Significant Dose Differences Research Articles

FDG PET/CT parameters and correlations with tumor-absorbed doses in a phase 1 trial of 177Lu-lilotomab satetraxetan for treatment of relapsed non-Hodgkin lymphoma

Purpose177Lu-lilotomab satetraxetan targets the CD37 antigen and has been investigated in a first-in-human phase 1/2a study for relapsed non-Hodgkin lymphoma (NHL). Tumor dosimetry and response evaluation can be challenging after radioimmunotherapy (RIT). Changes in FDG PET/CT parameters after RIT and correlations with tumor-absorbed doses has not been examined previously in patients with lymphoma. Treatment-induced changes were measured at FDG PET/CT and ceCT to evaluate response at the lesion level after treatment, and correlations with tumor-absorbed doses were investigated.MethodsForty-five tumors in 16 patients, with different pre-treatment and pre-dosing regimens, were included. Dosimetry was performed based on multiple SPECT/CT images. FDG PET/CT was performed at baseline and at 3 and 6 months. SUVmax, MTV, TLG, and changes in these parameters were calculated for each tumor. Lesion response was evaluated at 3 and 6 months (PET3months and PET6months) based on Deauville criteria. Anatomical changes based on ceCT at baseline and at 6 and 12 months were investigated by the sum of perpendiculars (SPD).ResultsTumor-absorbed doses ranged from 35 to 859 cGy. Intra- and interpatient variations were observed. Mean decreases in PET parameters from baseline to 3 months were ΔSUVmax-3months 61%, ΔMTV3months 80%, and ΔTLG3months 77%. There was no overall correlation between tumor-absorbed dose and change in FDG PET or ceCT parameters at the lesion level or significant difference in tumor-absorbed doses between metabolic responders and non-responders after treatment.ConclusionOur analysis does not show any correlation between tumor-absorbed doses and changes in FDG PET or ceCT parameters for the included lesions. The combination regimen, including cold antibodies, may be one of the factors precluding such a correlation. Increased intra-patient response with increased tumor-absorbed doses was observed for most patients, implying individual variations in radiation sensitivity or biology.Trial registrationClinicalTrials.gov Identifier (NCT01796171). Registered December 2012

Optimizing Hydroxyurea Therapy with Reduced Laboratory Monitoring for Children with Sickle Cell Anemia in Sub-Saharan Africa: The Reach Experience

Introduction: Realizing Effectiveness Across Continents with Hydroxyurea (REACH, NCT01966731) is an open-label study of hydroxyurea for children with sickle cell anemia (SCA) in sub-Saharan Africa (Angola, DR Congo, Kenya, and Uganda). Initial results documented the feasibility, safety, and benefits of hydroxyurea for SCA in sub-Saharan Africa but guidance for optimizing hydroxyurea therapy is needed. We describe 5 years of hydroxyurea dosing and monitoring in the largest prospective cohort of children with SCA receiving hydroxyurea to date. Methods: Children 1-10 years of age with SCA were enrolled. The hydroxyurea dose was fixed at 15-20 mg/kg/day for the first 6 months with monthly complete blood counts (CBCs) to ensure safety. From month 6-24, the dose was escalated (5 mg/kg every 8 weeks) to maximum tolerated dose (MTD), defined as mild myelosuppression with absolute neutrophil count (ANC) <4.0 x 109/L on 2 consecutive CBCs without hematological toxicities. CBCs were performed monthly until MTD or a stable dose was achieved, then subsequently every 3 months. Dose limiting toxicities (DLT) requiring a temporary treatment hold were defined as ANC <1.0 x 109/L, Hb <4.0 g/dL, reticulocyte count <80 x 109/L unless Hb >7.0 g/dL, or platelets <80 x 109/L. Known genetic modifiers of SCA, including G6PD deficiency and α-thalassemia trait, were determined for all participants. Results: A total of 606 children initiated hydroxyurea and currently 555 (92%) remain on treatment, with average treatment duration of 48 ± 12 months and a total of 2,441 patient-years of hydroxyurea treatment. Over 85% achieved MTD with an average hydroxyurea dose of 22.5 ± 5.0 mg/kg/day, ranging from 19.0 mg/kg/day in Angola to 25.4 mg/kg/day in Uganda. With dose increases over time, the most recent average dose is 23.9 ± 5.4 mg/kg/day (site range 22.9-24.6 mg/kg/day). Lab benefits have been sustained; Hb increased from 7.3 g/dL at baseline to 8.4 g/dL at MTD and remains 8.3 g/dL at Month 60. Similarly, the average HbF increased from 11% baseline to 25% at MTD and remains 23% at Month 60. The average ANC decreased from 6.8 x 109/L at baseline to 3.2 x 109/L at MTD and remains 3.5 x 109/L at Month 60. Lab toxicities are infrequent, transient, and mostly incidental. Of 19,730 CBCs obtained during the treatment phase, 421 (2.1%) in 225 participants included a DLT. The most common DLT was thrombocytopenia (33%), with only 4 platelet counts <20 x 109/L and no bleeding. Anemia was the second most common DLT (26%), most commonly associated with a high reticulocyte count and malarial infection, unrelated to hydroxyurea. Severe neutropenia (ANC <0.5 x 109/L) was rare (5 events) with no neutropenic infections. Over 2/3 of DLT events were identified incidentally during a scheduled visit when the study participant was asymptomatic, including all 5 severe neutropenic episodes. Weight-for-age and height-for-age Z-scores were not associated with higher rates of DLT during hydroxyurea treatment. Children with two-gene deletional α-thalassemia trait tolerated significantly lower hydroxyurea doses than the normal genotype (MTD dose 20.0 vs. 24.0 mg/kg/day, p <0.001) and had significantly different treatment responses at Month 60 including lower HbF (19.5 vs 24.3%, p <0.0001) and MCV (72 vs 99 fL, p<0.001) but higher hemoglobin (8.5 vs 8.1 g/dL, p=0.016). DLT frequency was unaffected by α-thalassemia status. Males with G6PD A- deficiency did not demonstrate significant differences in dosing, response, or toxicity. Conclusions: Hydroxyurea is safe, well-tolerated, and effective for children with SCA living in sub-Saharan Africa. Treatment responses are robust and sustained in REACH across all 4 clinical sites and unaffected by baseline Z-score. Hydroxyurea optimization requires periodic dose escalation for weight gain and titration to mild myelosuppression. Deletional α-thalassemia trait significantly influences the hydroxyurea dose and treatment responses, but the lab benefits with optimized dosing are still robust regardless of the α-globin genotype. Lab toxicities from hydroxyurea are uncommon and typically asymptomatic, suggesting that routine CBC monitoring is needed only at 3-month intervals once a stable dose is achieved, more to optimize the dose than to identify incidental toxicities. This approach to optimizing hydroxyurea therapy will allow more widespread utilization in low-resource settings with limited laboratory monitoring. Disclosures Aygun: National Heart, Lung, and Blood Institute: Research Funding; National Institute of Nursing Research: Research Funding; Patient-Centered Outsomes Research Institute: Research Funding; bluebird bio: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Impact of an Infusion Center on the Utilization of Hospital Based Care in Sickle Cell Disease

