Citations

11615 Background: Deficiencies and barriers exist to delivering comprehensive and affordable cancer care. Understanding the variation in organizational commitment, existing programs, and expected outcomes for screening and management of financial distress is needed. Methods: Representatives from 17 of 27 NCCN Member Institutions (63%) completed an online survey in November 2018 conducted by the NCCN Best Practices Committee. Centers were classified based on number of unique patients seen per year, as large ( > 10,000) (76%), or small ( < 10,000) (34%). The survey focused on institutions’ screening and management practices for patient financial distress, perceived barriers in implementation, and leadership attitudes. Results: Routine screening for financial distress was reported by 77% of centers, and most used social worker assessments (94%). 56% screened patients throughout the cancer journey. Help with drug costs, meal or gas vouchers and payment plans were offered by 100% of centers. Formal pre-authorization programs and assistance with claims and denials was offered by 81%. Charity care for medical costs was provided by 100% of the large centers compared to only 33% of small centers (p = 0.03). Median number of social workers (24 vs. 3; p = 0.01) and pharmacy representatives (6 vs. 2; p = 0.02) was also different between large and small centers. 76% evaluated the impact of financial advocacy services through number of patients assisted (85%), bad debt and charity write-offs (85%) or patient satisfaction surveys (54%). 6% and 12% reported overall effectiveness of institutional practice for screening and management of financial distress as poor/ very poor respectively. Inadequate staffing and real time resources (69%), limited institutional budget (50%), lack of reimbursement (50%), and clinical time constraints (50%) were reported as potential barriers in provision of these services. 94% agreed about stronger integration of financial advocacy services into oncology practice and 84% felt that success of these services should be a quality metric. 31% of large centers vs. 100% of small centers plan to increase staffing in this area in the next 5 years. Conclusions: Majority of NCCN Member Institutions report screening and management programs for financial distress, though the actual practices and range of services vary widely. Information from this study can help centers benchmark their performance relative to similar cancer programs and identify best practices in this area.

283 Background: Cancers of the esophagus, stomach, pancreas, gallbladder, liver, bile duct, colon and rectum will account for 17% of incident cancer diagnoses and 26% of cancer-related deaths in the US in 2019. We developed a methylation-based cfDNA early multi-cancer detection test that also can predict the tissue of origin (TOO) of these and other cancers types; performance of this test for gastrointestinal (GI) tract cancers is reported here. Methods: The Circulating Cell-free Genome Atlas (CCGA; NCT02889978) study is a prospective, multi-center, observational, case-control study with longitudinal follow-up, enrolling individuals with cancer ( > 20 cancers, all stages, newly diagnosed) and without cancer. Plasma cfDNA was subjected to a cross-validated targeted methylation (TM) sequencing assay. Methylation fragments were combined across targeted genomic regions and assigned a probability of cancer and a predicted TOO. GI cancer classes were upper GI (esophagus/stomach, n = 67), pancreas/gallbladder/extrahepatic bile duct (n = 95), liver/intrahepatic bile duct (n = 29), and colon/rectum (n = 121). Results: Detection across all GI cancers was 82% (95% CI 77-86) at a > 99% pre-set specificity. Overall predicted TOO accuracy was 92% (88-95) among the samples for which TOO was predicted (6/255 had indeterminate predicted TOO). The table shows performance by GI cancer type. Conclusions: Simultaneous detection at high specificity ( > 99%) of multiple cancer types, including GI cancers across stages at high sensitivity (82%), was shown using TM analysis of cfDNA. Accurate (92%) localization of cancers to specific regions of the GI tract was also achieved. Detection of multiple GI cancers from a single noninvasive blood test could be a practical method for detecting GI and other cancers, and may facilitate diagnostic work-ups. Clinical trial information: NCT02889978. [Table: see text]

