47 results on '"Konings, Inge R."'
Search Results
2. Machine learning-based somatic variant calling in cell-free DNA of metastatic breast cancer patients using large NGS panels
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Jongbloed, Elisabeth M., Jansen, Maurice P. H. M., de Weerd, Vanja, Helmijr, Jean A., Beaufort, Corine M., Reinders, Marcel J. T., van Marion, Ronald, van IJcken, Wilfred F. J., Sonke, Gabe S., Konings, Inge R., Jager, Agnes, Martens, John W. M., Wilting, Saskia M., and Makrodimitris, Stavros
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- 2023
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3. Prediction of pathologic complete response after single-dose MR-guided partial breast irradiation in low-risk breast cancer patients: the ABLATIVE-2 trial—a study protocol
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Civil, Yasmin A., Oei, Arlene L., Duvivier, Katya M., Bijker, Nina, Meijnen, Philip, Donkers, Lorraine, Verheijen, Sonja, van Kesteren, Zdenko, Palacios, Miguel A., Schijf, Laura J., Barbé, Ellis, Konings, Inge R. H. M., -van der Houven van Oordt, C. Willemien Menke, Westhoff, Paulien G., Meijer, Hanneke J. M., Diepenhorst, Gwen M. P., Thijssen, Victor, Mouliere, Florent, Slotman, Berend J., van der Velde, Susanne, and van den Bongard, H. J. G. Desirée
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- 2023
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4. Presenting decision-relevant numerical information to Dutch women aged 50–70 with varying levels of health literacy: Case example of adjuvant systemic therapy for breast cancer.
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van Strien-Knippenberg, Inge S., Timmermans, Daniëlle R. M., Engelhardt, Ellen G., Konings, Inge R. H. M, and Damman, Olga C.
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DUTCH people ,HEALTH literacy ,BREAST cancer ,SURVIVAL rate ,DECISION making ,OLDER women - Abstract
Background: If communicated adequately, numerical decision-relevant information can support informed and shared decision making. Visual formats are recommended, but which format supports patients depending on their health literacy (HL) levels for specific decisions is unclear. Study aim: The aim of this study is to investigate: 1) the effect of survival rates and side-effects presentation formats on comprehension and 'feeling informed'; 2) differential effects among women with higher/lower HL, with adjuvant systemic breast cancer therapy as case example. Methods: Two online experiments among women from the Dutch population without a history of breast cancer were conducted. Experiment 1 had a 3 (survival rate format: text block–bar graph–icon array) x 2 (HL: low–high) between-subjects design. Experiment 2 had a 5 (side-effects format: no probability information–probability information in numbers with or without a visualisation–probability information in numbers with or without a visualisation accompanied by a description of the side-effects) x 2 (HL: low–high) design. Primary outcomes were comprehension and feeling informed (Experiment 2 only). Formats were previously designed in co-creation with patients. Results: In Experiment 1, presentation format did not affect gist or verbatim comprehension. Higher HL was associated with higher gist comprehension. Experiment 2 showed an interaction between presentation format and HL on 'feeling informed'. When provided with visualised probability information without a description of the side-effects, women with lower HL felt better informed than women with higher HL. Conclusion: Visual formats did not enhance comprehension of survival rate information beyond a well-designed text block format. However, none of the formats could overcome HL differences. When designing decision-relevant information, visualisations might not necessarily provide an advantage over structured numerical information for both patients with lower and higher HL. However, a deeper understanding of presenting side-effect information is warranted. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Psychosocial well-being and mental adjustment of patients with stage III melanoma in the re-entry phase: a scoping review
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Visser, Anna, Post, Lenneke, Dekker, Joost, and Konings, Inge R.
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- 2022
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6. From accelerometer output to physical activity intensities in breast cancer patients
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Sweegers, Maike G., Buffart, Laurien M., Huijsmans, Rosalie J., Konings, Inge R., van Zweeden, Annette A., Brug, Johannes, Chinapaw, Mai J.M., and Altenburg, Teatske M.
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- 2020
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7. Genomic Alterations Associated with Estrogen Receptor Pathway Activity in Metastatic Breast Cancer Have a Differential Impact on Downstream ER Signaling
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Angus, Lindsay, primary, Smid, Marcel, additional, Wilting, Saskia M., additional, Bos, Manouk K., additional, Steeghs, Neeltje, additional, Konings, Inge R. H. M., additional, Tjan-Heijnen, Vivianne C. G., additional, van Riel, Johanna M. G. H., additional, van de Wouw, Agnes J., additional, Consortium, CPCT, additional, Cuppen, Edwin, additional, Lolkema, Martijn P., additional, Jager, Agnes, additional, Sleijfer, Stefan, additional, and Martens, John W. M., additional
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- 2023
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8. Machine learning-based somatic variant calling in cell-free DNA of metastatic breast cancer patients using large NGS panels
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Jongbloed, Elisabeth M., primary, Jansen, Maurice P.H.M., additional, de Weerd, Vanja, additional, Helmijr, Jean A., additional, Beaufort, Corine M., additional, Reinders, Marcel J. T., additional, Marion, Ronald van, additional, IJcken, Wilfred F. J. van, additional, Sonke, Gabe S., additional, Konings, Inge R. H. M., additional, Jager, Agnes, additional, Martens, John W.M., additional, Wilting, Saskia M., additional, and Makrodimitris, Stavros, additional
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- 2023
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9. Genomic Alterations Associated with Estrogen Receptor Pathway Activity in Metastatic Breast Cancer Have a Differential Impact on Downstream ER Signaling
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Externen Med. Onco, CMM Groep Van Mil, Cancer, Angus, Lindsay, Smid, Marcel, Wilting, Saskia M, Bos, Manouk K, Steeghs, Neeltje, Konings, Inge R H M, Tjan-Heijnen, Vivianne C G, van Riel, Johanna M G H, van de Wouw, Agnes J, Cpct Consortium, Cuppen, Edwin, Lolkema, Martijn P, Jager, Agnes, Sleijfer, Stefan, Martens, John W M, Externen Med. Onco, CMM Groep Van Mil, Cancer, Angus, Lindsay, Smid, Marcel, Wilting, Saskia M, Bos, Manouk K, Steeghs, Neeltje, Konings, Inge R H M, Tjan-Heijnen, Vivianne C G, van Riel, Johanna M G H, van de Wouw, Agnes J, Cpct Consortium, Cuppen, Edwin, Lolkema, Martijn P, Jager, Agnes, Sleijfer, Stefan, and Martens, John W M
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- 2023
10. Predictors for use of psychosocial services in patients with metastatic colorectal cancer receiving first line systemic treatment
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Schuurhuizen, Claudia S. E. W., Braamse, Annemarie M. J., Konings, Inge R. H. M., Verheul, Henk M. W., and Dekker, Joost
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- 2019
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11. Systemic Therapy for Patients with HER2-Positive Breast Cancer and Brain Metastases: A Systematic Review and Meta-Analysis
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Werter, Inge M., primary, Remmelzwaal, Sharon, additional, Burchell, George L., additional, de Gruijl, Tanja D., additional, Konings, Inge R., additional, van der Vliet, Hans J., additional, and Menke-van der Houven van Oordt, C. Willemien, additional
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- 2022
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12. Re-irradiation and hyperthermia for locoregional recurrent breast cancer: Outcome of 23x2Gy vs 8x4Gy
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Bakker, Akke, Tello Valverde, C. Paola, van Tienhoven, Geertjan, Kolff, Willemijn, Kok, Petra, Slotman, Ben J., Konings, Inge R., Oei, Arlene, Oldenburg, Hester, Rutgers, Emiel J. Th., Rasch, Coenraad R. N., van den Bongard, Desiree J. G. D., Crezee, Johannes, Radiotherapy, CCA - Cancer Treatment and Quality of Life, CCA - Imaging and biomarkers, CCA - Cancer biology and immunology, AII - Cancer immunology, and Center of Experimental and Molecular Medicine
- Abstract