Background: Sickle cell disease (SCD) consists of a group of hemoglobinopathies inherited in an autosomal recessive pattern whereby a single point mutation results in the formation of a hemoglobin protein with altered structure. Many of the complications of SCD and their end organ manifestations are the result of a vaso-occlusive process. These include acute chest syndrome, dactylitis, myocardial infarction, stroke, venous thromboemboli, avascular necrosis, and acute vaso-occlusive episodes (VOEs). VOEs are the most common reason for a patient with SCD to seek medical attention. This care is often provided at an emergency department (ED). It has been well documented that the management of VOEs are often delayed and fail to follow published guidelines. Numerous efforts have been undertaken to ensure appropriate and timely analgesic administration to patients with SCD who are experiencing a VOE. One such intervention is the creation of an infusion center (IC) that has the capability to administer parenteral opioids while avoiding the delays associated with an ED visit. Objectives: This study aims to evaluate the impact of a dedicated IC that was established for the treatment of SCD VOEs. The goal of the IC is to provide timely and appropriate pain management in an effort to reduce ED visits and hospital admissions related to treatment of VOEs in patients with SCD. The IC was available to adult patients with SCD who regularly sought care at our hospital and who did not have a care plan that excluded the administration of parenteral opioids. Methods: This is an observational, retrospective study comparing the rates of hospital utilization before and after the opening of a dedicated IC for patients treated for SCD VOE at a single, urban medical center that regularly provides care for approximately 150 adult patients with SCD. We compared the rates of ED visits, hospital admissions, and length of stay for six months prior and four months following the opening of the IC. Hospital utilization was standardized before and after the intervention using 30-day rates. Additionally, opioid usage, measured in Morphine Equivalent Dose (MED) was compared between the ED and the IC. Results: A total of 12 patients (Table 1) utilized the IC during the 4 months after its opening (6/20/19 - 10/16/19). During this time there were 92 total visits to the IC. Four patients were noted to be high utilizers accounting for 77 (83.7%) of the 92 visits (median = 20 visits, range 12 - 25). The other 8 patients were low utilizers and accounted for 15 (16.3%) of the visits (median = 2, range 1 - 4). Following implementation of the IC, there was found to be a statistically significant decrease in ED visits (pre- = 3.97/30d vs post- = 2.40/30d; p = 0.04) (Table 2, Fig. 1). No significant difference was found in hospital admissions (pre- = 1.47/30d vs post- = 1.17/30d; p = 0.18) or inpatient days (pre- = 6.47/30d vs post- = 5.47/30d; p = 0.23). The total number of acute care visits (sum of ED and IC visits) was found to increase after the opening of the IC, although the change was not statistically significant (pre- = 3.97/30d vs post- = 5.47/30d; p = 0.07). The change in acute care visits was largely driven by an increase in visits from the high utilizers (pre- = 2.00/30d vs post- = 3.53/30d; p = 0.05). In terms of parenteral opioid administration, there was a statistically significant decrease in amount of opioids given in the IC compared to the ED (ED = 251.64 MED vs IC = 177.17 MED; p = 0.04), although this was only seen in the low utilizer group (Table 3, Fig. 2). There was no significant difference in opioid doses received for the high utilizers (ED = 256.31 MED vs IC = 272.12 MED; p = 0.24) and for the group as a whole (ED = 253.34 MED vs IC = 208.84 MED; p = 0.10). Conclusion: The introduction of an IC for the management of SCD VOE led to a significant decrease ED visits but also led to an increase in overall acute care visits, although this was not statistically significant. This increase was largely driven by a subset of this population considered high utilizers. Additionally, the use of the IC was not associated with a decrease in the total amount of parenteral opioids that were administered. However, for the low utilizer group there was a decrease in parenteral opioid administration. The IC did not reduce admissions and duration of hospitalization in this population. Overall, the IC had variable success and further refinement of how it is used should be undertaken to ensure quality care for patients with SCD. Disclosures No relevant conflicts of interest to declare.

A Multicenter Prospective Study on Efficacy and Safety of Ponatinib in Patients with Chronic Myeloid Leukemia Resistant or Intolerant to Previous Therapy: A 3-Year Report

Introduction Tyrosine kinase inhibitors (TKIs) have transformed outcomes in chronic myeloid leukemia (CML). Patients who respond to imatinib, have a life expectancy comparable with that of the global population, however, up to 40% of patients discontinue imatinib due to resistance or intolerance. Ponatinib is a third-generation highly-potent-pan-inhibitor of tyrosine kinases, active in all single resistance ABL kinase mutations, including the T315l mutation. This report presents the results of a prospective analysis of 3-year ponatinib therapy available in Poland by Angelini's donation program for patients in all phases of CML resistant or intolerant to previous TKI therapy. Methods 43 CML patients (20 women, 24 men, aged 19 to 76 years, mean age 49 ± 15 years) were treated in 20 Polish Hematology Centers with ponatinib initiated between March 2016 and December 2019. 23 pts (53%) were in the chronic phase (CP), 3 pts (7%) in accelerated phase (AP), and 17 pts (40%) in blastic phase (BP) (9 myeloblastic and 8 lymphoblastic). The majority of patients received three lines of TKI therapy. The T315I mutation was detected in 30% of patients (the initial characteristics of the 43 analyzed patients are shown in Table 1). The indication for ponatinib and its dose schedule was made according to the discretion of the attending physician. The initial dose of ponatinib was 45 mg/d in 60% of all patients (without statistically significant differences in the initial dose between patients starting treatment in CP, AP, and BP). Molecular biology tests were performed according to ELN guidelines and BCR-ABL/ABL ratios were expressed as % [IS] in all patients. Treatment responses were calculated at each specific time points recommended by ELN. Statistica 12 software (StatSoft, Tulsa, OK, USA) was used for calculations. Results The follow-up ranged from one week to 35.4 months (median 11.4 months) (one male patient died on infection one week after ponatinib introduction and was excluded from further analysis, he did not achieve CHR and he transformed to blast phase-BP). The responses to ponatinib are shown in Table 2. Among 23 CP patients, 18 achieved CHR (78%), 6 (26%) MCyR, 5 (22%) CCyR, and 1 (4%) MMR at 1 month of treatment. There were only 2 patients in this group (9%) who did not achieve CHR. Eleven CP patients (48%) achieved stable MMR. In all 3 AP patients, the best responses (CHR, CCyR, and MMR) were maintained until the end of observation (Table 2). Among 17 BP patients, 8 (47%) achieved CHR. The overall survival was significantly better in those patients who achieved CHR at 1 month of therapy (Figure 1). 19 patients (44%) experienced toxicity of ponatinib including: increase in blood pressure overall 9 patients (21%), hematological toxicity grade 3-4- 12 patients (28%).A total of 19 patients (44%) remained on ponatinib at the end of the observation. Ponatinib dose was reduced during the study in 18 patients (42%): in 11 (61% of those requiring dose reduction) because of toxicity, in 6 (33%) because of good response to treatment, and in 1 patient (6%) because of both reasons. The need for dose reduction was not significantly associated with comorbidities (p=0.4). Eight patients (19%) underwent allo-SCT during the observation. Ponatinib was discontinued in eight patients (19%), in six CP and two BP-patients. In five patients (12%), ponatinib was discontinued because of toxicity (hematological in one, non-hematological in two, and both in one patient); all were CP patients. In two patients (one CP, one BP patient), ponatinib was discontinued as they underwent allo-SCT. Overall, 16 patients (37%) died during the study: 12 of them (28%) due to CML progression. In all 43 patients, median survival was not reached. The estimated 2-year survival was 60% (95% confidence interval 44-76%) (Figure 2A) 84% in CP patients, 100% in AP patients (Figure 2B), and 20% in BP patients. None of the CP patients progressed to AP or BP during the study, i.e. progression-free survival was 100% at the end of observation (35.4 months). The presence of T315I mutation (p=0.2) or the initial dose of ponatinib (p=0.4) was not significantly associated with the overall survival. Conclusion Our study confirmes that ponatinib could induce durable responses with acceptable toxicity profiles in highly pretreated patients with CML resistant or intolerant to previous TKIs treated in standard clinical practice. Disclosures Sacha: Adamed:Consultancy, Honoraria;Bristol-Myers Squibb Company:Consultancy, Honoraria, Speakers Bureau;Pfizer:Consultancy, Honoraria, Speakers Bureau;Novartis:Consultancy, Honoraria, Speakers Bureau;Incyte:Consultancy, Honoraria, Speakers Bureau.Niesiobedzka-Krezel:Angelini Pharma:Other: lecture fee and meeting partcipation.Ciepluch:Copernicus Wojewodzkie centrum Onkologii:Current Employment.

