Douglas S. Swords

Biomarkers in pancreatic adenocarcinoma: current perspectives

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9), which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA), CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC.

Causes of Death and Conditional Survival Estimates of Medium- and Long-term Survivors of Pancreatic Adenocarcinoma

Estimates of Mediumand Long-term Survivors of Pancreatic Adenocarcinoma Most patients who undergo resection of pancreatic ductal adenocarcinoma (PDAC) die within 5 years.1-5 Five-year survivors remain at risk for PDAC-related death,1,2,4,5 and recurrences more than 15 years after diagnosis are reported.4 A study reporting conditional survival (CS) extended only 6.5 years after diagnosis.3 Reported 10-year survival rates range from 3.9% in a National Cancer Database (NCDB) study to 12% to 13% in singleinstitution studies.1,5,6 In the NCDB study, the risk of death decreased for 6 years and then remained fairly constant at 10% per year in years 7 to 15, which was double that of an ageand sexmatched general population.6 Limited prognostic information exists for 5to 15-year survivors. We used the Surveillance, Epidemiology, and End Results (SEER) database (http://www.seer.cancer.gov) to quantify yearly risks of death due to PDAC vs other causes and calculate CS estimates extending 21 years after diagnosis. Editors Note page 1130

Impact of insurance status on receipt of definitive surgical therapy and posttreatment outcomes in early stage lung cancer

Background: The impact of insurance on outcomes in the modern era of evidence‐based guidelines is unclear. We sought to examine differences in receipt of therapy and outcomes for early stage, non‐small cell lung cancer patients by insurance coverage. Method: Clinical T1‐3 N0‐1 non‐small cell lung cancer cases were identified in the 2004 to 2014 National Cancer Database and compared across 4 groups: private, Medicare, Medicaid, and uninsured. A multivariable, linear regression model was used to examine the effects of insurance status on time to curative surgical therapy, adjusting for patient and facility characteristics. Receipt of different therapies was examined with multivariable logistic regression. Survival analysis was conducted with Cox regression. Results: A total of 240,361 patients presented with early stage non‐small cell lung cancer (60,532 private, 164,377 Medicare, 11,001 Medicaid, and 4,451 uninsured). After adjustment, Medicaid and uninsured patients received surgical therapy later than privately insured patients (9.5 days and 7.0 days, respectively, P < .001), were more likely to be delayed > 8 weeks (odds ratio 1.64, 95% confidence interval 1.55–1.73 and odds ratio 1.46, 95% confidence interval 1.34–1.58), and were significantly less likely to receive surgery (odds ratio 0.53, 95% confidence interval 0.50–0.56 and odds ratio 0.50, 95% confidence interval 0.47–0.55). Uninsured patients were more likely to receive no treatment (odds ratio 2.15, 95% confidence interval 1.92–2.41), followed by Medicaid patients (odds ratio 1.66, 95% confidence interval 1.53–1.80). The 5‐year overall survival was significantly worse in the Medicaid and uninsured populations. Conclusion: Even in the modern era, uninsured and Medicaid early stage non‐small cell lung cancer patients have decreased odds of receiving a potentially curative operation and experience inferior outcomes. Given substantial expenditures on the Medicaid program, strategies for increasing utilization of curative surgery in Medicaid patients with lung cancer are needed.

Surgical overtreatment of pancreatic intraductal papillary mucinous neoplasms: Do the 2017 International Consensus Guidelines improve clinical decision making?

Background: Significant overtreatment of intraductal papillary mucinous neoplasms can be attributed to low specificity of the current International Consensus Guidelines as well as nonconformity with the guidelines. We compare the ability of the 2012 and revised 2017 intraductal papillary mucinous neoplasms International Consensus Guidelines to predict high‐grade dysplasia/invasive cancer and to determine the preoperative variables that predict resection of benign or low‐grade dysplasia in tertiary care centers. Methods: Clinical, radiographic, and pathologic data for resected intraductal papillary mucinous neoplasms at 3 high‐volume National Cancer Institute Cancer Centers were reviewed and the 2012 and 2017 consensus criteria were retrospectively applied. When International Consensus Guidelines were not met, clinical decision analysis was used to determine the primary indication for resection. Logistic regression identified variables associated with pathologic grade. Results: Records for a total of 251 patients were reviewed, 129 of whom (52%) had low‐grade dysplasia. The revised 2017 International Consensus Guidelines had high sensitivity (98.4%) and negative predicted value (96.1%), and all high‐risk stigmata predicted high‐grade dysplasia/invasive cancer; however, specificity remained low (14.8%). Nonconformity with International Consensus Guidelines was the most powerful predictor of low‐grade dysplasia on final pathologic examination (9.5; 2.12–40.78). Independent predictors of low‐grade dysplasia included age younger than 50 (2.46; 1.08–5.62), fine‐needle aspiration without epithelial cells (2.6; 1.43–4.72), and normal duct diameter (3.07; 1.99–4.75). Diabetes developed in 30% of patients after resection. Conclusion: Management of intraductal papillary mucinous neoplasms remains clinically challenging. Low specificity of the International Consensus Guidelines and nonconformity with the guidelines continue to contribute to unnecessary pancreatic resections. Improved tools for disease classification as well as a better understanding of the natural history, biology, and rates of progression of intraductal papillary mucinous neoplasms are needed to avoid surgical overtreatment of low‐grade intraductal papillary mucinous neoplasms.

