Pancreatic cancer outcomes in Nova Scotia: Searching for small windows of opportunity.

e16219 Background: While pancreatic cancer (PC) globally has poor outcomes, there are still regional variation in PC outcomes in Canada. Nova Scotia (NS) has been documented to have some of the worst outcomes in PC but the details and barriers to the care of PC in NS have never been analyzed. Methods: A retrospective chart review was performed on PC patients (pts) diagnosed in NS from 2013 to 2017 for patient characteristics, referral pattern, treatments and wait times. Cox proportional hazards methods were used to analyze overall survival (OS) with Age, Stage, Eastern Cooperative Oncology Group Performance Status (PS), Charleston Comorbidity Index (CCI), receiving ERCP and receiving chemotherapy as covariates in the multivariate analysis. Results: 667 consecutive pts were identified, which included 357 males and 310 females with a median age of 71 at diagnosis. 42 (6.25%) lived beyond 2 years, while 163 (24.4%) survived for under 30 days and 260 (39%) survived for under 60 days. Patients with a limited survival (under 30 days) when compared to pts who survived &gt; 60 days are older (mean 75 vs 71, P &lt; 0.05), had a higher proportion of ECOG &gt; 2 (81.6% vs 20.3%, P &lt; 0.01), and a higher proportion of stage 4 disease (73.9% vs 41.2%, P &lt; 0.01). There was no significant difference in any measure of wait times. Pts with limited survival were less likely to be seen by Medical Oncology (MO) (20.9% vs 70.9%, P &lt; 0.001), and less likely to receive chemotherapy (1.2% vs 45%, P &lt; 0.001) or ERCP (27% vs 53.8%, P &lt; 0.01). Multivariate analysis showed that receiving ERCP (P = 0.027) and chemotherapy(P &lt; 0.001) are independent predictors of survival, even when accounting for PS, CCI, stage, and age. Conclusions: Analysis of PC outcomes in NS demonstrates a large proportion of pts dying within 30 days of diagnosis. Those pts are older and present with higher stage and worse PS but did not have any significant difference in diagnostic and referral wait times. Those pts receive fewer referrals to Oncology services, fewer potentially life prolonging treatments and we uniquely discovered ERCP as an independent predictor of survival in our population. While further work is needed, this study characterized some of the unique challenges of PC care in NS as a province with a higher proportional of older adults and highlights potential opportunities to improve early healthcare delivery in older adults with limited windows for care. </jats:p

Determination of quality of care for patients with hepatocellular carcinoma in Nova Scotia.

506 Background: Hepatocellular carcinoma (HCC) is the most common primary malignancy found in the liver. Little is known about the outcomes of HCC patients in the province of Nova Scotia (NS). There is suggestion that closer proximity to tertiary cancer center provides better outcomes for HCC patients. We postulate that cancer care for HCC patients differs based on a patient’s accessibility to an academic cancer care center. Methods: A retrospective chart review of HCC patients diagnosed from 2015 to 2017, looking at referrals patterns, treatments and wait time was undertaken. Patients who live within the urban area of Halifax, NS (N = 97), where the academic cancer center is, was compared to patients who live outside Halifax (rural, N = 70). Results: 167 patients were identified with a diagnosis of HCC, which included 139 males and 28 females with median age of 68 years old at HCC diagnosis. During that period, only 35.3% of patients diagnosed with HCC had a tissue diagnosis and 67.7% had a baseline AFP (16% had an AFP &gt; 400). Just over 76% were diagnosed based on clinical features. Surgical intervention occurred in 15.6% and local treatments including radiation and TACE occurred in 35.3% of patients .Referral rate to Medical Oncology (MO) was 37.7%, of which 34.1% of patients had seen a MO at the time of data cut off (09-15-2019). 22 patients were eligible for systemic therapy but only 14 patients received systemic treatment (sorafenib n = 14). Conclusions: Initial data suggests patients who live in Halifax appear to have better outcomes than those outside. Further analysis is required to identify what differs between the urban and rural centers accounting for the seen difference in survival. [Table: see text] </jats:p

Glypican-3 and Cytokeratin-19 Expression in Pancreatic Cancer in a Canadian Population