Purpose or Objective: Operable patients with locoregional (LR) recurrent breast cancer at high risk for re-recurrence are treated with postoperative re-irradiation combined with hyperthermia (HT), i.e. heating the target area to 40-43 °C for one hour, in the Netherlands. Early 2015, national consensus was reached using a new standard RT dose fractionation schedule of 23x2Gy, replacing the 8x4Gy RT schedule used in our center. We investigated the impact of both postoperative re-irradiation schedules combined with HT on LR control and late toxicity in patients with LR recurrent breast cancer treated at our center. Materials and Methods: In this retrospective study, 112 women with resected LR recurrent breast cancer treated in 2010-2017 with postoperative re-irradiation combined with 4-5 weekly HT sessions were included. RT treatment consisted of 8x4Gy (n=34, twice a week) until 2014, or 23x2Gy (n=78, 5 times a week) after 2014. Due to frailty or long travel distance 5 patients received 8x4Gy after 2014. Re-irradiation was delivered using 3 consecutive different RT planning techniques. From 2010 to mid-2014 the lateral chest wall and/or regional lymph nodes areas were irradiated using two opposing AP-PA fields and the anterior chest wall with electrons, the breast was treated with two tangential fields. From mid-2014 IMRT was applied using 5-7 beam angles, and from early 2016 onward VMAT using two (counter)clockwise partial arcs. Actuarial LR control and grade 2-5 late toxicity incidence (>3 months after the first re-irradiation fraction) were analyzed. Toxicity was defined according to CTC-AE v5.0. Patients had multiple late toxicities. The cause of late toxicity might be current or previous treatments or an cumulative effect. Backward multivariable Cox regression was performed. Results: Twenty-four patients (21.4%) developed an in-field recurrence. Median FU was 43 months (range 1-107 months). Threeyear LR control was 89.4% vs. 68.7% in the 23x2Gy and 8x4Gy group, respectively (p=0.01), LR control tended to be better for the 23x2Gy group after long FU (p=0.094; Fig 1A). In multivariate analysis, distant metastasis (HR 17.6; 95%CI 5.2-60.2), lymph node involvement (HR 2.9; 95%CI 1.2-7.2), recurrence site (chest wall vs. breast; HR 4.6; 95%CI 1.8-11.6) and thermal dose (low vs. high; HR 4.1; 95%CI 1.4-11.5) were associated with LR control. Three-year late grade 2, 3 and 4 toxicity was 63%, 39% and 0% vs. 54%, 19% and 8% for 23x2Gy and 8x4Gy groups, respectively. No grade 5 late toxicity occurred. The 23x2Gy group had a trend for more grade 3-4 late toxicity (p=0.064, Fig1B). Conclusion: Patients with LR recurrent breast cancer treated with 23x2Gy postoperative re-irradiation and HT tended to have better LR control at the cost of higher incidence of grade 3-4 late toxicity compared to patients treated with 8x4Gy.
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- 2022
13. Doelmatigheidsonderzoek naar dure geneesmiddelen:Meer bereiken met lagere kosten
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van Ommen-Nijhof, Annemiek, Retèl, Valesca P, Konings, Inge R H M, Sonke, Gabe S, van Ommen-Nijhof, Annemiek, Retèl, Valesca P, Konings, Inge R H M, and Sonke, Gabe S
- Abstract
Novel innovative drugs have improved disease control, survival and quality of life for many patients. The costs of these drugs, however, are extremely high and threaten the long-term affordability of our health care system. Efficient use of existing drugs can decrease drug expenditure whilst improving patients' quality of life at the same time. Efficiency adjustments should not compromise treatment efficacy and therefore, clinical research on the matter is crucial. In this article, we demonstrate that efficiency research is feasible, as exemplified by the SONIA study. We make the case for a 'revolving fund' in which savings from one study are used to fund a next one. A revolving fund thus stimulates efficiency research and capitalizes research investments in the interest of both patients and society.
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- 2022
14. Prophylactic treatment for delayed chemotherapy-induced nausea and vomiting after non-AC based moderately emetogenic chemotherapy: a systematic review of randomized controlled trials
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van der Vorst, Maurice J. D. L, Neefjes, Elisabeth C. W., Konings, Inge R. H. M., and Verheul, Henk M. W.
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- 2015
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15. Increasing tumoral 5-fluorouracil concentrations during a 5-day continuous infusion: a microdialysis study
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Konings, Inge R. H. M., Sleijfer, Stefan, Mathijssen, Ron H. J., de Bruijn, Peter, Ghobadi Moghaddam-Helmantel, Inge M., van Dam, Linda M., Wiemer, Erik A. C., Verweij, Jaap, and Loos, Walter J.
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- 2011
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16. Application of prolonged microdialysis sampling in carboplatin-treated cancer patients
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Konings, Inge R. H. M., Engels, Frederike K., Sleijfer, Stefan, Verweij, Jaap, Wiemer, Erik A. C., and Loos, Walter J.
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- 2009
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17. High-Dose Chemotherapy With Hematopoietic Stem Cell Transplant in Patients With High-Risk Breast Cancer and 4 or More Involved Axillary Lymph Nodes 20-Year Follow-up of a Phase 3 Randomized Clinical Trial: 20-Year Follow-up of a Phase 3 Randomized Clinical Trial
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Steenbruggen, Tessa G, Steggink, Lars C, Seynaeve, Caroline M, van der Hoeven, Jacobus J M, Hooning, Maartje J, Jager, Agnes, Konings, Inge R, Kroep, Judith R, Smit, Wim M, Tjan-Heijnen, Vivianne C G, van der Wall, Elsken, Bins, Adriaan D, Linn, Sabine C, Schaapveld, Michael, Jacobse, Judy N, van Leeuwen, Flora E, Schröder, Carolien P, van Tinteren, Harm, de Vries, Elisabeth G E, Sonke, Gabe S, Gietema, Jourik A, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)
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SUPPORT ,CYCLOPHOSPHAMIDE ,CONVENTIONAL ADJUVANT CHEMOTHERAPY ,EPIRUBICIN ,WOMEN ,BENEFIT ,RECURRENCE ,EFFICACY ,THERAPY - Abstract
Importance: Trials of adjuvant high-dose chemotherapy (HDCT) have failed to show a survival benefit in unselected patients with breast cancer, but long-term follow-up is lacking. Objective: To determine 20-year efficacy and safety outcomes of a large trial of adjuvant HDCT vs conventional-dose chemotherapy (CDCT) for patients with stage III breast cancer. Design, Setting, and Participants: This secondary analysis used data from a randomized phase 3 multicenter clinical trial of 885 women younger than 56 years with breast cancer and 4 or more involved axillary lymph nodes conducted from August 1, 1993, to July 31, 1999. Additional follow-up data were collected between June 1, 2016, and December 31, 2017, from medical records, general practitioners, the Dutch national statistical office, and nationwide cancer registries. Analysis was performed on an intention-to-treat basis. Statistical analysis was performed from February 1, 2018, to October 14, 2019. Interventions: Participants were randomized 1:1 to receive 5 cycles of CDCT consisting of fluorouracil, 500 mg/m2, epirubicin, 90 mg/m2, and cyclophosphamide, 500 mg/m2, or HDCT in which the first 4 cycles were identical to CDCT and the fifth cycle was replaced by cyclophosphamide, 6000 mg/m2, thiotepa, 480 mg/m2, and carboplatin, 1600 mg/m2, followed by hematopoietic stem cell transplant. Main Outcomes and Measures: Main end points were overall survival and safety and cumulative incidence risk of a second malignant neoplasm or cardiovascular events. Results: Of the 885 women in the study (mean [SD] age, 44.5 [6.6] years), 442 were randomized to receive HDCT, and 443 were randomized to receive CDCT. With 20.4 years median follow-up (interquartile range, 19.2-22.0 years), the 20-year overall survival was 45.3% with HDCT and 41.5% with CDCT (hazard ratio, 0.89; 95% CI, 0.75-1.06). The absolute improvement in 20-year overall survival was 14.6% (hazard ratio, 0.72; 95% CI, 0.54-0.95) for patients with 10 or more invoved axillary lymph nodes and 15.4% (hazard ratio, 0.67; 95% CI, 0.42-1.05) for patients with triple-negative breast cancer. The cumulative incidence risk of a second malignant neoplasm at 20 years or major cardiovascular events was similar in both treatment groups (20-year cumulative incidence risk for second malignant neoplasm was 12.1% in the HDCT group vs 16.2% in the CDCT group, P = .10), although patients in the HDCT group more often had hypertension (21.7% vs 14.3%, P = .02), hypercholesterolemia (15.7% vs 10.6%, P = .04), and dysrhythmias (8.6% vs 4.6%, P = .005). Conclusions and Relevance: High-dose chemotherapy provided no long-term survival benefit in unselected patients with stage III breast cancer but did provide improved overall survival in very high-risk patients (ie, with ≥10 involved axillary lymph nodes). High-dose chemotherapy did not affect long-term risk of a second malignant neoplasm or major cardiovascular events. Trial Registration: ClinicalTrials.gov Identifier: NCT03087409.
