Citations

Abstract Background: The utility of alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) surveillance is controversial. We aimed to identify factors associated with elevated AFP and define the patients for whom AFP is effective for surveillance. Methods: Data from the NCI Early Detection Research Network phase II HCC biomarker study (233 early-stage HCC and 412 cirrhotic patients) were analyzed. We analyzed 110 early-stage HCC and 362 cirrhotic hepatitis C virus (HCV) patients for external validation. Sensitivity, specificity, and area under the ROC curve (AUC) for HCC were calculated. Results: HCV etiology, non-White race, and serum alanine transaminase (ALT) predicted elevated AFP in cirrhotics. Non-White race and ALT predicted elevated AFP in HCC patients. Higher AUC of AFP for HCC was noted in patients with HBV (0.85) and alcohol (0.84), whereas it was lower in patients with hepatitis C virus (HCV; 0.80) and nonviral/alcohol etiology (0.76). The AUC was higher in HCV patients with serum ALT ≤40 U/L than patients with serum ALT >40 U/L (0.91 vs. 0.75, P < 0.01). At 90% specificity, the sensitivity of AFP increased from 44% to 74% in Whites with HCV and from 50% to 85% in non-Whites with HCV. There was a trend toward higher AUC in HCV patients with serum ALT ≤40 U/L than those with serum ALT >40 U/L (0.79 vs. 0.69, P = 0.10) in the validation cohort. Conclusions: The satisfactory performance of AFP in HCV patients with normal ALT should be further validated. Impact: The AFP may serve as a valuable surveillance test in HCV patients with normal ALT. Cancer Epidemiol Biomarkers Prev; 26(7); 1085–92. ©2017 AACR.

In this Technical Note, we describe an in‐house video goggles feedback system assembled using several commercially available products. This goggle video feedback system is currently being used at University of Louisville and Mayo Clinic for both CT simulation and linac treatment delivery. The setup details, including specific recommendations, are provided, along with an alternative option for using the video goggles system.PACS number: 07.07Hj

334 Background: Radical cystectomy (RC) represents the standard of care for patients with muscle-invasive urothelial carcinoma of the urinary bladder (UCUB). Alternative organ-conserving treatments such as chemotherapy and/or radiotherapy have gained interest. We sought to compare survival outcomes of patients according to treatment modalities, in a stage-for-stage analysis. Methods: We relied on the Surveillance, Epidemiology, and End Results Medicare-linked database to identify 12,950 patients diagnosed with T2–T4a N0/x M0 UCUB between years 1992 and 2009. Treatment types include RC (n=5207), chemotherapy/radiation (n=2,669), and surveillance (n=5,074). Following instrumental variable analysis, Cox- and competing-risks regression analyses were performed for prediction of overall survival (OS) and cancer-specific mortality (CSM), respectively. All analyses were stratified according to disease stage (T2, T3, T4a). Results: After adjusting for potential confounders, OS was more favorable for RC relative to chemotherapy/radiation (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.02–2.40) or surveillance (HR: 1.82, 95% CI: 1.20–2.78) in patients with T2 UCUB. For the same stage, CSM rates were lower in the surgery group compared to chemotherapy/radiation (HR: 2.05, 95% CI: 1.14–3.67) or surveillance (HR: 1.95, 95% CI: 1.09–3.48). When analyses focused on individuals with more advanced disease (T3–T4a), no statistically significant difference was observed between chemotherapy/radiation relative to RC for both OS and CSM. Conclusions: In the current retrospective population-based cohort, RC was associated with improved survival outcomes relative to its alternative treatment counterparts. However, this effect was only observable in patients with T2 disease. Conversely, no difference between chemotherapy/radiation vs. surgery was noted in patients with more advanced disease stage.