Background/Objectives: One study of pancreatic ductal adenocarcinoma has found expression of glypican-3 (GPC3) and cytokeratin-19 (CK19) determined by immunohistochemistry to be associated with higher stage and grade disease, with a more adverse prognosis. The reported 44% rate of GPC3 expression in pancreatic cancer raises the important possibility that targeted immunotherapies currently in development for hepatocellular carcinoma may also prove useful for GPC3-expressing pancreatic cancers. The present study aims to determine if a similar expression pattern of these markers and stage/grade/prognostic associations is present in our Canadian patient population. Methods: Patients with a pancreatic surgical resection for adenocarcinoma or neuroendocrine tumor (NET) were identified from pathology records over a 5-year period. Immunohistochemistry for GPC3 and CK19 was performed on archived tumor tissue and the proportion of positive cells and intensity of staining were recorded. Grade, stage, and overall survival were compared in patients with NETs that were CK19-positive versus -negative. Results: All 72 pancreatic adenocarcinomas and 20 NETs tested were negative for GPC3, apart from a single case of pancreatic adenocarcinoma. All 72 adenocarcinomas were positive for CK19 expression. Half of the NETs were positive for CK19. There was no correlation between CK19 expression in NETs and tumor grade, lymph node metastasis, distant metastasis, or overall survival. Conclusions: We are skeptical of the reported prognostic value of GPC3 and CK19 in pancreatic adenocarcinomas. CK19 as a prognostic marker in NETs has potential for further study. The results with our protocol for GPC3 immunohistochemistry suggest that pancreatic cancer may be a less promising target for GPC3-targeted immunotherapies than previously thought

The effects of immunotherapy and novel therapies on medical oncology work load in a Canadian province.

6532 Background: Both novel targeted therapies and immunotherapies have dramatically changed the landscape in a number of disease sites with previously limited treatment options. This has resulted in an impact on clinical workload for oncologists with subspecialty practices in the areas of non-small cell lung, (NSCLC), melanoma (M), and genitourinary (GU) cancer. Our aim was to investigate the shift in workload amongst these practices as compared to other disease sites within a single academic cancer center in Nova Scotia (NS), Canada. Methods: The NS Cancer Center is the academic cancer center for the province of NS providing consultative and ongoing care for approximately 72% of provincial patients. We manually quantified appointment visits (new consultation, treatment and follow up visits) as well as telephone toxicity and chart checks booked from February 1 to April 30 across a 3-year interval (2016, 2017, and 2018) and then extrapolated this data to derive full year estimates. Disease sites most impacted by therapies that have changed treatment landscape (NSCLC, M and GU) were compared with the Breast and Gastrointestinal disease sites. Results: Clinical workload increased across all domains over the 3 year period but the majority of the increase is attributed to the 3 disease sites (Table). Conclusions: Medical oncology workloads are increasing over time and novel treatments (including immunotherapy) in disease sites with previously limited options likely account for a significant portion of that increase. New patient consultation metrics, taken in isolation, do not reflect current trends in medical oncology workload. Hiring practices, space allocation and use of physician extenders must take into account these shifting workload dynamics to mitigate physician burnout and potential impacts on quality and timeliness of care. [Table: see text] </jats:p

Spontaneous regression of metastatic hepatocellular carcinoma following 3 weeks of lenvatinib

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality and is associated with a poor prognosis. Rarely, there is spontaneous regression of the tumour. We present a case of a middle-aged male with presumed metastatic HCC who experienced enduring regression following 3 weeks of lenvatinib, which was discontinued due to side effects. While this could represent an unusually successful response to therapy, spontaneous tumour regression or an alternative diagnosis should be considered. We discuss possible mechanisms that might explain this unusual case and advocate for tissue confirmation in select cases, where there is diagnostic doubt or when the disease pattern does not clearly follow the recognised natural history. Therefore, if regression occurs—whether spontaneous or in response to treatment—it can be better understood and subsequent therapies recommended.</jats:p

A retrospective study on the role of diabetes and metformin in colorectal cancer disease progression.