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- 2020
18. Appendix_1_Cost_categories_with_unit_prices_ – Supplemental material for Economic evaluation of a combined screening and stepped-care treatment program targeting psychological distress in patients with metastatic colorectal cancer: A cluster randomized controlled trial
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Alili, Mohamed El, Schuurhuizen, Claudia S.E.W, Braamse, Annemarie M.J., Aartjan T.F. Beekman, Mecheline H. Van Der Linden, Konings, Inge R., Dekker, Joost, and Bosmans, Judith E.
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FOS: Clinical medicine ,111702 Aged Health Care ,FOS: Health sciences ,110308 Geriatrics and Gerontology - Abstract
Supplemental material, Appendix_1_Cost_categories_with_unit_prices_ for Economic evaluation of a combined screening and stepped-care treatment program targeting psychological distress in patients with metastatic colorectal cancer: A cluster randomized controlled trial by Mohamed El Alili, Claudia S.E.W Schuurhuizen, Annemarie M.J. Braamse, Aartjan T.F. Beekman, Mecheline H. van der Linden, Inge R. Konings, Joost Dekker and Judith E. Bosmans in Palliative Medicine
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- 2020
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19. High-Dose Chemotherapy with Hematopoietic Stem Cell Transplant in Patients with High-Risk Breast Cancer and 4 or More Involved Axillary Lymph Nodes: 20-Year Follow-up of a Phase 3 Randomized Clinical Trial
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Speerpunt Cancer, Cancer, Steenbruggen, Tessa G., Steggink, Lars C., Seynaeve, Caroline M., Van Der Hoeven, Jacobus J.M., Hooning, Maartje J., Jager, Agnes, Konings, Inge R., Kroep, Judith R., Smit, Wim M., Tjan-Heijnen, Vivianne C.G., Van Der Wall, Elsken, Bins, Adriaan D., Linn, Sabine C., Schaapveld, Michael, Jacobse, Judy N., Van Leeuwen, Flora E., Schröder, Carolien P., Van Tinteren, Harm, De Vries, Elisabeth G.E., Sonke, Gabe S., Gietema, Jourik A., Speerpunt Cancer, Cancer, Steenbruggen, Tessa G., Steggink, Lars C., Seynaeve, Caroline M., Van Der Hoeven, Jacobus J.M., Hooning, Maartje J., Jager, Agnes, Konings, Inge R., Kroep, Judith R., Smit, Wim M., Tjan-Heijnen, Vivianne C.G., Van Der Wall, Elsken, Bins, Adriaan D., Linn, Sabine C., Schaapveld, Michael, Jacobse, Judy N., Van Leeuwen, Flora E., Schröder, Carolien P., Van Tinteren, Harm, De Vries, Elisabeth G.E., Sonke, Gabe S., and Gietema, Jourik A.
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- 2020
20. Clinical management of emotions in patients with cancer: introducing the approach “emotional support and case finding”
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Dekker, Joost, primary, Karchoud, Jeanet, additional, Braamse, Annemarie M J, additional, Buiting, Hilde, additional, Konings, Inge R H M, additional, van Linde, Myra E, additional, Schuurhuizen, Claudia S E W, additional, Sprangers, Mirjam A G, additional, Beekman, Aartjan T F, additional, and Verheul, Henk M W, additional
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- 2020
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21. Muscle contractile properties of cancer patients receiving chemotherapy: Assessment of feasibility and exercise effects
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Buffart, Laurien M., primary, Sweegers, Maike G., additional, de Ruijter, Cornelis J., additional, Konings, Inge R., additional, Verheul, Henk M.W., additional, van Zweeden, Annette A., additional, Grootscholten, Cecile, additional, Chinapaw, Mai J., additional, and Altenburg, Teatske M., additional
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- 2020
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22. Economic evaluation of a combined screening and stepped-care treatment program targeting psychological distress in patients with metastatic colorectal cancer: A cluster randomized controlled trial
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El Alili, Mohamed, primary, Schuurhuizen, Claudia S.E.W, additional, Braamse, Annemarie M.J., additional, Beekman, Aartjan T.F., additional, van der Linden, Mecheline H., additional, Konings, Inge R., additional, Dekker, Joost, additional, and Bosmans, Judith E., additional
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- 2020
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23. Substantially improving the cure rate of high-risk BRCA1-like breast cancer patients with personalized therapy (SUBITO) - an international randomized phase III trial
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Vliek, Sonja, Jager, Agnes, Jonge-Lavrencic, Mojca, Lotz, Jean-Pierre, Goncalves, Anthony, Graeser, Monika, Nitz, Ulrike, Mandjes, Ingrid A. M., Holtkamp, Marjo J., Schot, Margaret, Retel, Valesca P., Kuip, Evelien J., Wymenga, Machteld N., Konings, Inge R., Tjan-Heijnen, Vivianne C. G., Kroep, Judith R., Schr, der Carolien P., Wall, Elsken, Linn, Sabine C., Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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[SDV]Life Sciences [q-bio] - Abstract
San Antonio Breast Cancer Symposium, San Antonio, TX, DEC 05-09, 2017
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- 2018
24. Breast cancer risk in transgender people receiving hormone treatment: nationwide cohort study in the Netherlands
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de Blok, Christel J M, primary, Wiepjes, Chantal M, additional, Nota, Nienke M, additional, van Engelen, Klaartje, additional, Adank, Muriel A, additional, Dreijerink, Koen M A, additional, Barbé, Ellis, additional, Konings, Inge R H M, additional, and den Heijer, Martin, additional
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- 2019
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25. Higher Muscle Strength Is Associated with Prolonged Survival in Older Patients with Advanced Cancer
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Versteeg, Kathelijn Sophie, Blauwhoff-Buskermolen, Susanne, Buffart, Laurien M., de van der Schueren, Marian A.E., Langius, Jacqueline A.E., Verheul, Henk M.W., Maier, Andrea B., Konings, Inge R., Versteeg, Kathelijn Sophie, Blauwhoff-Buskermolen, Susanne, Buffart, Laurien M., de van der Schueren, Marian A.E., Langius, Jacqueline A.E., Verheul, Henk M.W., Maier, Andrea B., and Konings, Inge R.