Impact of Multi-criteria Optimization on 6-MV Flattening Filter-Free Volumetric Modulated Arc Therapy for Craniospinal Irradiation

Introduction: Volumetric modulated arc therapy (VMAT) is an advanced technique used for radiotherapy treatment using different optimization modes. The present study aimed to evaluate Multi-criteria Optimization (MCO) influence on VMAT for Craniospinal Irradiation. Material and Methods: Fifteen CSI patients treated with 23.4 Gy/13 fractions followed by a boost dose of 6-MV flattening filter-free beams were chosen for this study. Conventional VMAT (c-VMAT) plans were generated for Elekta Versa HD™ linear accelerator. Keeping all other parameters constant, c-VMAT plans combined with MCO (MCO-VMAT) were created for comparison. We compared homogeneity index (HI), conformity index (CI), planning target volume (PTV) dose coverage (D98%), organ at risk (OAR) dose, normal tissue integral dose (NTID), volume receiving ≥ 5 Gy and ≥ 10 Gy by normal tissue, delivery time (DT), monitor units (MUs), and calculation time (CT). Results: Our findings demonstrated that HI and CI improved slightly in MCO-VMAT, in comparison with c-VMAT (P>0.05). No significant dose difference was observed in D98% for PTV and volume receiving the dose of ≥ 5 Gy, ≥ 10 Gy, and NTID (P>0.05). A slight increase was found in maximum dose to PTV in VMAT-MCO, compared to c-VMAT (P>0.05). The mean dose, max dose, and dose received by OAR were significantly lower in VMAT-MCO as compared to c-VMAT (p 0.05). Conclusion: The MCO-VMAT can be used for CSI, without compromising target coverage, reduced OAR dose by accepting a slight increase of MUs, delivery and calculation time as compare to c-VMAT.

Clinico-Dosimetric Correlation Of Doses To Dysphagia Aspiration Related Structures (DARS) With Acute Toxicities In Post-Operative Patients Of Oral Cavity Carcinoma Treated With Dysphagia Optimized Versus Standard IMRT

Limiting the radiation dose to dysphagia aspiration related structures (DARS) may reduce toxicities in patients of oral cavity squamous cell carcinoma (OCSCC) treated with adjuvant radiotherapy. We analyzed acute toxicity in patients of OCSCC treated with adjuvant intensity modulated radiation therapy (IMRT) reducing the dose of radiation received by DARS: dysphagia optimized IMRT (Do-IMRT) and compared it with standard IMRT (S-IMRT: without dose constraints to DARS). Fifty OCSCC patients between 18-70 years of age were randomized in this prospective study to receive either adjuvant Do-IMRT or S-IMRT. None received concurrent chemoradiotherapy. Target volume was divided into high, intermediate and low risk areas receiving doses in the range of 60-66 Gy, 54-58 Gy, 51-56 Gy in 30-33 fractions over 6-6.5 weeks, respectively. In addition to the conventional organs at risk, dose constraints were given to DARS in Do-IMRT arm. The primary end point was acute toxicity evaluated by common terminology criteria for adverse events (CTCAE) version 5.0. Each arm had 25 patients. Median age was 46.5 years (range 28-74 years). Patient characteristics were balanced between two groups. Buccal mucosa: Tongue: other primary were seen in 72% vs. 48%:12% vs. 36%: 16% vs. 16% respectively in Do-IMRT vs. S-IMRT. Similarly, T1:T2:T3:T4 were 8% vs. 4%: 60% vs. 40%: 24% vs. 32%: 8% vs. 24%; N0:N1:N2 were 68% vs. 48%: 16% vs. 36%: 16% vs. 16% in Do-IMRT vs. S-IMRT arm. respectively. Lymphovascular invasion and peri-neural invasion were observed in 20% vs. 36% and 20% vs. 12% respectively in Do-IMRT vs. S-IMRT. There was a statistically significant difference in the mean doses to DARS in Do-IMRT vs. S-IMRT arm without compromising PTV coverage (Table 1). Grade 3 dysphagia was significantly lower in the Do-IMRT vs. S-IMRT group (0% vs. 16%; p = 0.067). Do-IMRT significantly delivers lesser doses to DARS as compared to S-IMRT and trended to lesser acute grade ≥3 dysphagia and grade ≥2 oral pain compared to S-IMRT. Longer follow up and correlation of late toxicities would better define the role of Do-IMRT compared to S-IMRT in post-operative OCSCC patients.Abstract 3845; Rest is summarized in Table 1Dosimetric AnalysisDo-IMRT (Mean ± SD)S-IMRT (Mean ± SD)P valuePTV-HR V9597.86±1.1797.57±1.530.463PTV-IR V9599.03±1.3198.59±1.280.402PTV-LR V9598.82±1.6198.92±1.120.809Superior constrictor43.24±7.1652.33±6.66<0.001Middle Constrictor40.33±5.9352.86±5.59<0.001Inferior Constrictor29.05±9.9248.76±7.10<0.001Supraglottic Larynx40.06±5.4253.86±5.60<0.001Glottic Larynx31.76±9.3747.54±7.51<0.001Cricopharyngeus33.77±11.9446.48±7.54<0.001Cervical esophagus22.12±15.2532.18±12.780.015Acute toxicityDo-IMRTS-IMRTp-valueDysphagia Grade ≥287%100%0.102Oral mucositis Grade ≥330.4%44%0.252Pharyngeal mucositis Grade ≥30%12%0.133Oral pain Grade ≥252.2%76%0.077Oropharyngeal pain Grade ≥256.5%72%0.207 Open table in a new tab

