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Background: While adjuvant therapy provides a survival benefit for patients (pts) with early-stage pancreatic cancer there are currently no biomarkers that define pts that are more or less likely to benefit from such treatment. This prospective study investigated the use of circulating tumour DNA (ctDNA) as a marker of residual disease, where detection could predict recurrence. Method(s): Patients newly diagnosed with operable pancreatic adenocarcinoma were enrolled. PCR-based-SafeSeqS assays were used to identify mutations at codons 12, 13 and 61 of KRAS in the primary tumor and to detect ctDNA in plasma samples. Patient management was as per standard of care, blinded to ctDNA data. Result(s): From January 2015 to June 2017, 42 pts with matched plasma samples, collected pre- and post-operatively, and tumor tissue available were evaluated. The median time between surgery and post-op blood collection was 6.3 (range:4-8) weeks. RAS mutations were identified in 38 (90.5%) tumor samples. ctDNA was detected in 23/37 (62.2%) pre-op and 13/35 (37.1%) post-op plasma samples. In multivariate analysis including stage, and resection margin, ctDNA status was the only statistically significant variable. Pre-op ctDNA detection was associated with worse median recurrence free survival (RFS), 10.3 months versus not reached, (Hazard Ratio (HR),3.4; 95% confidence interval (CI), 1.5- 7.6; P = 0.005) and 5.4 months versus 17.1 months, (HR, 5.4; 95% CI, 4.7-37.3; P < 0.0001) post-operatively. Similarly, the presence of ctDNA was associated with worse median overall survival (OS), 13.8 months versus not reached pre-operatively, (HR,3.4; 95% CI 1.1 to 8.3; P = 0.04) and 10.6 months versus not reached (HR,4.5; 95% CI 2.4-28.6; P = 0.001) post-operatively. Notably, recurrence occurred in 13 of 13 pts with detectable post-op ctDNA, despite more than half receiving standard adjuvant chemotherapy. Conclusion(s): ctDNA analysis is a promising prognostic marker in early-stage pancreatic cancer

Background: The optimal duration of ACT following surgery for colon cancer remains controversial. SCOT is an international, randomised trial that compared 3 months versus 6 months of ACT in this setting. We sought the survival benefits that patients participating in SCOT judged necessary to make extra 3 months of ACT worthwhile. Method(s): SCOT participants from Australia & New Zealand completed a validated questionnaire 3 and 18 months after randomisation to elicit the minimum survival benefit each participant judged necessary to make it worthwhile having ACT for 6 months rather than 3 months. Standardised hypothetical scenarios used the following baseline survivals with 3 months of ACT: life expectancies (LE) of 5 years (5Y) and 15 years (15Y), and 5-year survival rates (5YS) of 65% and 85%. Comparisons were nonparametric, 2-sided, and considered statistically significant if p < 0.05. Result(s): Questionnaires were completed by 160 participants, 82 allocated 3 months ACT, and 78 allocated 6 months ACT. ACT was FOLFOX in 121 (75%), XELOX in 39 (25%), and the mean age was 64. Preferences varied substantially among participants, and did not differ according to the randomly allocated treatment group. The median survival benefits judged necessary to make the extra 3 months of ACT worthwhile were an extra: 3 years beyond a LE of 5Y; 3 years beyond a LE of 15Y; 15% beyond a 65% 5YS; and 5% beyond an 85% 5YS. Preferences were similar at 3 months and 18 months. Participants with symptomatic peripheral neuropathy (132, 82%) judged a median benefit of an extra 5% beyond a 65% 5YS necessary to warrant their symptoms. Conclusion(s): Participants' preferences varied substantially, and many judged much larger benefits needed to warrant having ACT for 6 months rather than 3 months than the estimates of the benefits based on the IDEA meta-analysis.

Background: While adjuvant therapy provides a survival benefit for patients (pts) with early-stage pancreatic cancer there are currently no biomarkers that define pts that are more or less likely to benefit from such treatment. This prospective study investigated the use of circulating tumour DNA (ctDNA) as a marker of residual disease, where detection could predict recurrence. Method(s): Patients newly diagnosed with operable pancreatic adenocarcinoma were enrolled. PCR-based-SafeSeqS assays were used to identify mutations at codons 12, 13 and 61 of KRAS in the primary tumor and to detect ctDNA in plasma samples. Patient management was as per standard of care, blinded to ctDNA data. Result(s): From January 2015 to June 2017, 42 pts with matched plasma samples, collected pre- and post-operatively, and tumor tissue available were evaluated. The median time between surgery and post-op blood collection was 6.3 (range:4-8) weeks. RAS mutations were identified in 38 (90.5%) tumor samples. ctDNA was detected in 23/37 (62.2%) pre-op and 13/35 (37.1%) post-op plasma samples. In multivariate analysis including stage, and resection margin, ctDNA status was the only statistically significant variable. Pre-op ctDNA detection was associated with worse median recurrence free survival (RFS), 10.3 months versus not reached, (Hazard Ratio (HR),3.4; 95% confidence interval (CI), 1.5- 7.6; P = 0.005) and 5.4 months versus 17.1 months, (HR, 5.4; 95% CI, 4.7-37.3; P < 0.0001) post-operatively. Similarly, the presence of ctDNA was associated with worse median overall survival (OS), 13.8 months versus not reached pre-operatively, (HR,3.4; 95% CI 1.1 to 8.3; P = 0.04) and 10.6 months versus not reached (HR,4.5; 95% CI 2.4-28.6; P = 0.001) post-operatively. Notably, recurrence occurred in 13 of 13 pts with detectable post-op ctDNA, despite more than half receiving standard adjuvant chemotherapy. Conclusion(s): ctDNA analysis is a promising prognostic marker in early-stage pancreatic cancer

