Impact of timing and format of patient decision aids for breast cancer patients on their involvement in and preparedness for decision making - the IMPACTT randomised controlled trial protocol.

BACKGROUND: After curative surgery for early-stage breast cancer, patients face a decision on whether to undergo surgery alone or to receive one or more adjuvant treatments, which may lower the risk of recurrence. Variations in survival outcomes are often marginal but there are differences in the side effects and other features of the options that patients may value differently. Hence, the patient's values and preferences are critical in determining what option to choose. It is well-researched that the use of shared decision making and patient decision aids can support this choice in a discussion between patient and clinician. However, it is still to be investigated what impact the timing and format of the patient decision aid have on shared decision making outcomes. In this trial, we aim to investigate the impact of a digital pre-consult compared to a paper-based in-consult patient decision aid on patients' involvement in shared decision making, decisional conflict and preparedness to make a decision. METHODS: The study is a randomised controlled trial with 204 patients at two Danish oncology outpatient clinics. Eligible patients are newly diagnosed with early-stage breast cancer and offered adjuvant treatments after curative surgery to lower the risk of recurrence. Participants will be randomised to receive either an in-consult paper-based patient decision aid or a pre-consult digital patient decision aid. Data collection includes patient and clinician-reported outcomes as well as observer-reported shared decision making based on audio recordings of the consultation. The primary outcome is the extent to which patients are engaged in a shared decision making process reported by the patient. Secondary aims include the length of consultation, preparation for decision making, preferred role in shared decision making and decisional conflict. DISCUSSION: This study is the first known randomised, controlled trial comparing a digital, pre-consult patient decision aid to an identical paper-based, in-consult patient decision aid. It will contribute evidence on the impact of patient decision aids in terms of investigating if pre-consult digital patient decisions aids compared to in-consult paper-based decision aids support the cancer patients in being better prepared for decision making. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05573022).

Prognostic impact of early ctDNA dynamics during chemotherapy of metastatic cancer.

Aim: Clinical utility of the dynamics of ctDNA is sparse. This study aimed at evaluating the prognostic impact of early ctDNA dynamics in patients with metastatic cancer treated with chemotherapy. Materials & methods: The ctDNA dynamics were evaluated in 595 patients with metastatic cancer using droplet digital PCR. Results: Patients with an increase in ctDNA after one treatment cycle (n = 73; 12.2%) had an overall survival of 5.6 months compared with 8.6 months in patients with stable or decreasing ctDNA (n = 328; 55.1%) and 21.0 months in patients with undetectable ctDNA (p < 0.001; hazard ratio: 0.47; 95% CI: 0.41-0.53). Conclusion: Early ctDNA dynamics hold important prognostic information and have great implications for evaluation with the perspective of a more individualized treatment strategy.

Single-cell and bulk RNA sequencing reveal ligands and receptors associated with worse overall survival in serous ovarian cancer.

BACKGROUND: Serous ovarian carcinoma is the most frequent histological subgroup of ovarian cancer and the leading cause of death among gynecologic tumors. The tumor microenvironment and cancer-associated fibroblasts (CAFs) have a critical role in the origin and progression of cancer. We comprehensively characterized the crosstalk between CAFs and ovarian cancer cells from malignant fluids to identify specific ligands and receptors mediating intercellular communications and disrupted pathways related to prognosis and therapy response. METHODS: Malignant fluids of serous ovarian cancer, including tumor-derived organoids, CAFs-enriched (eCAFs), and malignant effusion cells (no cultured) paired with normal ovarian tissues, were explored by RNA-sequencing. These data were integrated with single-cell RNA-sequencing data of ascites from ovarian cancer patients. The most relevant ligand and receptor interactions were used to identify differentially expressed genes with prognostic values in ovarian cancer. RESULTS: CAF ligands and epithelial cancer cell receptors were enriched for PI3K-AKT, focal adhesion, and epithelial-mesenchymal transition signaling pathways. Collagens, MIF, MDK, APP, and laminin were detected as the most significant signaling, and the top ligand-receptor interactions THBS2/THBS3 (CAFs)-CD47 (cancer cells), MDK (CAFs)-NCL/SDC2/SDC4 (cancer cells) as potential therapeutic targets. Interestingly, 34 genes encoding receptors and ligands of the PI3K pathway were associated with the outcome, response to treatment, and overall survival in ovarian cancer. Up-regulated genes from this list consistently predicted a worse overall survival (hazard ratio > 1.0 and log-rank P < 0.05) in two independent validation cohorts. CONCLUSIONS: This study describes critical signaling pathways, ligands, and receptors involved in the communication between CAFs and cancer cells that have prognostic and therapeutic significance in ovarian cancer. Video abstract.

