IntroductionColorectal cancer (CRC) is a common but largely preventable disease with suboptimal screening rates despite national guidelines to screen individuals age 50–75. Single-component interventions aimed to improve screening uptake only modestly improve rates; data suggest that multi-modal approaches may be more effective.MethodsWe designed, implemented, and evaluated the impact of a multi-modal intervention on CRC screening uptake among unscreened patients in a large managed care population. Patient-level components included a mailed letter with education about screening options and pre-colonoscopy telephone counseling. For providers, we facilitated communication of screening test results and work-flow for abnormal results. System-level modifications included establishment of a patient navigator, expedited work-up for abnormal results, and stream-lined colonoscopy scheduling. We measured the rate of screening uptake overall, screening uptake by modality, change in the proportion of the population screened, and positive fecal immunochemical test (FIT) follow-up rates in the 1-year study period.ResultsThere were 5093 patients in the intervention cohort. Of these, 33.2% participated in FIT or colonoscopy screening within 1 year of the mailing. A total of 1078 (21.2%) participants completed a FIT and 611 (12.0%) completed a screening colonoscopy. The screening rate in the managed care population increased from 65.1 to 76.6%. Fifty-nine patients (5.5%) had a positive FIT, of which 30 (50.8%) completed a diagnostic colonoscopy.ConclusionMulti-modal interventions can result in substantial improvement in CRC screening uptake in large and diverse managed care populations.Translational ImpactHealth systems should shift their focus from single-level to multi-level interventions when addressing barriers to CRC screening.

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Background: Hypercalcemia is a common complication of advanced malignancy, affecting up to 30% of cancer patients through various mechanisms (1). Hypercalcemia has rarely been described in gastrointestinal stromal tumors (GIST), with fewer than ten case reports as of 2018 (1,2). We describe a case of calcitriol-mediated hypercalcemia in a patient with GIST. Clinical Case: An 80-year-old woman with a history of metastatic GIST and nivolumab-induced type 1 diabetes and thyroiditis presented with dramatic progression of metastatic peritoneal disease and new severe hypercalcemia with acute kidney injury. On hospital admission, calcium (Ca) was 15.1 mg/dL (8.6-10.3 mg/dL), ionized Ca was 1.98 mmol/L (1.09-1.29 mmol/L), and creatinine was 2.56 mg/dL (0.6-1.3 mg/dL, baseline 1.8 mg/dL). She was treated with IV fluids and 45 mg of IV pamidronate with initial Ca improvement to 10.7 mg/dL over the next 48 hours. Additional workup showed that 25-hydroxyvitamin D was 18 ng/dL (20-50 ng/dL), PTH was 9 pg/mL (11-51 pg/mL), PTHrP was 3.1 pmol/L (0.0-3.4 pmol/L), and calcitriol was elevated to 172 pg/mL (19.9-79.3 pg/mL). Prior chest/abdomen/pelvis CT scans had not shown bony metastases or granulomas. After stopping IV fluids, Ca rose to 12.2 mg/dL the next day. Prednisone 20 mg daily was started which stabilized Ca levels and lowered calcitriol to 17.4 pg/mL after two weeks. She also began a new regimen of cabozantinib. Prednisone was tapered to 10 mg daily and she continues to maintain normal Ca levels with the addition of home health IV fluids three times a week. Conclusion: GIST tumors are a rare cause of hypercalcemia of malignancy. Although hypercalcemia of malignancy is most often due to tumor-secreted PTHrP or bony metastases, a small percentage of cases are mediated by excess calcitriol production. There is a growing number of case reports, including this case, to suggest that calcitriol-mediated hypercalcemia is the most common cause of hypercalcemia in GIST tumors (2-4). Glucocorticoids may be used to decrease calcitriol production and help maintain eucalcemia. Definitive therapy for hypercalcemia in these patients involves decreasing tumor burden by treatment of the underlying malignancy (3). References: (1) Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005;352(4):373-9. (2) Hart T, Sinitsky D, Shamsiddinova A, Rohatgi A. Refractory hypercalcaemia secondary to localised gastrointestinal stromal tumour. Ann R Coll Surg Engl. 2018;100(6):e136-e138. (3) Hygum K, Wulff CN, Harsløf T, et al. Hypercalcemia in metastatic GIST caused by systemic elevated calcitriol: a case report and review of the literature. BMC Cancer. 2015;15:788. (4) Barbaryan A, Bailuc S, Poddutoori P, et al. Gastrointestinal Stromal Tumor Induced Hypercalcemia. Case Rep Oncol Med.2017;4972017.

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588 Background: Establishing the pathologic basis of focal brain lesions caused by disease processes such as CNS lymphoma is often difficult. Results of standard MRI-based neuro-imaging are non-specific and cytological testing of cerebrospinal fluid (CSF) is highly insensitive. We tested the hypothesis that the metabolic constituents of the CSF reflect pathologic processes within the brain and thus might lead to the identification of novel diagnostic and prognostic biomarkers and provide insight into mechanisms of CNS lymphoma pathogenesis and its impact on cognitive function. We have pursued two novel approaches to define and model the metabolic microenvironment in CNS lymphoma: (1) Differential metabolite profiling of CSF; (2) Metabolic imaging using hyperpolarized 13C probes using preclinical models involving intracranial xenografts of CNS lymphoma. Methods: We are using GC/MS, in collaboration with Metabolon, to profile a broad spectrum of metabolites (> 140) in CSF from CNS lymphoma patients at diagnosis, relapse as well as from control subjects without brain tumors. In parallel, we are using high resolution MRI (14T) to perform anatomic and contrast enhanced imaging plus hyperpolarized metabolic imaging using 13C-metabolic probes such as [1-13C] pyruvate to monitor the production of intratumoral metabolites such as lactate within highly infiltrative xenograft models of CNS lymphoma. Results: Metabolite concentrations in CSF from 15 subjects with active CNS lymphoma were compared to 15 controls without brain tumors. Seventeen metabolites were significantly upregulated in CSF (> two-fold) compared to controls (p<0.05). Notably, despite similar tumor burdens, the CSF concentrations of lactate, malate and succinate were highest in patients with refractory lymphoma compared to chemotherapy-sensitive tumors. Another TCA intermediate, citrate, was detected at similar concentrations in CSF from controls and lymphoma patients. CSF concentrations of N-acetyl-aspartyl-glutamate, a neurotransmitter, were significantly lower in subjects with CNS lymphoma compared to controls. Metabolic imaging of murine CNS lymphoma xenograft (Raji lymphoma) using hyperpolarized [1-13C] pyruvate demonstrated intratumoral Warburg metabolism with a striking elevation of [1-13C] lactate that was apparent beyond the anatomical margins of the contrast enhancing lymphoma, as demonstrated by T1-weighted post-gadolinium images. Conclusions: These preliminary results suggest that 13C imaging may be able to identify regions of metabolic abnormality in CNS lymphoma outside those identified by 1H methods, and thus potentially provide insight into the metabolic features of the lymphoma as well as its stromal microenvironment. Our hypothesis is that MRI-based, non-invasive metabolic imaging will provide insights into the molecular differences between newly-diagnosed and relapsed cases as well as provide novel, non-invasive diagnostic and prognostic biomarkers. Supported by a grant from CFAR and the Sandler Program for Breakthrough Biomedical Research. Disclosures: No relevant conflicts of interest to declare.