Background: The optimal duration of ACT following surgery for colon cancer remains controversial. SCOT is an international, randomised trial that compared 3 months versus 6 months of ACT in this setting. We sought the survival benefits that patients participating in SCOT judged necessary to make extra 3 months of ACT worthwhile. Method(s): SCOT participants from Australia & New Zealand completed a validated questionnaire 3 and 18 months after randomisation to elicit the minimum survival benefit each participant judged necessary to make it worthwhile having ACT for 6 months rather than 3 months. Standardised hypothetical scenarios used the following baseline survivals with 3 months of ACT: life expectancies (LE) of 5 years (5Y) and 15 years (15Y), and 5-year survival rates (5YS) of 65% and 85%. Comparisons were nonparametric, 2-sided, and considered statistically significant if p < 0.05. Result(s): Questionnaires were completed by 160 participants, 82 allocated 3 months ACT, and 78 allocated 6 months ACT. ACT was FOLFOX in 121 (75%), XELOX in 39 (25%), and the mean age was 64. Preferences varied substantially among participants, and did not differ according to the randomly allocated treatment group. The median survival benefits judged necessary to make the extra 3 months of ACT worthwhile were an extra: 3 years beyond a LE of 5Y; 3 years beyond a LE of 15Y; 15% beyond a 65% 5YS; and 5% beyond an 85% 5YS. Preferences were similar at 3 months and 18 months. Participants with symptomatic peripheral neuropathy (132, 82%) judged a median benefit of an extra 5% beyond a 65% 5YS necessary to warrant their symptoms. Conclusion(s): Participants' preferences varied substantially, and many judged much larger benefits needed to warrant having ACT for 6 months rather than 3 months than the estimates of the benefits based on the IDEA meta-analysis.

Background: ASCOLT is an international Phase III randomized control trial (NCT00565708) investigating the impact of adjuvant aspirin on recurrence and survival after curative resection of colorectal cancer (CRC). Retrospective data suggest that COX2 and HLA Class 1 antigen expression may predict for aspirin benefit (Reimers MS, JAMA internal medicine, 2014;174(5):732-739; and Chan AT, JAMA, 2009;302(6):649-658.) Translational studies aim to confirm putative biomarkers of aspirin sensitivity in this prospective trial. This study reports the IHC assessment of COX2 and HLA in representative samples. Method(s): FFPE slides from consenting Australian patients were stained with COX2 and HLA Class 1 antibodies (Chan AT, JAMA, 2009;302(6):649-658.). Digital images were captured using Aperio software. IHC expression was scored by a pathologist (DW) blinded to sample identification. Intensity was assessed semi-quantitatively for each antibody in one area of dominant (primary) intensity and one of secondary intensity in each section. A scale was applied for staining intensity: 0=absent, 1=weak, 2=moderate and 3=strong; and for amount of tumor epithelium stained: 1= 5%-24%, 2= 25%-49%, 3=50%-74% 4= >75%. Normal epithelium, which typically has strong COX2 and HLA staining, was used as internal control. Only tumor epithelium was scored (not inflammatory cells). Result(s): 90 tumors were stained for both COX2 and HLA Class 1. All tumors showed diffuse staining for both markers, mostly strong, but with many tumors having regions with lesser degrees of expression (Table). Conclusion(s): COX2 expression was generally strong and HLA Class 1 was more likely to show regions of weak to moderate expression. No significant correlation was detected between COX2 and HLA expression levels. Further pathological analysis is underway and correlations will be made with outcome once trial data has matured in 2020.

Background: ASCOLT is an international Phase III randomized control trial (NCT00565708) investigating the impact of adjuvant aspirin on recurrence and survival after curative resection of colorectal cancer (CRC). Retrospective data suggest that COX2 and HLA Class 1 antigen expression may predict for aspirin benefit (Reimers MS, JAMA internal medicine, 2014;174(5):732-739; and Chan AT, JAMA, 2009;302(6):649-658.) Translational studies aim to confirm putative biomarkers of aspirin sensitivity in this prospective trial. This study reports the IHC assessment of COX2 and HLA in representative samples. Method(s): FFPE slides from consenting Australian patients were stained with COX2 and HLA Class 1 antibodies (Chan AT, JAMA, 2009;302(6):649-658.). Digital images were captured using Aperio software. IHC expression was scored by a pathologist (DW) blinded to sample identification. Intensity was assessed semi-quantitatively for each antibody in one area of dominant (primary) intensity and one of secondary intensity in each section. A scale was applied for staining intensity: 0=absent, 1=weak, 2=moderate and 3=strong; and for amount of tumor epithelium stained: 1= 5%-24%, 2= 25%-49%, 3=50%-74% 4= >75%. Normal epithelium, which typically has strong COX2 and HLA staining, was used as internal control. Only tumor epithelium was scored (not inflammatory cells). Result(s): 90 tumors were stained for both COX2 and HLA Class 1. All tumors showed diffuse staining for both markers, mostly strong, but with many tumors having regions with lesser degrees of expression (Table). Conclusion(s): COX2 expression was generally strong and HLA Class 1 was more likely to show regions of weak to moderate expression. No significant correlation was detected between COX2 and HLA expression levels. Further pathological analysis is underway and correlations will be made with outcome once trial data has matured in 2020.