A Dosimetric Evaluation of the Impact of Seroma Volume During Breast Boost Radiotherapy

Whole breast irradiation (WBI) followed by tumor bed boost is the standard of care for patients who have undergone breast conservation surgery. However, seroma which forms at the tumor bed may affect the tumor bed boost volume. This study aims to evaluate the changes in seroma volume during WBI and determine the dosimetric benefits of a re-plan for the boost. We hypothesized that re-planning on a reduced target volume resulting from a reduction in seroma volume meaningfully reduces doses to normal tissues. A retrospective study of 15 right-sided and 15 left-sided breast cancer patients treated with radiotherapy to the breast (40Gy/15# and a 10Gy/5# boost) between 2012-2019 was performed. CT simulation scans were performed before WBI (CT1) and also midway during WBI (CT2) if patient had a seroma measuring >5cm in any dimension during CT1. The tumor bed boost, referred to as the gross target volume (GTV), was contoured based on seroma and surgical clips on both CT1 and CT2. For each patient, a tumor bed boost plan was retrospectively generated on CT1 for comparison against the as-treated plan based on CT2. CT1 and CT2 treatment boosts, planned using the most appropriate 3D technique as per the contoured GTV were compared based on the 5Gy dose volume to the ipsilateral normal breast tissue (Irradiated breast-GTV), mean ipsilateral lung dose and mean heart dose (for left-sided patients). Data was analyzed using the Wilcoxon signed-rank test. Subsequently, changes in seroma volume (CT2-CT1) were correlated to the difference in irradiated breast-GTV volume, mean ipsilateral lung and mean heart dose using Spearman Rho correlation regression. Median (IQR) reduction in left and right seroma volume between CT1 and CT2 was 60.7% (36.82% -76.71%) (p = 0.001), and 45.7% (16.63% -58.31%) (p = 0.002) respectively. Median (IQR) reduction in left and right irradiated breast-GTV volume between CT1 and CT2 was 17.9% (1.41% -33.85%) (p = 0.01), and 11.9% (8.59% -33.25%) (p = 0.001) respectively. No statistically significant differences in mean ipsilateral lung and mean heart dose were observed for all patients. Similarly, the change in seroma volume between CT1 and CT2 was not significantly correlated to the differences in irradiated breast-GTV volume, mean lung and mean heart dose. Patients experienced a significant reduction in seroma volume during WBI. Re-CT and re-planning will reduce the volume of normal breast tissues irradiated, which may improve cosmesis. However, a re-CT and re-plan does not lead to a meaningful reduction in lung and heart doses.Tabled 1Abstract 2654; Table; Differences in seroma volume, irradiated breast-GTV volume, mean lung and mean heart dose (CT2-CT1).LeftRightMedian Reduction (%)/ Dose (Gy)P valueMedian Reduction (%)/ Dose (Gy)P valueSeroma Vol60.7%0.00145.7%0.0025Gy Dose Vol/ (Irradiated breast Vol – GTV)17.9%0.1111.9%0.001Mean Ipsilateral Lung Dose25.7%/ 0.08Gy0.2934.2%/ 0.05Gy0.691Mean Heart Dose19.5%/ 0.03Gy0.532 Open table in a new tab

Risk Factors for Gemcitabine-Induced Vascular Pain in Patients With Pancreatic Cancer.

Peripheral intravenous injection of gemcitabine often causes vascular pain; however, preventive measures have not yet been established. This study focused on identifying predictive factors for gemcitabine-induced vascular pain. We retrospectively analyzed risk factors for developing vascular pain in patients with pancreatic cancer receiving gemcitabine infusions at our institution. Infusions were divided into groups according to presence or absence of vascular pain symptoms, and variables were compared. Odds ratios for risk factors were calculated using logistic regression analyses. Overall, 272 patients with pancreatic cancer were subjected to 725 gemcitabine infusions, and of these, 18.4% (n = 50) experienced vascular pain. There were significant differences in the gemcitabine dose (P = 0.025), dose of gemcitabine/body surface area (BSA; P = 0.004), concentration of gemcitabine (P = 0.025), and hot pack use (P = 0.011) between the vascular pain and no vascular pain groups. Multivariable analyses indicated that gemcitabine dose/BSA and lack of hot pack use were risk factors for developing vascular pain. Moreover, on administration of a higher dosage (>930 mg/m2), the incidence of vascular pain in patients using a hot pack (6.7%) was significantly lower than that in patients not provided a hot pack (16.2%). High gemcitabine dosages and lack of hot pack use were predictive factors for gemcitabine-induced vascular pain in patients with pancreatic cancer. Patients receiving gemcitabine treatment should apply a hot pack to the injection site. Scrupulous clinical attention is required for patients presenting with these risk factors to improve pain management.

Comparison of Cardiopulmonary Sparing and Dose Conformality in Distal Esophageal Cancer: Intensity Modulated Proton Therapy (IMPT), MR-guided Radiotherapy (MRgRT), and Volumetric Modulated Arc Therapy (VMAT)