Abstract Comorbid Lewy body pathology is very common in Alzheimer’s disease and may confound clinical trial design, yet there is no in vivo test to identify patients with this. Tissue (and/or radioligand imaging) studies have shown cardiac sympathetic denervation in Parkinson’s disease and dementia with Lewy bodies, but this has not been explored in Alzheimer’s subjects with Lewy bodies not meeting dementia with Lewy bodies clinicopathological criteria. To determine if Alzheimer’s disease with Lewy bodies subjects show sympathetic cardiac denervation, we analysed epicardial and myocardial tissue from autopsy-confirmed cases using tyrosine hydroxylase and neurofilament immunostaining. Comparison of tyrosine hydroxylase fibre density in 19 subjects with Alzheimer’s disease/dementia with Lewy bodies, 20 Alzheimer’s disease with Lewy bodies, 12 Alzheimer’s disease subjects without Lewy body disease, 19 Parkinson’s disease, 30 incidental Lewy body disease and 22 cognitively normal without Alzheimer’s disease or Lewy body disease indicated a significant group difference (P &lt; 0.01; Kruskal–Wallis analysis of variance) and subsequent pair-wise Mann–Whitney U tests showed that Parkinson’s disease (P &lt; 0.05) and Alzheimer’s disease/dementia with Lewy bodies (P &lt; 0.01) subjects, but not Alzheimer’s disease with Lewy bodies subjects, had significantly reduced tyrosine hydroxylase fibre density as compared with cognitively normal. Both Parkinson’s disease and Alzheimer’s disease/dementia with Lewy bodies subjects also showed significant epicardial losses of neurofilament protein-immunoreactive nerve fibre densities within the fibre bundles as compared with cognitively normal subjects (P &lt; 0.01) and both groups showed high pathologic alpha-synuclein densities (P &lt; 0.0001). Cardiac alpha-synuclein densities correlated significantly with brain alpha-synuclein (P &lt; 0.001), while cardiac tyrosine hydroxylase and neurofilament immunoreactive nerve fibre densities were negatively correlated with the densities of both brain and cardiac alpha-synuclein, as well as Unified Parkinson’s Disease Rating Scale scores (P &lt; 0.05). The clear separation of Alzheimer’s disease/dementia with Lewy bodies subjects from Alzheimer’s disease and cognitively normal, based on cardiac tyrosine hydroxylase fibre density, is the first report of a statistically significant difference between these groups. Our data do not show significant sympathetic cardiac denervation in Alzheimer’s disease with Lewy bodies, but strongly confirm that cardiac nuclear imaging with a noradrenergic radioligand is worthy of further study as a potential means to separate Alzheimer’s disease from Alzheimer’s disease/dementia with Lewy bodies during life.

Spontaneous portosystemic shunts (SPSSs) have been associated with worse clinical outcomes in the pre–liver transplantation (LT) setting, but little is known about their post‐LT impacts. Our aim was to compare LT candidates with and without SPSSs and assess the impact of SPSSs on patient mortality and graft survival in the post‐LT setting. Patients 18 years or older with abdominal imaging done prior to LT were included. Exclusion criteria were the presence of pre‐LT surgical shunts, LT indications other than cirrhosis, and combined solid organ transplantations. SPSSs were classified as absent, small, or large according to their maximum diameter (8 mm). Multiple variables that could influence the post‐LT course were extracted for analysis. Patient and graft survival were estimated using the Kaplan‐Meier method and were compared between groups using a log‐rank test. The project received institutional review board approval. We extracted data from 326 patients. After comparing patients without SPSS or with small or large SPSSs, no statistical difference was found for overall patient survival: no SPSS (n = 8/63), reference; small SPSS (n = 18/150), hazard ratio (HR), 1.05 (95% confidence interval [CI], 0.45‐2.46); and large SPSS (n = 6/113), HR, 0.60 (95% CI, 0.20‐1.78); P = 0.20. Also, no difference was found for graft survival: no SPSS (n = 11/63), reference; small SPSS (n = 21/150), HR, 0.80 (95% CI, 0.38‐1.70); large SPSS (n = 11/113), HR, 0.59 (95% CI, 0.25‐1.40); P = 0.48. Similarly, no statistical significance was found for these variables when comparing if the graft used was procured from a donation after circulatory death donor versus a donation after brain death donor. In conclusion, the previously described association between SPSSs and worse clinical outcomes in pre‐LT patients seems not to persist once patients undergo LT. This study suggests that no steps to correct SPSS intraoperatively are necessary.

Objective:Radiation therapy (RT) is the primary treatment of intracranial metastasis (ICM) from lung cancer (LC). Radiation necrosis (RN) has been reported post-RT with an incidence of 5% to 24%. We reviewed the spectrum of imaging changes in patients treated with RT for ICM from LC in an effort to identify potential risk factors for RN.Methods:We reviewed 63 patients with LC and ICM who received RT (radiosurgery [stereotactic radiosurgery] with/without whole brain radiation therapy) at our institution between 2013 and 2018. Data evaluated included demographics, tumor type, ICM burden and location, chemotherapy, surgery, and RT details as well as treatment choices and outcomes.Results:Of the 63 patients, clinical and radiographic criteria for RN were noted in 24 (38%) as early as 2 months and as late as 5 years posttreatment. Six patients required surgical resection due to refractory symptoms revealing pathology-proven RN and occasionally tumor. Patients were significantly more likely to develop RN if they had surgical resection of an ICM (45.8% vs. 20.5%,P=0.05). No differences were found in location, size, or genetic profile of lesions. In total, 80% of patients received treatment for symptoms and/or radiographic change. This was generally a combination of steroids, bevacizumab, laser interstitial thermal treatment, or surgical resection. Most patients required >1 treatment modality.Conclusions:This review of outcomes of RT for ICM in LC demonstrates a higher rate of RN than previously reported in the literature in those having had a surgical resection plus stereotactic radiosurgery. Our observation of RN as late as 5 years post-RT for ICM necessitates clinician awareness.

