130 results on '"Sonke, G. S."'
Search Results
2. Updated overall survival from the MONALEESA-3 trial in postmenopausal women with HR+/HER2− advanced breast cancer receiving first-line ribociclib plus fulvestrant
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Neven, P., Fasching, P. A., Chia, S., Jerusalem, G., De Laurentiis, M., Im, S.-A., Petrakova, K., Bianchi, G. V., Martín, M., Nusch, A., Sonke, G. S., De la Cruz-Merino, L., Beck, J. T., Zarate, J. P., Wang, Y., Chakravartty, A., Wang, C., and Slamon, D. J.
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- 2023
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3. BluePrint molecular subtypes predict response to neoadjuvant pertuzumab in HER2-positive breast cancer
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Liefaard, M. C., van der Voort, A., van Ramshorst, M. S., Sanders, J., Vonk, S., Horlings, H. M., Siesling, S., de Munck, L., van Leeuwen, A. E., Kleijn, M., Mittempergher, L., Kuilman, M. M., Glas, A. M., Wesseling, J., Lips, E. H., and Sonke, G. S.
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- 2023
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4. Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: a randomized controlled trial (PAM study)
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Koevoets, E. W., Schagen, S. B., de Ruiter, M. B., Geerlings, M. I., Witlox, L., van der Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., Menke-Pluijmers, M. B. E., Göker, E., van der Pol, C. C., Bos, M. E. M. M., Tick, L. W., van Holsteijn, N. A., van der Palen, J., May, A. M., and Monninkhof, E. M.
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- 2022
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5. Effect of physical exercise on brain perfusion in chemotherapy-treated breast cancer patients: a randomized controlled trial (PAM study)
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Koevoets, E. W., (0000-0002-3201-6002) Petr, J., Monninkhof, E. M., Geerlings, M. I., Witlox, L., Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., Palen, J., Jmm Mutsaerts, H., Ruiter, M. B., May, A. M., Schagen, S. B., Koevoets, E. W., (0000-0002-3201-6002) Petr, J., Monninkhof, E. M., Geerlings, M. I., Witlox, L., Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., Palen, J., Jmm Mutsaerts, H., Ruiter, M. B., May, A. M., and Schagen, S. B.
- Abstract
BACKGROUND Breast cancer patients may experience cognitive difficulties after chemotherapy. PURPOSE To investigate whether an exercise intervention can affect cerebral blood flow (CBF) in breast cancer patients and if CBF changes relate to memory function. STUDY TYPE Prospective. POPULATION Chemotherapy-treated breast cancer patients with cognitive problems, and with relatively low physical activity levels were randomized to an exercise intervention (n=91) or control group (n=90). FIELDSTRENGTH/SEQUENCE A 3-T arterial spin labeling CBF scan was performed. ASSESSMENT The 6-month intervention consisted of (supervised) aerobic and strength training, 4x1 hour/week. Measurements at baseline (2-4 years post-diagnosis) and after six months included the arterial spin labeling CBF scan, from which we calculated gray matter CBF in the whole brain, hippocampus, anterior cingulate cortex, and posterior cingulate cortex. Furthermore, we measured physical fitness and memory functioning. STATISTICAL TESTS Multiple regression analyses with a two-sided alpha of 0.05 for all analyses. RESULTS We observed significant improvement in physical fitness (VO2peak) in the intervention group (n=53) compared to controls (n=51, B1.47, 95%CI:0.44; 2.50), nevertheless no intervention effects on CBF were found (e.g. whole brain: B0.98, 95%CI:-2.38; 4.34). Highly fatigued patients showed larger, but not significant, treatment effects. Additionally, change in physical fitness, from baseline to post-intervention, was positively associated with changes in CBF (e.g., whole brain: B0.75, 95%CI:0.07; 1.43). However, we observed no relation between CBF changes and change in memory performance. DATA CONCLUSION The exercise intervention did not affect CBF of cognitively affected breast cancer patients. However, a change in physical fitness was related to a change in CBF, but a change in CBF was not associated with memory functioning.
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- 2024
6. Effect of physical exercise on the hippocampus and global grey matter volume in breast cancer patients:A randomized controlled trial (PAM study)
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Koevoets, E. W., Geerlings, M. I., Monninkhof, E. M., Mandl, R., Witlox, L., van der Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., van der Palen, J., Bos, M. E.M.M., Göker, E., Menke-Pluijmers, M. B.E., Sommeijer, D. W., May, A. M., Haringhuizen, Annebeth W., van der Steeg, Wim A., Terheggen, Frederiek, Blanken-Peeters, Charlotte, Fliervoet, Harold, Schlooz-Vries, Margrethe S., Frakking, Tanja G., van Tilburg, Marc W.A., Oldenhuis, Corina, Sier, Maartje F., van der Pol, Carmen C., Tick, Lidwine W., van Holsteijn, Nel A., de Ruiter, M. B., Schagen, S. B., Koevoets, E. W., Geerlings, M. I., Monninkhof, E. M., Mandl, R., Witlox, L., van der Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., van der Palen, J., Bos, M. E.M.M., Göker, E., Menke-Pluijmers, M. B.E., Sommeijer, D. W., May, A. M., Haringhuizen, Annebeth W., van der Steeg, Wim A., Terheggen, Frederiek, Blanken-Peeters, Charlotte, Fliervoet, Harold, Schlooz-Vries, Margrethe S., Frakking, Tanja G., van Tilburg, Marc W.A., Oldenhuis, Corina, Sier, Maartje F., van der Pol, Carmen C., Tick, Lidwine W., van Holsteijn, Nel A., de Ruiter, M. B., and Schagen, S. B.
- Abstract
Background: Physical exercise in cancer patients is a promising intervention to improve cognition and increase brain volume, including hippocampal volume. We investigated whether a 6-month exercise intervention primarily impacts total hippocampal volume and additionally hippocampal subfield volumes, cortical thickness and grey matter volume in previously physically inactive breast cancer patients. Furthermore, we evaluated associations with verbal memory. Methods: Chemotherapy-exposed breast cancer patients (stage I-III, 2–4 years post diagnosis) with cognitive problems were included and randomized in an exercise intervention (n = 70, age = 52.5 ± 9.0 years) or control group (n = 72, age = 53.2 ± 8.6 years). The intervention consisted of 2x1 hours/week of supervised aerobic and strength training and 2x1 hours/week Nordic or power walking. At baseline and at 6-month follow-up, volumetric brain measures were derived from 3D T1-weighted 3T magnetic resonance imaging scans, including hippocampal (subfield) volume (FreeSurfer), cortical thickness (CAT12), and grey matter volume (voxel-based morphometry CAT12). Physical fitness was measured with a cardiopulmonary exercise test. Memory functioning was measured with the Hopkins Verbal Learning Test-Revised (HVLT-R total recall) and Wordlist Learning of an online cognitive test battery, the Amsterdam Cognition Scan (ACS Wordlist Learning). An explorative analysis was conducted in highly fatigued patients (score of ≥ 39 on the symptom scale ‘fatigue’ of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire), as previous research in this dataset has shown that the intervention improved cognition only in these patients. Results: Multiple regression analyses and voxel-based morphometry revealed no significant intervention effects on brain volume, although at baseline increased physical fitness was significantly related to larger brain volume (e.g., total hippocampal volume: R = 0.32, B =
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- 2023
7. Selecting the optimal position of CDK4/6 inhibitors in hormone receptor-positive advanced breast cancer – the SONIA study: study protocol for a randomized controlled trial
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van Ommen-Nijhof, A., Konings, I. R., van Zeijl, C. J. J., Uyl-de Groot, C. A., van der Noort, V., Jager, A., Sonke, G. S., and On behalf of the SONIA study steering committee
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- 2018
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8. Additional file 1 of BluePrint molecular subtypes predict response to neoadjuvant pertuzumab in HER2-positive breast cancer
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Liefaard, M. C., van der Voort, A., van Ramshorst, M. S., Sanders, J., Vonk, S., Horlings, H. M., Siesling, S., de Munck, L., van Leeuwen, A. E., Kleijn, M., Mittempergher, L., Kuilman, M. M., Glas, A. M., Wesseling, J., Lips, E. H., and Sonke, G. S.
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Additional file 1. Supplementary Figures.
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- 2023
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9. Additional file 2 of BluePrint molecular subtypes predict response to neoadjuvant pertuzumab in HER2-positive breast cancer
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Liefaard, M. C., van der Voort, A., van Ramshorst, M. S., Sanders, J., Vonk, S., Horlings, H. M., Siesling, S., de Munck, L., van Leeuwen, A. E., Kleijn, M., Mittempergher, L., Kuilman, M. M., Glas, A. M., Wesseling, J., Lips, E. H., and Sonke, G. S.
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Additional file 2. Supplementary Tables.
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- 2023
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10. P11.61.B Capecitabine treatment of CNS metastases from breast cancer: intracranial response and survival
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Luitse, M J A, primary, Boles, G, additional, Sonke, G S, additional, and Brandsma, D, additional
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- 2022
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11. Overall survival in the OlympiA phase Ill trial of adjuvant olaparib in patients with germime pathogenic variants in BRCA1/2 and high-risk, early breast cancer
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Geyer, C. E., Jr., Garber, J. E., Gelber, R. D., Yothers, G., Taboada, M., Ross, L., Rastogi, P., Cui, K., Arahmani, A., Aktan, G., Armstrong, A. C., Arnedos, M., Balmana, J., Bergh, J., Bliss, J., Delaloge, S., Domchek, S. M., Eisen, A., Elsafy, F., Fein, L. E., Fielding, A., Ford, J. M., Friedman, S., Gelmon, K. A., Gianni, L., Gnant, M., Hollingsworth, S. J., Im, S-A, Jager, A., Lakhani, S. R., Janni, W., Linderholm, B., Liu, T-W, Loman, N., Korde, L., Loibl, S., Lucas, P. C., Marme, F., de Duenas, E. Martinez, McConnell, R., Phillips, K-A, Piccart, M., Rossi, G., Schmutzler, R., Senkus, E., Shao, Z., Sharma, P., Singer, C. F., Spanic, T., Stickeler, E., Toi, M., Traina, T. A., Viale, G., Zoppoli, G., Park, Y. H., Yerushalmi, R., Yang, H., Pang, D., Jung, K. H., Mailliez, A., Fan, Z., Tennevet, I, Zhang, J., Nagy, T., Sonke, G. S., Sun, Q., Parton, M., Colleoni, M. A., Schmidt, M., Brufsky, A. M., Razaq, W., Kaufman, B., Cameron, D., Campbell, C., Tutt, A. N. J., Johannsson, O. Th, Geyer, C. E., Jr., Garber, J. E., Gelber, R. D., Yothers, G., Taboada, M., Ross, L., Rastogi, P., Cui, K., Arahmani, A., Aktan, G., Armstrong, A. C., Arnedos, M., Balmana, J., Bergh, J., Bliss, J., Delaloge, S., Domchek, S. M., Eisen, A., Elsafy, F., Fein, L. E., Fielding, A., Ford, J. M., Friedman, S., Gelmon, K. A., Gianni, L., Gnant, M., Hollingsworth, S. J., Im, S-A, Jager, A., Lakhani, S. R., Janni, W., Linderholm, B., Liu, T-W, Loman, N., Korde, L., Loibl, S., Lucas, P. C., Marme, F., de Duenas, E. Martinez, McConnell, R., Phillips, K-A, Piccart, M., Rossi, G., Schmutzler, R., Senkus, E., Shao, Z., Sharma, P., Singer, C. F., Spanic, T., Stickeler, E., Toi, M., Traina, T. A., Viale, G., Zoppoli, G., Park, Y. H., Yerushalmi, R., Yang, H., Pang, D., Jung, K. H., Mailliez, A., Fan, Z., Tennevet, I, Zhang, J., Nagy, T., Sonke, G. S., Sun, Q., Parton, M., Colleoni, M. A., Schmidt, M., Brufsky, A. M., Razaq, W., Kaufman, B., Cameron, D., Campbell, C., Tutt, A. N. J., and Johannsson, O. Th
- Abstract
Background: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Delta 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Delta 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Delta 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion: With 35 years of median follow-up, OlympiA demonstrates statistical
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- 2022
12. Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ENGOT Ov-21 trial
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Frenel, J, Kim, J, Aryal, N, Asher, R, Berton, D, Vidal, L, Pautier, P, Ledermann, J, Penson, R, Oza, A, Korach, J, Huzarski, T, Pignata, S, Colombo, N, Park-Simon, T, Tamura, K, Sonke, G, Freimund, A, Lee, C, Pujade-Lauraine, E, Frenel J. S., Kim J. W., Aryal N., Asher R., Berton D., Vidal L., Pautier P., Ledermann J. A., Penson R. T., Oza A. M., Korach J., Huzarski T., Pignata S., Colombo N., Park-Simon T. W., Tamura K., Sonke G. S., Freimund A. E., Lee C. K., Pujade-Lauraine E., Frenel, J, Kim, J, Aryal, N, Asher, R, Berton, D, Vidal, L, Pautier, P, Ledermann, J, Penson, R, Oza, A, Korach, J, Huzarski, T, Pignata, S, Colombo, N, Park-Simon, T, Tamura, K, Sonke, G, Freimund, A, Lee, C, Pujade-Lauraine, E, Frenel J. S., Kim J. W., Aryal N., Asher R., Berton D., Vidal L., Pautier P., Ledermann J. A., Penson R. T., Oza A. M., Korach J., Huzarski T., Pignata S., Colombo N., Park-Simon T. W., Tamura K., Sonke G. S., Freimund A. E., Lee C. K., and Pujade-Lauraine E.