Impact of veliparib, paclitaxel dosing regimen, and germline BRCA status on the primary treatment of serous ovarian cancer - an ancillary data analysis of the VELIA trial.

OBJECTIVE: In 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. METHODS: Women 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. RESULTS: 1132 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. CONCLUSIONS: DD paclitaxel was tolerable and associated with longer PFS in the HR proficient and gBRCAwt groups, versus Q3W. gBRCA status did not impact safety.

Impact of homologous recombination status and responses with veliparib combined with first-line chemotherapy in ovarian cancer in the Phase 3 VELIA/GOG-3005 study.

OBJECTIVE: In the Phase 3 VELIA trial (NCT02470585), PARP inhibitor (PARPi) veliparib was combined with first-line chemotherapy and continued as maintenance for patients with ovarian carcinoma enrolled regardless of chemotherapy response or biomarker status. Here, we report exploratory analyses of the impact of homologous recombination deficient (HRD) or proficient (HRP) status on progression-free survival (PFS) and objective response rates during chemotherapy. METHODS: Women with Stage III-IV ovarian carcinoma were randomized to veliparib-throughout, veliparib-combination-only, or placebo. Stratification factors included timing of surgery and germline BRCA mutation status. HRD status was dichotomized at genomic instability score 33. During combination therapy, CA-125 levels were measured at baseline and each cycle; radiographic responses were assessed every 9 weeks. RESULTS: Of 1140 patients randomized, 742 had BRCA wild type (BRCAwt) tumors (HRP, n = 373; HRD/BRCAwt, n = 329). PFS hazard ratios between veliparib-throughout versus control were similar in both BRCAwt populations (HRD/BRCAwt: 22.9 vs 19.8 months; hazard ratio 0.76; 95% confidence interval [CI] 0.53-1.09; HRP: 15.0 vs 11.5 months; hazard ratio 0.765; 95% CI 0.56-1.04). By Cycle 3, the proportion with ≥90% CA-125 reduction from baseline was higher in those receiving veliparib (pooled arms) versus control (34% vs 23%; P = 0.0004); particularly in BRCAwt and HRP subgroups. Complete response rates among patients with measurable disease after surgery were 24% with veliparib (pooled arms) and 18% with control. CONCLUSIONS: These results potentially broaden opportunities for PARPi utilization among patients who would not qualify for frontline PARPi maintenance based on other trials.

When life gives you no choice: Context of decision-making when offered an oncology clinical trial.

BACKGROUND: Patients with advanced cancer are faced with a wide variety of challenges and difficult treatment decisions made while in a vulnerable life-threatening situation, including decisions about clinical trial participation. Internationally, there is a great focus on shared decision-making as a way to help patients and healthcare professionals to make informed decisions together; nevertheless, research focusing on patient experiences shows that information about clinical trials is insufficient in supporting patients to make trial decisions in the context of their course of disease and managing life with advanced cancer. AIM: To explore where and how decisions about participation in oncology clinical trials are made and the role of the patients and healthcare professionals. METHODS: Participant observation was used as a qualitative research method to gain knowledge about decision-making in different clinical situations. Data were analysed using thematic analysis. RESULTS: Four themes were developed: (a) preformed decisions, (b) dissimilar perceptions of successful treatment, (c) cues and concerns stated by patients and (d) creating common ground. CONCLUSION: There are underexposed aspects to be aware of in the decision-making process for clinical trial participation. Preformed decisions made by the physicians before the encounter with patients seemed to narrow down the patients' options and could have benefited from including the patients' views. Cues and concerns stated by patients were often neglected. However, when physicians talked with the patients about truly difficult issues such as treatment expectations, hope and death, it led to another kind of conversation about treatment decisions involving the patients' preferences. IMPLICATIONS FOR PRACTICE: Awareness of preformed decisions and an increased focus on picking up cues and concerns about existential issues in the clinical encounter may improve the quality of the decisions and increase shared decision-making.

