anatomical sites were analyzed in order to obtain dosimetric characteristics, and to determine plan quality and deliverability.Methods: Treatment plans for thirty patients treated with TomoTherapy were reviewed and analyzed. The distribution of treatment sites was: abdomen (n=4), brain (n=4), head and neck (H&N n=6), lung (n=6), pelvis (n=5) and prostate (n=5). Prescription dose (PD), D90%, PTV, max, mean and min doses of PTV were extracted from the plans and DVH data. Metrics calculated include: homogeneity index (H.I.=max dose in PTV/ PD), mean dose of PTV over PD, max dose of PTV over min dose in PTV, and D90%/PD were calculated for the different treatment sites. In order to verify plan delivery, absolute and relative dose measurements were performed and analyzed using an ion chamber and GafChromic films. Results: Mean prescription isodose lines were 95.7% (n=30). The PTV ranged from 11.7 to 982.2 cc. For H.I. the prostate site yielded the smallest H.I. of 0.99 while the pelvis site yielded the greatest H.I. of 1.14. The prostate site produced the smallest mean dose over PD (0.97) and H&N produced the greatest (1.03). The overall H.I. was 1.06 and the overall ratio of mean dose over PD was 1.02. The overall max dose over min dose was 1.18. The mean difference for absolute point dose measurements was −0.9%. Measured film profiles demonstrated excellent agreement with calculated profiles in plan delivery QA Conclusions: For the treatment sites reviewed prostate had the most homogeneous plans, while lung had the most inhomogeneous plans in this study. The overall mean dose over PD and QA results were excellent in TomoTherapy. TomoTherapy is capable of planning and delivering high quality IMRT treatments for a wide variety of treatment sites