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Background: In the SOLO2 trial (ENGOT Ov-21; NCT01874353), maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSROC) and BRCA mutation significantly improved progression-free survival (PFS) and prolonged overall survival (OS). Following disease progression on olaparib, efficacy of subsequent chemotherapy remains unknown. Patients and methods: We conducted a post-hoc hypothesis-generating analysis of SOLO2 data to determine the efficacy of different chemotherapy regimens following RECIST disease progression in patients who received olaparib or placebo. We evaluated time to second progression (TTSP) calculated from the date of RECIST progression to the next progression/death. Results: The study population comprised 147 patients who received chemotherapy as their first subsequent treatment after RECIST progression. Of these, 69 (47%) and 78 (53%) were originally randomized to placebo and olaparib arms, respectively. In the placebo-treated cohort, 27/69 and 42/69 received non-platinum and platinum-based chemotherapy, respectively, compared with 24/78 and 54/78, respectively, in the olaparib-treated cohort. Among patients treated with chemotherapy (N = 147), TTSP was significantly longer in the placebo than in the olaparib arm: 12.1 versus 6.9 months [hazard ratio (HR) 2.17, 95% confidence interval (CI) 1.47-3.19]. Similar result was obtained on multivariable analysis adjusting for prognostic factors at RECIST progression (HR 2.13, 95% CI 1.41-3.22). Among patients treated with platinum-based chemotherapy (n = 96), TTSP was significantly longer in the placebo arm: 14.3 versus 7.0 months (HR 2.89, 95% CI 1.73-4.82). Conversely, among patients treated with non-platinum-based chemotherapy (n = 51), the TTSP was comparable in the placebo and olaparib arms: 8.3 versus 6.0 months (HR 1.58, 95% CI 0.86-2.90). Conclusions: Following progression from maintenance olaparib in the recurrent setting, the efficacy of platinum-based subsequent chemotherap
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- 2022
13. Efficacy and safety of durvalumab with olaparib in metastatic or recurrent endometrial cancer (phase II DOMEC trial)
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Post, C. C.B., Westermann, A. M., Boere, I. A., Witteveen, P. O., Ottevanger, P. B., Sonke, G. S., Lalisang, R. I., Putter, H., Meershoek-Klein Kranenbarg, E., Braak, J. P.B.M., Creutzberg, C. L., Bosse, T., Kroep, J. R., Post, C. C.B., Westermann, A. M., Boere, I. A., Witteveen, P. O., Ottevanger, P. B., Sonke, G. S., Lalisang, R. I., Putter, H., Meershoek-Klein Kranenbarg, E., Braak, J. P.B.M., Creutzberg, C. L., Bosse, T., and Kroep, J. R.
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Background: Patients with advanced endometrial cancer have a poor prognosis, and treatment options are limited. The investigator-initiated, multicenter, phase II DOMEC trial (NCT03951415) is the first trial to report data on efficacy and safety of combined treatment with PD-L1 and PARP inhibition for advanced endometrial cancer. Patients and methods: Patients with metastatic or recurrent endometrial cancer were enrolled. Patients received durvalumab 1500 mg intravenously q4w and olaparib 300 mg 2dd until disease progression, unacceptable toxicity, or patient withdrawal. Patients with at least 4 weeks of treatment were evaluable for analysis. The primary endpoint was progression-free survival at 6 months. Evidence for efficacy was defined as progression-free survival at 6 months in ≥50% of patients. Secondary endpoints included safety, objective response and overall survival. Results: From July 2019, through November 2020, 55 patients were enrolled. At data cut-off (September 2021), 4 of the 50 evaluable patients were still on treatment. Seventeen patients (34%) were progression-free at 6 months. Objective response rate was 16% (95% CI, 8.3 to 28.5) with 1 complete and 7 partial responses. With a median follow-up of 17.6 months, median progression-free survival was 3.4 months (95% CI, 2.8 to 6.2) and median overall survival was 8.0 months (95% CI, 7.5 to 14.3). Grade 3 treatment-related adverse events occurred in 8 patients (16%), predominantly anemia. There were no grade 4 or 5 treatment-related adverse events. Conclusion: The combination of durvalumab and olaparib was well tolerated, but did not meet the prespecified 50% 6-month progression-free survival in this heterogeneous patient population with advanced endometrial cancer.
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- 2022
14. Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer:a randomized controlled trial (PAM study)
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Koevoets, E. W., Schagen, S. B., de Ruiter, M. B., Geerlings, M. I., Witlox, L., van der Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., Menke-Pluijmers, M. B.E., Göker, E., van der Pol, C. C., Bos, M. E.M.M., Tick, L. W., van Holsteijn, N. A., van der Palen, J., May, A. M., Monninkhof, E. M., Koevoets, E. W., Schagen, S. B., de Ruiter, M. B., Geerlings, M. I., Witlox, L., van der Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., Menke-Pluijmers, M. B.E., Göker, E., van der Pol, C. C., Bos, M. E.M.M., Tick, L. W., van Holsteijn, N. A., van der Palen, J., May, A. M., and Monninkhof, E. M.
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Background: Up to 60% of breast cancer patients treated with chemotherapy is confronted with cognitive problems, which can have a significant impact on daily activities and quality of life (QoL). We investigated whether exercise training improves cognition in chemotherapy-exposed breast cancer patients 2–4 years after diagnosis. Methods: Chemotherapy-exposed breast cancer patients, with both self-reported cognitive problems and lower than expected performance on neuropsychological tests, were randomized to an exercise or control group. The 6-month exercise intervention consisted of supervised aerobic and strength training (2 h/week), and Nordic/power walking (2 h/week). Our primary outcome was memory functioning (Hopkins Verbal Learning Test-Revised; HVLT-R). Secondary outcomes included online neuropsychological tests (Amsterdam Cognition Scan; ACS), self-reported cognition (MD Anderson Symptom Inventory for multiple myeloma; MDASI-MM), physical fitness (relative maximum oxygen uptake; VO2peak), fatigue (Multidimensional Fatigue Inventory), QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ C-30), depression (Patient Health Questionnaire-9, Hospital Anxiety and Depression Scale; HADS), and anxiety (HADS). HVLT-R total recall was analyzed with a Fisher exact test for clinically relevant improvement (≥ 5 words). Other outcomes were analyzed using multiple regression analyses adjusted for baseline and stratification factors. Results: We randomized 181 patients to the exercise (n = 91) or control group (n = 90). Two-third of the patients attended ≥ 80% of the exercise sessions, and physical fitness significantly improved compared to control patients (B VO2peak 1.4 ml/min/kg, 95%CI:0.6;2.2). No difference in favor of the intervention group was seen on the primary outcome. Significant beneficial intervention effects were found for self-reported cognitive functioning [MDASI
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- 2022
15. Efficacy and safety of olaparib according to age in BRCA1/2-mutated patients with recurrent platinum-sensitive ovarian cancer: Analysis of the phase III SOLO2/ENGOT-Ov21 study
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Trillsch, F., Mahner, S., Ataseven, B., Asher, R., Aryal, N., Dubot, C., Clamp, A., Penson, R. T., Oza, A., Amit, A., Huzarski, T., Casado, A., Scambia, Giovanni, Friedlander, M., Colombo, N., Fujiwara, K., Sonke, G. S., Denys, H., Lowe, E. S., Lee, C. K., Pujade-Lauraine, E., Scambia G. (ORCID:0000-0003-2758-1063), Trillsch, F., Mahner, S., Ataseven, B., Asher, R., Aryal, N., Dubot, C., Clamp, A., Penson, R. T., Oza, A., Amit, A., Huzarski, T., Casado, A., Scambia, Giovanni, Friedlander, M., Colombo, N., Fujiwara, K., Sonke, G. S., Denys, H., Lowe, E. S., Lee, C. K., Pujade-Lauraine, E., and Scambia G. (ORCID:0000-0003-2758-1063)
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Background: Olaparib has significantly improved outcome and patient-centered endpoints in BRCA1/2-mutated patients with recurrent platinum-sensitive ovarian cancer (PSOC). Specific information on efficacy and safety of olaparib for older patients appears of special interest. Methods: 295 patients from the SOLO2 trial randomly assigned to olaparib or placebo were categorized according to age-cutoff at 65 years. Efficacy, tolerability, and quality of life (QoL) of olaparib relative to placebo within in each age group was analyzed. Results: Baseline characteristics were similar in patients ≥65 years (N = 62;21.0%) compared to patients <65 years (N = 233;78.9%). No significant difference in the magnitude of progression-free survival (PFS) benefit from olaparib for older patients (N = 40, hazard ratio [HR]≥65 0.43, 95%-confidence interval [CI] 0.24–0.81) as compared with younger patients (N = 155, HR<65 0.31 (95%-CI 0.22–0.43) was seen (interaction P = 0.33). The overall survival (OS)benefit seen in younger patients in the olaparib arm was not observed in older patients. Older and younger patients had comparable safety profiles and QoL scores although higher discontinuation rates for toxicity, and higher frequency of AML/MDS were noted in the older subset. TWiST analysis revealed clinically meaningful duration of good QoL on olaparib for both age groups (≥65: 13.5 vs <65: 18.4 months, P = 0.05). Conclusions: Results of this large phase III cohort of BRCA1/2-mutated PSOC patients treated with olaparib underline impressive efficacy of olaparib maintenance irrespective of age. Although toxicity and tolerability did not raise significant concerns, some caution, close monitoring, and follow-up needs to be exercised for older patients given higher discontinuation rates, frequency of AML/MDS, and no clear effects on OS.
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- 2022
16. Efficacy and safety of olaparib according to age in BRCA1/2-mutated patients with recurrent platinum-sensitive ovarian cancer: Analysis of the phase III SOLO2/ENGOT-Ov21 study
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Trillsch, F, Mahner, S, Ataseven, B, Asher, R, Aryal, N, Dubot, C, Clamp, A, Penson, R, Oza, A, Amit, A, Huzarski, T, Casado, A, Scambia, G, Friedlander, M, Colombo, N, Fujiwara, K, Sonke, G, Denys, H, Lowe, E, Lee, C, Pujade-Lauraine, E, Trillsch F., Mahner S., Ataseven B., Asher R., Aryal N., Dubot C., Clamp A., Penson R. T., Oza A., Amit A., Huzarski T., Casado A., Scambia G., Friedlander M., Colombo N., Fujiwara K., Sonke G. S., Denys H., Lowe E. S., Lee C. K., Pujade-Lauraine E., Trillsch, F, Mahner, S, Ataseven, B, Asher, R, Aryal, N, Dubot, C, Clamp, A, Penson, R, Oza, A, Amit, A, Huzarski, T, Casado, A, Scambia, G, Friedlander, M, Colombo, N, Fujiwara, K, Sonke, G, Denys, H, Lowe, E, Lee, C, Pujade-Lauraine, E, Trillsch F., Mahner S., Ataseven B., Asher R., Aryal N., Dubot C., Clamp A., Penson R. T., Oza A., Amit A., Huzarski T., Casado A., Scambia G., Friedlander M., Colombo N., Fujiwara K., Sonke G. S., Denys H., Lowe E. S., Lee C. K., and Pujade-Lauraine E.