Treosulfan in platinum-resistant ovarian cancer.

OBJECTIVES: Treosulfan is offered as last-line treatment in patients with end-stage ovarian cancer. This retrospective study aimed to evaluate the response rates, overall survival, and adverse events of treosulfan in this patient population. METHODS: The study included patients with end-stage platinum-resistant ovarian cancer treated with treosulfan from October 2015 to October 2020 at the Department of Oncology, Lillebaelt Hospital, University Hospital of Southern Denmark, Vejle, Denmark. Patients were included for treatment if their cancer had progressed and if other treatment options were limited. Patients receiving treosulfan as first-line treatment were excluded from the study. Response rates were evaluated according to the combined criteria of CA125 and Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Kaplan-Meier survival analyses were used to illustrate progression-free and overall survival. Adverse events were graded 1-5 according to the Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Sixty-seven patients with a median age of 72 years (range 33-92) were identified. Sixty-three (94%) patients were diagnosed with serous adenocarcinoma. Fifty-seven (85%) patients were Federation of International Gynecology and Obstetrics (FIGO) stage III or IV at the time of diagnosis. The median number of treatments prior to treosulfan treatment was 3 (range 1-8). One patient had a complete response (2%), eight patients had a partial response (13%), and 22 patients (35%) had stable disease as the best response. The median duration of response (complete or partial) was 239 days (range 43-572). Median progression-free survival was 63 days (95% CI 41 to 77). The most common adverse events were anemia (83%), fatigue (83%), anorexia (62%), nausea (57%), and constipation (41%). CONCLUSIONS: Treosulfan is an alternative for the treatment of relapsed ovarian cancer when other treatment options are limited, with response rates of approximately 15%. In general, the treatment was well tolerated. Taking the mild adverse events and the response rates into account, palliative treosulfan mainly seems beneficial for patients with performance status 0-1.

Association of patient-reported outcomes and ovarian cancer recurrence.

BACKGROUND: The vast majority of patients with advanced ovarian cancer experience disease recurrence after primary treatment. OBJECTIVE: To explore the diagnostic accuracy of repeated measurement of patient-reported outcomes and quality-of-life scores in relation to ovarian cancer recurrence. METHODS: Patients with ovarian cancer were recruited to the PROMova study by the end of their primary treatment at eight centers in Denmark. The purpose of the PROMova study was to explore the applicability of repeated use of patient-reported outcomes, which consisted of the European Organization for Research and Treatment of Cancer generic questionnaire and the ovarian specific questionnaire. The patient-reported outcomes were completed 3, 6, 9, 12, and 15 months after enrollment or until recurrence. The 3-month interval between completions was the period in which recurrence was assessed. Imaging and the biomarker CA125 were used as reference modality for recurrence. Mixed effects logistic regression was used to investigate the association between mean patient-reported outcome scores and recurrence. Receiver operating curves were used to establish cut-off scores. The diagnostic accuracy of patient-reported outcomes, including sensitivity, specificity, and positive and negative predictive values was estimated based on the Youden index. For combined scales, diagnostic accuracy was investigated based on multivariate analysis. RESULTS: The analysis included 196 patients with an overall recurrence rate of 50.5% and an overall mean time to recurrence of 302 days. With imaging as reference, patients with recurrence reported significantly lower global health, worse physical functioning, and more abdominal symptoms preceding recurrence. With CA125 as reference, global health, physical and emotional functioning were impaired. Despite the worsening of a number of symptoms prior to recurrence whichever reference modality was applied, the patient-reported outcome scores did not provide adequate diagnostic accuracy. CONCLUSION: Repeated use of patient-reported outcomes during surveillance of ovarian cancer was not of diagnostic value. Future efforts should be directed at improving the administration of patient-reported outcomes as well as exploring the potential of using these outcomes as an indicator of clinical relevance.

