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ObjectiveIn the Phase 3 VELIA trial (NCT02470585), veliparib added to carboplatin plus paclitaxel concomitantly and as maintenance for women with newly-diagnosed advanced ovarian cancer significantly improved progression-free survival (PFS) versus chemotherapy alone. Here we present exploratory analyses by paclitaxel dosing schedule and germline BRCA (gBRCA) status.MethodsWomen with untreated ovarian carcinoma were randomized (1:1:1) to: veliparib during chemotherapy and maintenance (veliparib-throughout), veliparib during chemotherapy followed by placebo maintenance (veliparib-combination only), or placebo during chemotherapy and maintenance (control). Chemotherapy included carboplatin plus dose-dense (DD; weekly) or every-3-week (Q3W) paclitaxel (a stratification factor at randomization), selected at the investigator's discretion pre-randomization. PFS was assessed by paclitaxel dosing schedule using a Cox proportional hazard model adjusted by treatment arm and stratification factors; safety was analyzed based on paclitaxel dosing schedule and gBRCA status.Results1132 patients were analyzed by paclitaxel schedule. Pooled treatment arms demonstrated longer median PFS with DD (n = 586) versus Q3W (n = 546) paclitaxel (ITT: 20.5 vs 15.7 months, hazard ratio [HR] 0.77; homologous recombination proficient cancer: 15.1 vs 11.8 months, HR 0.64; BRCAwt: 18.0 vs 12.9 months, HR 0.70). Comparison between arms favored veliparib-throughout versus control in both DD (PFS, 24.2 vs 18.3 months, hazard ratio 0.67) and Q3W (19.3 vs 14.6, hazard ratio 0.69) subgroups. DD paclitaxel was associated with higher incidence of Grade 3/4 neutropenia, fatigue, and anemia versus Q3W. There were no differences in toxicity between gBRCAm (n = 211) and gBRCAwt (n = 902) subgroups.ConclusionsDD paclitaxel was tolerable and associated with longer PFS in the HR proficient and gBRCAwt groups, versus Q3W. gBRCA status did not impact safety.

Background: Patients with cancer often have to make complex decisions about treatment, with the options varying in risk profiles and effects on survival and quality of life. Moreover, inefficient care paths make it hard for patients to participate in shared decision-making. Data-driven decision-support tools have the potential to empower patients, support personalized care, improve health outcomes and promote health equity. However, decision-support tools currently seldom consider quality of life or individual preferences, and their use in clinical practice remains limited, partly because they are not well integrated in patients' care paths. Aim and objectives: The central aim of the 4D PICTURE project is to redesign patients' care paths and develop and integrate evidence-based decision-support tools to improve decision-making processes in cancer care delivery. This article presents an overview of this international, interdisciplinary project. Design, methods and analysis: In co-creation with patients and other stakeholders, we will develop data-driven decision-support tools for patients with breast cancer, prostate cancer and melanoma. We will support treatment decisions by using large, high-quality datasets with state-of-the-art prognostic algorithms. We will further develop a conversation tool, the Metaphor Menu, using text mining combined with citizen science techniques and linguistics, incorporating large datasets of patient experiences, values and preferences. We will further develop a promising methodology, MetroMapping, to redesign care paths. We will evaluate MetroMapping and these integrated decision-support tools, and ensure their sustainability using the Nonadoption, Abandonment, Scale-Up, Spread, and Sustainability (NASSS) framework. We will explore the generalizability of MetroMapping and the decision-support tools for other types of cancer and across other EU member states. Ethics: Through an embedded ethics approach, we will address social and ethical issues. Discussion: Improved care paths integrating comprehensive decision-support tools have the potential to empower patients, their significant others and healthcare providers in decision-making and improve outcomes. This project will strengthen health care at the system level by improving its resilience and efficiency. Plain language summary: Improving the cancer patient journey and respecting personal preferences: an overview of the 4D PICTURE project The 4D PICTURE project aims to help cancer patients, their families and healthcare providers better undertstand their options. It supports their treatment and care choices, at each stage of disease, by drawing on large amounts of evidence from different types of European data. The project involves experts from many different specialist areas who are based in nine European countries. The overall aim is to improve the cancer patient journey and ensure personal preferences are respected. [ABSTRACT FROM AUTHOR]

Background: When people who can use or benefit from research findings are engaged as partners on study teams, the quality and impact of findings are better. These people can include patients/consumers and clinicians who do not identify as researchers. They are referred to as "knowledge users". This partnered approach is called integrated knowledge translation (IKT). We know little about knowledge users' involvement in the conduct of systematic reviews. We aimed to evaluate team members' degree of meaningful engagement and their perceptions of having used an IKT approach when updating the Cochrane Review of Patient Decision Aids. Methods: We conducted a pre-post mixed methods study. We surveyed all team members at two time points. Before systematic review conduct, all participating team members indicated their preferred level of involvement within each of the 12 steps