- Abstract
Background: Olaparib has significantly improved outcome and patient-centered endpoints in BRCA1/2-mutated patients with recurrent platinum-sensitive ovarian cancer (PSOC). Specific information on efficacy and safety of olaparib for older patients appears of special interest. Methods: 295 patients from the SOLO2 trial randomly assigned to olaparib or placebo were categorized according to age-cutoff at 65 years. Efficacy, tolerability, and quality of life (QoL) of olaparib relative to placebo within in each age group was analyzed. Results: Baseline characteristics were similar in patients ≥65 years (N = 62;21.0%) compared to patients <65 years (N = 233;78.9%). No significant difference in the magnitude of progression-free survival (PFS) benefit from olaparib for older patients (N = 40, hazard ratio [HR]≥65 0.43, 95%-confidence interval [CI] 0.24–0.81) as compared with younger patients (N = 155, HR<65 0.31 (95%-CI 0.22–0.43) was seen (interaction P = 0.33). The overall survival (OS)benefit seen in younger patients in the olaparib arm was not observed in older patients. Older and younger patients had comparable safety profiles and QoL scores although higher discontinuation rates for toxicity, and higher frequency of AML/MDS were noted in the older subset. TWiST analysis revealed clinically meaningful duration of good QoL on olaparib for both age groups (≥65: 13.5 vs <65: 18.4 months, P = 0.05). Conclusions: Results of this large phase III cohort of BRCA1/2-mutated PSOC patients treated with olaparib underline impressive efficacy of olaparib maintenance irrespective of age. Although toxicity and tolerability did not raise significant concerns, some caution, close monitoring, and follow-up needs to be exercised for older patients given higher discontinuation rates, frequency of AML/MDS, and no clear effects on OS.
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- 2022
17. Efficacy and safety of durvalumab with olaparib in metastatic or recurrent endometrial cancer (phase II DOMEC trial)
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MS Radiotherapie, MS Medische Oncologie, Cancer, Post, C C B, Westermann, A M, Boere, I A, Witteveen, P O, Ottevanger, P B, Sonke, G S, Lalisang, R I, Putter, H, Meershoek-Klein Kranenbarg, E, Braak, J P B M, Creutzberg, C L, Bosse, T, Kroep, J R, MS Radiotherapie, MS Medische Oncologie, Cancer, Post, C C B, Westermann, A M, Boere, I A, Witteveen, P O, Ottevanger, P B, Sonke, G S, Lalisang, R I, Putter, H, Meershoek-Klein Kranenbarg, E, Braak, J P B M, Creutzberg, C L, Bosse, T, and Kroep, J R
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- 2022
18. Additional file 1 of Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: a randomized controlled trial (PAM study)
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Koevoets, E. W., Schagen, S. B., de Ruiter, M. B., Geerlings, M. I., Witlox, L., van der Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., Menke-Pluijmers, M. B. E., Göker, E., van der Pol, C. C., Bos, M. E. M. M., Tick, L. W., van Holsteijn, N. A., van der Palen, J., May, A. M., and Monninkhof, E. M.
- Abstract
Additional file 1. Table S1. Intervention effects on cognitive functioning. Table S2. Intervention effects on cognitive functioning, per protocol. Table S3. Intervention effects, separately for patients with and without endocrine therapy. Table S4. Intervention effects, separately for patients of different age categories (30-44, 45-59, 60-75 years). Table S5. Intervention effects, separately for patients of with pre- and peri- menopausal status and patients with postmenopausal status. Table S6. Intervention effects on cognitive functioning, stratified for low versus high levels of fatigue measured with the EORTC QLQ C-30 fatigue scale. Table S7. Intervention effects on patient-reported outcomes.
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- 2022
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19. Effect of physical exercise on the hippocampus and global grey matter volume in breast cancer patients: A randomized controlled trial (PAM study)
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Koevoets, E. W., Geerlings, M. I., Monninkhof, E. M., Mandl, R., Witlox, L., van der Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., van der Palen, J., Bos, M. E. M. M., Göker, E., Menke-Pluijmers, M. B. E., Sommeijer, D. W., May, A. M., Haringhuizen, Annebeth W., van der Steeg, Wim A., Terheggen, Frederiek, Blanken-Peeters, Charlotte, Fliervoet, Harold, Schlooz-Vries, Margrethe S., Frakking, Tanja G., van Tilburg, Marc W. A., Oldenhuis, Corina, Sier, Maartje F., van der Pol, Carmen C., Tick, Lidwine W., van Holsteijn, Nel A., de Ruiter, M. B., Schagen, S. B., Psychology Other Research (FMG), Medical Oncology, General practice, Master Evidence Based Practice, CCA - Cancer Treatment and Quality of Life, APH - Quality of Care, APH - Health Behaviors & Chronic Diseases, Oncology, Radiology and Nuclear Medicine, and Rehabilitation medicine
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Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10] ,All institutes and research themes of the Radboud University Medical Center ,Breast cancer ,SDG 3 - Good Health and Well-being ,Neurology ,Cognitive Neuroscience ,Radiology, Nuclear Medicine and imaging ,Neurology (clinical) ,Grey matter volume ,Exercise ,Hippocampus ,Fatigue ,Cortical thickness - Abstract
Contains fulltext : 291410.pdf (Publisher’s version ) (Open Access) BACKGROUND: Physical exercise in cancer patients is a promising intervention to improve cognition and increase brain volume, including hippocampal volume. We investigated whether a 6-month exercise intervention primarily impacts total hippocampal volume and additionally hippocampal subfield volumes, cortical thickness and grey matter volume in previously physically inactive breast cancer patients. Furthermore, we evaluated associations with verbal memory. METHODS: Chemotherapy-exposed breast cancer patients (stage I-III, 2-4 years post diagnosis) with cognitive problems were included and randomized in an exercise intervention (n = 70, age = 52.5 ± 9.0 years) or control group (n = 72, age = 53.2 ± 8.6 years). The intervention consisted of 2x1 hours/week of supervised aerobic and strength training and 2x1 hours/week Nordic or power walking. At baseline and at 6-month follow-up, volumetric brain measures were derived from 3D T1-weighted 3T magnetic resonance imaging scans, including hippocampal (subfield) volume (FreeSurfer), cortical thickness (CAT12), and grey matter volume (voxel-based morphometry CAT12). Physical fitness was measured with a cardiopulmonary exercise test. Memory functioning was measured with the Hopkins Verbal Learning Test-Revised (HVLT-R total recall) and Wordlist Learning of an online cognitive test battery, the Amsterdam Cognition Scan (ACS Wordlist Learning). An explorative analysis was conducted in highly fatigued patients (score of ≥ 39 on the symptom scale 'fatigue' of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire), as previous research in this dataset has shown that the intervention improved cognition only in these patients. RESULTS: Multiple regression analyses and voxel-based morphometry revealed no significant intervention effects on brain volume, although at baseline increased physical fitness was significantly related to larger brain volume (e.g., total hippocampal volume: R = 0.32, B = 21.7 mm(3), 95 % CI = 3.0 - 40.4). Subgroup analyses showed an intervention effect in highly fatigued patients. Unexpectedly, these patients had significant reductions in hippocampal volume, compared to the control group (e.g., total hippocampal volume: B = -52.3 mm(3), 95 % CI = -100.3 - -4.4)), which was related to improved memory functioning (HVLT-R total recall: B = -0.022, 95 % CI = -0.039 - -0.005; ACS Wordlist Learning: B = -0.039, 95 % CI = -0.062 - -0.015). CONCLUSIONS: No exercise intervention effects were found on hippocampal volume, hippocampal subfield volumes, cortical thickness or grey matter volume for the entire intervention group. Contrary to what we expected, in highly fatigued patients a reduction in hippocampal volume was found after the intervention, which was related to improved memory functioning. These results suggest that physical fitness may benefit cognition in specific groups and stress the importance of further research into the biological basis of this finding.
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- 2023
20. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial
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Banerjee, S., Moore, K. N., Colombo, N., Scambia, Giovanni, Kim, B. -G., Oaknin, A., Friedlander, M., Lisyanskaya, A., Floquet, A., Leary, A., Sonke, G. S., Gourley, C., Oza, A., Gonzalez-Martin, A., Aghajanian, C., Bradley, W. H., Holmes, E., Lowe, E. S., Disilvestro, P., Scambia G. (ORCID:0000-0003-2758-1063), Banerjee, S., Moore, K. N., Colombo, N., Scambia, Giovanni, Kim, B. -G., Oaknin, A., Friedlander, M., Lisyanskaya, A., Floquet, A., Leary, A., Sonke, G. S., Gourley, C., Oza, A., Gonzalez-Martin, A., Aghajanian, C., Bradley, W. H., Holmes, E., Lowe, E. S., Disilvestro, P., and Scambia G. (ORCID:0000-0003-2758-1063)
- Abstract
Background: There is a high unmet need for treatment regimens that increase the chance of long-term remission and possibly cure for women with newly diagnosed advanced ovarian cancer. In the primary analysis of SOLO1/GOG 3004, the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib significantly improved progression-free survival versus placebo in patients with a BRCA mutation; median progression-free survival was not reached. Here, we report an updated, post-hoc analysis of progression-free survival from SOLO1, after 5 years of follow-up. Methods: SOLO1 was a randomised, double-blind, placebo-controlled, phase 3 trial, done across 118 centres in 15 countries, that enrolled patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0–1 and with BRCA-mutated, newly diagnosed, advanced, high-grade serous or endometrioid ovarian cancer with a complete or partial clinical response after platinum-based chemotherapy. Patients were randomly assigned (2:1) via a web-based or interactive voice-response system to receive olaparib (300 mg twice daily) or placebo tablets orally as maintenance monotherapy for up to 2 years; randomisation was by blocks and was stratified according to clinical response after platinum-based chemotherapy. Patients, treatment providers, and data assessors were masked to group assignment. The primary endpoint was investigator-assessed progression-free survival. Efficacy is reported in the intention-to-treat population and safety in patients who received at least one dose of treatment. The data cutoff for this updated, post-hoc analysis was March 5, 2020. This trial is registered with ClinicalTrials.gov (NCT01844986) and is ongoing but closed to new participants. Findings: Between Sept 3, 2013, and March 6, 2015, 260 patients were randomly assigned to olaparib and 131 to placebo. The median treatment duration was 24·6 months (IQR 11·2–24·9) in the olaparib group and 13·9 months (8·0–24·8) in the placebo group; me
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- 2021
21. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial
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Banerjee, S, Moore, K, Colombo, N, Scambia, G, Kim, B, Oaknin, A, Friedlander, M, Lisyanskaya, A, Floquet, A, Leary, A, Sonke, G, Gourley, C, Oza, A, Gonzalez-Martin, A, Aghajanian, C, Bradley, W, Holmes, E, Lowe, E, Disilvestro, P, Banerjee S., Moore K. N., Colombo N., Scambia G., Kim B. -G., Oaknin A., Friedlander M., Lisyanskaya A., Floquet A., Leary A., Sonke G. S., Gourley C., Oza A., Gonzalez-Martin A., Aghajanian C., Bradley W. H., Holmes E., Lowe E. S., DiSilvestro P., Banerjee, S, Moore, K, Colombo, N, Scambia, G, Kim, B, Oaknin, A, Friedlander, M, Lisyanskaya, A, Floquet, A, Leary, A, Sonke, G, Gourley, C, Oza, A, Gonzalez-Martin, A, Aghajanian, C, Bradley, W, Holmes, E, Lowe, E, Disilvestro, P, Banerjee S., Moore K. N., Colombo N., Scambia G., Kim B. -G., Oaknin A., Friedlander M., Lisyanskaya A., Floquet A., Leary A., Sonke G. S., Gourley C., Oza A., Gonzalez-Martin A., Aghajanian C., Bradley W. H., Holmes E., Lowe E. S., and DiSilvestro P.