Use of PROM during follow-up of patients with ovarian cancer: the PROMova study protocol.

BACKGROUND: There is a paucity of high-level evidence on the optimal follow-up of patients with ovarian cancer after primary treatment. A debate is ongoing on the extent to which follow-up should consider patient preferences and patient-reported outcome measures. Incorporation of patient-reported outcome measures supports the dialog between patient and clinician and may be instrumental in symptom monitoring and detection of underlying issues, especially when used actively during the clinical consultation. PRIMARY OBJECTIVE AND ENDPOINT: The PROMova study aims to assess whether proactive use of patient-reported outcome measures during follow-up care increases patient involvement as perceived by the patient compared with standard care. Another objective is to measure satisfaction with the care provided. STUDY HYPOTHESIS: It is hypothesized that proactive use of patient-reported outcome measures during the clinical encounter will improve patients' experience of involvement in follow-up care. TRIAL DESIGN: PROMova is a multi-center, observational cohort study collecting data from eight departments in Denmark. Five departments use the patient-reported outcome measures proactively during the consultation and three provide standard care. Participants are followed up with patient-reported outcome measures for up to 3 years. The patient-reported outcome measures package comprises EORTC QLQ-C30, EORTC QLQ-OV28, a questionnaire screening tool for recurrence, CollaboRATE, and selected questions from the Patient Experience Questionnaire. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients older than 18 years diagnosed with ovarian, fallopian tube, or primary peritoneal cancer are eligible when entering the follow-up program after primary treatment. Participants must be able to speak and read Danish. SAMPLE SIZE: 223 patients with ovarian cancer. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The protocol closed for enrollment in 2019. Publication of final results is expected in spring 2022. TRIAL REGISTRATION: PROMova was registered with ClinicalTrials.gov November 2016 Identifier: NCT02916875.

Delta tocotrienol in recurrent ovarian cancer. A phase II trial.

Delta tocotrienol has anti-neoplastic activity as demonstrated in several in-vitro and in-vivo investigations. The effect relies on inhibition of different pathways. It also has antiangiogenic activity, and an additive effect to bevacizumab may be expected. The present study was a phase II trial of bevacizumab combined with tocotrienol in chemotherapy refractory ovarian cancer. The study also included analysis of circulating tumor specific HOXA9 methylated DNA (HOXA9 meth-ctDNA) during treatment. The study included 23 patients. The rate of disease stabilization was 70% with very low toxicity. The median PFS was 6.9 months and the median OS 10.9 months, which is rather high compared to the current literature. A division of the patients according to level of HOXA9 meth-ctDNA already after the first cycle of chemotherapy resulted in two groups of patients with different prognoses. Patients with an increasing level of HOXA9 meth-ctDNA had a median PFS and OS of 1.4 and 4.3 months, respectively, compared to 7.8 and 12 months in the group with stable or decreasing levels. The combination of bevacizumab and tocotrienol is potent in chemotherapy refractory ovarian cancer. The level of HOXA9 meth-ctDNA after one cycle of chemotherapy holds important prognostic information.

Shared decision making when patients consider surgery for lumbar herniated disc: development and test of a patient decision aid.