Perioperative antibiotics should be used for placement of implanted central venous ports: A propensity analysis evaluating risk

OBJECTIVE To quantify risk for CRI based on PABX use in CVAP placement for cancer patients. SUMMARY BACKGROUND DATA Central venous access ports (CVAP) are totally implanted devices used for chemotherapy. There is a temporal risk for catheter related infection (CRI) to insertion and perioperative prophylactic antibiotics (PABX) use is a contested issue among practitioners. METHODS Data was collected from a single center, academic oncology center. Treatment with a perioperative PABX was compared to non-treatment, to examine the incidence of 14-day CRI. Propensity scores with matched weights controlled for confounding, using 15 demographic, procedural and clinical variables. RESULTS From 2007 to 2012, 1,091 CVAP were placed, where 59.7 % received PABX. The 14-day CRI rate was 0.82%, with 78% of those not receiving PABX. While results did not achieve statistical significance, use of PABX was associated with a 58% reduction in the odds of a 14-day CRI (OR = 0.42, 95% CI: 0.08-2.24, p = 0.31). CONCLUSION The findings suggest a reduction in early CRI with the use of PABX. Since CRI treatment can range from a course of oral antibiotics, port removal, to hospital admission, we suggest clinicians consider these data when considering PABX in this high-risk population.

Association of time-to-surgery with outcomes in clinical stage I-II pancreatic adenocarcinoma treated with upfront surgery

Background. Time‐to‐surgery from cancer diagnosis has increased in the United States. We aimed to determine the association between time‐to‐surgery and oncologic outcomes in patients with resectable pancreatic ductal adenocarcinoma undergoing upfront surgery. Methods. The 2004–2012 National Cancer Database was reviewed for patients undergoing curative‐intent surgery without neoadjuvant therapy for clinical stage I–II pancreatic ductal adenocarcinoma. A multivariable Cox model with restricted cubic splines was used to define time‐to‐surgery as short (1–14 days), medium (15–42), and long (43–120). Overall survival was examined using Cox shared frailty models. Secondary outcomes were examined using mixed‐effects logistic regression models. Results. Of 16,763 patients, time‐to‐surgery was short in 34.4%, medium in 51.6%, and long in 14.0%. More short time‐to‐surgery patients were young, privately insured, healthy, and treated at low‐volume hospitals. Adjusted hazards of mortality were lower for medium (hazard ratio 0.94, 95% confidence interval, .90, 0.97) and long time‐to‐surgery (hazard ratio 0.91, 95% confidence interval, 0.86, 0.96) than short. There were no differences in adjusted odds of node positivity, clinical to pathologic upstaging, being unresectable or stage IV at exploration, and positive margins. Medium time‐to‐surgery patients had higher adjusted odds (odds ratio 1.11, 95% confidence interval, 1.03, 1.20) of receiving an adequate lymphadenectomy than short. Ninety‐day mortality was lower in medium (odds ratio 0.75, 95% confidence interval, 0.65, 0.85) and long time‐to‐surgery (odds ratio 0.72, 95% confidence interval, 0.60, 0.88) than short. Conclusion. In this observational analysis, short time‐to‐surgery was associated with slightly shorter OS and higher perioperative mortality. These results may suggest that delays for medical optimization and referral to high volume surgeons are safe.

Implications of inaccurate clinical nodal staging in pancreatic adenocarcinoma

Background. Many patients with stage I‐II pancreatic adenocarcinoma do not undergo resection. We hypothesized that (1) clinical staging underestimates nodal involvement, causing stage IIB to have a greater percent of resected patients and (2) this stage‐shift causes discrepancies in observed survival. Methods. The Surveillance, Epidemiology, and End Results (SEER) research database was used to evaluate cause‐specific survival in patients with pancreatic adenocarcinoma from 2004–2012. Survival was compared using the log‐rank test. Single‐center data on 105 patients who underwent resection of pancreatic adenocarcinoma without neoadjuvant treatment were used to compare clinical and pathologic nodal staging. Results. In SEER data, medium‐term survival in stage IIB was superior to IB and IIA, with median cause‐specific survival of 14, 9, and 11 months, respectively (P < .001). Seventy‐two percent of stage IIB patients underwent resection vs 28% in IB and 36% in IIA (P < .001). In our institutional data, 12.4% of patients had clinical evidence of nodal involvement vs 69.5% by pathologic staging (P < .001). Among clinical stage IA–IIA patients, 71.6% had nodal involvement by pathologic staging. Conclusion. Both SEER and institutional data support substantial underestimation of nodal involvement by clinical staging. This finding has implications in decisions regarding neoadjuvant therapy and analysis of outcomes in the absence of pathologic staging.

489 Initial Misdiagnosis of Proximal Pancreatic Adenocarcinoma Is Associated With Delays in Diagnosis and Advanced Stage at Presentation

Introduction Delay in diagnosis of pancreatic ductal adenocarcinoma (PDAC) is associated with decreased survival. The effect of an initial misdiagnosis on delay in diagnosis and stage of PDAC is unknown.