Karina Dahl Steffensen

Blood natural killer cells during treatment in recurrent ovarian cancer

Recent research indicated favorable prognostic impact of intratumoral natural killer (NK) cells in ovarian carcinoma (OC). The role of NK cells during chemotherapy in OC is unknown. We investigated impact of NK cells in OC patients treated with palliative chemotherapy. Participants receiving palliative chemotherapy for recurrent OC ( Median OS in patients with low vs. high NK cell count at baseline was 7.1 months vs. 15.6 months ( A low blood NK cell count in recurrent metastatic ovarian cancer during chemotherapy is associated with unfavorable prognostic impact. Early increase in survival difference based on NK cell status suggests an association between NK cell count and treatment benefit.

Neurofilament light chain as a biomarker of axonal damage in sensory neurons and paclitaxel-induced peripheral neuropathy in patients with ovarian cancer

Abstract 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.

Favorable prognostic impact of Natural Killer cells and T cells in high-grade serous ovarian carcinoma

The PROMova study comparing active and passive use of patient-reported outcome measures in ovarian cancer follow-up: effect on patient-perceived involvement, satisfaction with care, and usefulness

Patients with ovarian cancer often experience substantial health problems and side effects resulting in reduced quality of life (QoL). Different models of using patient-reported outcome measures (PROMs) during follow-up may improve the quality of care. This national, multicenter observational study investigated the effect of active use of PROMs on patient-perceived involvement, satisfaction with care, unmet needs, and QoL during follow-up of ovarian cancer. Ovarian cancer patients were recruited at the end of primary treatment at eight centers in Denmark. During 18 months of follow-up patients repeatedly completed European Organization for Research and Treatment of Cancer (EORTC) questionnaires covering health related QoL and symptoms. At the sites using PROMs actively (ACT), the clinician had access to an overview of the patient's scores during the clinical encounter. Clinicians using PROMs passively were alerted in case of severe development of symptoms. Following each encounter, patients evaluated their health service experience by completing the CollaboRATE scale of involvement in decision making, the Patient Experience Questionnaire, and ad hoc questions covering patient-perceived usefulness of the PROMs. A total of 223 patients were enrolled, i.e., 168 (75.3%) at five sites using ACT and 53 (23.8%) at three sites using them passively. We found no statistically significant difference in involvement in the decision making, satisfaction with care, unmet needs, and QoL between the two groups. The majority of patients found it useful to complete the PROMs, although it did not seem to significantly support them in raising issues with the oncologist. Active use of PROMs did not improve patients' experience of involvement in follow-up care as compared to passive use.

CA-125 KELIM as a Potential Complementary Tool for Predicting Veliparib Benefit: An Exploratory Analysis From the VELIA/GOG-3005 Study

PURPOSE In VELIA trial, veliparib combined with carboplatin-paclitaxel, followed by maintenance (veliparib-throughout) was associated with improved progression-free survival (PFS) compared with carboplatin-paclitaxel alone in patients with high-grade ovarian carcinomas. We explored the prognostic value of the modeled cancer antigen (CA)-125 elimination rate constant K (KELIM), which is known to be an indicator of the intrinsic tumor chemosensitivity (the faster the rate of CA-125 decline, the higher the KELIM and the higher the chemosensitivity), and its association with benefit from veliparib. PATIENTS AND METHODS Individual KELIM values were estimated from longitudinal CA-125 kinetics. Patients were categorized as having favorable (≥ median) or unfavorable (< median) KELIM. The prognostic value of KELIM for veliparib-related PFS benefit was explored in cohorts treated with primary or interval debulking surgery, according to the surgery completeness, the disease progression risk group, and the homologous recombination (HR) status ( BRCA mutation, HR deficiency [HRD], or HR proficiency [HRP]). RESULTS The data from 854 of 1,140 enrolled patients were analyzed (primary debulking surgery, n = 700; interval debulking surgery, n = 154). Increasing KELIM values were associated with higher benefit from veliparib in HRD cancer, as were decreasing KELIM values in HRP cancer. The highest PFS benefit from veliparib was observed in patients with both favorable KELIM and BRCA mutation (hazard ratio, 0.28; 95% CI, 0.13 to 0.61) or BRCA wild-type HRD cancer (hazard ratio, 0.43; 95% CI, 0.26 to 0.70), consistent with the association between poly (adenosine diphosphate-ribose) polymerase inhibitor efficacy and platinum sensitivity. In contrast, seventy-four percent of patients with a BRCA mutation and unfavorable KELIM progressed within 18 months while on veliparib. The patients with HRP cancer and unfavorable KELIM might have benefited from the veliparib chemosensitizing effect. CONCLUSION In addition to HRD/ BRCA status, the tumor primary chemosensitivity observed during the first-line chemotherapy might be another complementary determinant of poly (adenosine diphosphate-ribose) polymerase inhibitor efficacy.

Veliparib concomitant with first-line chemotherapy and as maintenance therapy in ovarian cancer: Final overall survival and disease-related symptoms results

In the VELIA trial, the addition of veliparib to standard first-line platinum-based chemotherapy and continued as maintenance resulted in significantly longer median progression-free survival (PFS) compared with carboplatin plus paclitaxel induction therapy alone (23.5 vs 17.3 months; p < 0.001) in patients with ovarian cancer. We now report final overall survival (OS) and updated safety and disease-related symptoms (DRS) from patient-reported outcomes of the trial. This randomized, placebo-controlled, double-blind, multicenter, phase 3 study enrolled adult women with an initial diagnosis of stage III/IV high-grade serous ovarian cancer undergoing primary or interval cytoreductive surgery. Patients were randomized 1:1:1 to chemotherapy plus veliparib followed by veliparib maintenance (veliparib-throughout), chemotherapy plus veliparib followed by placebo maintenance (veliparib-combination-only), or chemotherapy plus placebo followed by placebo maintenance (placebo-throughout). PFS was the primary endpoint; OS and DRS were secondary endpoints. In the intention-to-treat population (N = 1140), median OS was 59.2 months (95 % confidence interval: 52.1, 68.2) for the veliparib-throughout group, 58.0 (50.6, 64.1) months for veliparib-combination-only, and 57.8 (52.3, 63.8) months for placebo-throughout. OS outcomes were not significantly different between arms overall or in the BRCA-deficient and homologous recombination-deficient cohorts. No new safety signals were identified during the longer follow-up period and DRS analyses indicated there was no significant additional symptom-related burden overall when veliparib was added to chemotherapy or used for maintenance. No OS or DRS benefit of addition of veliparib to platinum-based chemotherapy and continued as maintenance therapy was detected in this study, despite an observed benefit over chemotherapy alone in PFS.