BACKGROUND: Shared decision making (SDM) is a systematic approach aimed at improving patient involvement in preference-sensitive health care decisions. Choosing between surgical or non-surgical treatment for lumbar disc herniation, can be difficult as the evidence of a superior treatment is unclear, which makes it a preference-sensitive decision. The objectives of this study was therefore to assess the degree of SDM and afterwards to develop and test a patient decision aid (PtDA) to support SDM during the clinical encounter between surgeon and patient, when patients choose between surgical and non-surgical treatment for Lumbar disc herniation (LDH). METHODS: The study was conducted in four steps. 1) Assessment of the extent to which SDM was practiced in the spine clinic. 2) Development of a PtDA to support SDM. 3) Testing its usability and acceptability amongst potential users (patients). 4) Pilot-test of its usability in the clinical setting. RESULTS: Results from our small baseline study (n = 40) showed that between a third and two-thirds of the patients reported not being fully engaged in a shared decision. A pre-designed template (BESLUTNINGSHJÆLPER™) was adapted to support the decision about whether or not to have surgery for LDH. Testing the prototype with patients led to minor refinements. A subsequent pilot test of its usability in a clinical setting achieved positive responses from both patients and clinicians. CONCLUSION: Our baseline study demonstrated that SDM was not universally practiced in the clinic. The PtDA we have developed was rated as acceptable and usable by both patients and clinicians for helping those with LDH choose between surgical or non- surgical treatment. This tool now requires further testing to assess its effectiveness.

What matters in clinical trial decision-making: a systematic review of interviews exploring cancer patients' experiences.

BACKGROUND: Being diagnosed with cancer is an existential challenge and involves difficult treatment decisions, including treatment in clinical trials. Therapy for advanced cancer is potentially life-prolonging and only rarely cures advanced cancer, which often renders these patients in a special situation where dealing with end of life, hope and meaning, become an important part of life. Many existing reviews include both patients with advanced cancer and patients undergoing adjuvant cancer treatment, and there is a lack of reviews with consistent study designs and methods. AIM: To systematically review and thematically synthesise the experiences of patients and relatives when they have to decide whether or not to participate in a clinical oncology trial and to provide knowledge about the decision-making process. METHOD: A qualitative systematic literature review was conducted based on methods for thematic synthesis by Thomas and Hardens. RESULTS: Eleven full-text articles were included in this study. Six descriptive themes appeared and were grouped under two analytical themes: Individualised decisions and Hope and existential matters, which, through discussion, developed into the synthesis of What matters in treatment-related decisions close to the end of life? This review has shown that existential matters are important in the decision-making and that addressing these might be of great importance in medical decision-making, whether it concerns the existential matters of the patients, of their relatives or of the health care professionals. CONCLUSION: This review points to existential issues as important contributors in making decisions about treatment. It can be beneficial if health care professionals address the role of existential matters in patients' decision-making in terms of clinical trial participation and involve the relatives more directly to increase individualised decisions. Future research should include the health care professionals' experiences when going in depth with decision-making, with a focus on the existential matters and uncertainties of the health care professionals.

Veliparib Monotherapy to Patients With BRCA Germ Line Mutation and Platinum-Resistant or Partially Platinum-Sensitive Relapse of Epithelial Ovarian Cancer: A Phase I/II Study.

OBJECTIVE: A new treatment principle, which seems to radically change the treatment approach in ovarian cancer (OC), has developed over the past few years. Poly(ADP-ribose) polymerase inhibitors work by interfering with mechanisms important to DNA damage repair. Cancer cells that already have defects in the BRCA genes are particularly sensitive to treatment with poly(ADP-ribose) polymerase inhibitors. The main purpose of this study was to investigate the effect of veliparib in patients with known BRCA1/2 mutations and with a platinum-resistant or intermediate sensitive relapse of OC. METHODS: Major eligibility criteria were primary epithelial ovarian/fallopian/peritoneal cancer patients with a platinum-resistant or intermediate sensitive relapse of OC and with evaluable disease by either Response Evaluation Criteria In Solid Tumors or Gynecological Cancer Intergroup CA-125 criteria. Patients were treated with oral veliparib twice daily on days 1 to 28. RESULTS: Sixteen patients were enrolled in the phase I part, and a maximum tolerable dose of 300 mg twice daily was established. The phase II part enrolled 32 patients with a median of 4 previous treatment regimens. The overall response rate combining Response Evaluation Criteria In Solid Tumors and CA-125 response was 65% (6% complete response and 59% partial response). Progression-free and overall survival rates of the intention-to-treat population were 5.6 months (95% confidence interval, 5.2-7.3 months) and 13.7 months (95% confidence interval, 10.2-17.3 months), respectively. The most common phase II treatment-related grade 2 toxicities included fatigue (22%), nausea (22%), and vomiting (9%). CONCLUSIONS: Treatment with veliparib in heavily pretreated patients with relapse of OC demonstrates a considerable efficacy with an acceptable toxicity profile.