167 Background: Physicians have a variety of resources available about the treatment of localized prostate cancer. Yet, it is largely unknown what resources and evidence radiation oncologists and urologists commonly use to inform patients and possibly alter clinical practice. In this national survey study, we assessed the types of resources prostate cancer specialists’ use and the level of evidence needed to change treatment recommendations in localized prostate cancer. Methods: From a random sample, 1,422 physicians were sent a mail survey assessing what type of information was used to guide prostate cancer treatment. The survey also queried what level of evidence could alter recommendations. Multivariable logistic regression models were used to identify for differences in physician characteristics for each outcome. Results: Survey response rates were similar for radiation oncologists and urologists (44% vs. 46%; p=0.46). Specialty-specific journals represented the most commonly used resource to inform the clinical practice for radiation oncologists (65%) and urologists (70%). Relative to radiation oncologists, urologists were less likely to utilize medical journals (25% vs. 38.7%, OR: 0.50; p=0.01), cancer journals (21.7% vs. 50.8%, OR: 0.50; p<0.001), but more likely to rely on clinical guidelines (46.3% vs. 37.7%,OR: 1.6; p=0.006). Radiation oncologists and urologists both viewed RCT’s as the most likely source of evidence needed to change treatment recommendations (85% vs. 77%). Conclusions: Both specialties most commonly rely on their specialty-specific journals to inform their clinical practice and view RCT’s as the level of evidence needed to change treatment recommendations for localized prostate cancer. Radiation oncologists embraced greater diversity in literature, while urologists were more likely to use clinical guidelines. Utilizing this information may overcome barriers to the dissemination and adoption of new treatment paradigms for localized prostate cancer.

284 Background: ODSH, a low anticoagulant heparin derivative, interferes with several important pancreatic cancer cell survival pathways. A randomized phase II trial was initiated to determine if ODSH improves the activity of G/A, a promising pancreatic cancer investigational therapy. Preliminary data are presented here for the first 10 patients administered ODSH as part of an initial run-in phase prior to patient randomization. Methods: Patients with previously untreated, metastatic pancreatic cancer were treated with G (1,000 mg/m2) and A (125 mg/m2) plus ODSH (4 mg/kg bolus followed by a 48 hr. continuous IV infusion at a dose of 0.375 mg/kg/hr) on days 1, 8, and 15 every 28 days until disease progression or unacceptable toxicity. Patients were required to have ECOG ≤ 1 and appropriate blood and liver function levels. The primary endpoint was progression-free survival (PFS). Results: 10 patients (median age, 66 years) were administered up to 5 cycles of G/A plus ODSH. Per RECIST criteria, a partial response (PR) was achieved in 5 patients (50%) and the median PFS will exceed 6 months. Disease control (PR or stable disease for > 16 weeks) occurred in all 10 patients. Of 9 patients with baseline elevated CA 19-9 levels, 8 had > 60% reduction. ODSH was well tolerated and unexpectedly appeared to preserve marrow function as no patients had grade 3/4 thrombocytopenia or grade 4 neutropenia during any of the cycles. Conclusions: Although G/A and FOLFIRINOX are important advances, additional progress is necessary for metastatic pancreatic cancer patients. ODSH may interfere with pancreatic cancer invasion, metastasis, and chemo-resistance by inhibiting P- and L-selectins, heparanase, and the HMGB1-RAGE axis, respectively, suggesting that ODSH may enhance chemotherapy activity. This preliminary analysis in a small number of patients is encouraging and consistent with a previous report for this regimen (Von Hoff, J Clin Oncol, 2011). ODSH has also been very well tolerated and early data suggests that it may preserve platelet and neutrophil levels. Further follow-up of the ongoing randomized phase II trial is warranted. Clinical trial information: NCT01461915.

238 Background: To compare post-transplant recurrence rates of hepatocellular carcinoma (HCC) and differences in percent tumor necrosis in patients with pre-operative superselective chemoembolization (CE) vs. non-superselective CE. Methods: Retrospective review of 147 patients with liver transplant (LT) for HCC treated with pre-operative CE. Those transplanted less than 24 hours after CE and those who had other concomitant treatments were excluded. The angiographic studies and written reports were reviewed to categorize patients into superselective and non-superselective groups. CE was done with an emulsion of lipiodol, cisplatin, doxorubicin, mitomycin C, and contrast, with or without embolization particles. Superselective CE was defined as treatment directly into the vessel(s) feeding the tumor. Treatment from more proximal vessels was considered non-superselective. Data gathered included age, gender, date of CE, date of LT, tumor size and number, tumor stage, MELD score, Child-Pugh class, alpha fetoprotein, percent tumor necrosis at explant, date of recurrence, date and cause of death, and date of last follow-up. Patient and disease characteristics and percent tumor necrosis were analyzed with a Wilcoxon rank sum test or Fisher’s exact test. The Kaplan-Meier method was used to estimate the cumulative incidences of death due to recurrent disease after LT. Results: 99 patients were included, 53 had superselective CE and 46 non-superselective. HCC recurrence rates at 1, 3, 5, and 8 years were all significantly less for superselective CE compared to non-superselective CE (p = 0.039 single, p = 0.011 multivariable). Using multivariable analysis, superselective CE had a lower risk of death due to recurrent HCC at 1, 3, 5, and 8 years (p = 0.046). There was a trend toward more percent tumor necrosis after superselective CE, but it did not reach significance (p = 0.057). Conclusions: This study provides evidence that HCC recurrence after LT and death due to recurrent HCC is lower after pre-LT superselective CE versus non-superselective CE. The strong trend for greater percent tumor necrosis with superselective CE may explain the differences in recurrence rate.