Abstract INTRODUCTION Locations of gliomas may influence clinical presentations, molecular profiles, treatment options, and prognoses. Using the Mayo Clinic Arizona Cancer Center registry, we analyzed the frequency at which gliomas were identified in different regions of the brain. We evaluated molecular profiles, clinical courses and survival by anatomic location. METHODS Registry was queried to include patients with glioma over a 10-year period. Statistical analyses were used to compare demographic, genetic, and clinical characteristics among patients with gliomas in different locations. RESULTS 182 gliomas were identified. Of the tumors confined to a single lobe, there were 51 frontal (28.0%), 50 temporal (27.5%), 22 parietal (12.1%), and 7 occipital tumors (3.8%) identified. Multifocal disease was noted in 38 patients (20.9%). Tumors affecting temporal lobe were associated with reduced overall survival when compared to all other tumors (11.0 months vs. 13.0 months, log-rank p=0.0068). However, this disparity became insignificant when adjusted for tumor grade, age, and surgical approach [HR(95% CI) 1.26(0.87, 1.82), p=0.212]. Out of 82 cases tested for IDH-1, 10 were mutated (5.5%). IDH-1 mutation was present in 6 frontal, 2 temporal, 1 thalamic, and 1 multifocal tumor. Out of 21 cases tested for 1p19q deletions, 12 were co-deleted, 9 of which were frontal lobe tumors. MGMT methylation was assessed in 45 cases; 7 of 14 frontal tumors and 6 of 13 temporal tumors were methylated. ATRX loss was detected in 2/42 assessed cases. CONCLUSION Our results support the hypothesis that the anatomical locations of gliomas influence patients’ clinical courses. Tumors involving the temporal lobe were associated with poorer survival, though this association appeared to be driven by these patients’ more aggressive tumor profiles and higher risk baseline demographics. Molecular analysis was limited by low prevalence of genetic testing in the study sample, highlighting the importance of capturing this information for all gliomas.

Abstract BACKGROUND Radiation is an integral component of the multidisciplinary treatment of patients with intracranial metastasis (ICM) from melanoma. The risk of radiation necrosis (RN) post-treatment can range from 5–25%. We retrospectively evaluated pre- and post-radiation clinical and radiographical characteristics in patients with ICM from melanoma to identify potential risk factors for RN. METHODS After IRB approval, patients with ICM from melanoma who received radiation at our institution between 2013 and 2018 were retrospectively reviewed. We recorded demographics, intracranial metastasis (burden and location), systemic therapy, resection, stereotactic radiosurgery versus whole brain radiation, and outcomes. Brain MRI was evaluated using the Response Assessment in Neuro-Oncology criteria (RANO). RESULTS A total of 27 patients were included in the study. RN was diagnosed in 14 patients (52%) at one month to three years following radiation. Cerebellar location (n=7) was significantly associated with RN (p=0.0058). Metastasis-associated hemorrhage was present in 7 patients, 6 of which developed RN (43% vs 8%, p=0.08). Surgical resection prior to radiation was performed in 9 patients, 7 of which developed RN (50% vs 15%, p=0.1). RN appeared to be less often diagnosed when ICM were treated with higher doses of radiation (24 Gy vs 20 Gy, p=0.07). Systemic treatment was administered prior to radiation in 25 patients and we found no relationship with systemic therapy type and RN. Presumed RN was treated in 12 of 14 patients (86%). Steroids or surgical resection were the primary treatment modalities, with laser ablation used in 1 case. Following treatment, improvement was noted in 3 patients radiographically and in 1 of these clinically. CONCLUSIONS This series of patients with radiotherapy-treated brain metastases from melanoma reveals cerebellar involvement, hemorrhage, and prior surgical resection as potential risk factors for radiation necrosis. Neoadjuvant systemic treatment did not appear to be a risk factor in our review.

Abstract Keratoconus (KCN) is a leading cause for cornea grafting worldwide. Keratoconus is a multifactorial disease that causes progressive thinning of the cornea and whose etiology is poorly understood. Several studies have used proteomics on patient tear fluids to identify potential biomarkers. However, proteome of the cornea itself has not been investigated fully. We report here new findings from a case–control study using multiplexed mass spectrometry (MS) on individual (unpooled) corneas to gain deeper insights into proteins and biomarkers relevant to keratoconus. We employed a high-pressure approach to extract total protein from individual corneas from five cases and five controls, followed by trypsin digestion and tandem mass tag (TMT) labeling. The MS-derived data were searched using the Human NCBI RefSeq protein database v92, with peptides and proteins filtered at 1% false discovery rate. A total of 3132 proteins were detected, of which 627 were altered significantly ( p ≤ 0.05) in keratoconus corneas. The increases were overwhelmingly in the mTOR/PI3/AKT signal-mediated regulations of cell survival and proliferation, nonsense-mediated decay of transcripts, and proteasomal pathways. The decreases were in several extracellular matrix proteins and in many members of the complement system. Importantly, this multiplexed proteomic study of keratoconus corneas identified, to our knowledge, the largest number of corneal proteins. The novel findings include changes in pathways that regulate transcript stability, proteasomal degradation, and the complement system in corneas with keratoconus. These observations offer new prospects toward future discovery of novel molecular targets for diagnostic and therapeutic innovations for patients with keratoconus.