To investigate the tradeoff of esophageal treatment between real-time breath hold (BH) MR-guided radiotherapy (MRgRT), free breathing (FB) CT-based intensity modulated proton therapy (IMPT), and FB VMAT. We hypothesize that improved cardiopulmonary sparing would be achieved with BH MRgRT or FB IMPT compared to FB VMAT. We retrospectively evaluated differences in heart/lung dose and treatment plan conformality among 28 patients with distal esophageal cancer who were each treated with either IMPT (n = 10), MRgRT on an MR-guided Linac (n = 11), or VMAT (n = 7). All were prescribed 50.4 Gy/28 fractions. IMPT and VMAT patients received a 4DCT simulation scan to quantify the internal target volume margin (ITV) for respiratory motion. MRgRT patients were simulated and treated in an inspiration BH with a 3 mm CTV to PTV margin. In lieu of a PTV margin for IMPT cases, robust optimization for range and setup uncertainty was performed on iCTV (i.e., CTV with respiratory ITV). RTOG plan quality metrics were used to evaluate target coverage (TC) (PTV V100%/PTV vol), homogeneity index (HI) (PTV D2%/ D98%), high dose conformity (PITV), low dose conformity (D2cm), and gradient (R50%). For all coverage metrics, the CTV was used. Mean cardiac sparing among all patients between respective IMPT, MRgRT, and VMAT was 65.3cc, 73.0cc, and 141.5cc (V30Gy); 45.4cc, 38.5cc, and 84.7cc (V40Gy), 19.7cc, 12.5cc, 39.0cc, (V50Gy), 6.4cc, 15.0cc, 19.2cc (mean dose). Lung and liver sparing between respective IMPT, MRgRT and VMAT plans was 86.8cc, 299.7cc, and 909.0cc (lung, V20), 4.2Gy, 6.8Gy, and 15.6Gy (lung, mean dose), 3.8Gy, 19.5Gy, 16.2Gy (liver, mean dose). Homogeneity and conformity indices between IMPT, MRgRT, and VMAT were 1.6, 1.3, 1.5 (PITV), 1.1, 1.2, 1.1 (HI), 5.2, 5.2, 6.3 (R50%), and 45.3%, 56.6%, 54.1%(D2cm), respectively. CTV coverages for IMPT and MRgRT plans were 50.7, 50.5, 51.1 (D90%) and 0.99, 0.99, 0.98 (TC), respectively. Statistically significant differences in heart and lung dose are demonstrated in the Table below; no statistical difference was observed for coverage or conformality. FB IMPT and BH MRgRT both achieve significant lung and/or heart sparing compared to FB VMAT while maintaining excellent plan conformality. The varying extent of cardiopulmonary sparing achieved across these advanced radiation therapy modalities warrants prospective evaluation.Abstract 3498; TableHeart (V30)Heart (V40)Heart (V50)Heart (Mean)Lung (Mean)Lung (V20)Liver (Mean)MRgRT vs IMPTp = 0.695p = 0.602p = 0.792p = 0.0001p = 0.079p = 0.001p = 0.0001MRgRT vs VMATp = 0.048p = 0.058p = 0.053p = 0.101p = 0.0001p = 0.001p = 0.258IMPT vs VMATp = 0.031p = 0.134p = 0.218p = 0.0001p = 0.0001p = 0.0002p = 0.001 Open table in a new tab

Non-Coplanar Many-Isocenter Optimization for Radiotherapy on Robotic Arm Platform

4π non-coplanar radiotherapy significantly improves dosimetry, but its clinical implementation on the widely available C-arm gantry system is limited by the restricted non-colliding beam angles and the complex coordination of gantry and couch motion. Alternatively, a robotic arm platform is more favorable for the non-coplanar and non-isocentric treatment, but the conflict between field size and modulation resolution needs to be managed. This study investigates the dosimetry and delivery efficiency by creating many isocenters to achieve simultaneously large field-of-view (FOV) and high modulation resolution for robotic radiotherapy. The many-isocenter optimization framework includes a least-square dose fidelity objective, a total variation term for regularizing the fluence smoothness, and a group sparsity term for simultaneous beam orientation optimization (BOO) and isocenter selection. A minimal number of candidates isocenters were identified before the optimization for efficient target coverage. The proposed algorithm was evaluated on the intensity-modulated radiotherapy (IMRT) treatment plans of 10 Head and Neck (H&N) cancer patients. Colliding beams excluded, high-resolution small-field non-isocentric 4π IMRT plans with 50cm source-to-isocenter distance (SID-50) were compared with low-resolution large-field isocentric plans with 100cm SID (SID-100). The table reports the planning target volume (PTV) and organs at risk (OARs) statistics, and the corresponding Wilcoxon signed-rank test, showing significant difference (p<0.05) in PTV homogeneity, PTV Dmax, R50, Integral dose, and OAR Dmean and Dmax. With better target coverage, SID-50 substantially improved dose conformality and reduced OAR dose. R50 and integral dose were reduced by 5.3% and 9.6% respectively. The average reduction of [Dmean, Dmax] of SID-50 from SID-100 were [2.09 Gy, 1.19 Gy] for OAR overall, [3.05 Gy, 0.04 Gy] for parotid gland, [3.62 Gy, 5.19 Gy] for larynx, and [3.27 Gy, 1.10 Gy] for mandible. The estimated delivery time of 20-beam [SID-50, SID-100] plans were [19, 18] minutes and [14, 9] minutes, assuming 5 fractions and 30 fractions, respectively. With clinically acceptable delivery efficiency, the proposed non-coplanar many-isocenter optimization is dosimetrically favorable for treating large targets with high modulation resolution.Tabled 1Abstract 2832; Table 2832Wilcoxon signed rank test of PTV and OAR statistics of SID-100 (isocentric) and SID-50 (non-isocentric) for all 10 patients.Statisticsp-valueSigned rankNumber of samplesSID-100SID-50MeanSTDMeanSTDPTV Homogeneity0.00385290.9010.0450.9060.045PTV Dmin0.749202290.9740.0190.9750.016PTV Dmax<.001380291.1270.0621.1180.061R500.00653102.3810.2362.2540.256Integral Dose0.0025510139.37738.481126.0236.139OAR Dmean0.002551017.8223.72715.7293.273OAR Dmax0.002551034.5156.31733.3256.173 Open table in a new tab

Evaluation of Synthetic CT Image Generated Using a Neural Network for MR-Only Radiotherapy

The MR-only radiotherapy workflow has been an active topic because of the increasing use of Magnetic Resonance (MR) image in the identification and delineation of tumors, while a fast generation of synthetic Computer Tomography (sCT) image from MR image is still one of the key challenges. This study aims to develop a neural network to generate the sCT and evaluate its performance in terms of both CT number difference and dosimetry accuracy. A generative adversarial network (GAN) is designed to translate MRI to sCT. For the generation of sCT, we use a "U-net” shaped encoder-decoder network with some image translation-specific modifications. Then a discriminator network is designed to distinguish between synthetic and real CT images. We enrolled 30 patients with brain tumors who have undergone external beam radiotherapy acquiring both CT and MRI for their simulation. 24 pairs of 2D T1-weighted turbo dark fluid MR images and rigidly registered CT are used to train the GAN, and the remaining 6 pairs are used to access the translation through the metric of mean absolute error. Furthermore, the dose distribution of the clinical VMAT treatment plan on sCT is calculated and compared with those on real CT using gamma analysis. On average, 5 and 10 seconds are needed to generate one sCT on GPU and CPU respectively. The mean absolute error between synthetic and real CT is 52±15 HU over six testing patients. For dose distribution on sCT and CT, the average gamma pass rates using the 3%,3mm and 2%,2mm criteria are above 97 and 92%, respectively. The GAN model is able to generate synthetic CT based on a single MRI sequence within seconds, and no significant radiotherapy dose difference is found between sCT-based and real CT-based plans.