Through Clinicians Eyes: Use of an In-consultation Patient Decision Aid in Radiation Treatment for Early Breast Cancer. A Qualitative Study.

INTRODUCTION: Shared decision making (SDM) has become a crucial element on the political agenda and represents a vital aspect of modern healthcare. However, successful implementation of SDM highly depends on the attitude of clinicians towards SDM. The overall aim of our study was to explore the experience of oncologists and nurses with SDM using the Decision Helper, an in-consultation decision aid, at four Danish radiotherapy departments. METHODS: Semi-structured interviews were conducted with 20 clinicians. The participants were selected using purposive sampling to include nurses and oncologists, male and female, with different levels of experience with SDM and clinical work. The analysis was a data-driven, iterative process with inductive coding of all interviews and meaning condensation. RESULTS: Two main themes emerged: "Using the Decision Helper changes the consultation" and "Change of attitude among Danish oncologists." Each of the two themes included four elaborative subthemes, which are reported with supporting citations in this paper. In brief, the use of SDM and the Decision Helper should ideally be adjusted to the individual patient and depends highly on the oncologist. The participants described ambitions towards "making the right decision for this patient at this time." The healthcare system, however, has pitfalls that may hinder SDM, e.g., rigid interpretation of guideline-based recommendations. CONCLUSION: Using an in-consultation Decision Helper has the potential for individualized, structured patient engagement in decision making. There is a need for patient decision aids in clinical guidelines to ensure patient engagement in decision making.

Early integration of basic palliative care in cancer: scoping review of cross-sectorial models - components, facilitators, barriers.

BACKGROUND: Shared care between oncology specialists and general practice regarding the delivery of palliative care (PC) is necessary to meet the demands for a cohesive PC. The primary objective of this study is to investigate models of cross-sectorial integration between primary care and oncology specialists that have been developed to promote early and basic PC and factors influencing the process. METHOD: A scoping review was conducted using publications dated up until April 2023. Searches were conducted in MEDLINE, CINAHL, Embase, Web of Science and ProQuest Dissertations and Theses. Complementary searches were performed via reference lists and grey literature. Explicit early PC models aimed at patients with cancer aged ≥18 years with healthcare professionals from primary care and oncology constituted the inclusion criteria. The screening of the papers was performed independently by two reviewers. The reporting adheres to the extension for scoping reviews of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: The search provided 5630 articles of which six met the eligibility criteria, each describing a different model of early and cross-sectorial, integrated PC. 12 active components were identified. Education of staff as well as good communication and cooperation skills are essential factors to succeed with integrated, early PC. CONCLUSION: Integration of PC between general practice and oncology specialists has potential. The components of basic PC have been established. Factors known to influence the process are trust, communication and a common goal. Further research is required into strategies for approaching different levels of integration.

Shared decision making with breast cancer patients - does it work? Results of the cluster-randomized, multicenter DBCG RT SDM trial.