- Abstract
Background: There is a high unmet need for treatment regimens that increase the chance of long-term remission and possibly cure for women with newly diagnosed advanced ovarian cancer. In the primary analysis of SOLO1/GOG 3004, the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib significantly improved progression-free survival versus placebo in patients with a BRCA mutation; median progression-free survival was not reached. Here, we report an updated, post-hoc analysis of progression-free survival from SOLO1, after 5 years of follow-up. Methods: SOLO1 was a randomised, double-blind, placebo-controlled, phase 3 trial, done across 118 centres in 15 countries, that enrolled patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0–1 and with BRCA-mutated, newly diagnosed, advanced, high-grade serous or endometrioid ovarian cancer with a complete or partial clinical response after platinum-based chemotherapy. Patients were randomly assigned (2:1) via a web-based or interactive voice-response system to receive olaparib (300 mg twice daily) or placebo tablets orally as maintenance monotherapy for up to 2 years; randomisation was by blocks and was stratified according to clinical response after platinum-based chemotherapy. Patients, treatment providers, and data assessors were masked to group assignment. The primary endpoint was investigator-assessed progression-free survival. Efficacy is reported in the intention-to-treat population and safety in patients who received at least one dose of treatment. The data cutoff for this updated, post-hoc analysis was March 5, 2020. This trial is registered with ClinicalTrials.gov (NCT01844986) and is ongoing but closed to new participants. Findings: Between Sept 3, 2013, and March 6, 2015, 260 patients were randomly assigned to olaparib and 131 to placebo. The median treatment duration was 24·6 months (IQR 11·2–24·9) in the olaparib group and 13·9 months (8·0–24·8) in the placebo group; me
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- 2021
22. Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial
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Poveda, A, Floquet, A, Ledermann, J, Asher, R, Penson, R, Oza, A, Korach, J, Huzarski, T, Pignata, S, Friedlander, M, Baldoni, A, Park-Simon, T, Tamura, K, Sonke, G, Lisyanskaya, A, Kim, J, Filho, E, Milenkova, T, Lowe, E, Rowe, P, Vergote, I, Pujade-Lauraine, E, Byrski, T, Pautier, P, Harter, P, Colombo, N, Scambia, G, Nicoletto, M, Nussey, F, Clamp, A, Poveda Velasco, A, Rodrigues, M, Lotz, J, Selle, F, Ray-Coquard, I, Provencher, D, Prat Aparicio, A, Vidal Boixader, L, Scott, C, Yunokawa, M, Medioni, J, Pecuchet, N, Dubot, C, De La Motte Rouge, T, Kaminsky, M, Weber, B, Lortholary, A, Parkinson, C, Williams, S, Banerjee, S, Cosin, J, Hoffman, J, Plante, M, Covens, A, Joly, F, Hirte, H, Amit, A, Matsumoto, K, Tjulandin, S, Hoon Kim, J, Gladieff, L, Sabbatini, R, O'Malley, D, Timmins, P, Kredentser, D, Lainez Milagro, N, Barretina Ginesta, M, Tibau Martorell, A, Gomez De Liano Lista, A, Ojeda Gonzalez, B, Mileshkin, L, Mandai, M, Boere, I, Ottevanger, P, Nam, J, Hamizi, S, Cognetti, F, Warshal, D, Dickson-Michelson, E, Kamelle, S, Mckenzie, N, Rodriguez, G, Armstrong, D, Chalas, E, Celano, P, Behbakht, K, Davidson, S, Welch, S, Helpman, L, Fishman, A, Bruchim, I, Sikorska, M, Slowinska, A, Rogowski, W, Bidzinski, M, Spiewankiewicz, B, Casado Herraez, A, Mendiola Fernandez, C, Gropp-Meier, M, Saito, T, Takehara, K, Enomoto, T, Watari, H, Choi, C, Kim, B, Weon Kim, J, Hegg, R, Poveda A., Floquet A., Ledermann J. A., Asher R., Penson R. T., Oza A. M., Korach J., Huzarski T., Pignata S., Friedlander M., Baldoni A., Park-Simon T. -W., Tamura K., Sonke G. S., Lisyanskaya A., Kim J. -H., Filho E. A., Milenkova T., Lowe E. S., Rowe P., Vergote I., Pujade-Lauraine E., Byrski T., Pautier P., Harter P., Colombo N., Scambia G., Nicoletto M., Nussey F., Clamp A., Penson R., Poveda Velasco A., Rodrigues M., Lotz J. -P., Selle F., Ray-Coquard I., Provencher D., Prat Aparicio A., Vidal Boixader L., Scott C., Yunokawa M., Medioni J., Pecuchet N., Dubot C., De La Motte Rouge T., Kaminsky M. -C., Weber B., Lortholary A., Parkinson C., Ledermann J., Williams S., Banerjee S., Cosin J., Hoffman J., Plante M., Covens A., Sonke G., Joly F., Hirte H., Amit A., Matsumoto K., Tjulandin S., Hoon Kim J., Gladieff L., Sabbatini R., O'Malley D., Timmins P., Kredentser D., Lainez Milagro N., Barretina Ginesta M. P., Tibau Martorell A., Gomez De Liano Lista A., Ojeda Gonzalez B., Mileshkin L., Mandai M., Boere I., Ottevanger P., Nam J. -H., Filho E., Hamizi S., Cognetti F., Warshal D., Dickson-Michelson E., Kamelle S., McKenzie N., Rodriguez G., Armstrong D., Chalas E., Celano P., Behbakht K., Davidson S., Welch S., Helpman L., Fishman A., Bruchim I., Sikorska M., Slowinska A., Rogowski W., Bidzinski M., Spiewankiewicz B., Casado Herraez A., Mendiola Fernandez C., Gropp-Meier M., Saito T., Takehara K., Enomoto T., Watari H., Choi C. H., Kim B. -G., Weon Kim J., Hegg R., Poveda, A, Floquet, A, Ledermann, J, Asher, R, Penson, R, Oza, A, Korach, J, Huzarski, T, Pignata, S, Friedlander, M, Baldoni, A, Park-Simon, T, Tamura, K, Sonke, G, Lisyanskaya, A, Kim, J, Filho, E, Milenkova, T, Lowe, E, Rowe, P, Vergote, I, Pujade-Lauraine, E, Byrski, T, Pautier, P, Harter, P, Colombo, N, Scambia, G, Nicoletto, M, Nussey, F, Clamp, A, Poveda Velasco, A, Rodrigues, M, Lotz, J, Selle, F, Ray-Coquard, I, Provencher, D, Prat Aparicio, A, Vidal Boixader, L, Scott, C, Yunokawa, M, Medioni, J, Pecuchet, N, Dubot, C, De La Motte Rouge, T, Kaminsky, M, Weber, B, Lortholary, A, Parkinson, C, Williams, S, Banerjee, S, Cosin, J, Hoffman, J, Plante, M, Covens, A, Joly, F, Hirte, H, Amit, A, Matsumoto, K, Tjulandin, S, Hoon Kim, J, Gladieff, L, Sabbatini, R, O'Malley, D, Timmins, P, Kredentser, D, Lainez Milagro, N, Barretina Ginesta, M, Tibau Martorell, A, Gomez De Liano Lista, A, Ojeda Gonzalez, B, Mileshkin, L, Mandai, M, Boere, I, Ottevanger, P, Nam, J, Hamizi, S, Cognetti, F, Warshal, D, Dickson-Michelson, E, Kamelle, S, Mckenzie, N, Rodriguez, G, Armstrong, D, Chalas, E, Celano, P, Behbakht, K, Davidson, S, Welch, S, Helpman, L, Fishman, A, Bruchim, I, Sikorska, M, Slowinska, A, Rogowski, W, Bidzinski, M, Spiewankiewicz, B, Casado Herraez, A, Mendiola Fernandez, C, Gropp-Meier, M, Saito, T, Takehara, K, Enomoto, T, Watari, H, Choi, C, Kim, B, Weon Kim, J, Hegg, R, Poveda A., Floquet A., Ledermann J. A., Asher R., Penson R. T., Oza A. M., Korach J., Huzarski T., Pignata S., Friedlander M., Baldoni A., Park-Simon T. -W., Tamura K., Sonke G. S., Lisyanskaya A., Kim J. -H., Filho E. A., Milenkova T., Lowe E. S., Rowe P., Vergote I., Pujade-Lauraine E., Byrski T., Pautier P., Harter P., Colombo N., Scambia G., Nicoletto M., Nussey F., Clamp A., Penson R., Poveda Velasco A., Rodrigues M., Lotz J. -P., Selle F., Ray-Coquard I., Provencher D., Prat Aparicio A., Vidal Boixader L., Scott C., Yunokawa M., Medioni J., Pecuchet N., Dubot C., De La Motte Rouge T., Kaminsky M. -C., Weber B., Lortholary A., Parkinson C., Ledermann J., Williams S., Banerjee S., Cosin J., Hoffman J., Plante M., Covens A., Sonke G., Joly F., Hirte H., Amit A., Matsumoto K., Tjulandin S., Hoon Kim J., Gladieff L., Sabbatini R., O'Malley D., Timmins P., Kredentser D., Lainez Milagro N., Barretina Ginesta M. P., Tibau Martorell A., Gomez De Liano Lista A., Ojeda Gonzalez B., Mileshkin L., Mandai M., Boere I., Ottevanger P., Nam J. -H., Filho E., Hamizi S., Cognetti F., Warshal D., Dickson-Michelson E., Kamelle S., McKenzie N., Rodriguez G., Armstrong D., Chalas E., Celano P., Behbakht K., Davidson S., Welch S., Helpman L., Fishman A., Bruchim I., Sikorska M., Slowinska A., Rogowski W., Bidzinski M., Spiewankiewicz B., Casado Herraez A., Mendiola Fernandez C., Gropp-Meier M., Saito T., Takehara K., Enomoto T., Watari H., Choi C. H., Kim B. -G., Weon Kim J., and Hegg R.
- Abstract
Background: Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has previously been shown to extend progression-free survival versus placebo when given to patients with relapsed high-grade serous or endometrioid ovarian cancer who were platinum sensitive and who had a BRCA1 or BRCA2 (BRCA1/2) mutation, as part of the SOLO2/ENGOT-Ov21 trial. The aim of this final analysis is to investigate the effect of olaparib on overall survival. Methods: This double-blind, randomised, placebo-controlled, phase 3 trial was done across 123 medical centres in 16 countries. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status at baseline of 0–1, had histologically confirmed, relapsed, high-grade serous or high-grade endometrioid ovarian cancer, including primary peritoneal or fallopian tube cancer, and had received two or more previous platinum regimens. Patients were randomly assigned (2:1) to receive olaparib tablets (300 mg in two 150 mg tablets twice daily) or matching placebo tablets using an interactive web or voice-response system. Stratification was by response to previous chemotherapy and length of platinum-free interval. Treatment assignment was masked to patients, treatment providers, and data assessors. The primary endpoint of progression-free survival has been reported previously. Overall survival was a key secondary endpoint and was analysed in all patients as randomly allocated. Safety was assessed in all patients who received at least one treatment dose. This trial is registered with ClinicalTrials.gov, NCT01874353, and is no longer recruiting patients. Findings: Between Sept 3, 2013 and Nov 21, 2014, 295 patients were enrolled. Patients were randomly assigned to receive either olaparib (n=196 [66%]) or placebo (n=99 [34%]). One patient, randomised in error, did not receive olaparib. Median follow-up was 65·7 months (IQR 63·6–69·3) with olaparib and 64·5 months (63·4–68·7) with placebo. Median overall survi
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- 2021
23. Tolerability of maintenance olaparib in newly diagnosed patients with advanced ovarian cancer and a BRCA mutation in the randomized phase III SOLO1 trial
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Colombo, N, Moore, K, Scambia, G, Oaknin, A, Friedlander, M, Lisyanskaya, A, Floquet, A, Leary, A, Sonke, G, Gourley, C, Banerjee, S, Oza, A, Gonzalez-Martin, A, Aghajanian, C, Bradley, W, Kim, J, Mathews, C, Liu, J, Lowe, E, Bloomfield, R, Disilvestro, P, Colombo N., Moore K., Scambia G., Oaknin A., Friedlander M., Lisyanskaya A., Floquet A., Leary A., Sonke G. S., Gourley C., Banerjee S., Oza A., Gonzalez-Martin A., Aghajanian C., Bradley W. H., Kim J. -W., Mathews C., Liu J., Lowe E. S., Bloomfield R., DiSilvestro P., Colombo, N, Moore, K, Scambia, G, Oaknin, A, Friedlander, M, Lisyanskaya, A, Floquet, A, Leary, A, Sonke, G, Gourley, C, Banerjee, S, Oza, A, Gonzalez-Martin, A, Aghajanian, C, Bradley, W, Kim, J, Mathews, C, Liu, J, Lowe, E, Bloomfield, R, Disilvestro, P, Colombo N., Moore K., Scambia G., Oaknin A., Friedlander M., Lisyanskaya A., Floquet A., Leary A., Sonke G. S., Gourley C., Banerjee S., Oza A., Gonzalez-Martin A., Aghajanian C., Bradley W. H., Kim J. -W., Mathews C., Liu J., Lowe E. S., Bloomfield R., and DiSilvestro P.