Vaginal Dose Surface Maps and Morbidity in Cervical Cancer Brachytherapy

To develop a methodology for generating vagina dose-surface maps (DSMs) in cervix cancer patients. To investigate the association of dose level and spatial distribution with vaginal stenosis (St) and mucositis (Muc). A mono-institutional series of 31 patients, enrolled in the EMBRACE I study, with no vaginal St/Muc (CTCAE v3) at baseline were selected for this analysis. Patients were divided in 3 morbidity groups: 16 had St/Muc G0/1, 8 had St G≥2 (3 also had Muc G≥2), 10 had Muc G≥2 (3 also had St G≥2) within 24 months after treatment. 16 patients had vaginal involvement at diagnosis and 10 at BT. Patients received EBRT and 2 insertions and 4 fractions of HDR BT using tandem and ovoids. DSMs were generated from delineated contours of the vagina surface (VS). VS contours were unfolded by cutting them anteriorly through the urethra and inferiorly through the posterior–inferior border of the symphysis (PIBS). DSMs of EBRT and each BT fraction, converted to Gy EQD2 (α/β = 3), were added based on a system of homologous points, to generate cumulative DSMs. Dose D20cm2 (Gy), surface S60Gy (%), including their spatial location on the VS, rectovaginal (ICRU-RV) point dose, vaginal lateral 5 mm point dose and vagina length (VL measured from the vagina top to the PIBS) were compared between morbidity groups. Average/difference VS DSMs and one-way ANOVA statistical testing were used to compare between groups. A total of 96 DSMs (31 EBRT and 62 BT) were generated. Table shows mean/difference values for each parameter, according to morbidity groups. Patients in the St G≥2 and Muc G≥2 groups had significantly higher D20cm2 and ICRU-RV point doses compared to St/Muc G0/1 group. Moreover, average/difference DSMs showed that the most irradiated 20 cm2 in the St G≥2 group (mean dose 103 Gy EQD23) was spatially distributed over entire upper 1-2 cm VS circumference. St G≥2 vs St/Muc G0/1 patients had also larger S60Gy (by 27%) and shorter VL (by 9 mm). Muc G≥2 vs St/Muc G0/1 patients had significantly higher vaginal lateral 5mm point doses (by 14 Gy EQD23), while average/difference DSMs showed significant dose differences mainly in the latero-posterior area of the VS. Vaginal dose reporting is currently based on dose points. A novel method was developed to generate vaginal DSMs that incorporate 3D spatial information and new spatial dose descriptors for a more comprehensive view on vaginal doses and correlation with morbidity. St G≥2 patients had significantly higher doses over the whole VS circumference. Muc G≥2 patients showed higher D20cm2, ICRU-RV point and vagina lateral 5mm point doses. Generally, ventral vagina received lower dose than the dorsal and lateral vagina, in the majority of patients.Tabled 1Abstract 3029; TableSt/Muc G0/1 MeanSt G≥2 MeanMuc G≥2 MeanSt G≥2 - St/Muc G0/1Muc G≥2 - St/Muc G0/1Diff.pDiff.pD20cm2 (Gy)7910396240.0000*170.0031*S60Gy (%)376451270.0018*140.0176*ICRU-RV Point (Gy)637678130.0041*150.0015*Vag LAT-5mm (Gy)85909850.2465140.0085*VL (mm)595053-90.0501-60.1427 Open table in a new tab

Cognitive phenotypes 1\xa0month after ICU discharge in mechanically ventilated patients: a prospective observational cohort study

BackgroundICU patients undergoing invasive mechanical ventilation experience cognitive decline associated with their critical illness and its management. The early detection of different cognitive phenotypes might reveal the involvement of diverse pathophysiological mechanisms and help to clarify the role of the precipitating and predisposing factors. Our main objective is to identify cognitive phenotypes in critically ill survivors 1 month after ICU discharge using an unsupervised machine learning method, and to contrast them with the classical approach of cognitive impairment assessment. For descriptive purposes, precipitating and predisposing factors for cognitive impairment were explored.MethodsA total of 156 mechanically ventilated critically ill patients from two medical/surgical ICUs were prospectively studied. Patients with previous cognitive impairment, neurological or psychiatric diagnosis were excluded. Clinical variables were registered during ICU stay, and 100 patients were cognitively assessed 1 month after ICU discharge. The unsupervised machine learning K-means clustering algorithm was applied to detect cognitive phenotypes. Exploratory analyses were used to study precipitating and predisposing factors for cognitive impairment.ResultsK-means testing identified three clusters (K) of patients with different cognitive phenotypes: K1 (n = 13), severe cognitive impairment in speed of processing (92%) and executive function (85%); K2 (n = 33), moderate-to-severe deficits in learning-memory (55%), memory retrieval (67%), speed of processing (36.4%) and executive function (33.3%); and K3 (n = 46), normal cognitive profile in 89% of patients. Using the classical approach, moderate-to-severe cognitive decline was recorded in 47% of patients, while the K-means method accurately classified 85.9%. The descriptive analysis showed significant differences in days (p = 0.016) and doses (p = 0.039) with opioid treatment in K1 vs. K2 and K3. In K2, there were more women, patients were older and had more comorbidities (p = 0.001) than in K1 or K3. Cognitive reserve was significantly (p = 0.001) higher in K3 than in K1 or K2.ConclusionOne month after ICU discharge, three groups of patients with different cognitive phenotypes were identified through an unsupervised machine learning method. This novel approach improved the classical classification of cognitive impairment in ICU survivors. In the exploratory analysis, gender, age and the level of cognitive reserve emerged as relevant predisposing factors for cognitive impairment in ICU patients.Trial registrationClinicalTrials.gov Identifier:NCT02390024; March 17,2015.

Pattern of anticoagulation prescription for patients with Covid-19 acute respiratory distress syndrome admitted to ICU. Does it impact outcome?