of the systematic review process from "Screen titles/abstracts" to "Provide feedback on draft article". After, they reported on their degree of satisfaction with their achieved level of engagement across each step and the degree of meaningful engagement using the Patient Engagement In Research Scale (PEIRS-22) across 7 domains scored from 100 (extremely meaningful engagement) to 0 (no meaningful engagement). We solicited their experiences with the IKT approach using open-ended questions. We analyzed quantitative data descriptively and qualitative data using content analysis. We triangulated data at the level of study design and interpretation. Results: Of 21 team members, 20 completed the baseline survey (95.2% response rate) and 17/20 (85.0% response rate) the follow-up survey. There were 11 (55%) researchers, 3 (15%) patients/consumers, 5 (25%) clinician-researchers, and 1 (5%) graduate student. At baseline, preferred level of involvement in the 12 systematic review steps varied from n = 3 (15%) (search grey literature sources) to n = 20 (100%) (provide feedback on the systematic review article). At follow-up, 16 (94.1%) participants were totally or very satisfied with the extent to which they were involved in these steps. All (17, 100%) agreed that the process was co-production. Total PEIRS-22 scores revealed most participants reported extremely (13, 76.4%) or very (2, 11.8%) meaningful degree of engagement. Triangulated data revealed that participants indicated benefit to having been engaged in an authentic research process that incorporated diverse perspectives, resulting in better and more relevant outputs. Reported challenges were about time, resources, and the logistics of collaborating with a large group. Conclusion: Following the use of an IKT approach during the conduct of a systematic review, team members reported high levels of meaningful engagement. These results contribute to our understanding of ways to co-produce systematic reviews. Plain English Summary: When people who can use or benefit from research findings are engaged as partners on study teams, the quality and impact of findings are better. These people can include patients/consumers and clinicians who do not identify as researchers. This partnered approach is called integrated knowledge translation (IKT). This approach is rarely used and there is little information about using it with systematic reviews. A systematic review is a type of study that provides the best available evidence on a given topic by combining data from all existing studies. The aim of this study was to find out how engaged our team members felt when partnering on our systematic review about patient decision aids. Twenty of 21 team members participated in the study, including 11 researchers, 3 patients/consumers, 5 clinician-researchers, and 1 graduate student. We asked our team members to complete a survey about their experience as part of our IKT research process at two time points: before starting the study and after the study was done. Most team members felt extremely or very engaged in the process. All team members felt like partners. They gave examples of how this was achieved. Advantages to using the IKT approach included knowledge sharing, inclusion of more diverse voices, a more authentic research process, better and more relevant results, and personal benefits (e.g. enjoyment from being involved). Disadvantages to using this approach was that it took more time and resources. Three team members said there were no disadvantages. It is possible for patients/consumers and clinicians to partner and feel engaged with research teams doing systematic reviews. Our findings may help researchers engage knowledge users as equal partners on study teams. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Neurofilament light chain is an objective biomarker that reflects axonal damage in sensory neurons and might predict risk of paclitaxel-induced peripheral neuropathy in patients with cancer. Paclitaxel-induced peripheral neuropathy (PIPN) is a barrier to effective cancer treatment and impacts quality of life among patients with cancer. We used a translational approach to assess the utility of neurofilament light chain (NFL) as a biomarker of PIPN in a human cell model and in patients with ovarian cancer. We measured NFL in medium from human induced pluripotent stem cell–derived sensory neurons (iPSC-SNs) exposed to paclitaxel. Serum NFL (sNFL) levels were quantified in 190 patients with ovarian cancer receiving paclitaxel/carboplatin chemotherapy at baseline and after each of the following 2 or 6 cycles. Adverse outcomes related to PIPN were retrospectively obtained, and Cox regression model was performed with different sNFL cut-offs after first cycle. The apparent elimination half-life of sNFL was estimated in patients who discontinued paclitaxel. Paclitaxel neurotoxicity in iPSC-SNs was accompanied by NFL release in a concentration-dependent manner (P < 0.001, analysis of variance). Serum NFL levels increased substantially in patients during paclitaxel/carboplatin chemotherapy with considerable interindividual variability. Patients with sNFL >150 pg/mL after first cycle had increased risk to discontinue paclitaxel early (unadjusted HR: 2.47 [95% CI 1.16-5.22], adjusted HR: 2.25 [95% CI: 0.88-5.79]). Similar trends were shown for risk of severe PIPN and paclitaxel dose reduction because of PIPN. The median elimination half-life of sNFL was 43 days (IQR 27-82 days). Neurofilament light chain constitutes an objective biomarker of neurotoxicity in iPSC-SNs and in ovarian cancer patients with high sNFL predicting PIPN-related adverse outcomes. If prospectively validated, NFL can be used to study PIPN and may guide clinical decision making and personalize treatment with paclitaxel. [ABSTRACT FROM AUTHOR]