- Abstract
Objectives: In the phase III SOLO1 trial (NCT01844986), maintenance olaparib provided a substantial progression-free survival benefit in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation who were in response after platinum-based chemotherapy. We analyzed the timing, duration and grade of the most common hematologic and non-hematologic adverse events in SOLO1. Methods: Eligible patients were randomized to olaparib tablets 300 mg twice daily (N = 260) or placebo (N = 131), with a 2-year treatment cap in most patients. Safety outcomes were analyzed in detail in randomized patients who received at least one dose of study drug (olaparib, n = 260; placebo, n = 130). Results: Median time to first onset of the most common hematologic (anemia, neutropenia, thrombocytopenia) and non-hematologic (nausea, fatigue/asthenia, vomiting) adverse events was <3 months in olaparib-treated patients. The first event of anemia, neutropenia, thrombocytopenia, nausea and vomiting lasted a median of <2 months and the first event of fatigue/asthenia lasted a median of 3.48 months in the olaparib group. These adverse events were manageable with supportive treatment and/or olaparib dose modification in most patients, with few patients requiring discontinuation of olaparib. Of 162 patients still receiving olaparib at month 24, 64.2% were receiving the recommended starting dose of olaparib 300 mg twice daily. Conclusions: Maintenance olaparib had a predictable and manageable adverse event profile in the newly diagnosed setting with no new safety signals identified. Adverse events usually occurred early, were largely manageable and led to discontinuation in a minority of patients.
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- 2021
24. Patient-centred outcomes and effect of disease progression on health status in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation receiving maintenance olaparib or placebo (SOLO1): a randomised, phase 3 trial
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Friedlander, M, Moore, K, Colombo, N, Scambia, G, Kim, B, Oaknin, A, Lisyanskaya, A, Sonke, G, Gourley, C, Banerjee, S, Oza, A, Gonzalez-Martin, A, Aghajanian, C, Bradley, W, Liu, J, Mathews, C, Selle, F, Lortholary, A, Lowe, E, Hettle, R, Flood, E, Parkhomenko, E, Disilvestro, P, Friedlander M., Moore K. N., Colombo N., Scambia G., Kim B. -G., Oaknin A., Lisyanskaya A., Sonke G. S., Gourley C., Banerjee S., Oza A., Gonzalez-Martin A., Aghajanian C., Bradley W. H., Liu J., Mathews C., Selle F., Lortholary A., Lowe E. S., Hettle R., Flood E., Parkhomenko E., DiSilvestro P., Friedlander, M, Moore, K, Colombo, N, Scambia, G, Kim, B, Oaknin, A, Lisyanskaya, A, Sonke, G, Gourley, C, Banerjee, S, Oza, A, Gonzalez-Martin, A, Aghajanian, C, Bradley, W, Liu, J, Mathews, C, Selle, F, Lortholary, A, Lowe, E, Hettle, R, Flood, E, Parkhomenko, E, Disilvestro, P, Friedlander M., Moore K. N., Colombo N., Scambia G., Kim B. -G., Oaknin A., Lisyanskaya A., Sonke G. S., Gourley C., Banerjee S., Oza A., Gonzalez-Martin A., Aghajanian C., Bradley W. H., Liu J., Mathews C., Selle F., Lortholary A., Lowe E. S., Hettle R., Flood E., Parkhomenko E., and DiSilvestro P.
- Abstract
Background: In the phase 3 SOLO1 trial, maintenance olaparib provided a significant progression-free survival benefit versus placebo in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation in response after platinum-based chemotherapy. We analysed health-related quality of life (HRQOL) and patient-centred outcomes in SOLO1, and the effect of radiological disease progression on health status. Methods: SOLO1 is a randomised, double-blind, international trial done in 118 centres and 15 countries. Eligible patients were aged 18 years or older; had an Eastern Cooperative Oncology Group performance status score of 0–1; had newly diagnosed, advanced, high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer with a BRCA mutation; and were in clinical complete or partial response to platinum-based chemotherapy. Patients were randomly assigned (2:1) to either 300 mg olaparib tablets or placebo twice per day using an interactive voice and web response system and were treated for up to 2 years. Treatment assignment was masked for patients and for clinicians giving the interventions, and those collecting and analysing the data. Randomisation was stratified by response to platinum-based chemotherapy (clinical complete or partial response). HRQOL was a secondary endpoint and the prespecified primary HRQOL endpoint was the change from baseline in the Functional Assessment of Cancer Therapy–Ovarian Cancer Trial Outcome Index (TOI) score for the first 24 months. TOI scores range from 0 to 100 (higher scores indicated better HRQOL), with a clinically meaningful difference defined as a difference of at least 10 points. Prespecified exploratory endpoints were quality-adjusted progression-free survival and time without significant symptoms of toxicity (TWiST). HRQOL endpoints were analysed in all randomly assigned patients. The trial is ongoing but closed to new participants. This trial is registered with ClinicalTrials.go
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- 2021
25. Cardiotoxicity during long-term trastuzumab use in patients with HER2-positive metastatic breast cancer:who needs cardiac monitoring?
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Bouwer, N. I., Steenbruggen, T. G., van Rosmalen, J., Rier, H. N., Kitzen, J. J.E.M., van Bekkum, M. L., Tije, A. J.Ten, de Jong, P. C., Drooger, J. C., Holterhues, C., Smorenburg, C. H., Kofflard, M. J.M., Boersma, E., Sonke, G. S., Levin, M. D., Jager, A., Bouwer, N. I., Steenbruggen, T. G., van Rosmalen, J., Rier, H. N., Kitzen, J. J.E.M., van Bekkum, M. L., Tije, A. J.Ten, de Jong, P. C., Drooger, J. C., Holterhues, C., Smorenburg, C. H., Kofflard, M. J.M., Boersma, E., Sonke, G. S., Levin, M. D., and Jager, A.
- Abstract
Purpose: Patients with HER2-positive metastatic breast cancer (MBC) usually receive many years of trastuzumab treatment. It is unknown whether these patients require continuous left ventricular ejection fraction (LVEF) monitoring. We studied a real-world cohort to identify risk factors for cardiotoxicity to select patients in whom LVEF monitoring could be omitted. Methods: We included patients with HER2-positive MBC who received > 1 cycle of trastuzumab-based therapy in eight Dutch hospitals between 2000 and 2014. Cardiotoxicity was defined as LVEF < 50% that declined > 10%-points and was categorized into non-severe cardiotoxicity (LVEF 40–50%) and severe cardiotoxicity (LVEF < 40%). Multivariable Cox and mixed model analyses were performed to identify risk factors associated with cardiotoxicity. Additionally, we explored the reversibility of cardiotoxicity in patients who continued trastuzumab. Results: In total, 429 patients were included. Median follow-up for cardiotoxicity was 15 months (interquartile range 8–31 months). The yearly incidence of non-severe + severe cardiotoxicity in the first and second year was 11.7% and 9.1%, respectively, which decreased thereafter. The yearly incidence of severe cardiotoxicity was low (2.8%) and stable over time. In non-smoking patients with baseline LVEF > 60% and no cardiotoxicity during prior neoadjuvant/adjuvant treatment, the cumulative incidence of severe cardiotoxicity was 3.1% after 4 years of trastuzumab. Despite continuing trastuzumab, LVEF decline was reversible in 56% of patients with non-severe cardiotoxicity and in 33% with severe cardiotoxicity. Conclusions: Serial cardiac monitoring can be safely omitted in non-smoking patients with baseline LVEF > 60% and without cardiotoxicity during prior neoadjuvant/adjuvant treatment.
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- 2021
26. Health-related quality of life after interval cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with stage III ovarian cancer
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MS Gynaecologische Oncologie, Cancer, Arts-assistenten Radiotherapie, MS CGO, Koole, S N, Kieffer, J M, K Sikorska, Schagen van Leeuwen, J H, Schreuder, H W R, Hermans, R H, de Hingh, I H, van der Velden, J, Arts, H J, van Ham, M A P C, Aalbers, A G, Verwaal, V J, Van de Vijver, K K, Sonke, G S, van Driel, W J, Aaronson, N K, MS Gynaecologische Oncologie, Cancer, Arts-assistenten Radiotherapie, MS CGO, Koole, S N, Kieffer, J M, K Sikorska, Schagen van Leeuwen, J H, Schreuder, H W R, Hermans, R H, de Hingh, I H, van der Velden, J, Arts, H J, van Ham, M A P C, Aalbers, A G, Verwaal, V J, Van de Vijver, K K, Sonke, G S, van Driel, W J, and Aaronson, N K
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- 2021
27. Intraperitoneal treatment for advanced ovarian cancer, the dutch experience. What did we learn?
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Rietveld, M. J. A., Jacobus van der Velden, Westermann, A. M., Driel, W. J., Sonke, G. S., Witteveen, P. O., Ploos Amstel, F. K., Massuger, L. F. A. G., Ottevanger, P. B., Obstetrics and Gynaecology, Cancer Center Amsterdam, Oncology, and CCA - Cancer Treatment and Quality of Life
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Treatment ,All institutes and research themes of the Radboud University Medical Center ,Survival ,Toxicity ,Ovarian cancer ,Intraperitoneal ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] - Abstract
Background: Combined administration of intravenous (iv) and intraperitoneal (ip) (iv/ip) chemotherapy is an effective adjuvant treatment option after primary debulking surgery (PDS) for advanced ovarian cancer (OC). Increased toxicity and patient burden limit its use in daily practice. Objective: To assess toxicity and survival outcomes of iv/ip chemotherapy in daily practice in the Netherlands. Methods: This retrospective cohort study included 81 women who underwent at least an optimal PDS for FIGO stage III OC followed by iv/ip chemotherapy according to the Armstrong regimen, in four hospitals in the Netherlands between January 2007 and May 2016. We collected information on surgical procedure, abdominal port implantation, toxicity, and recurrence-free and overall survival. Results: All participants underwent PDS, of whom 60 (74%) had their ip catheter implanted during PDS. Most frequently reported all grade toxicity was haematological n = 44 (54%). Forty-four patients (54%) completed all six cycles of iv/ip chemotherapy. The most frequent causes of discontinuation of iv/ip administration were renal dysfunction (12/37 = 32%) and catheter problems (7/37 = 19%). Median recurrence-free survival and overall survival were 24 months (range 0 – 108) and 80 months (range 4-115), respectively. Surgical outcome, completion of more than three courses of treatment and intra-abdominal localisation of recurrent disease were associated with better survival outcomes. Conclusion: In daily practice, 54% of patients with advanced OC could complete all scheduled cycles of iv/ ip chemotherapy with acceptable morbidity and toxicity, leading to outcomes comparable with the results of published trials on iv/ip chemotherapy.
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- 2020
28. Efficacy of Maintenance Olaparib for Patients with Newly Diagnosed Advanced Ovarian Cancer with a BRCA Mutation: Subgroup Analysis Findings from the SOLO1 Trial
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Disilvestro, P, Colombo, N, Scambia, G, Kim, B, Oaknin, A, Friedlander, M, Lisyanskaya, A, Floquet, A, Leary, A, Sonke, G, Gourley, C, Banerjee, S, Oza, A, Gonzalez-Martin, A, Aghajanian, C, Bradley, W, Mathews, C, Liu, J, Lowe, E, Bloomfield, R, Moore, K, DiSilvestro P., Colombo N., Scambia G., Kim B. -G., Oaknin A., Friedlander M., Lisyanskaya A., Floquet A., Leary A., Sonke G. S., Gourley C., Banerjee S., Oza A., Gonzalez-Martin A., Aghajanian C. A., Bradley W. H., Mathews C. A., Liu J., Lowe E. S., Bloomfield R., Moore K. N., Disilvestro, P, Colombo, N, Scambia, G, Kim, B, Oaknin, A, Friedlander, M, Lisyanskaya, A, Floquet, A, Leary, A, Sonke, G, Gourley, C, Banerjee, S, Oza, A, Gonzalez-Martin, A, Aghajanian, C, Bradley, W, Mathews, C, Liu, J, Lowe, E, Bloomfield, R, Moore, K, DiSilvestro P., Colombo N., Scambia G., Kim B. -G., Oaknin A., Friedlander M., Lisyanskaya A., Floquet A., Leary A., Sonke G. S., Gourley C., Banerjee S., Oza A., Gonzalez-Martin A., Aghajanian C. A., Bradley W. H., Mathews C. A., Liu J., Lowe E. S., Bloomfield R., and Moore K. N.