Covid-19 has affected 16Millions people worldwide with 644 K death as of July 26th, 2020. It is associated with inflammation and microvascular thrombosis—anticoagulation in widely used in these patients especially in patients with elevated d-Dimers. The significance of anticoagulation in these patients is not yet established. We aim to define the anticoagulation pattern and its impact on outcomes (28-day survival, LOSICU, DVT, and PE and bleeding complications. We also observe if levels of d-Dimers affect the anticoagulation prescription.Methods: We analyzed data of all consecutive patients with Covid-19 ARDS admitted to ICU retrospectively. The primary variable of interest was anticoagulation. The daily dose of anticoagulant medication for each patient was recorded. Survival (28-day survival), Length of stay in ICU (LOSICU), the occurrence of DVT, PE, or bleeding were primary outcome variables. We also recorded confounding factors with potential impact on clinical outcomes. We assign Patients to one of the four groups based on anticoagulant dosing during the ICU (increasing dose, decreasing dose, increase followed by a decrease, multiple changes). We analyze the effect of different anticoagulation dosing strategies on 28-day survival, LOSICU, the occurrence of DVT, PE, and bleeding. We also observe if levels of d-Dimers affect the anticoagulation prescription.Results: The sample includes 149 patients. The most frequently used medication was subcutaneous Enoxaparin (85.2%). The Enoxaparin mean dose per day for the whole sample was 49.5 mg + 15.7 (mean + SD). There was no significant difference in doses of anticoagulants between survivors and nonsurvivors (62.8 mg + 21.7 mg vs. 61.2 mg + 25.7 mg, p 0.3). Multinomial regression showed no difference in 28-day survival among four-dose modification (increasing dose, decreasing dose, increase followed by a decrease, multiple changes). Logistic regression showed that BMI, d-Dimers, platelets, and the use of mechanical ventilation predict 28-day survival. Kaplan-Meier Survival plots for 4 anticoagulant groups showed no survival advantage for any anticoagulant strategy. Secondary outcome analysis showed that d-dimer levels significantly affect anticoagulants doses.Conclusion: Prescription of anticoagulation is quite variable in patients admitted to ICU for Covid-19 associated ARDS. Anticoagulation dosing strategy has no significant effect on 28-day survival, LOSICU, the occurrence of DVT, PE, or bleeding.

Methotrexate use does not increase the prevalence of hepatic steatosis: a real-world retrospective nested case-control study.

We aimed to determine whether methotrexate (MTX) treatment in patients with rheumatoid arthritis (RA) leads to the development of non-alcoholic fatty liver (NAFL). Data were derived from records of all patients with RA who underwent abdominal ultrasonography at the Jeonbuk National University Hospital. Patients with ultrasound-proven NAFL were identified, and those without NAFL were matched by age and sex using the propensity score matching method at 1:3 ratio. We also analyzed the Health Insurance Review and Assessment Service-National Patient Samples, a nationwide cohort database, to determine the association between MTX use and NAFL in a large number of patients (n = 24,653). In the hospital cohort, 92 patients with NAFL did not show significant differences in the cumulative MTX dose when compared with the no-NAFL group (n = 276) (1908.5 ± 1757.5 vs. 1948.6 ± 2118.8mg, p = 0.911). The prevalence of NAFL was not significantly different across strata of cumulative MTX dose. Multiple logistic analyses identified hypertriglyceridemia (OR, 4.88 [95% CI, 1.13-20.93]) and higher body mass index (OR, 1.22 [95% CI, 1.05-1.41]) as being associated with an increased risk of NAFL. In the nationwide cohort, the MTX exposure rate between the NAFL and no-NAFL groups was not significantly different. Collectively, no significant association between NAFL development and administration of MTX was detected in this study. Our results suggest that it is more efficient to adjust for individualized risk factors for NAFL prevention rather than discontinuation of MTX in patients with RA. Key Points • NAFLD has been highlighted with increasing prevalence worldwide and possible progression to end-stage liver disease. • Cumulative dose or exposure history of MTX does not show a significant association with NAFLD prevalence. • Modifying well-established risk factors is more efficient in NAFLD prevention rather than discontinuation of MTX.

The Safety and Efficacy of Transcatheter Pulmonary Valve Replacement Combined with Electrophysiology Procedures.

The objective of this study was to evaluate the safety and efficacy of combining transcatheter pulmonary valve replacement (TPVR) and electrophysiology (EP) procedures. A retrospective review was undertaken to identify TPVR and EP procedures that were concomitantly performed in the cardiac catheterization laboratory at University of Iowa Stead Family Children's Hospital from January 2011 to October 2019. Procedural and follow-up data were compared between patients who underwent TPVR and EP procedures in the same setting to those who received TPVR or EP procedure separately and that were similar in age and cardiac anatomy. A total of 8 patients underwent combined TPVR and EP procedures. One patient was excluded due to lack of adequate control, leaving seven study subjects (57% female; median age at time of procedure 16years). The median follow-up time was 11.5months (range 2-36months). Patients who received combined TPVR and EP had shorter recovery times (combined: median 18.9h; IQR 18.35-19.5 vs separate: median 27.98h; IQR 21.42-39.25; p-value 0.031), shorter hospital length of stay (combined: median 27.5h; IQR 26.47-31.4 vs separate: median 38.4h; IQR 33.42-51.50; p-value 0.016), and a 51% reduction in total hospital charges (combined: median $171,640; IQR 135.43-219.22 vs separate: median $333,560 IQR 263.20-400.98; p-value 0.016). There were no significant differences in radiation dose or procedure time between the combined and control groups. The median radiation time for those who had the combination procedure was 30.5min [IQR 29.6-47.9], and the median dose area product was 215mGy [IQR 158-935].In conclusion, combining TPVR and EP procedures is feasible, safe, and economically advantageous.

Consequences of selecting different subsets of meteorological data to utilize in deterministic safety analysis

Atmospheric dispersion calculation of radiological releases can be done for different purposes such as deterministic or probabilistic safety analysis, environmental impact assessment, emergency preparedness and response. The characteristics of the weather conditions used in such assessments have a significant effect on the results, thus it is vital to select appropriate meteorological data for the calculation. In this paper, we conduct a study on deterministic safety analysis of radiological releases and investigate the effects of using different subsets of a meteorological database for such assessments.We demonstrate that conducting deterministic dose assessment with a large site specific dataset of meteorological measurements and the use of a dose percentile is more beneficial than using one set of meteorological parameters. This is because variations in the meteorological condition have considerable effect on the dose results when using one set of meteorological parameters (e.g. worst case scenario) and less when a large meteorological database is used. We show that there can be a significant difference in the maximum dose computed with a large (at least annual with hourly resolution) meteorological database when there is a lack of data points or conversion of the parameters is needed, thus the 100th dose percentile is not optimal for verification of safety criteria fulfillment. It is better to use a relatively high percentile (e.g. from 80th to 99th), partly because it behaves more robustly and also because the use of the maximum dose (100th percentile) would be overly conservative. In case of meteorological data not being available for a sufficient temporal domain (e.g. data available for only one year or less), a multiplication factor – determined based on conservative assumptions and extensive studies on the possible spread of meteorological conditions and their effect at a given location – can be used for the comparison of a selected dose percentile with the safety limit.A 5-years long meteorological database provided by a meteorological measurement system was used in this study as an example to demonstrate and calibrate the methodology on a real database. The methods presented in this work are universal, they can be used in deterministic safety analysis of other nuclear facilities, and the results can facilitate the development of optimal meteorological databases.

Permethrin resistance associated with inherited genes in a near-isogenic line of Musca domestica.