- Abstract
BACKGROUND: Identifying predictors of treatment toxicity and overall survival (OS) is important for selecting patients who will benefit from chemotherapy. In younger patients with cancer, muscle mass and radiodensity are associated with treatment toxicity and OS. In this study, we investigated whether muscle mass, radiodensity, and strength were associated with treatment toxicity and OS in patients with advanced cancer aged 60 years or older.MATERIALS AND METHODS: Before starting palliative chemotherapy, muscle mass and radiodensity were assessed using computed tomography scans and muscle strength was assessed using a hydraulic hand grip dynamometer. Treatment toxicity was defined as any toxicity resulting in dose reduction and/or discontinuation of treatment. Multiple logistic and Cox regression analyses were performed to study potential associations of muscle mass, radiodensity, and strength with treatment toxicity and OS, respectively.RESULTS: The participants were 103 patients, with a mean age of 70 years, with advanced colorectal, prostate, or breast cancer. Muscle parameters were not significantly associated with treatment toxicity. Higher muscle strength was associated with longer OS (hazard ratio 1.03; 95% confidence interval 1.00-1.05). Muscle mass and radiodensity were not significantly associated with OS.CONCLUSION: Higher muscle strength at the start of palliative chemotherapy is associated with significantly better OS in older patients with advanced cancer. None of the investigated muscle parameters were related to treatment toxicity. Future studies are needed to evaluate whether muscle strength can be used for treatment decisions in older patients with advanced cancer.IMPLICATIONS FOR PRACTICE: This study in older patients with advanced cancer showed that adequate muscle strength is associated with longer overall survival. The results of this study imply that muscle strength might be helpful in estimating survival and the
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- 2018
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26. ‘Oncokompas’, a web-based self-management application to support patient activation and optimal supportive care: a feasibility study among breast cancer survivors
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Melissant, Heleen C., primary, Verdonck-de Leeuw, Irma M., additional, Lissenberg-Witte, Birgit I., additional, Konings, Inge R., additional, Cuijpers, Pim, additional, and Van Uden-Kraan, Cornelia F., additional
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- 2018
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27. Higher Muscle Strength Is Associated with Prolonged Survival in Older Patients with Advanced Cancer
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Versteeg, Kathelijn Sophie, primary, Blauwhoff-Buskermolen, Susanne, additional, Buffart, Laurien M., additional, de van der Schueren, Marian A.E., additional, Langius, Jacqueline A.E., additional, Verheul, Henk M.W., additional, Maier, Andrea B., additional, and Konings, Inge R., additional
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- 2017
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28. Olanzapine prevents nausea and vomiting from chemotherapy
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Mammatas, Lemonitsa H., Konings, Inge R., Internal medicine, CCA - Clinical Therapy Development, and Medical oncology
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- 2016
29. Tailoring exercise interventions to comorbidities and treatment-induced adverse effects in patients with early stage breast cancer undergoing chemotherapy: a framework to support clinical decisions
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van der Leeden, Marike, primary, Huijsmans, Rosalie J., additional, Geleijn, Edwin, additional, de Rooij, Mariëtte, additional, Konings, Inge R., additional, Buffart, Laurien M., additional, Dekker, Joost, additional, and Stuiver, Martijn M., additional
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- 2017
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30. Multilineage Cytotoxic Treatment for Advanced Colorectal Cancer in Nonagenarians
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Versteeg, Kathelijn S, primary, Buskermolen, Susanne Blauwhoff, additional, Maier, Andrea B, additional, Konings, Inge R, additional, and Verheul, Henk M W, additional
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- 2016
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31. Tailoring exercise interventions to comorbidities and treatment-induced adverse effects in patients with early stage breast cancer undergoing chemotherapy: a framework to support clinical decisions.
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van der Leeden, Marike, Huijsmans, Rosalie J., Geleijn, Edwin, de Rooij, Mariëtte, Konings, Inge R., Buffart, Laurien M., Dekker, Joost, and Stuiver, Martijn M.
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ALGORITHMS ,BREAST tumors ,CANCER chemotherapy ,CANCER patients ,EXERCISE therapy ,MEDICAL protocols ,DECISION making in clinical medicine ,COMORBIDITY - Abstract
Purpose:Delivery of exercise interventions to patients with early-stage breast cancer undergoing chemotherapy requires complex clinical decisions. The purpose of this study was to develop a framework to support clinical decisions for tailoring exercise interventions to common comorbidities and cancer treatment-induced adverse effects. Method:Tailored exercise prescriptions were developed in four steps, following the i3-S strategy. All steps were based on current best available evidence, complemented with expert opinions. First, common comorbidities and treatment-induced adverse effects were identified. In the subsequent steps, contra-indications and restrictions for exercise were described, along with possible exercise adaptations. In the final step, the obtained information was synthesized into a framework. Results:Prevalent comorbidities were hypertension, heart disease, diabetes mellitus, (osteo)arthritis, chronic obstructive pulmonary disease, and obesity. Adverse effects included conditions induced by pretreatment (e.g., lymphedema as a result of surgery) or by chemotherapy (e.g., reduced blood cell counts). Adaptations to the recommended exercise program were related to exercise tolerance, safety, and hygiene. A framework was proposed to guide clinical decisions during the exercise intervention. Conclusion:Comorbidities and adverse effects of breast cancer treatment require exercise adaptations. The proposed framework provides guidance on tailored exercise prescriptions in patients with breast cancer undergoing chemotherapy.Implications for RehabilitationExercise is recommended for patients with breast cancer undergoing chemotherapy, but requires complex clinical decisions of the health professional.We identified the most important comorbidities and adverse effects of breast cancer treatment, and the resultant contra-indications and restrictions to exercise.We incorporated these findings into a clinical decision framework that provides suggestions for exercise adaptations in patients with breast cancer undergoing chemotherapy. [ABSTRACT FROM PUBLISHER]
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- 2018
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32. Increasing tumoral 5-fluorouracil concentrations during a 5-day continuous infusion: a microdialysis study
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Konings, Inge R. H. M., primary, Sleijfer, Stefan, additional, Mathijssen, Ron H. J., additional, de Bruijn, Peter, additional, Ghobadi Moghaddam-Helmantel, Inge M., additional, van Dam, Linda M., additional, Wiemer, Erik A. C., additional, Verweij, Jaap, additional, and Loos, Walter J., additional
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- 2010
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33. Abstract A108: A phase I and pharmalogical study of the broad‐spectrum tyrosine kinase inhibitor JNJ‐26483327, administered to subjects with advanced or refractory solid tumors
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Konings, Inge R., primary, de Jonge, Maja J., additional, Burger, Herman, additional, van der Gaast, Ate, additional, van Bijsterveld, Ludy EC, additional, Winkler, Hans, additional, Hellemans, Peter, additional, and Eskens, Ferry A., additional
- Published
- 2009
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34. Application of prolonged microdialysis sampling in carboplatin-treated cancer patients
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Konings, Inge R. H. M., primary, Engels, Frederike K., additional, Sleijfer, Stefan, additional, Verweij, Jaap, additional, Wiemer, Erik A. C., additional, and Loos, Walter J., additional
- Published
- 2008
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35. Screening and treatment of psychological distress in patients with metastatic colorectal cancer: study protocol of the TES trial.