1593 Background: Recent studies have suggested a potential epidemiological role for diabetes as an independent risk factor for the development of colorectal cancer (CRC). These studies have furthermore suggested patients with diabetes who develop colorectal cancer have an increased mortality. Methods: To identify a potential correlation between CRC and diabetes, we are performing a retrospective chart review of CRC patients treated at the Cancer Center of Southeastern Ontario diagnosed from January 2005 to December 2011. 1,300 colorectal cancer patient charts have been identified through Ontario Cancer Registry Data based on confirmed ICD-10 diagnosis codes and the variables of 200 random patients have been extracted into our database thus far. The final analysis will be completed April 2013. Results: Preliminary analysis of the database has indicated that the average age of patients with CRC was 69 years with 55% being women. The incidence of diabetes in our CRC population was 19%, double the rate of diabetes in the general population in Canada. As expected, the rate of co-morbidities excluding diabetes was higher in the diabetic group (92.9% vs 69.3%; p=0.004). When we looked at the diabetic population specifically, the rate of death was not significantly different compared to the non-diabetic population (13.2% vs 12.7%, p=0.94), however those with diabetes presented with later-stage (stage 2/3/4) disease (92.1% versus 88.6%). The average number of days from the time of diagnosis to death in the diabetic group (200 days) was half compared to the non-diabetic group (420 days, p=0.014). However, there was no statistical difference in the percentage of progression, number of different metastatic sites or the burden of metastatic disease amongst the two populations. A subgroup analysis of diabetic patients on metformin illustrated that the death rate (p=0.06), rate of progression (33% vs 20%) and those presenting with later stage disease was higher in patients not on metformin compared to those on the drug. Conclusions: Our preliminary work suggests diabetics with CRC may have a worst prognosis however taking metformin may have a positive impact on prognosis. </jats:p

Palliative Care Consultation and Aggressive Care at End of Life in Unresectable Pancreatic Cancer

Background: Palliative care (pc) consultation has been associated with less aggressive care at end of life in a number of malignancies, but the effect of the consultation timing has not yet been fully characterized. For patients with unresectable pancreatic cancer (upcc), aggressive and resource-intensive treatment at the end of life can be costly, but not necessarily of better quality. In the present study, we investigated the association, if any, between the timing of specialist pc consultation and indicators of aggressive care at end of life in patients with upcc. Methods: This retrospective cohort study examined the potential effect of the timing of specialist pc consultation on key indicators of aggressive care at end of life in all patients diagnosed with upcc in Nova Scotia between 1 January 2010 and 31 December 2015. Statistical analysis included univariable and multivariable logistic regression. Results: In the 365 patients identified for inclusion in the study, specialist pc consultation was found to be associated with decreased odds of experiencing an indicator of aggressive care at end of life; however, the timing of the consultation was not significant. Residency in an urban area was associated with decreased odds of experiencing an indicator of aggressive care at end of life. We observed no association between experiencing an indicator of aggressive care at end of life and consultation with medical oncology or radiation oncology. Conclusions: Regardless of timing, specialist pc consultation was associated with decreased odds of experiencing an indicator of aggressive care at end of life. That finding provides further evidence to support the integral role of pc in managing patients with a life-limiting malignancy

Involvement of Integrin α_vβ₃and Cell Adhesion Molecule L1 in Transendothelial Migration of Melanoma Cells

Tumor metastasis involves many stage-specific adhesive interactions. The expression of several cell adhesion molecules, notably the integrin αvβ3, has been associated with the metastatic potential of tumor cells. In this study, we used a novel in vitro assay to examine the role of αvβ3in the transmigration of melanoma cells through a monolayer of human lung microvascular endothelial cells. Confocal microscopy revealed the presence of the integrin αvβ3on melanoma membrane protrusions and pseudopods penetrating the endothelial junction. αvβ3was also enriched in heterotypic contacts between endothelial cells and melanoma cells. Transendothelial migration of melanoma cells was inhibited by either a cyclic Arg-Gly-Asp peptide or the anti-αvβ3monoclonal antibody LM609. Although both platelet endothelial cell adhesion molecule-1 and L1 are known to bind integrin αvβ3, only L1 serves as a potential ligand for αvβ3during melanoma transendothelial migration. Also, polyclonal antibodies against L1 partially inhibited the transendothelial migration of melanoma cells. However, addition of both L1 and αvβ3antibodies did not show additive effects, suggesting that they are components of the same adhesion system. Together, the data suggest that interactions between the integrin αvβ3on melanoma cells and L1 on endothelial cells play an important role in the transendothelial migration of melanoma cells.</jats:p