Permethrin has been used frequently in the control of Musca domestica worldwide including Pakistan, with reports of resistance development in different field strains. A near-isogenic line of M. domestica with permethrin resistance (Perm-R) was constructed to elucidate mode of inheritance and cross-resistance analyses. Toxicity responses of reciprocal progenies F1 and F1' showed no significant difference in median lethal dose (LD50 ) values, suggesting that permethrin resistance was inherited in an autosomal fashion with neither sex linkage nor maternal effects in the Perm-R strain of M. domestica. Degree of dominance was 0.6 and 0.7 for F1 and F1' progenies, respectively, which suggests that permethrin resistance was expressed as an incompletely dominant trait. Chi-square analyses for self-bred (F2), and backcross progenies (BC1, BC2, BC3 and BC4) revealed significant differences between the observed and expected mortality, indicating the possibility of multiple genes responsible for permethrin resistance. Moreover, the Perm-R strain did not show cross-resistance to propoxur, chlorpyrifos, profenofos or spinetoram. Permethrin resistance in the Perm-R strain of M. domestica was inherited as autosomal, incompletely dominant and governed by more than one gene. Lack of cross-resistance between permethrin and propoxur, chlorpyrifos, profenofos or spinetoram provides an opportunity for rotational use of these insecticides in the control of M. domestica. These data could help to manage M. domestica and the problem of permethrin resistance.

DIPHENHYDRAMINE AS ADJUNCTIVE THERAPY DURING MODERATE SEDATION FOR ENDOBRONCHIAL ULTRASOUND

SESSION TITLE: Procedures Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Endobronchial ultrasound (EBUS) and real-time guidance of transbronchial needle aspiration (TBNA) has become a widely adopted tool in evaluation of intrathoracic lymphadenopathy for malignant or non-malignant disease. EBUS has been shown to have comparable diagnostic yield and safety profile when done with either moderate sedation (MS) or deep sedation (DS). The purpose of this study was to assess the use of diphenhydramine in bronchoscopies and specifically EBUS/TBNA. METHODS: Patient data was collected via chart review of all bronchoscopies done at the Kansas City VA Medical Center between July 2018 and June 2019. Only procedures done under MS were included. Sedation medications used were fentanyl and midazolam. The use of intravenous diphenhydramine, dose and timing was at the discretion of the proceduralist. RESULTS: A total of 165 bronchoscopies were performed under MS; 84 were EBUS procedures. Of the EBUS patients, 81 (96.4%) patients were male; mean age was 66.4±10.7. No patients had a documented history of chronic opioid use.Midazolam and fentanyl were used for induction and maintenance of sedation in all EBUS patients. The mean doses were 5.3±3.3 mg of midazolam and 203.9±52.1 mcg of fentanyl. Diphenhydramine was used in 62 (73.8%) of EBUS procedures. Twenty (32.3%) patients received diphenhydramine at induction compared to 42 (67.7%) who only received it during the procedure. The mean dose of diphenhydramine was 41.5±12.7 mg.Comparing EBUS in which any diphenhydramine was used to cases in which it was not, there was no significant difference in the cumulative doses of midazolam (5.6±3.5 vs. 4.5±2.5mg, p=0.161) and fentanyl (204.8±57.6 vs. 201.1±33.2mcg, p= 0.777). The time to adequate sedation was significantly higher in patients who received diphenhydramine (11.1±4.9 vs. 8.6±2.9 min, p=0.006). Procedure time (64.0±25.1 vs 61.4±20.2 min, p=0.660) and recovery time (81.4±32.4 vs. 81.3±47.9 min, p=0.995) were not significantly different.Compared to no use at all, any diphenhydramine use (at induction or during the procedure) was associated with a lower fentanyl dose per minute (4.2±2.6 vs. 7.2±5.0 mcg/min, p<0.001) and a trend towards a lower midazolam dose per minute although not statistically significant (0.1±0.1 vs. 0.2±0.6 mg/min, p=0.271). CONCLUSIONS: Use of diphenhydramine in our cohort was associated with a mean of 3.0 mcg/min lower fentanyl dose, equivalent to an average fentanyl dose reduction of 193mcg per procedure. Further randomized controlled trials with a protocol for sedation including diphenhydramine or placebo would be the next endeavor to fully evaluate this hypothesis. CLINICAL IMPLICATIONS: Diphenhydramine appears to reduce fentanyl requirements and therefore should be considered as adjuctive therapy for moderate sedation in EBUS procedures. DISCLOSURES: No relevant relationships by Abdallah Abboud, source=Web Response No relevant relationships by Sonia Castillo, source=Web Response

S0950 A Comparison of Radiation Exposure During ERCP by Different Fluoroscope Techniques

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) is an endoscopic procedure performed for multiple diagnostic and therapeutic indications. It carries benefits and risks like all other interventions. We focused on radiation exposure to patients and staff. In the literature review, we found that radiation dose is lower when radiation administration is physician-controlled, and as the physician becomes more experienced, they utilize less radiation. The aim was to compare different operation techniques of radiation administration during ERCP. METHODS: This was a retrospective study of all 437 ERCP procedures performed at a tertiary care hospital between April 2015 and April 2017. Data were collected from the hospital electronic system and included demographics, procedure indication, fluoroscopy time (FT), dose area product (DAP), degree of difficulty as per American Society of Gastrointestinal Endoscopy (ASGE) recommendations. Median and mean FT and DAP between endoscopist- controlled (EC) compared to technician-controlled (TC). RESULTS: Of the 437 cases analyzed 45.5%males, and the mean age was 56.7. EC was 187 cases, representing 42.79%. The mean fluoroscopy time (FT) was 2.107 ± 2.0 minutes. The mean dose–area product (DAP) was 15227.371 ± 16784.738 Gy·cm2 for all procedures. The degree of ERCP difficulty was graded from 1-4 as per ASGE. Level I TC procedures had a mean FT and DAP of 1.600 minutes and 12644.72 Gy·cm2, respectively; level I EC procedures were1.514 minutes and 12966.71 Gy·cm2, respectively. For level IV, TC procedures the mean FT, 2.539 minutes, and the mean DAP was 19469.94 Gy·cm2. For level IV EC procedures, the mean FT was 4.890 minutes; the mean DAP was 37921.00 Gy·cm2. CONCLUSION: This study did not show a significant difference in radiation dose between EC and TC except in ASGE level IV, where a significant increase noticed in the EC group. The results of multiple other fluoroscopic studies in urology and cardiology showed that when the procedure is physician-controlled, radiation administered is similar or lower than TC. This difference in comparison to the other studies could be attributed to the endoscopist attention divided into multiple fronts, including doing the procedure that predisposes them to push on the pedal for longer than intended while manipulating the scope and leading the team. Although these results are inconclusive, it does shed light on the importance of further studies on radiation administration techniques for patients and staff safety.