| 1. |
- King, Madeleine T., et al.
(författare)
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Measuring what matters MOST: validation of the Measure of Ovarian Symptoms and Treatment, a patient-reported outcome measure of symptom burden and impact of chemotherapy in recurrent ovarian cancer
- 2018
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Ingår i: Quality of Life Research. - : SPRINGER. - 0962-9343 .- 1573-2649. ; 27:1, s. 59-74
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Tidskriftsartikel (refereegranskat)abstract
- Gynecologic Cancer Intergroup Symptom Benefit Study (GCIG-SBS) Stage 2 aimed to review, revise, and validate a patient-reported outcome measure (PROM), the Measure of Ovarian Symptoms and Treatment concerns (MOST), developed in GCIG-SBS Stage 1 (MOSTv1, 35 items), and document recurrent ovarian cancer (ROC) symptom burden and benefit. GCIG-SBS Stage 2 recruited patients with platinum-resistant/refractory ROC (PRR-ROC) or potentially platinum-sensitive ROC with aeamp;lt;yenamp;gt; 3 lines of prior chemotherapy (PPS-ROC aeamp;lt;yenamp;gt; 3). Patients completed MOSTv1, QLQ-C30, QLQ-OV28, and FACT-O/FOSI at baseline and before cycle 3 of chemotherapy (pre-C3), and global assessments of change (MOST-Change) pre-C3. Clinicians rated patients cancer-related symptoms, performance status, and adverse events. Convergent and divergent validity (Spearmans correlations), discriminative validity (effect sizes between groups classified by clinician-rated characteristics), and responsiveness (paired t tests in patients expected to experience clinically meaningful change) were assessed. Of 948 recruits, 903 completed PROMs at baseline and 685 pre-C3. Baseline symptom burden was substantial for PRR-ROC and PPS-ROC aeamp;lt;yenamp;gt; 3. MOSTv2 has 24 items and five multi-item scales: abdominal symptoms (MOST-Abdo), disease or treatment-related symptoms (MOST-DorT), chemotherapy-related symptoms (MOST-Chemo), psychological symptoms (MOST-Psych), and MOST-Well-being. Correlations confirmed concurrent and divergent validity. Discriminative validity was confirmed by effect sizes that conformed with a priori hypotheses. MOST-Abdo was responsive to improvements in abdominal symptoms and MOST-Chemo detected the adverse effects of chemotherapy. The MOSTv2 validly quantifies patient-reported symptom burden, adverse effects, and symptom benefit in ROC, and as such is fit-for-purpose for clinical trials of palliative chemotherapy in ROC. Further research is required to assess test-retest reliability.
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| 2. |
- Pujade-Lauraine, Eric, et al.
(författare)
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Volasertib Versus Chemotherapy in Platinum-Resistant or -Refractory Ovarian Cancer : A Randomized Phase II Groupe des Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire Study
- 2016
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 34:7, s. 706-
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Volasertib is a potent and selective cell-cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinase. This phase II trial evaluated volasertib or single-agent chemotherapy in patients with platinum-resistant or -refractory ovarian cancer who experienced failure after treatment with two or three therapy lines. Patients and Methods Patients were randomly assigned to receive either volasertib 300 mg by intravenous infusion every 3 weeks or an investigator's choice of single-agent, nonplatinum, cytotoxic chemotherapy. The primary end point was 24-week disease control rate. Secondary end points included best overall response, progression-free survival (PFS), safety, quality of life, and exploratory biomarker analyses. Results Of the 109 patients receiving treatment, 54 received volasertib and 55 received chemotherapy; demographics were well balanced. The 24-week disease control rates for volasertib and chemotherapy were 30.6% (95% CI, 18.0% to 43.2%) and 43.1% (95% CI, 29.6% to 56.7%), respectively, with partial responses in seven (13.0%) and eight (14.5%) patients, respectively. Median PFS was 13.1 weeks and 20.6 weeks for volasertib and chemotherapy (hazard ratio, 1.01; 95% CI, 0.66 to 1.53). Six patients (11%) receiving volasertib achieved PFS fore more than 1 year, whereas no patient receiving chemotherapy achieved PFS greater than 1 year. No relationship between the expression of the biomarkers tested and their response was determined. Patients treated with volasertib experienced more grade 3 and 4 drug-related hematologic adverse events (AEs) and fewer nonhematologic AEs than did patients receiving chemotherapy. Discontinuation resulting from AEs occurred in seven (13.0%) and 15 (27.3%) patients in the volasertib and chemotherapy arms, respectively. Both arms showed similar effects on quality of life. Conclusion Single-agent volasertib showed antitumor activity in patients with ovarian cancer. AEs in patients receiving volasertib were mainly hematologic and manageable.
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| 3. |
- Roncolato, Felicia T., et al.
(författare)
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Reducing Uncertainty: Predictors of Stopping Chemotherapy Early and Shortened Survival Time in Platinum Resistant/Refractory Ovarian Cancer-The GCIG Symptom Benefit Study
- 2017
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Ingår i: The Oncologist. - : WILEY. - 1083-7159 .- 1549-490X. ; 22:9, s. 1117-1124
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Tidskriftsartikel (refereegranskat)abstract
- Background. Clinicians and patients often overestimate the benefits of chemotherapy, and overall survival (OS), in platinum resistant/refractory ovarian cancer (PRROC). This study sought to determine aspects of health-related quality of life and clinicopathological characteristics before starting chemotherapy that were associated with stopping chemotherapy early, shortened survival, and death within 30 days of chemotherapy. Materials and Methods. This study enrolled women with PRROC before starting palliative chemotherapy. Health-related quality of life was measured with EORTC QLQ-C30/QLQ-OV28. Chemotherapy stopped within 8 weeks of starting was defined as stopping early. Logistic regression was used to assess univariable and multivariable associations with stopping chemotherapy early and death within 30 days of chemotherapy; Cox proportional hazards regression was used to assess associations with progression-free and OS. Results. Low baseline global health status (GHS), role function (RF), physical function (PF), and high abdominal/gastrointestinal symptom (AGIS) were associated with stopping chemotherapy early (all pamp;lt;.007); low PF and RF remained significant after adjusting for clinicopathological factors (both pamp;lt;.0401). Most who stopped chemotherapy early had Eastern Cooperative Oncology Group Performance Score 0-1 at baseline (79%); PF, RF, and GHS remained independently significant predictors of stopping chemotherapy early in this subgroup. Death within 30 days of chemotherapy occurred in 14%. Low-GHS, RF, and PF remained significantly associated with death within 30 days of chemotherapy after adjusting for clinicopathological factors (all pamp;lt;.012). Conclusion. Women with low GHS, RF, or PF before starting chemotherapy were more likely to stop chemotherapy early, with short OS. Self-ratings of GHS, RF, and PF could improve patient-clinician communication regarding prognosis and help decision-making in women considering chemotherapy for PRROC.
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| 4. |
- Zeng, Chenjie, et al.
(författare)
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Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus
- 2016
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.
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