BACKGROUND AND PURPOSE: Shared decision making (SDM) is a patient engaging process advocated especially for preference-sensitive decisions, such as adjuvant treatment after breast cancer. An increasing call for patient engagement in decision making highlights the need for a systematic SDM approach. The objective of this trial was to investigate whether the Decision Helper (DH), an in-consultation patient decision aid, increases patient engagement in decisions regarding adjuvant whole breast irradiation. MATERIAL AND METHODS: Oncologists at four radiotherapy units were randomized to practice SDM using the DH versus usual practice. Patient candidates for adjuvant whole breast irradiation after breast conserving surgery for node-negative breast cancer were eligible. The primary endpoint was patient-reported engagement in the decision process assessed with the Shared Decision Making Questionnaire (SDM-Q-9) (range 0-100, 4 points difference considered clinical relevant). Other endpoints included oncologist-reported patient engagement, decisional conflict, fear of cancer recurrence, and decision regret after 6 months. RESULTS: Of the 674 included patients, 635 (94.2%) completed the SDM-Q-9. Patients in the intervention group reported higher level of engagement (median 80; IQR 68.9 to 94.4) than the control group (71.1; IQR 55.6 to 82.2; p < 0.0001). Oncologist-reported patient engagement was higher in the invention group (93.3; IQR 82.2 to 100) compared to control group (73.3; IQR 60.0 to 84.4) (p < 0.0001). CONCLUSION: Patient engagement in medical decision making was significantly improved with the use of an in-consultation patient decision aid compared to standard. The DH on adjuvant whole breast irradiation is now recommended as standard of care in the Danish guideline.

The strong prognostic value of KELIM, a model-based parameter from CA 125 kinetics in ovarian cancer: data from CALYPSO trial (a GINECO-GCIG study).

BACKGROUND: Unexpected results were recently reported about the poor surrogacy of Gynecologic Cancer Intergroup (GCIG) defined CA-125 response in recurrent ovarian cancer (ROC) patients. Mathematical modeling may help describe CA-125 decline dynamically and discriminate prognostic kinetic parameters. METHODS: Data from CALYPSO phase III trial comparing 2 carboplatin-based regimens in ROC patients were analyzed. Based on population kinetic approach, serum [CA-125] concentration-time profiles during first 50 treatment days were fit to a semi-mechanistic model with following parameters: "d[CA-125]/dt=(KPROD∗exp (BETA∗t))∗Effect-KELIM∗[CA-125]" with time, t; tumor growth rate, BETA; CA-125 tumor production rate, KPROD; CA-125 elimination rate, KELIM and K-dependent treatment indirect Effect. The predictive values of kinetic parameters were tested regarding progression-free survival (PFS) against other reported prognostic factors. RESULTS: Individual CA-125 kinetic profiles from 895 patients were modeled. Three kinetic parameters categorized by medians had predictive values using univariate analyses: K; KPROD and KELIM (all P<0.001). Using Cox multivariate analysis, 5 independent predictors of PFS remained significant: GCIG CA-125 response (favoring carboplatin-paclitaxel arm), treatment arm, platinum free-interval, measurable lesions and KELIM (HR=0.53; 95% CI 0.45-0.61; P<0.001). CONCLUSIONS: Mathematical modeling of CA-125 kinetics in ROC patients enables understanding of the time-change components during chemotherapy. The contradictory surrogacy of GCIG-defined CA-125 response was confirmed. The modeled CA-125 elimination rate KELIM, potentially assessable in routine, may have promising predictive value regarding PFS. Further validation of this predictive marker is warranted.

Panitumumab and pegylated liposomal doxorubicin in platinum-resistant epithelial ovarian cancer with KRAS wild-type: the PaLiDo study, a phase II nonrandomized multicenter study.