- Abstract
PURPOSE In SOLO1, maintenance olaparib (300 mg twice daily) significantly improved progression-free survival (PFS) for patients with newly diagnosed BRCA1- and/or BRCA2-mutated advanced ovarian cancer compared with placebo (hazard ratio [HR], 0.30; 95% CI, 0.23 to 0.41; median not reached v 13.8 months). We investigated PFS in SOLO1 for subgroups of patients based on preselected baseline factors. PATIENTS AND METHODS Investigator-assessed PFS subgroup analyses of SOLO1 included clinical response after platinum-based chemotherapy (complete [CR] or partial response [PR]), surgery type (upfront or interval surgery), disease status after surgery (residual or no gross residual disease), and BRCA mutation status (BRCA1 or BRCA2). Additionally, we evaluated PFS in patients with stage III disease who underwent upfront surgery and had no gross residual disease. We also report objective response rate. RESULTS The risk of disease progression or death was reduced with olaparib compared with placebo by 69% (HR, 0.31; 95% CI, 0.21 to 0.46) and 63% (HR, 0.37; 95% CI, 0.24 to 0.58) in patients undergoing upfront or interval surgery; 56% (HR, 0.44; 95% CI, 0.25 to 0.77) and 67% (HR, 0.33; 95% CI, 0.23 to 0.46) in patients with residual or no residual disease after surgery; 66% (HR, 0.34; 95% CI, 0.24 to 0.47) and 69% in women with clinical CR or PR at baseline (HR, 0.31; 95% CI, 0.18 to 0.52); and 59% (HR, 0.41; 95% CI, 0.30 to 0.56) and 80% (HR 0.20; 95% CI, 0.10 to 0.37) in patients with a BRCA1 or BRCA2 mutation, respectively. CONCLUSION Patients with newly diagnosed advanced ovarian cancer achieve substantial benefit from maintenance olaparib treatment regardless of baseline surgery outcome, response to chemotherapy, or BRCA mutation type.
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- 2020
29. Intraperitoneal treatment for advanced ovarian cancer, the Dutch experience. What did we learn?
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Arts-assistenten Radiotherapie, MS Medische Oncologie, Cancer, Rietveld, M J A, van der Velden, J, Westermann, A M, van Driel, W J, Sonke, G S, Witteveen, P O, Ploos van Amstel, F K, Massuger, L F A G, Ottevanger, P B, Arts-assistenten Radiotherapie, MS Medische Oncologie, Cancer, Rietveld, M J A, van der Velden, J, Westermann, A M, van Driel, W J, Sonke, G S, Witteveen, P O, Ploos van Amstel, F K, Massuger, L F A G, and Ottevanger, P B
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- 2020
30. Additional value and potential use of the 70-gene prognosis signature in node-negative breast cancer in daily clinical practice
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Bueno-de-Mesquita, J. M., Sonke, G. S., van de Vijver, M. J., and Linn, S. C.
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- 2011
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31. Abstract GS5-06: Towards omitting breast surgery in patients with a pathologic complete response after neoadjuvant systemic treatment: interim analysis of the MICRA trial (Minimally Invasive Complete Response Assessment)
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Peeters, Marie-Jeanne T.F.D. Vrancken, primary, van Loevezijn, A, additional, van der Noordaa, M EM, additional, van Duijnhoven, F H, additional, Loo, C E, additional, van Werkhoven, E, additional, van de Vijver, K K, additional, Wiersma, T, additional, Winter-Warnars, H AO, additional, Sonke, G S, additional, Blanken, C., additional, and Zonnevels, B., additional
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- 2020
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32. Symptomatic brain metastases from small-cell carcinoma of the urinary bladder: The Netherlands Cancer Institute experience and literature review
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Bex, A., Sonke, G. S., Pos, F. J., Brandsma, D., Kerst, J. M., and Horenblas, S.
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- 2010
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33. A simple system for grading the response of breast cancer to neoadjuvant chemotherapy
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Rodenhuis, S., Mandjes, I. A., Wesseling, J., van de Vijver, M. J., Peeters, M.-J. T., Sonke, G. S., and Linn, S. C.
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- 2010
34. Study protocols of three parallel phase 1 trials combining radical radiotherapy with the PARP inhibitor olaparib
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de Haan, R, van Werkhoven, E, van den Heuvel, M M, Peulen, H M U, Sonke, G S, Elkhuizen, P, van den Brekel, M W M, Tesselaar, M E T, Vens, C, Schellens, J H M, van Triest, B, Verheij, M, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Arbeids- en Organisatie Psychologie (Psychologie, FMG), FMG, MKA AMC (OII, ACTA), Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, CCA - Cancer Treatment and quality of life, Academic Medical Center, and Maxillofacial Surgery (AMC)
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0301 basic medicine ,Oncology ,Cancer Research ,Lung Neoplasms ,medicine.medical_treatment ,Piperazines ,Study Protocol ,chemistry.chemical_compound ,Olaparib ,0302 clinical medicine ,TITE-CRM ,Surgical oncology ,Carcinoma, Non-Small-Cell Lung ,Neoplasms ,Doselimiting toxicity ,Dose limiting toxicity ,Common Terminology Criteria for Adverse Events ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Tolerability ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,PARP inhibitor ,Carcinoma, Squamous Cell ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] ,medicine.medical_specialty ,Maximum Tolerated Dose ,Antineoplastic Agents ,Breast Neoplasms ,Phase 1 ,Poly(ADP-ribose) Polymerase Inhibitors ,Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] ,lcsh:RC254-282 ,03 medical and health sciences ,Breast cancer ,SDG 3 - Good Health and Well-being ,Internal medicine ,Genetics ,medicine ,Humans ,Radiotherapy ,Dose escalation ,business.industry ,Radiosensitisation ,medicine.disease ,Head and neck squamous-cell carcinoma ,Radiation therapy ,030104 developmental biology ,chemistry ,Phthalazines ,Radiotherapy, Adjuvant ,business - Abstract
BackgroundPoly (ADP-ribose) Polymerase (PARP) inhibitors are promising novel radiosensitisers. Pre-clinical models have demonstrated potent and tumour-specific radiosensitisation by PARP inhibitors. Olaparib is a PARP inhibitor with a favourable safety profile in comparison to clinically used radiosensitisers including cisplatin when used as single agent. However, data on safety, tolerability and efficacy of olaparib in combination with radiotherapy are limited.MethodsOlaparib is dose escalated in combination with radical (chemo-)radiotherapy regimens for non-small cell lung cancer (NSCLC), breast cancer and head and neck squamous cell carcinoma (HNSCC) in three parallel single institution phase 1 trials. All trials investigate a combination treatment of olaparib and radiotherapy, the NSCLC trial also investigates a triple combination of olaparib, radiotherapy and concurrent low dose cisplatin. The primary objective is to identify the maximum tolerated dose of olaparib in these combination treatments, defined as the dose closest to but not exceeding a 15% probability of dose limiting toxicity. Each trial has a separate dose limiting toxicity definition, taking into account incidence, duration and severity of expected toxicities without olaparib. Dose escalation is performed using a time-to-event continual reassessment method (TITE-CRM). TITE-CRM enables the incorporation of late onset toxicity until one year after treatment in the dose limiting toxicity definition while maintaining an acceptable trial duration. Olaparib treatment starts two days before radiotherapy and continues during weekends until two days after radiotherapy. Olaparib will also be given two weeks and one week before radiotherapy in the breast cancer trial and HNSCC trial respectively to allow for translational research. Toxicity is scored using common terminology criteria for adverse events (CTCAE) version 4.03. Blood samples, and tumour biopsies in the breast cancer trial, are collected for pharmacokinetic and pharmacodynamic analyses.DiscussionWe designed three parallel phase 1 trials to assess the safety and tolerability of the PARP inhibitor olaparib in combination with radical (chemo-)radiotherapy treatment regimens. PARP inhibitors have the potential to improve outcomes in patients treated with radical (chemo-)radiotherapy, by achieving higher locoregional control rates and/or less treatment associated toxicity.Trial registrationClinicalTrials.govIdentifiers: NCT01562210 (registered March 23, 2012), NCT02227082 (retrospectively registered August 27, 2014), NCT02229656 (registered September 1, 2014).
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- 2019
35. Incidence of cardiotoxicity over time in patients with HER2-positive metastatic breast cancer on long term treatment with trastuzumab and the potential risk factors
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Bouwer, N. Nathalie, Steenbruggen, T. G., Rier, H. N., Kitzen, J. J. E. M., Beelen, K. J., Ten Tije, A. J., De Jong, P. C., Drooger, J. C., Holterhues, C., Van Rosmalen, J., Kofflard, M. J. M., Boersma, E., Sonke, G. S., Levin, M-D, Jager, A., Epidemiology, Cardiology, and Medical Oncology
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SDG 3 - Good Health and Well-being - Published
- 2019
36. Effects and moderators of exercise on sleep in adults with cancer : Individual patient data and aggregated meta-analyses
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Bernard, P, Savard, J, Steindorf, K, Sweegers, M G, Courneya, K S, Newton, R U, Aaronson, N K, Jacobsen, P B, May, A M, Galvao, D A, Chinapaw, M J, Stuiver, M M, Griffith, K A, Mesters, I, Knoop, H, Goedendorp, M M, Bohus, M, Thorsen, L, Schmidt, M E, Ulrich, C M, Sonke, G S, van Harten, W, Winters-Stone, K M, Velthuis, M J, Taaffe, D R, van Mechelen, W, Kersten, M J, Nollet, F, Wenzel, J, Wiskemann, J, Verdonck-de Leeuw, I M, Brug, J, Buffart, L M, Bernard, P, Savard, J, Steindorf, K, Sweegers, M G, Courneya, K S, Newton, R U, Aaronson, N K, Jacobsen, P B, May, A M, Galvao, D A, Chinapaw, M J, Stuiver, M M, Griffith, K A, Mesters, I, Knoop, H, Goedendorp, M M, Bohus, M, Thorsen, L, Schmidt, M E, Ulrich, C M, Sonke, G S, van Harten, W, Winters-Stone, K M, Velthuis, M J, Taaffe, D R, van Mechelen, W, Kersten, M J, Nollet, F, Wenzel, J, Wiskemann, J, Verdonck-de Leeuw, I M, Brug, J, and Buffart, L M
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- 2019
37. Study protocols of three parallel phase 1 trials combining radical radiotherapy with the PARP inhibitor olaparib
- Author
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Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, de Haan, R, van Werkhoven, E, van den Heuvel, M M, Peulen, H M U, Sonke, G S, Elkhuizen, P, van den Brekel, M W M, Tesselaar, M E T, Vens, C, Schellens, J H M, van Triest, B, Verheij, M, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, de Haan, R, van Werkhoven, E, van den Heuvel, M M, Peulen, H M U, Sonke, G S, Elkhuizen, P, van den Brekel, M W M, Tesselaar, M E T, Vens, C, Schellens, J H M, van Triest, B, and Verheij, M
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- 2019
38. Effects and moderators of exercise on sleep in adults with cancer: Individual patient data and aggregated meta-analyses
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Bernard, P. A., Savard, J., Steindorf, K., Sweegers, M. G., Courneya, K. S., Newton, R. U., Aaronson, N. K., Jacobsen, P. B., May, A. M., Galvao, D. A., Chinapaw, M. J., Stuiver, M. M., Griffith, K. A., Mesters, I, Knoop, H., Goedendorp, M. M., Bohus, M., Thorsen, L., Schmidt, M. E., Ulrich, C. M., Sonke, G. S., van Harten, W., Winters-Stone, K. M., Velthuis, M. J., Taaffe, D. R., van Mechelen, W., Kersten, M. J., Nollet, F., Wenzel, J., Wiskemann, J., Verdonck-de Leeuw, I. M., Brug, J., Buffart, L. M., Bernard, P. A., Savard, J., Steindorf, K., Sweegers, M. G., Courneya, K. S., Newton, R. U., Aaronson, N. K., Jacobsen, P. B., May, A. M., Galvao, D. A., Chinapaw, M. J., Stuiver, M. M., Griffith, K. A., Mesters, I, Knoop, H., Goedendorp, M. M., Bohus, M., Thorsen, L., Schmidt, M. E., Ulrich, C. M., Sonke, G. S., van Harten, W., Winters-Stone, K. M., Velthuis, M. J., Taaffe, D. R., van Mechelen, W., Kersten, M. J., Nollet, F., Wenzel, J., Wiskemann, J., Verdonck-de Leeuw, I. M., Brug, J., and Buffart, L. M.
