82 Background: Patients ≥ 55 years of age with high-risk acute myeloid leukemia (AML) may benefit from an allogeneic hematopoietic stem cell transplantation (HSCT), which is often the only potentially curative therapy available. However, complete remission (CR) is usually a prerequisite for most centers to perform HSCT, as CR predicts an optimal outcome. Many older patients with relapsed/refractory (R/R) AML do not receive HSCT, as they do not achieve the required CR. Additionally, many are unable to tolerate the myeloablative conditioning required for eradication of disease. While the reduced intensity conditioning is better tolerated, it often exhibits high rates of relapse. SIERRA trial is a prospective, randomized, phase 3 trial for older patients with R/R AML to address this unmet need. Iomab-B (131I labeled apamistamab) targets CD45, which is highly expressed in leukemia cells. We hypothesized that the targeted delivery of therapeutic Iomab-B with an imaging-based dosimetry enables successful engraftment despite active disease in the marrow.Methods: Eligible patients with active R/R AML, adequate organ function, and related/unrelated 8/8 HLA-matched donors were randomized (1:1) to the Iomab-B or Conventional Care (CC) arm. Patients randomized to Iomab-B received a low dose of Iomab-B, followed by 3 sequential gamma camera images (Fig 1) to determine the personalized therapeutic dose that would deliver maximal radiation to the marrow while limiting the liver dose to 24 Gy. Dosimetry was performed using serial imaging data and Olinda program (V2.1, Hermes Medical). Following a therapeutic infusion of Iomab-B and a non-myeloablative conditioning backbone of fludarabine (30 mg/m2 x 3) and 2 Gy Total Body Irradiation, HSCT was performed 12-14 days later. Each patient on the CC arm received the investigator’s choice of non-radioactive salvage therapy and could proceed to HSCT if they achieved CR. If no CR, the study allowed patients to cross over and receive Iomab-B-based conditioning followed by allogeneic HSCT. Patient age, donor type, bone marrow cellularity, blast percentage, type of donor, stem cell dose, administered Iomab-B activity (mCi), and radiation dose to marrow (Gy), were analyzed for a relationship to days to engraftment among each group. Results: Preliminary data were available from 113 patients (Table 1). 56 patients were randomized to Iomab-B for which 49 patients received allogeneic transplant. In the CC arm, 82% (47/57) of patients failed salvage therapy. 30 of the 47 (64%) CC patients crossed over and received Iomab-B followed by allogeneic HSCT. Median time to neutrophil and platelet engraftment were 14 days (range 9-22) and 18 days (range 4-39), respectively, in Iomab-B group, with 89% of evaluable patients achieving full donor chimerism (> 95% by day 100). All patients who received Iomab-B treatment achieved engraftment, including the Iomab-B group and the cross-over patients. Neither the radiation dose delivered to marrow (median 14.7 Gy; range 4.6-32 Gy) nor the administered activity (median 646 mCi; range 354-1027 mCi) showed correlation with the time to either neutrophil (p = 0.525) or platelet engraftment (p = 0.952). Regression analyses, considering all the variables individually, did not indicate a statistically significant correlation (p > 0.1) between days to engraftment and marrow dose. These results were consistent for the cross-over group. Furthermore, the marrow radiation dose did not show a significant correlation with % chimerism at day 28 in patients on the Iomab-B arm or in cross-over patients. Conclusion: No significant relationship between total administered activity or radiation dose to marrow with the speed of engraftment was found, indicating the dosimetry estimates for ablative doses appear to be adequate and successful in ablation, despite a heavy leukemia burden prior to HSCT.

1324 Objectives: In patients undergoing evaluation for primary lung cancer, 2-deoxy-2-(18F) fluoro-D-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) is a commonly used imaging examination for staging and treatment evaluation. Maximum and mean standardized uptake values (SUV) are commonly reported for these patients in practice, and metabolic tumor volume (MTV) and total lesion glycolysis (TLG) may have prognostic and treatment-related implications. Respiratory motion can result in displacement of lesions and degrade images of the lower chest in these patients, potentially reducing sensitivity of lesion detection and affecting the quantitative values that may have an effect on disease staging and treatment. We aim to assess the differences in quantitative values on non-respiratory gated versus respiratory gated FDG PET/CT imaging for discrete pulmonary lesions in patients undergoing evaluation for primary lung cancer. Methods: This study retrospectively reviewed 35 patients (13 males, 22 females, median age 69) evaluated for primary lung cancer with both non-respiratory gated and respiratory gated FDG PET/CT imaging obtained, including 36 separate FDG PET/CT exams and 49 discrete pulmonary lesions. Standard non-respiratory gated whole body FDG PET/CT was obtained at multiple bed positions (2 min each) except for sequentially obtained respiratory gated PET imaging at two bed positions (4 min each), encompassing the lower lung fields. An abdominal pressure sensor was used for respiratory cycle gating from peak inspiration to peak inspiration with data gathered from mid-expiration to mid-inspiration. The mean SUV (SUVmean) metabolic tumor volume (MTV41%), and total lesion glycolysis (TLG41%) were segmented using the software default adaptive threshold of 41% from the maximum in the volume of interest. SUVmax, SUVmean, MTV41%, and TLG41% were measured for each discrete pulmonary lesion on both non-respiratory gated and respiratory gated imaging utilizing automated software to calculate values within the volume of interest. Results: Data analysis demonstrates an increase in SUVmax in 81.6% of lesions, an increase in SUVmean in 87.7% of lesions, a decrease in MTV41% in 87.7% of lesions, and a decrease in TLG41% in 83.7% of lesions on respiratory gated FDG PET/CT imaging when compared to non-respiratory gated imaging. Utilizing a paired samples T-test, there was a significant difference between non-respiratory gated and respiratory gated imaging, respectively, for SUVmax (mean=8.5, SD=6.7 and mean=9.2, SD=6.8, p= Conclusions: Overall, respiratory gated FDG PET/CT imaging demonstrates a significant increase in SUVmax and SUVmean and a significant decrease in MTV and TLG when compared to non-respiratory gated PET/CT imaging in patients undergoing evaluation for primary lung cancer. The decrease in TLG with respiratory gated PET/CT imaging was an unexpected consequence. Further data analysis can evaluate the effect of lesion size, lesion location, and patient weight on these values.