OBJECTIVE: The increasing number of negative trials for ovarian cancer treatment has prompted an evaluation of new biologic agents, which in combination with chemotherapy may improve survival. The aim of this study was to investigate the response rate in platinum-resistant, KRAS wild-type ovarian cancer patients treated with pegylated liposomal doxorubicin (PLD) supplemented with panitumumab. PATIENTS AND METHODS: Major eligibility criteria were relapsed ovarian/fallopian/peritoneal cancer patients with platinum-resistant disease, measurable disease by GCIG CA125 criteria and KRAS wild-type. Patients were treated with panitumumab 6 mg/kg day 1 and day 15 and with PLD 40 mg/m2 day 1, every 4 weeks. RESULTS: Forty-six patients were enrolled by 6 study sites in this multi-institutional phase II trial. The response rate in the intention-to-treat population (n = 43) was 18.6%. Progression-free and overall survival in the intention-to-treat population was 2.7 months (2.5-3.2 months, 95% confidence interval) and 8.1 months (5.6-11.7 months, 95% confidence interval), respectively. The most common treatment-related grade 3 toxicities included skin toxicity (42%), fatigue (19%), and vomiting (12%). CONCLUSIONS: The combination of PLD and panitumumab demonstrates efficacy in platinum refractory/resistant patients but the skin toxicity was considerable.

Impact of an in-consult patient decision aid on treatment choices and outcomes of management for patients with an endoscopically resected malignant colorectal polyp: a study protocol for a non-randomised clinical phase II study.

INTRODUCTION: Management of an endoscopically resected malignant colorectal polyps can be challenging due to the risk of residual tumour and lymphatic spread. International studies have shown, that of those choosing surgical management instead of surveillance strategy, there are between 54% and 82% of bowel resections without evidence of residual tumour or lymphatic spread. As surgical management entails risks of complications and surveillance strategy entails risks of residual tumour or recurrence, a clinical dilemma arises when choosing a management strategy. Shared decision-making is a concept that can be used in preference-sensitive decision-making to facilitate patient involvement and empowerment to facilitate active patient participation in the decision-making process. METHODS AND ANALYSIS: This study protocol describes our clinical multi-institutional, non-randomised, interventional phase II study at Danish surgical departments planned to commence in the second quarter of 2024. The aim of this study is to examine whether shared decision-making and using a patient decision aid in consultations affect patients' choice of management, comparing with retrospective data. The secondary aim is to investigate patients' experiences, perceived involvement, satisfaction, decision conflict and other outcomes using questionnaire feedback directly from the patients. ETHICS AND DISSEMINATION: There are no conflicts of interest for principal or local investigators in any of the study sites. All results will be published at Danish and international meetings, and in English language scientific peer-reviewed journals. Our study underwent evaluation by the Regional Committees on Health Research Ethics for Southern Denmark (file number 20232000-47), concluding that formal approval was not required for this kind of research. TRIAL REGISTRATION NUMBER: NCT05776381.

"SDM:HOSP"- a generic model for hospital-based implementation of shared decision making.

BACKGROUND: Shared decision making (SDM) is a core element in the meeting between patient and healthcare professionals, but has proved difficult to implement and sustain in routine clinical practice. One of five Danish regions set out to succeed and to develop a model that ensures lasting SDM based on learnings from large-scale real-world implementation initiatives that go beyond the 'barriers' and 'facilitators' research approach. This paper describes this process and development of a generic implementation model, SDM:HOSP. METHODS: This project was carried out in the Region of Southern Denmark with five major hospital units. Based on existing theory of SDM, SDM implementation, implementation science and improvement methodology, a process of four phases were described; development of conceptual elements, field-testing, evaluation, and development of the final implementation model. The conceptual elements developed aimed to prepare leaders, train SDM teachers, teach clinicians to perform SDM, support development of patient decision aids, and support systematic planning, execution and follow-up. Field testing was done including continuous participant evaluations and an overall evaluation after one year. RESULTS: Data from field testing and learnings from the implementation process, illustrated the need for a dynamic and easy adjustable model. The final SDM:HOSP model included four themes; i)Training of Leaders, ii) Training of Teachers and Clinicians, iii) Decision Helper, and iv) 'Process', each with details in three levels, 1) shared elements, 2) recommendations, and 3) local adaption. CONCLUSIONS: A feasible and acceptable model for implementation of SDM across hospitals and departments that accounts for different organizations and cultures was developed. The overall design can easily be adapted to other organizations and can be adjusted to fit the specific organization and culture. The results from the ongoing and overall evaluation suggest promising avenues for future work in further testing and research of the usability of the model.