- Abstract
Objectives: To evaluate the effects of exercise interventions on sleep disturbances and sleep quality in patients with mixed cancer diagnoses, and identify demographic, clinical, and intervention-related moderators of these effects. Methods: Individual patient data (IPD) and aggregated meta-analyses of randomized controlled trials (RCTs). Using data from the Predicting OptimaL cAncer RehabIlitation and Supportive care project, IPD of 2173 adults (mean age = 54.8) with cancer from 17 RCTs were analyzed. A complementary systematic search was conducted (until November 2018) to study the overall effects and test the representativeness of analyzed IPD. Effect sizes of exercise effects on self-reported sleep outcomes were calculated for all included RCTs. Linear mixed-effect models were used to evaluate the effects of exercise on post-intervention outcome values, adjusting for baseline values. Moderator effects were studied by testing interactions for demographic, clinical and intervention-related characteristics. Results: For all 27 eligible RCTs from the updated search, exercise interventions significantly decreased sleep disturbances in adults with cancer (g = −0.09, 95% CI [−0.16; −0.02]). No significant effect was obtained for sleep quality. RCTs included in IPD analyses constituted a representative sample of the published literature. The intervention effects on sleep disturbances were not significantly moderated by any demographic, clinical, or intervention-related factor, nor by sleep disturbances. Conclusions: This meta-analysis provides some evidence that, compared to control conditions, exercise interventions may improve sleep disturbances, but not sleep quality, in cancer patients, although this effect is of a small magnitude. Among the investigated variables, none was found to significantly moderate the effect of exercise interventions on sleep disturbances.
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- 2019
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39. Effects and moderators of exercise on sleep in adults with cancer: Individual patient data and aggregated meta-analyses
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JC onderzoeksprogramma Kanker, Cancer, Epidemiology & Health Economics, Epi Kanker Team 1, Bernard, P, Savard, J, Steindorf, K, Sweegers, M G, Courneya, K S, Newton, R U, Aaronson, N K, Jacobsen, P B, May, A M, Galvao, D A, Chinapaw, M J, Stuiver, M M, Griffith, K A, Mesters, I, Knoop, H, Goedendorp, M M, Bohus, M, Thorsen, L, Schmidt, M E, Ulrich, C M, Sonke, G S, van Harten, W, Winters-Stone, K M, Velthuis, M J, Taaffe, D R, van Mechelen, W, Kersten, M J, Nollet, F, Wenzel, J, Wiskemann, J, Verdonck-de Leeuw, I M, Brug, J, Buffart, L M, JC onderzoeksprogramma Kanker, Cancer, Epidemiology & Health Economics, Epi Kanker Team 1, Bernard, P, Savard, J, Steindorf, K, Sweegers, M G, Courneya, K S, Newton, R U, Aaronson, N K, Jacobsen, P B, May, A M, Galvao, D A, Chinapaw, M J, Stuiver, M M, Griffith, K A, Mesters, I, Knoop, H, Goedendorp, M M, Bohus, M, Thorsen, L, Schmidt, M E, Ulrich, C M, Sonke, G S, van Harten, W, Winters-Stone, K M, Velthuis, M J, Taaffe, D R, van Mechelen, W, Kersten, M J, Nollet, F, Wenzel, J, Wiskemann, J, Verdonck-de Leeuw, I M, Brug, J, and Buffart, L M
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- 2019
40. Perioperative change in CA125 is an independent prognostic factor for improved clinical outcome in advanced ovarian cancer
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Timmermans, M., Zwakman, N., Sonke, G. S., Van de Vijver, K. K., Duk, M. J., van der Aa, M. A., Kruitwagen, R. F., Timmermans, M., Zwakman, N., Sonke, G. S., Van de Vijver, K. K., Duk, M. J., van der Aa, M. A., and Kruitwagen, R. F.
- Abstract
Objective: Despite being the most important prognostic factor for prolonged overall survival in epithelial ovarian cancer (EOC), the measurement of residual disease is hampered by its subjective character. Additional assessment tools are needed to establish the success of cytoreductive surgery in order to predict patients' prognosis more accurately. The aim of this study is to evaluate the independent prognostic value of perioperative CA125 change in advanced stage EOC patients.Study design: We identified all patients who underwent primary cytoreductive surgery for advanced stage (FIGO IIB-IV) EOC between 2008 and 2015, from the Netherlands Cancer Registry. The relative perioperative change in CA125 was categorized into four groups; increase, = 80% decline. Overall survival (OS) was analyzed using Kaplan-Meier survival curves and multivariable cox regression models.Results: We included 1232 eligible patients with known pre- and postoperative CA125 serum levels. Patients with a decline of >= 80% in CA125 levels experienced improved OS compared to those with a decline of = 80% 0.52(0.41-0.66)).Conclusions: This study shows that the perioperative change in CA125 is an independent prognostic factor for overall survival after primary surgery for EOC patients. This pleads for the use of a combined model, consisting of perioperative CA125 change and the outcome of residual disease, in order to predict the prognosis of EOC patients more accurately. (C) 2019 Elsevier B.V. All rights reserved.
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- 2019
41. Outcome of surgery in advanced ovarian cancer varies between geographical regions; opportunities for improvement in The Netherlands
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Timmermans, M., Sonke, G. S., Slangen, B. F. M., Baalbergen, A., Bekkers, R. L. M., Fons, G., Gerestein, C. G., Kruse, A. J., Roes, E. M., Zusterzeel, P. L. M., Van de Vijver, K. K., Kruitwagen, R. F. P. M., van der Aa, M. A., Timmermans, M., Sonke, G. S., Slangen, B. F. M., Baalbergen, A., Bekkers, R. L. M., Fons, G., Gerestein, C. G., Kruse, A. J., Roes, E. M., Zusterzeel, P. L. M., Van de Vijver, K. K., Kruitwagen, R. F. P. M., and van der Aa, M. A.
- Abstract
Introduction: The care for patients with epithelial ovarian cancer(EOC) is organised in eight different geographical regions in the Netherlands. This situation allows us to study differences in practice patterns and outcomes between geographical regions for patients with FIGO stage IIIC and IV.Methods: We identified all EOC patients who were diagnosed with FIGO stage IIIC or IV between 01.01.2008 and 31.12.2015 from the Netherlands Cancer Registry. Descriptive statistics were used to summarize treatment and treatment sequence(primary cytoreductive surgery(PCS) or neoadjuvant chemotherapy and interval cytoreductive surgery(NACT-ICS)). Moreover, outcome of surgery was compared between geographical regions. Multilevel logistic regression was used to assess whether existing variation is explained by geographical region and case-mix factors.Results: Overall, 6,741 patients were diagnosed with FIGO IIIC or IV disease. There were no differences in the percentage of patients that received any form of treatment between the geographical regions(range 80-86%, P=0.162). In patients that received cytoreductive surgery and chemotherapy, a significant variation between the geographical regions was observed in the use of PCS and NACT-ICS(PCS: 24-48%, P <0.001). The percentage of complete cytoreductive surgeries after PCS ranged from 10 to 59%(P <0.001) and after NACT-ICS from 37 to 70%(P <0.001). Moreover, geographical region was independently associated with the outcome of surgery, also when adjusted for treatment sequence(P <0.001).Conclusion: We observed a significant variation in treatment approach for advanced EOC between geographical regions in the Netherlands. Furthermore, the probability to achieve no residual disease differed significantly between regions, regardless of treatment sequence. This may suggest that surgical outcomes can be improved across geographical regions. (C) 2019 Elsevier Ltd, BASO similar to The Association for Cancer
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- 2019
42. The prognostic value of residual disease after neoadjuvant chemotherapy in advanced ovarian cancer: A systematic review
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Timmermans, M., van der Hel, O., Sonke, G. S., Van de Vijver, K. K., van der Aa, M. A., Kruitwagen, R. F., Timmermans, M., van der Hel, O., Sonke, G. S., Van de Vijver, K. K., van der Aa, M. A., and Kruitwagen, R. F.
- Abstract
Introduction. The ability to minimize residual disease during primary cytoreductive surgery is the strongest predictor for improved overall survival in advanced ovarian cancer. But while the probability to achieve a macroscopic complete resection increases if surgery is preceded by neoadjuvant chemotherapy (NACT), survival rates after NACT are similar to those observed after primary surgery. This may suggest that the prognostic effect of residual disease is altered after NACT. More specifically, randomized data suggest that there is no difference between optimal (0.1-1 cm) and suboptimal (>1 cm) cytoreductive surgery after NACT. Therefore, the aim of the current review is to establish the prognostic effect of the amount of residual disease after interval cytoreductive surgery (ICS) on overall survival.Methods. Potential articles for inclusion in the current review were systematically searched through Medline, Embase and Cochrane in September 2017. Median overall survival (mOS) was summarized by the outcome of ICS per study. In addition, mOS was summarized for all studies together stratified by the outcome of ICS, based on the principle of a weighted average.Results. In total, 3677 unique manuscripts were individually screened on title and abstract, which resulted in 11 individual studies that comprised a total of 2178 patients. MOS was 41 months for patients with no residual disease (range 33-54 months), 27 months for patients with 0.1-1 cm of residual disease (range 19-38 months) and 21 months with >1 cm of residual disease (range 14-27 months). Six studies showed significant differences between optimal and suboptimal ICS, while five studies showed no differences.Conclusion. The summary of the currently available literature showed that after NACT, patients with optimal cytoreductive surgery experience lengthened survival compared to patients with suboptimal cytoreductive surgery. Patients with no macroscopic residual disease have, howe
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- 2019
43. Localization of distant metastases defines prognosis and treatment efficacy in patients with FIGO stage IV ovarian cancer
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Timmermans, Maite, Sonke, G. S., Van de Vijver, K. K., Ottevanger, P. B., Nijman, H. W., van der Aa, M. A., Kruitwagen, R. F. P. M., Timmermans, Maite, Sonke, G. S., Van de Vijver, K. K., Ottevanger, P. B., Nijman, H. W., van der Aa, M. A., and Kruitwagen, R. F. P. M.
- Abstract
Background Patients with ovarian cancer who are diagnosed with Federation of Gynecology and Obstetrics (FIGO) stage IV disease are a highly heterogeneous group with possible survival differences. The FIGO staging system was therefore updated in 2014.Objective To evaluate the 2014 changes to FIGO stage IV ovarian cancer on overall survival.Methods We identified all patients diagnosed with FIGO stage IV disease between January 2008 and December 2015 from the Netherlands Cancer Registry. We analyzed the prognostic effect of FIGO IVa versus IVb. In addition, patients with extra-abdominal lymph node involvement as the only site of distant disease were analyzed separately. Overall survival was analyzed by Kaplan-Meier curves and multivariable Cox regression models.Results We identified 2436 FIGO IV patients, of whom 35% were diagnosed with FIGO IVa disease. Five-year overall survival of FIGO IVa and IVb patients (including those with no or limited therapy) was 8.9% and 13.0%, respectively (p=0.51). Patients with only extra-abdominal lymph node involvement had a significant better overall survival than all other FIGO IV patients (5-year overall survival 25.9%, hazard ratio 0.77 [95% CI 0.62 to 0.95]).Conclusion Our study shows that the FIGO IV sub-classification into FIGO IVa and IVB does not provide additional prognostic information. Patients with extra-abdominal lymph node metastases as the only site of FIGO IV disease, however, have a better prognosis than all other FIGO IV patients. These results warrant a critical appraisal of the current FIGO IV sub-classification.
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- 2019
44. Overview of non-epithelial ovarian tumours: Incidence and survival in the Netherlands, 1989-2015
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Van der Hel, O. L., Timmermans, M., van Altena, A. M., Kruitwagen, R. F. P. M., Slangen, B. F. M., Sonke, G. S., van de Vijver, K. K., Van der Aa, M. A., Van der Hel, O. L., Timmermans, M., van Altena, A. M., Kruitwagen, R. F. P. M., Slangen, B. F. M., Sonke, G. S., van de Vijver, K. K., and Van der Aa, M. A.