106 Background: Androgen deprivation therapy (ADT) is one of the main treatment options for locally advanced and metastatic prostate cancer. Neuroendocrine prostate cancer (NEPC) is inherently less sensitive or even resistant to ADT. NEPC can be observed de novo (e.g., small cell prostate cancer) but more commonly arises after exposure to ADT. We hypothesized that a gene expression signature of NEPC when measured in primary tumor specimens (RP) of prostatic adenocarcinoma may be useful for predicting patients with innate resistance to ADT. Methods: Expression profiles of 1023 PCa patients treated with RP were obtained from the Decipher GRID database. These were split into training (n=529) and validation (n=494) sets and stratified by the receipt of adjuvant ADT (n=243) or no adjuvant ADT (n=780). A literature review of ADT resistance and neuroendocrine genes identified 1,557 genes as candidates. This set was further filtered, using logistic regression to select a 52-gene ADT resistance signature (ARS). ARS was trained using a generalized linear model with lasso regularization. Survival c-index and Kaplan Meier was used to compare survival differences between treated and untreated patients with high and low ARS scores (defined by median split). Results: In validation cohorts, the ARS was predictive of metastasis in cohorts receiving adjuvant ADT (10-year metastasis free survival c-index of 0.69 (95% CI 0.59-0.78) as compared to 0.45 (95% CI 0.29-0.61) in patients not treated with ADT). Similarly in a separate cohort of untreated patients that received no ADT until after metastatic onset, ARS was not prognostic (c-index 0.53). Among ADT treated patients, those with low ARS scores had a 10 year MFS of 87%, versus 70% in those with high ARS scores (p<0.001). In the subset of men who received ADT after metastatic onset and who developed castrate-resistant prostate cancer (CRPC, n = 41), median time to treatment failure was 1 year in patients with high ARS compared to 2 years for those with low ARS scores (p=0.07). Conclusions: A 52-gene ADT resistance signature was developed which showed significant differences in metastasis-free survival among adjuvant hormone treated but not untreated patients.

1 Background: To determine whether the efficacy of a hypofractionated (H) schedule is no worse than a conventional (C) schedule in men with low-risk prostate cancer. Methods: From April 2006 to December 2009, one thousand one hundred fifteen men with low-risk prostate cancer (clinical stage T1-2a, Gleason ≤ 6, PSA < 10) were randomly assigned 1:1 to a conventional (C) schedule (73.8 Gy in 41 fractions over 8.2 weeks) or to a hypofractionated (H) schedule (70 Gy in 28 fractions over 5.6 weeks). The trial was designed to establish with 90% power and alpha = 0.05 that (H) results in 5-year disease-free survival (DFS) that is not lower than (C) by more than 7% (hazard ratio (HR) < 1.52). Secondary endpoints include freedom from biochemical recurrence (FFBR) and overall survival. At the third planned interim analysis (July 2015), the NRG Oncology Data Monitoring Committee recommended that the results of the trial be reported. Results: One thousand one hundred and one protocol eligible men were randomized: 547 to C and 554 to H. Median follow-up is 5.9 years. Baseline characteristics are not different according to treatment arm. At the time of analysis 185 DFS events have been observed; 99 in the C arm and 86 in the H arm. The estimated 7-year disease-free survival is 75.6% (95% CI 70.3, 80.1) in the C arm and 81.8% (77.5, 85.3) in the H arm. The DFS HR (C/H) is 0.85 (0.64, 1.14). Comparison of biochemical recurrence (HR = 0.77, (0.51, 1.17)) and overall survival (HR = 0.95, (0.65, 1.41)) also met protocol non-inferiority criteria. Grade ≥ 3 GI toxicity is 3.0% (C) vs. 4.6% (H), Relative risk (RR) for H vs. C 1.53, (95% CI 0.86, 2.83); grade ≥ 3 GU toxicity is 4.5% (C) vs. 6.4% (H), RR = 1.43 (0.86,2.37). Conclusions: In men with low-risk prostate cancer, 70 Gy in 28 fractions over 5.6 weeks is non-inferior to 73.8 Gy in 41 fractions over 8.2 weeks. Clinical trial information: NCT00331773.