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Schuurhuizen, Claudia S. E. W., Braamse, Annemarie M. J., Beekman, Aartjan T. F., Bomhof-Roordink, Hanna, Bosmans, Judith E., Cuijpers, Pim, Hoogendoorn, Adriaan W., Konings, Inge R. H. M., van der Linden, Mecheline H. M., Neefjes, Elisabeth C. W., Verheul, Henk M. W., and Dekker, Joost
- Subjects
PSYCHOLOGICAL distress ,COLON cancer patients ,CANCER & psychology ,MEDICAL screening ,MENTAL depression ,CANCER chemotherapy - Abstract
Background/Introduction: Psychological distress occurs frequently in patients with cancer. Psychological distress includes mild and severe forms of both anxious and depressive mood states. Literature indicates that effective management of psychological distress seems to require targeted selection of patients (T), followed by enhanced care (E), and the application of evidence based interventions. Besides, it is hypothesized that delivering care according to the stepped care (S) approach results in an affordable program. The aim of the current study is to evaluate the (cost)-effectiveness of the TES program compared to usual care in reducing psychological distress in patients with metastatic colorectal cancer (mCRC). Methods: This study is designed as a cluster randomized trial with 2 treatment arms: TES program for screening and treatment of psychological distress versus usual care. Sixteen hospitals participate in this study, recruiting patients with mCRC. Outcomes are evaluated at the beginning of chemotherapy and after 3, 10, 24, and 48 weeks. Primary outcome is the difference in treatment effect over time in psychological distress, assessed with the Hospital Anxiety and Depression Scale. Secondary outcomes include quality of life, patient evaluation of care, recognition and management of psychological distress, and societal costs. Discussion: We created optimal conditions for an effective screening and treatment program for psychological distress in patients with mCRC. This involves targeted selection of patients, followed by enhanced and stepped care. Our approach will be thoroughly evaluated in this study. We expect that our results will contribute to the continuing debate on the (cost-) effectiveness of screening for and treatment of psychological distress in patients with cancer. Trial Registration: This trial is registered in the Netherlands Trial Register NTR4034 [ABSTRACT FROM AUTHOR]
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- 2015
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36. Successful Trastuzumab-Deruxtecan Rechallenge After Interstitial Lung Disease: A Case Report.
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de Weger VA, Schutte T, Konings IRHM, and Menke-van der Houven van Oordt CW
- Abstract
Trastuzumab deruxtecan (T-DXd) is used to treat human epidermal growth factor receptor 2-positive advanced breast cancer. Interstitial lung disease (ILD) is a severe adverse event associated with T-DXd. Current guidelines recommend permanent discontinuation of T-DXd after Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2 ILD. Here, we describe a case of successful rechallenge with T-DXd after CTCAE grade 2 treatment-induced ILD. After discontinuation of T-DXd, ILD was treated with steroids until complete resolution. Given the initial beneficial antitumor response, retreatment was discussed during disease progression. In a shared decision with the patient, T-DXd was restarted at the lowest registered dose, along with low-dose steroids. ILD did not reoccur. Importantly, both clinical and radiological responses to the treatment were observed, with an improvement in the patient's quality of life. This case demonstrates that retreatment with T-DXd after a grade 2 ILD event is feasible and yields clinical benefit., Competing Interests: Inge R.H.M. Konings reports travel expenses from AstraZeneca/Daiichi Sankyo and research funding from Novartis and Gilead for research related to breast cancer outside of the submitted work. Catharina Willemien Menke-van der Houven van Oordt reports travel expenses from AstraZeneca/Daiichi Sankyo and research funding from Astra Zeneca, Pfizer, and G1 Therapeutics for research related to breast cancer outside the submitted work. Other authors declare that they have no competing interests., (© 2023 Korean Breast Cancer Society.)
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- 2023
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37. [Clinical efficiency research with expensive drugs: doing more with less investment].
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van Ommen-Nijhof A, Retèl VP, Konings IRHM, and Sonke GS
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- Humans, Health Expenditures, Quality of Life
- Abstract
Novel innovative drugs have improved disease control, survival and quality of life for many patients. The costs of these drugs, however, are extremely high and threaten the long-term affordability of our health care system. Efficient use of existing drugs can decrease drug expenditure whilst improving patients' quality of life at the same time. Efficiency adjustments should not compromise treatment efficacy and therefore, clinical research on the matter is crucial. In this article, we demonstrate that efficiency research is feasible, as exemplified by the SONIA study. We make the case for a 'revolving fund' in which savings from one study are used to fund a next one. A revolving fund thus stimulates efficiency research and capitalizes research investments in the interest of both patients and society.
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- 2022
38. Post-operative re-irradiation with hyperthermia in locoregional breast cancer recurrence: Temperature matters.
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Bakker A, Tello Valverde CP, van Tienhoven G, Kolff MW, Kok HP, Slotman BJ, Konings IRHM, Oei AL, Oldenburg HSA, Rutgers EJT, Rasch CRN, van den Bongard HJGD, and Crezee H
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- Combined Modality Therapy, Female, Humans, Neoplasm Recurrence, Local pathology, Retrospective Studies, Temperature, Breast Neoplasms radiotherapy, Breast Neoplasms surgery, Hyperthermia, Induced adverse effects, Re-Irradiation adverse effects
- Abstract
Purpose: To investigate the impact of hyperthermia thermal dose (TD) on locoregional control (LRC), overall survival (OS) and toxicity in locoregional recurrent breast cancer patients treated with postoperative re-irradiation and hyperthermia., Methods: In this retrospective study, 112 women with resected locoregional recurrent breast cancer treated in 2010-2017 with postoperative re-irradiation 8frx4Gy (n = 34) or 23frx2Gy (n = 78), combined with 4-5 weekly hyperthermia sessions guided by invasive thermometry, were subdivided into 'low' (n = 56) and 'high' TD (n = 56) groups by the best session with highest median cumulative equivalent minutes at 43 °C (Best CEM43T50) < 7.2 min and ≥7.2 min, respectively. Actuarial LRC, OS and late toxicity incidence were analyzed. Backward multivariable Cox regression and inverse probability weighting (IPW) analysis were performed., Results: TD subgroups showed no significant differences in patient/treatment characteristics. Median follow-up was 43 months (range 1-107 months). High vs. low TD was associated with LRC (p = 0.0013), but not with OS (p = 0.29) or late toxicity (p = 0.58). Three-year LRC was 74.0% vs. 92.3% in the low and high TD group, respectively (p = 0.008). After three years, 25.0% and 0.9% of the patients had late toxicity grade 3 and 4, respectively. Multivariable analysis showed that distant metastasis (HR 17.6; 95%CI 5.2-60.2), lymph node involvement (HR 2.9; 95%CI 1.2-7.2), recurrence site (chest wall vs. breast; HR 4.6; 95%CI 1.8-11.6) and TD (low vs. high; HR 4.1; 95%CI 1.4-11.5) were associated with LRC. TD was associated with LRC in IPW analysis (p = 0.0018)., Conclusions: High thermal dose (best CEM43T50 ≥ 7.2 min) was associated with significantly higher LRC for patients with locoregional recurrent breast cancer treated with postoperative re-irradiation and hyperthermia, without augmenting toxicity., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2022
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39. Predicting outcome in older patients with cancer: Comprehensive geriatric assessment and clinical judgment.
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Versteeg KS, Looijaard SMLM, Slee-Valentijn MS, Verheul HMW, Maier AB, and Konings IRHM
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- Aged, Comorbidity, Humans, Judgment, Prospective Studies, Geriatric Assessment, Neoplasms drug therapy, Neoplasms epidemiology
- Abstract
Objectives: Comprehensive Geriatric Assessment (CGA) has been incorporated into geriatric oncology to prevent unfavorable outcome from anticancer treatment. This study determined the value of CGA and medical oncologist's clinical judgment in predicting unfavorable outcome and explored whether treatment decisions can be based on CGA., Patients and Methods: In this prospective cohort study, a multidomain CGA was performed by a geriatric nurse and geriatrician in 110 consecutive patients aged ≥70 years, newly referred to a multidisciplinary oncology clinic. CGA domains included comorbidity, polypharmacy, mood, cognition, nutrition, functionality and physical performance. Medical oncologist's clinical judgment on expected tolerance of standard treatment was noted (N = 62). Unfavorable outcome was defined as any ≥grade three chemotherapy toxicity, dose reduction, postponement of treatment, death before start of treatment and early progression before first evaluation of treatment (N = 80)., Results: CGA identified multidomain problems in 77 out of 110 patients (70.0%) and the medical oncologist had doubts about standard treatment tolerance in 30 out of 62 patients (48.4%). Unfavorable outcome occurred in 48 out of 80 patients (60%) who received anticancer treatment but could not be predicted by CGA, medical oncologists' clinical judgment or their combination. There was discrepancy between CGA and clinical judgment in 24 out of 62 patients (38.7%)., Conclusion: Neither CGA, medical oncologist's clinical judgment or a combination could predict unfavorable outcome in our heterogeneous sample. CGA and clinical judgment did not align in more than one-third of patients., Competing Interests: Declaration of Competing Interest Kathelijn S. Versteeg, Stéphanie M.L.M. Looijaard, Monique S. Slee-Valentijn, Henk M.W. Verheul, Andrea B. Maier and Inge R.H.M. Konings declare that they have no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2021
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40. High-Dose Chemotherapy With Hematopoietic Stem Cell Transplant in Patients With High-Risk Breast Cancer and 4 or More Involved Axillary Lymph Nodes: 20-Year Follow-up of a Phase 3 Randomized Clinical Trial.
