Impact of symptom and functional burden on survival in pancreatic ductal adenocarcinoma (PDAC)

BackgroundPatient reported outcomes (PROs) can be used to assess the symptom and functional impact of PDAC on patient wellbeing but its use as a prognostic utility is still evolving.MethodsHealth-related quality of life (HRQOL) was prospectively evaluated using EORTC QLQC30, PAN26, and EQ5D5L in patients referred to the Australian Molecular Screening and Therapeutics (MoST) Program. Individual item scores were dichotomized by mean and assessed for correlation with survival via uni- and multivariate Cox regression (p<0.05, adjusted for multiple hypothesis testing). Descriptive statistics were used for demographic and clinical details.ResultsBetween Dec 2021-Dec 2023, 300 patients referred; 94% (n=282) completed baseline questionnaires; 144 patients died, median time from referral to death 149 days (IQR 86-214); median age at diagnosis 64yrs; 51% female; de novo metastatic 56%; ECOG 0 45%; systemic therapy ≥2 lines 63%. As expected, baseline Global Health Status 57.2 [23.2] (mean[SD]) was substantially reduced compared to a well population. The HRQOL items significant on univariate analysis were physical, emotional, and social function, fatigue, pain, appetite loss, financial issues [QLQC30]; pancreatic pain, bloating, digestive, taste, indigestion weight loss, weakness, dry mouth, body image, side effects, future worries, planning, sexual functioning [PAN26]; and all EQ5D5L items. In multivariate analysis, only ECOG (p=0.02) and de novo metastatic disease (p=0.001) correlated with survival. To explore which HRQOL items contributed most to outcomes, we excluded ECOG and de novo metastatic and identified significant associations with indigestion (p=0.037), sexual functioning (p=0.004), and impaired personal care (p=0.02); fatigue trended towards significance (p=0.072).ConclusionsECOG and de novo metastatic disease correlate with survival in patients with PDAC; our results also indicate that PROs may be a reliable and complementary addition to conventional prognostic factors. Leveraging this data, we are employing machine learning to develop a prognostic model using a combination of HRQOL indices to further understand the impact of PROs on survival within the clinical setting and to guide optimisation of supportive care measures.Clinical trial identificationACTRN12616000908437 - Cancer Molecular Screening and Therapeutics (MoST) Program.Legal entity responsible for the studyThe Australian Genomic Cancer Medicine Programme (Omico Ltd).FundingThe Australian Genomic Cancer Medicine Programme (Omico Ltd) is a non-profit, nationwide network of research and treatment centres that facilitates, supports and promotes clinical trials in genomic cancer medicine, funded by the Office for Health and Medical Research, State of New South Wales and Australian Federal Government. Cancer Institute NSW (Translational Program Grant; 2020/TPG2100).DisclosureF.P. Lin: Financial Interests, Institutional, Trial Chair: Roche, Amgen. D.M. Thomas: Financial, Personal, Full or part-time employment: Australian Unity, Omico. Financial, Personal, Other, Honoraria: Roche. Financial, Personal, Research funding: Amgen, AstraZeneca, Bayer. Elevation Oncology, InterVenn Biosciences. Financial, Institutional, Research funding: George Clinical. Financial, Institutional, Research funding: Lilly, Microba. Seagen, Sun Pharma. Financial, Personal, Research funding: Pfizer, Roche. Financial, Personal, Other, Travel, Accommodations, Expenses: Amgen. K.M. Sjoquist: Financial, Personal, Other, Honoraria: BMS, Merck, MSD, Servier, Astellas Pharma. Financial, Institutional, Other, Honoraria: Novotech, Lisata, Bayer. Financial, Institutional, Research funding: Bayer. L.A. Chantrill: Financial, Personal, Advisory Role: Amgen Australia, Servier. Financial, Personal, Invited speaker: Pierre Fabre. D. Goldstein: Non-financial, Institutional, Coordinating PI: Bayer, Amplificare. Financial, Personal, Advisory Board: Takeda, Merck. Non-financial, Institutional, Funding, Biliary grant: AstraZeneca. Financial, Institutional, Coordinating PI: Pfizer. Financial, Personal, Advisory Board, Expert trial advisory group: Boehringer Ingelheim. Financial, Personal, Advisory Role, DSMB member: Panbela. Non-financial, Personal, Advisory Role: Duo. All other authors have declared no conflicts of interest.