442 Background: Upper abdominal irradiation for pancreas cancer is given in close proximity to the radiation sensitive kidneys. While contemporary 3D and intensity modulated radiation therapy (IMRT) can decrease the total dose of radiation delivered to the kidneys; these plans may potentially exceed the established kidney dose constraints, especially if one kidney is providing most of the renal function. Less than 10% of the general population is estimated to have asymmetrical kidney function. Functional kidney scans using MAG3 clearance can give information about the contribution of each kidney to total renal function. We sought to determine if functional renal scans should be used to identify patients with occult renal dysfunction. Methods: Patients with resectable and borderline resectable pancreatic cancer who received abdominal irradiation therapy and had pre-radiation functional renal scans between 2009-2015 were studied. Asymmetrical kidney function was defined as a difference between the two kidneys that was ≥ 40%/60% on a functional renal scan. Serum studies (BUN, Cr, GFR) were routinely obtained pre-simulation. Restaging abdominal CT scans prior to radiation were screened for disparity in kidney size. Medical history that suggested decreased renal function was also collected. Results: Of the 205 patients examined, 24 (11.7%) had asymmetrical kidney function identified on pre-radiation functional renal scans. Of the patients with asymmetrical kidney function, 4 (2%) had a 75%/25% split or greater and 20 (9.7%) had kidney function between 60%/40% and 75%/25%. Elevated Cr or BUN, a GFR < 60, or a past medical history suggesting abnormal renal function were not significantly associated with asymmetrical kidney function. Only six (25%) of patients with asymmetrical kidney function scans had a notable difference in kidney size. Conclusions: In our series, approximately 12% of patients with pancreatic cancer have asymmetrical kidney function not identified by size, serum BUN, Cr, GFR, or a significant past medical history of renal compromise. These results provide important insight for cases when radiation plans may approach or exceed accepted dose constraints for the kidneys.

OBJECTIVES: Autonomic dysfunction is associated with a wide variety of gastrointestinal symptoms. It is unclear how many patients with autonomic dysfunction have slow or rapid gastric emptying. The aim of this study was to determine the prevalence of rapid and delayed solid phase gastric emptying in patients with autonomic dysfunction referred for evaluation of gastrointestinal symptoms and the association of emptying rate with clinical symptoms.METHODS: Retrospective review of all patients with autonomic dysfunction who had a gastric emptying test from January, 1996 to March, 2005. Demographic data, clinical symptoms, composite autonomic scoring scale (CASS) score, and gastric emptying parameters were analyzed.RESULTS: Sixty-one subjects (women 49, age 42 [16-74] yr) with autonomic dysfunction were reviewed. Patients had mild-to-moderate (mean CASS score 3) autonomic dysfunction. Twenty-seven, 17, and 17 patients had rapid, normal, and delayed gastric emptying t(1/2), respectively. In addition, 10 patients had initially rapid emptying in phase 1, with subsequent slowing in phase 2 to produce an overall normal or delayed t(1/2). There was no difference in demographic data or CASS score among the three groups. More patients with initial or overall rapid emptying had diarrhea (70%) compared to patients with normal (33%) or delayed (33%) emptying (P = 0.018).CONCLUSIONS: Unexpectedly, more patients with autonomic dysfunction have rapid rather than delayed gastric emptying. The presence of diarrhea in patients with autonomic symptoms should prompt consideration for the presence of rapid gastric emptying. Conversely, the finding of rapid gastric emptying in patients with gastrointestinal symptoms should prompt consideration for the presence of underlying autonomic dysfunction.

An in vitro study was designed to evaluate the uptake of sestamibi (MIBI) in P-glycoprotein (Pgp) and glutathione-associated (GSH) multidrug-resistant (MDR) cell lines. MIBI uptake was studied in various human breast carcinoma cell lines, i.e. in wild-type (MCF7/wt) cells, in adriamycin-resistant (MCF7/adr) cells which express Pgp and in melphalan-resistant (MCF7/mph) cells with increased levels of GSH. The effects of buthiomine sulphoximine (BSO) and verapamil on MIBI uptake were also studied in the MCF7/mph and MCF7/adr cells respectively. The cells were incubated for 1 h with a dose of 0.1 MBq thallium-201 and technetium-99m MIBI. Both MIBI and201Tl uptakes were higher for MCF7/mph cells than for the other cells studied. The mean MIBI uptake in MCF7/adr cells was significantly lower than that in MCF7/wt cells (1.9%±0.5% vs 3.1%.0.6%;P <0.01). Verapamil treatment increased the MIBI uptake in MCF7/adr cells (to 2.6%.0.3%;P <0.05). Treatment of MCF7/mph cells with BSO resulted in a significant reduction in GSH content (from 243.2±81.1 nmoUmg protein to 17.6±4.4 nmol/mg protein;P <0.001). However, MIBI uptake in BSO-treated and untreated MCF7/mph cells was similar (4.43%±0.5% and 5.93%±1.7%, respectively;P >0.1). This study suggests that the uptake of MIBI is not diminished by glutathione-associated drug resistance and that MIBI uptake in a tumour sample does not necessarily indicate that a cancer is sensitive to drugs.