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Steenbruggen TG, Steggink LC, Seynaeve CM, van der Hoeven JJM, Hooning MJ, Jager A, Konings IR, Kroep JR, Smit WM, Tjan-Heijnen VCG, van der Wall E, Bins AD, Linn SC, Schaapveld M, Jacobse JN, van Leeuwen FE, Schröder CP, van Tinteren H, de Vries EGE, Sonke GS, and Gietema JA
- Subjects
- Adult, Axilla pathology, Breast drug effects, Breast pathology, Breast Neoplasms epidemiology, Breast Neoplasms pathology, Cardiovascular Abnormalities chemically induced, Cardiovascular Abnormalities pathology, Child, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Disease-Free Survival, Dose-Response Relationship, Drug, Epirubicin administration & dosage, Epirubicin adverse effects, Female, Fluorouracil administration & dosage, Fluorouracil adverse effects, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Lymph Nodes drug effects, Lymph Nodes pathology, Lymphatic Metastasis, Middle Aged, Breast Neoplasms therapy, Cardiovascular Abnormalities epidemiology, Hematopoietic Stem Cell Transplantation methods
- Abstract
Importance: Trials of adjuvant high-dose chemotherapy (HDCT) have failed to show a survival benefit in unselected patients with breast cancer, but long-term follow-up is lacking., Objective: To determine 20-year efficacy and safety outcomes of a large trial of adjuvant HDCT vs conventional-dose chemotherapy (CDCT) for patients with stage III breast cancer., Design, Setting, and Participants: This secondary analysis used data from a randomized phase 3 multicenter clinical trial of 885 women younger than 56 years with breast cancer and 4 or more involved axillary lymph nodes conducted from August 1, 1993, to July 31, 1999. Additional follow-up data were collected between June 1, 2016, and December 31, 2017, from medical records, general practitioners, the Dutch national statistical office, and nationwide cancer registries. Analysis was performed on an intention-to-treat basis. Statistical analysis was performed from February 1, 2018, to October 14, 2019., Interventions: Participants were randomized 1:1 to receive 5 cycles of CDCT consisting of fluorouracil, 500 mg/m2, epirubicin, 90 mg/m2, and cyclophosphamide, 500 mg/m2, or HDCT in which the first 4 cycles were identical to CDCT and the fifth cycle was replaced by cyclophosphamide, 6000 mg/m2, thiotepa, 480 mg/m2, and carboplatin, 1600 mg/m2, followed by hematopoietic stem cell transplant., Main Outcomes and Measures: Main end points were overall survival and safety and cumulative incidence risk of a second malignant neoplasm or cardiovascular events., Results: Of the 885 women in the study (mean [SD] age, 44.5 [6.6] years), 442 were randomized to receive HDCT, and 443 were randomized to receive CDCT. With 20.4 years median follow-up (interquartile range, 19.2-22.0 years), the 20-year overall survival was 45.3% with HDCT and 41.5% with CDCT (hazard ratio, 0.89; 95% CI, 0.75-1.06). The absolute improvement in 20-year overall survival was 14.6% (hazard ratio, 0.72; 95% CI, 0.54-0.95) for patients with 10 or more invoved axillary lymph nodes and 15.4% (hazard ratio, 0.67; 95% CI, 0.42-1.05) for patients with triple-negative breast cancer. The cumulative incidence risk of a second malignant neoplasm at 20 years or major cardiovascular events was similar in both treatment groups (20-year cumulative incidence risk for second malignant neoplasm was 12.1% in the HDCT group vs 16.2% in the CDCT group, P = .10), although patients in the HDCT group more often had hypertension (21.7% vs 14.3%, P = .02), hypercholesterolemia (15.7% vs 10.6%, P = .04), and dysrhythmias (8.6% vs 4.6%, P = .005)., Conclusions and Relevance: High-dose chemotherapy provided no long-term survival benefit in unselected patients with stage III breast cancer but did provide improved overall survival in very high-risk patients (ie, with ≥10 involved axillary lymph nodes). High-dose chemotherapy did not affect long-term risk of a second malignant neoplasm or major cardiovascular events., Trial Registration: ClinicalTrials.gov Identifier: NCT03087409.
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- 2020
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41. High ctDNA molecule numbers relate with poor outcome in advanced ER+, HER2- postmenopausal breast cancer patients treated with everolimus and exemestane.
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Kruger DT, Jansen MPHM, Konings IRHM, Dercksen WM, Jager A, Oulad Hadj J, Sleijfer S, Martens JWM, and Boven E
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- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Breast Neoplasms blood, Breast Neoplasms mortality, Breast Neoplasms pathology, Circulating Tumor DNA blood, Female, High-Throughput Nucleotide Sequencing, Humans, Middle Aged, Mutation, Missense, Neoplasm Metastasis, Postmenopause, Progression-Free Survival, Retrospective Studies, Androstadienes therapeutic use, Breast Neoplasms drug therapy, Circulating Tumor DNA genetics, Everolimus therapeutic use, Receptor, ErbB-2 metabolism, Receptors, Estrogen metabolism
- Abstract
We determined whether progression-free survival (PFS) in metastatic breast cancer (MBC) patients receiving everolimus plus exemestane (EVE/EXE) varies depending on circulating tumour DNA (ctDNA) characteristics. Baseline plasma cell-free DNA (cfDNA) from 164 postmenopausal women with ER-positive, HER2-negative MBC refractory to a nonsteroidal aromatase inhibitor and treated with standard EVE/EXE (Everolimus Biomarker Study, Eudract 2013-004120-11) was characterised for 10 relevant breast cancer genes by next-generation sequencing with molecular barcoding. ctDNA molecule numbers, number of mutations and specific variants were related with PFS and overall survival (OS). Missense hotspot mutations in cfDNA were detected in 125 patients. The median of 54 ctDNA molecules per mL plasma distinguished patients with high and low/no ctDNA load. Patients with low/no ctDNA load (N = 102) showed longer median PFS of 5.7 months (P = 0.006) and OS of 124.8 months (P = 0.008) than patients with high ctDNA load (N = 62; 4.4 months and 107.7 months, respectively) in multivariate analyses. Patients with < 3 specific mutations (N = 135) had longer median PFS of 5.4 months compared to those with ≥ 3 mutations (3.4 months; P < 0.001). In conclusion, MBC patients with low/no ctDNA load or < 3 hotspot mutations experience longer PFS while treated with EVE/EXE., (© 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)
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- 2020
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42. Screening and Stepped Care Targeting Psychological Distress in Patients With Metastatic Colorectal Cancer: The TES Cluster Randomized Trial.