- Abstract
Introduction: About 5% of ovarian tumours have a non-epithelial histology, including germ cell tumours (GCTs), sex cord-stromal tumours (SCSTs) and sarcomas. Because these non-epithelial ovarian tumours are rare and population-based studies are scarce, the aim of this population-based study is to describe trends in the incidence, treatment and survival of women with these tumours in the Netherlands.Methods: All women diagnosed with non-epithelial ovarian malignant tumours in the Netherlands between 1989 and 2015 were identified from the Netherlands Cancer Registry. Data on demographics, tumour characteristics and initial treatment were collected, and overall survival was analysed.Results: A total of 1258 non-epithelial ovarian tumours were identified comprising 752 GCTs (60%), 341 SCSTs (27%) and 165 sarcomas (13%). The European age-standardised incidence rate (ESR) was 0.4 per 100,000 persons per year for GCTs, 0.2 for SCSTs and 0.1 for sarcomas. Approximately 97% of patients underwent surgical resection for the primary tumour, 31% received systemic treatment and 3% radiotherapy. Between the late 1980s and 2015, five-year overall survival improved for all histologic subtypes: GCTs rose from 73% to 88% (p = 0.03), SCSTs from 64% to 81% (p = 0.57) and sarcomas from 20% to 29% (p = 0.14).Conclusion: Malignant GCTs and SCSTs are rare, and their incidence has not significantly changed over recent decades. They have a good prognosis, which also improved slightly during this period. Primary sarcomas of the ovary are extremely rare and still have a poor prognosis. (C) 2019 Elsevier Ltd. All rights reserved.
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- 2019
45. Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study
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Matulonis, U, Shapira-Frommer, R, Santin, A, Lisyanskaya, A, Pignata, S, Vergote, I, Raspagliesi, F, Sonke, G, Birrer, M, Provencher, D, Sehouli, J, Colombo, N, González-Martín, A, Oaknin, A, Ottevanger, P, Rudaitis, V, Katchar, K, Wu, H, Keefe, S, Ruman, J, Ledermann, J, Matulonis, U A, Santin, A D, Lisyanskaya, A S, Sonke, G S, Provencher, D M, Ottevanger, P B, Ledermann, J A, Matulonis, U, Shapira-Frommer, R, Santin, A, Lisyanskaya, A, Pignata, S, Vergote, I, Raspagliesi, F, Sonke, G, Birrer, M, Provencher, D, Sehouli, J, Colombo, N, González-Martín, A, Oaknin, A, Ottevanger, P, Rudaitis, V, Katchar, K, Wu, H, Keefe, S, Ruman, J, Ledermann, J, Matulonis, U A, Santin, A D, Lisyanskaya, A S, Sonke, G S, Provencher, D M, Ottevanger, P B, and Ledermann, J A
- Abstract
Background: Advanced recurrent ovarian cancer (ROC) is the leading cause of gynecologic cancer-related death in developed countries and new treatments are needed. Previous studies of immune checkpoint blockade showed low objective response rates (ORR) in ROC with no identified predictive biomarker. Patients and methods: This phase II study of pembrolizumab (NCT02674061) examined two patient cohorts with ROC: cohort A received one to three prior lines of treatment with a platinum-free interval (PFI) or treatment-free interval (TFI) between 3 and 12 months and cohort B received four to six prior lines with a PFI/TFI of ≥3 months. Pembrolizumab 200 mg was administered intravenously every 3 weeks until cancer progression, toxicity, or completion of 2 years. Primary end points were ORR by Response Evaluation Criteria in Solid Tumors version 1.1 per blinded independent central review by cohort and by PD-L1 expression measured as combined positive score (CPS). Secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: Cohort A enrolled 285 patients; the first 100 served as the training set for PD-L1 biomarker analysis. Cohort B enrolled 91 patients. ORR was 7.4% for cohort A and 9.9% for cohort B. Median DOR was 8.2 months for cohort A and not reached for cohort B. DCR was 37.2% and 37.4%, respectively, in cohorts A and B. Based on the training set analysis, CPS 1 and 10 were selected for evaluation in the confirmation set. In the confirmation set, ORR was 4.1% for CPS <1, 5.7% CPS ≥1, and 10.0% for CPS ≥10. PFS was 2.1 months for both cohorts. Median OS was not reached for cohort A and was 17.6 months for cohort B. Toxicities were consistent with other single-agent pembrolizumab trials. Conclusions: Single-agent pembrolizumab showed modest activity in patients with ROC. Higher PD-L1 expression was correlated with higher response.
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- 2019
46. Interval between debulking surgery and adjuvant chemotherapy is associated with overall survival in patients with advanced ovarian cancer
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Timmermans, M., van der Aa, M. A., Lalisang, R., I, Witteveen, P. O., Van de Vijver, K. K., Kruitwagen, R. F., Sonke, G. S., Timmermans, M., van der Aa, M. A., Lalisang, R., I, Witteveen, P. O., Van de Vijver, K. K., Kruitwagen, R. F., and Sonke, G. S.
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- 2018
47. Interval between debulking surgery and adjuvant chemotherapy is associated with overall survival in patients with advanced ovarian cancer
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MS Medische Oncologie, Cancer, Timmermans, M., van der Aa, M. A., Lalisang, R., I, Witteveen, P. O., Van de Vijver, K. K., Kruitwagen, R. F., Sonke, G. S., MS Medische Oncologie, Cancer, Timmermans, M., van der Aa, M. A., Lalisang, R., I, Witteveen, P. O., Van de Vijver, K. K., Kruitwagen, R. F., and Sonke, G. S.
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- 2018
48. Neoadjuvant chemotherapy or primary debulking surgery in FIGO IIIC and IV patients: results from a survey study in the Netherlands
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Timmermans, M., Sonke, G. S., van Driel, W. J., Lalisang, R. I., Ottevanger, P. B., de Kroon, C. D., Van de Vijver, K. K., van der Aa, M. A., Kruitwagen, R. F., Timmermans, M., Sonke, G. S., van Driel, W. J., Lalisang, R. I., Ottevanger, P. B., de Kroon, C. D., Van de Vijver, K. K., van der Aa, M. A., and Kruitwagen, R. F.
- Abstract
Introduction: Primary debulking surgery (PDS) followed by adjuvant chemotherapy is historically recommended as first line treatment for advanced stage ovarian cancer. Two randomized controlled trials, however, showed similar efficacy and reduced toxicity with neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS). Nevertheless, uptake of NACT-IDS varies widely between hospitals, which cannot be explained by difference in patient populations. In this survey, we therefore aimed to evaluate the views on NACT-IDS among all Dutch gynaecologists and medical oncologists involved in the treatment of ovarian cancer. Study design: An e-mail link to the online questionnaire was sent to all medical oncologists and gynaecologists in the Netherlands, regardless of their (sub)specializations. The data was analysed using descriptive statistics and chi-square tests were used to analyse differences between groups. Results: Three-hundred-forty physicians were invited to fill out the questionnaire. After two reminders, 167 of them responded (49%). Among the responders, 82% of the gynaecologists versus 93% of the medical oncologists considered the available evidence sufficiently convincing to treat advanced stage ovarian cancer patients with NACT-IDS (p = 0.076). Moreover, 33% of gynaecologists and 62% of medical oncologists preferred NACT-IDS to PDS as first line treatment (p = 0.001). While most responders (86%) indicated that selecting the right patients for NACT-IDS is difficult, those with bulky disease, FIGO stage IV or metastases near the porta hepatica were most likely to undergo NACT-IDS. Conclusion: The majority of Dutch gynaecologists and medical oncologists adopted NACT-IDS as an alternative treatment approach for advanced stage primary ovarian cancer. About two-thirds of medical oncologists and one-third of gynaecologists prefer NACT-IDS to PDS as first line treatment in this setting. Improving patient selection is considered of paramount importance. (C)
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- 2018
49. No improvement in long-term survival for epithelial ovarian cancer patients: A population-based study between 1989 and 2014 in the Netherlands
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Timmermans, M., Sonke, G. S., de Vijver, K. K. Van, van der Aa, M. A., Kruitwagen, R. F. P. M., Timmermans, M., Sonke, G. S., de Vijver, K. K. Van, van der Aa, M. A., and Kruitwagen, R. F. P. M.
- Abstract
Aim: This study investigates changes in therapy and long-term survival for patients with epithelial ovarian cancer (EOC) in the Netherlands. Methods: All patients with EOC, including peritoneal and fallopian tube carcinoma, diagnosed in the Netherlands between 1989 and 2014 were selected from the Netherlands Cancer Registry. Changes in therapy were studied and related to overall survival (OS) using multivariable Cox regression models. Results: A total of 32,540 patients were diagnosed with EOC of whom 22,047 (68%) had advanced stage disease. In early stage, lymph node dissection as part of surgical staging procedures increased over time from 4% in 1989-1993 to 62% in 2009-2014 (P < 0.001). In advanced stage, the number of patients receiving optimal treatment with surgery and chemotherapy increased from 55% in 1989-1993 to 67% in 2009-2014 (P < 0.001). Five-year survival rates improved in both early stage (74% versus 79%) and advanced stage (16% versus 24%) as well as in all patients combined (31% versus 34%). Ten-year survival rates, however, slightly improved in early stage (62% versus 67%) and advanced stage (10% versus 13%) but remained essentially unchanged at 24% for all patients combined. Conclusion: Despite intensified treatment and staging procedures, long-term survival for women with EOC has not improved in the last 25 years. The observed improvements in 5-year OS reflect a more prolonged disease control rather than better chances for cure. Furthermore, the apparent better long-term outcome, when early and advanced stage patients are analysed separately, is largely due to improved staging procedures and the ensuing stage migration. These effects disappear in a combined analysis of all patients. (C) 2017 Elsevier Ltd. All rights reserved.
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- 2018
50. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer
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Moore, K., Colombo, N., Scambia, Giovanni, Kim, B. -G., Oaknin, A., Friedlander, M., Lisyanskaya, A., Floquet, A., Leary, A., Sonke, G. S., Gourley, C., Banerjee, S., Oza, A., González-Martín, A., Aghajanian, C., Bradley, W., Mathews, C., Liu, J., Lowe, E. S., Bloomfield, R., Disilvestro, P., Scambia, G. (ORCID:0000-0003-2758-1063), Moore, K., Colombo, N., Scambia, Giovanni, Kim, B. -G., Oaknin, A., Friedlander, M., Lisyanskaya, A., Floquet, A., Leary, A., Sonke, G. S., Gourley, C., Banerjee, S., Oza, A., González-Martín, A., Aghajanian, C., Bradley, W., Mathews, C., Liu, J., Lowe, E. S., Bloomfield, R., Disilvestro, P., and Scambia, G. (ORCID:0000-0003-2758-1063)
- Abstract
3 years after standard treatment with surgery and platinum-based chemotherapy. The benefit of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib in relapsed disease has been well established, but the benefit of olaparib as maintenance therapy in newly diagnosed disease is uncertain. METHODS We conducted an international, randomized, double-blind, phase 3 trial to evaluate the efficacy of olaparib as maintenance therapy in patients with newly diagnosed advanced (International Federation of Gynecology and Obstetrics stage III or IV) high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian-Tube cancer (or a combination thereof) with a mutation in BRCA1, BRCA2, or both (BRCA1/2) who had a complete or partial clinical response after platinumbased chemotherapy. The patients were randomly assigned, in a 2:1 ratio, to receive olaparib tablets (300 mg twice daily) or placebo. The primary end point was progression-free survival. RESULTS Of the 391 patients who underwent randomization, 260 were assigned to receive olaparib and 131 to receive placebo. A total of 388 patients had a centrally confirmed germline BRCA1/2 mutation, and 2 patients had a centrally confirmed somatic BRCA1/2 mutation. After a median follow-up of 41 months, the risk of disease progression or death was 70% lower with olaparib than with placebo (Kaplan-Meier estimate of the rate of freedom from disease progression and from death at 3 years, 60% vs. 27%; hazard ratio for disease progression or death, 0.30; 95% confidence interval, 0.23 to 0.41; P<0.001). Adverse events were consistent with the known toxic effects of olaparib. CONCLUSIONS The use of maintenance therapy with olaparib provided a substantial benefit with regard to progression-free survival among women with newly diagnosed advanced ovarian cancer and a BRCA1/2 mutation, with a 70% lower risk of disease progression or death with olaparib than with placebo. (Funded by AstraZeneca and Merck; S
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- 2018
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