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14 results on '"Konings, Inge R."'

2. 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

Author

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

Published
2023
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3. Genomic Alterations Associated with Estrogen Receptor Pathway Activity in Metastatic Breast Cancer Have a Differential Impact on Downstream ER Signaling

Author

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

Published
2023
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6. Re-irradiation and hyperthermia for locoregional recurrent breast cancer: Outcome of 23x2Gy vs 8x4Gy

Author

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.

Published
2022

7. 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

Author

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)

Subjects
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.

Published
2020

8. Substantially improving the cure rate of high-risk BRCA1-like breast cancer patients with personalized therapy (SUBITO) - an international randomized phase III trial

Author

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)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

San Antonio Breast Cancer Symposium, San Antonio, TX, DEC 05-09, 2017

Published
2018

10. Higher Muscle Strength Is Associated with Prolonged Survival in Older Patients with Advanced Cancer.

Author

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.

Subjects
ANTINEOPLASTIC agents, BREAST tumors, COLON tumors, COMPUTED tomography, CONFIDENCE intervals, DRUG toxicity, EXERCISE tests, GRIP strength, LONGITUDINAL method, METASTASIS, MUSCLE contraction, MUSCLE strength, PROSTATE tumors, RECTUM tumors, MULTIPLE regression analysis, PROPORTIONAL hazards models, ODDS ratio, OLD age, PROGNOSIS
Abstract

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. [ABSTRACT FROM AUTHOR]

Published
2018
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11. Screening and treatment of psychological distress in patients with metastatic colorectal cancer: study protocol of the TES trial.

Author

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]

Published
2015
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12. Successful Trastuzumab-Deruxtecan Rechallenge After Interstitial Lung Disease: A Case Report.

Author

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.)

Published
2023
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13. High ctDNA molecule numbers relate with poor outcome in advanced ER+, HER2- postmenopausal breast cancer patients treated with everolimus and exemestane.

Author

Kruger DT, Jansen MPHM, Konings IRHM, Dercksen WM, Jager A, Oulad Hadj J, Sleijfer S, Martens JWM, and Boven E

Subjects
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.)

Published
2020
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14. 213Bi-[DOTA0, Tyr3]octreotide peptide receptor radionuclide therapy of pancreatic tumors in a preclinical animal model.

Author

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
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