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Schuurhuizen CSEW, Braamse AMJ, Beekman ATF, Cuijpers P, van der Linden MHM, Hoogendoorn AW, Berkhof H, Sommeijer DW, Lustig V, Vrijaldenhoven S, Bloemendal HJ, van Groeningen CJ, van Zweeden AA, van der Vorst MJDL, Rietbroek R, Tromp-van Driel CS, Wymenga MNW, van der Linden PW, Beeker A, Polee MB, Batman E, Los M, van Bochove A, Brakenhoff JAC, Konings IRHM, Verheul HMW, and Dekker J
- Subjects
- Aged, Colorectal Neoplasms epidemiology, Colorectal Neoplasms therapy, Disease Management, Female, Humans, Male, Medical Futility, Middle Aged, Neoplasm Metastasis, Neoplasm Staging, Netherlands epidemiology, Quality of Life, Randomized Controlled Trials as Topic, Trauma and Stressor Related Disorders diagnosis, Trauma and Stressor Related Disorders epidemiology, Colorectal Neoplasms complications, Psychological Distress, Stress, Psychological, Trauma and Stressor Related Disorders etiology, Trauma and Stressor Related Disorders therapy
- Abstract
Background: This study evaluated the effectiveness of a screening and stepped care program (the TES program) in reducing psychological distress compared with care as usual (CAU) in patients with metastatic colorectal cancer starting with first-line systemic palliative treatment., Patients and Methods: In this cluster randomized trial, 16 hospitals were assigned to the TES program or CAU. Patients in the TES arm were screened for psychological distress with the Hospital Anxiety and Depression Scale and the Distress Thermometer/Problem List (at baseline and 10 and 18 weeks). Stepped care was offered to patients with distress or expressed needs, and it consisted of watchful waiting, guided self-help, face-to-face problem-solving therapy, or referral to specialized mental healthcare. The primary outcome was change in psychological distress over time, and secondary outcomes were quality of life, satisfaction with care, and recognition and referral of distressed patients by clinicians. Linear mixed models and effect sizes were used to evaluate differences., Results: A total of 349 patients were randomized; 184 received the TES program and 165 received CAU. In the TES arm, 60.3% of the patients screened positive for psychological distress, 26.1% of which entered the stepped care program (14.7% used only watchful waiting and 11.4% used at least one of the other treatment steps). The observed low use of the TES program led us to pursue a futility analysis, which showed a small conditional power and therefore resulted in halted recruitment for this study. No difference was seen in change in psychological distress over time between the 2 groups (effect size, -0.16; 95% CI, -0.35 to 0.03; P>.05). The TES group reported higher satisfaction with the received treatment and better cognitive quality of life (all P<.05)., Conclusions: As a result of the low use of stepped care, a combined screening and treatment program targeting psychological distress in patients with metastatic colorectal cancer did not improve psychological distress. Our results suggest that enhanced evaluation of psychosocial concerns may improve aspects of patient well-being.
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- 2019
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43. Impact of Patient- and Clinician-Reported Cumulative Toxicity on Quality of Life in Patients With Metastatic Castration-Naïve Prostate Cancer.
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Schuurhuizen CSEW, Marino P, Braamse AMJ, Buffart LM, Joly F, Fizazi K, Habibian M, Boher JM, Soulie M, Oudard S, Konings IRHM, Verheul HMW, Dekker J, and Gravis G
- Subjects
- Aged, Aged, 80 and over, Androgen Antagonists adverse effects, Antineoplastic Agents, Hormonal adverse effects, Docetaxel adverse effects, Drug-Related Side Effects and Adverse Reactions diagnosis, Goserelin adverse effects, Humans, Longitudinal Studies, Male, Middle Aged, Progression-Free Survival, Prospective Studies, Prostatic Neoplasms mortality, Prostatic Neoplasms pathology, Severity of Illness Index, Surveys and Questionnaires statistics & numerical data, Time Factors, Antineoplastic Combined Chemotherapy Protocols adverse effects, Drug-Related Side Effects and Adverse Reactions complications, Patient Reported Outcome Measures, Prostatic Neoplasms drug therapy, Quality of Life
- Abstract
Background: Current toxicity evaluation is primarily focused on high-grade adverse events (AEs) reported by clinicians. However, the cumulative effect of multiple lower-grade AEs may also impact patients' quality of life (QoL). Further, patient-reported toxicity may be more representative of patients' treatment experiences. This study aimed to determine whether cumulative toxicity comprising all-grade AEs is more associated with QoL than cumulative toxicity comprising high-grade AEs only, and whether patient-reported cumulative toxicity is more associated with QoL than clinician-reported cumulative toxicity. Methods: Patients with metastatic castration-naïve prostate cancer participating in the phase III GETUG-AFU 15 trial completed questionnaires on AEs (at 3 and 6 months) and QoL (at baseline and 3 and 6 months). Clinicians reported AEs during clinical visits. Cumulative toxicity scores were calculated for clinicians and patients in 3 ways: total number of high-grade AEs, total number of all-grade AEs, and total number of all AEs multiplied by their grade (severity score). Relationships between cumulative toxicity scores and QoL were studied using longitudinal regression analyses; unstandardized (B) and standardized regression coefficients (β) are reported. Results: Of 385 patients, 184 with complete QoL and toxicity data were included. Clinician-reported all-grade AEs (B, -2.2; 95% CI, -3.3 to -1.1; P <.01) and severity score (B, -1.4; 95% CI, -2.2 to -0.7; P <.01) were associated with deteriorated physical QoL, whereas the total number of high-grade AEs was not. All patient-reported scores were significantly ( P <.01 for all) associated with deteriorated physical and global QoL. Standardized regression coefficients indicated that patient-reported toxicity scores were more associated with QoL outcomes than clinician-reported scores, with the strongest association found for the all-grade AEs and severity cumulative toxicity scores. Conclusions: Patient- and clinician-based cumulative toxicity scores comprising all-grade AEs better reflect impact on patient QoL than toxicity scores comprising high-grade AEs only. To assess the effect of toxicity on QoL, patient-reported cumulative toxicity scores are preferred., (Copyright © 2018 by the National Comprehensive Cancer Network.)
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- 2018
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44. Higher Muscle Strength Is Associated with Prolonged Survival in Older Patients with Advanced Cancer.
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Versteeg KS, Blauwhoff-Buskermolen S, Buffart LM, de van der Schueren MAE, Langius JAE, Verheul HMW, Maier AB, and Konings IR
- Subjects
- Aged, Female, Humans, Male, Neoplasms mortality, Muscle Strength physiology, Neoplasms diagnosis, Sarcopenia physiopathology
- Abstract
Background: Identifying predictors of treatment toxicity and overall survival (OS) is important for selecting patients who will benefit from chemotherapy. In younger patients with cancer, muscle mass and radiodensity are associated with treatment toxicity and OS. In this study, we investigated whether muscle mass, radiodensity, and strength were associated with treatment toxicity and OS in patients with advanced cancer aged 60 years or older., Materials and Methods: Before starting palliative chemotherapy, muscle mass and radiodensity were assessed using computed tomography scans and muscle strength was assessed using a hydraulic hand grip dynamometer. Treatment toxicity was defined as any toxicity resulting in dose reduction and/or discontinuation of treatment. Multiple logistic and Cox regression analyses were performed to study potential associations of muscle mass, radiodensity, and strength with treatment toxicity and OS, respectively., Results: The participants were 103 patients, with a mean age of 70 years, with advanced colorectal, prostate, or breast cancer. Muscle parameters were not significantly associated with treatment toxicity. Higher muscle strength was associated with longer OS (hazard ratio 1.03; 95% confidence interval 1.00-1.05). Muscle mass and radiodensity were not significantly associated with OS., Conclusion: Higher muscle strength at the start of palliative chemotherapy is associated with significantly better OS in older patients with advanced cancer. None of the investigated muscle parameters were related to treatment toxicity. Future studies are needed to evaluate whether muscle strength can be used for treatment decisions in older patients with advanced cancer., Implications for Practice: This study in older patients with advanced cancer showed that adequate muscle strength is associated with longer overall survival. The results of this study imply that muscle strength might be helpful in estimating survival and therefore in identifying older patients who will benefit from anticancer treatment., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2017.)
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- 2018
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45. Effect of omeprazole on the pharmacokinetics and toxicities of irinotecan in cancer patients: a prospective cross-over drug-drug interaction study.
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van der Bol JM, Loos WJ, de Jong FA, van Meerten E, Konings IR, Lam MH, de Bruijn P, Wiemer EA, Verweij J, and Mathijssen RH
- Subjects
- Adult, Aged, Camptothecin adverse effects, Camptothecin pharmacokinetics, Cross-Over Studies, Drug Interactions, Female, Humans, Irinotecan, Male, Middle Aged, Prospective Studies, Tumor Cells, Cultured, Antineoplastic Agents, Phytogenic adverse effects, Antineoplastic Agents, Phytogenic pharmacokinetics, Camptothecin analogs & derivatives, Neoplasms drug therapy, Omeprazole pharmacology, Proton Pump Inhibitors pharmacology
- Abstract
Background: Omeprazole is one of the most prescribed medications worldwide and within the class of proton pump inhibitors, it is most frequently associated with drug interactions. In vitro studies have shown that omeprazole can alter the function of metabolic enzymes and transporters that are involved in the metabolism of irinotecan, such as uridine diphosphate glucuronosyltransferase subfamily 1A1 (UGT1A1), cytochrome P-450 enzymes subfamily 3A (CYP3A) and ATP-binding cassette drug-transporter G2 (ABCG2). In this open-label cross-over study we investigated the effects of omeprazole on the pharmacokinetics and toxicities of irinotecan., Methods: Fourteen patients were treated with single agent irinotecan (600mg i.v., 90min) followed 3weeks later by a second cycle with concurrent use of omeprazole 40mg once daily, which was started 2weeks prior to the second cycle. Plasma samples were obtained up to 55h after infusion and analysed for irinotecan and its metabolites 7-ethyl-10-hydroxycampothecin (SN-38), SN-38-glucuronide (SN-38G), 7-ethyl-10-[4-(1-piperidino)-1-amino]-carbonyloxycamptothecin (NPC) and 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin (APC) by high-performance liquid chromatography (HPLC). Non-compartmental modelling was performed. Toxicities were monitored during both cycles. Paired statistical tests were performed with SPSS., Results: The exposure to irinotecan and its metabolites was not significantly different between both cycles. Neither were there significant differences in the absolute nadir and percentage decrease of WBC and ANC, nor on the incidence and severity of neutropenia, febrile neutropenia, diarrhoea, nausea and vomiting when irinotecan was combined with omeprazole., Conclusion: Omeprazole 40mg did not alter the pharmacokinetics and toxicities of irinotecan. This widely used drug can, therefore, be safely administered during a 3-weekly single agent irinotecan schedule., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2011
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46. The addition of pravastatin to chemotherapy in advanced gastric carcinoma: a randomised phase II trial.
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Konings IR, van der Gaast A, van der Wijk LJ, de Jongh FE, Eskens FA, and Sleijfer S
- Subjects
- Adult, Aged, Capecitabine, Cisplatin administration & dosage, Cisplatin adverse effects, Deoxycytidine administration & dosage, Deoxycytidine adverse effects, Deoxycytidine analogs & derivatives, Epirubicin administration & dosage, Epirubicin adverse effects, Female, Fluorouracil administration & dosage, Fluorouracil adverse effects, Fluorouracil analogs & derivatives, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Pravastatin administration & dosage, Pravastatin adverse effects, Adenocarcinoma drug therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Stomach Neoplasms drug therapy
- Abstract
Purpose: Statins have for long been considered to play a potential role in anticancer treatment based upon their ability to inhibit the mevalonate synthesis pathway. This randomised phase II trial compared the efficacy and safety of pravastatin added to epirubicin, cisplatin and capecitabine (ECC versus ECC+P) in patients with advanced gastric carcinoma., Methods: Patients were randomised to receive up to six cycles of 3-weekly ECC with or without pravastatin (40 mg, once daily from day 1 of the first cycle until day 21 of the last cycle). Primary end-point was progression-free rate at 6 months (PFR(6 months)). Secondary end-points were response rate (RR), progression-free survival (PFS), overall survival (OS) and safety. For early termination in case of futility, a two-stage design was applied (P(0) = 50%; P(1) = 70%; α = 0.05; β = 0.10)., Results: Thirty patients were enrolled. PFR(6 months) was 6/14 patients (42.8%) in the ECC+P arm, and 7/15 patients (46.7%) in the control arm, and therefore the study was terminated after the first stage. In the ECC and ECC+P arm, RR was 7/15 (46.7%) and 5/15 (33.3%), median PFS was 5 and 6 months and median OS was 6 and 8 months, respectively. Toxicity data showed no significant differences, although there was a trend towards more gastrointestinal side-effects such as diarrhoea and stomatitis in the ECC+P arm., Conclusion: In this randomised phase II trial the addition of pravastatin to ECC did not improve outcome in patients with advanced gastric cancer. Therefore, further testing of this combination in a randomised phase III trial cannot be recommended., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
47. 213Bi-[DOTA0, Tyr3]octreotide peptide receptor radionuclide therapy of pancreatic tumors in a preclinical animal model.
- Author
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Norenberg JP, Krenning BJ, Konings IR, Kusewitt DF, Nayak TK, Anderson TL, de Jong M, Garmestani K, Brechbiel MW, and Kvols LK
- Subjects
- Animals, Disease Models, Animal, Drug Evaluation, Preclinical, Male, Octreotide toxicity, Radioisotopes, Rats, Rats, Inbred Lew, Time Factors, Bismuth therapeutic use, Bismuth toxicity, Octreotide analogs & derivatives, Octreotide therapeutic use, Pancreatic Neoplasms radiotherapy, Receptors, Somatostatin drug effects
- Abstract
Purpose: The somatostatin analogue [DOTA0, Tyr3]octreotide (DOTATOC) has previously been labeled with low linear energy transfer (LET) beta-emitters, such as 177Lu or 90Y, for tumor therapy. In this study, DOTATOC labeled with the high-LET alpha-emitter, 213Bi, was evaluated., Experimental Design: The radiolabeling, stability, biodistribution, toxicity, safety, and therapeutic efficacy of 213Bi-DOTATOC (specific activity 7.4 MBq/microg) were investigated. Biodistribution studies to determine somatostatin receptor specificity were done in Lewis rats at 1 and 3 hours postinjection. Histopathology of various organs was used to evaluated toxicity and safety. Therapeutic efficacy of 4 to 22 MBq 213Bi-DOTATOC was determined in a rat pancreatic carcinoma model., Results: Radiolabeling of the 213Bi-DOTATOC was achieved with radiochemical purity >95% and an incorporation yield > or = 99.9%. Biodistribution data showed specific binding to somatostatin receptor-expressing tissues. Administration of free 213Bi, compared with 213Bi-DOTATOC, resulted in higher radioactivity accumulation at 3 hours postinjection in the kidneys [34.47 +/- 1.40% injected dose/g (ID/g) tissue versus 11.15 +/- 0.46%, P < 0.0001] and bone marrow (0.31 +/- 0.01% ID/g versus 0.06 +/- 0.02%, P < 0.0324). A significant decrease in tumor growth rate was observed in rats treated with >11 MBq of 213Bi-DOTATOC 10 days postinjection compared with controls (P < 0.025). Treatment with >20 MBq of 213Bi-DOTATOC showed significantly greater tumor reduction when compared with animals receiving <11 MBq (P < 0.02)., Conclusions: 213Bi-DOTATOC showed dose-related antitumor effects with minimal treatment-related organ toxicity. No acute or chronic hematologic toxicities were observed. Mild, acute nephrotoxicity was observed without evidence of chronic toxicity. 213Bi-DOTATOC is a promising therapeutic radiopharmaceutical for further evaluation.
- Published
- 2006
- Full Text
- View/download PDF
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