813 results on '"Hans Gelderblom"'
Search Results
102. Supplementary Table from Patients with Rare Cancers in the Drug Rediscovery Protocol (DRUP) Benefit from Genomics-Guided Treatment
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Emile E. Voest, Henk M.W. Verheul, Hans Gelderblom, Edwin Cuppen, Martijn P. Lolkema, Hans Morreau, Ann Hoeben, Mariette Labots, Carla M.L. van Herpen, Winette T.A. van der Graaf, Egbert F. Smit, Mathijs P. Hendriks, Laurens V. Beerepoot, Frans Erdkamp, Derk Jan de Groot, Emile D. Kerver, Jan Willem B. de Groot, Eelke H. Gort, Alwin D.R. Huitema, Vincent van der Noort, Erik van Werkhoven, Anne M.L. Jansen, Wendy J. de Leng, Paul Roepman, Joris van de Haar, Daphne L. van der Velden, Laurien J. Zeverijn, Hanneke van der Wijngaart, Jade M. van Berge Henegouwen, and Louisa R. Hoes
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Supplementary Table from Patients with Rare Cancers in the Drug Rediscovery Protocol (DRUP) Benefit from Genomics-Guided Treatment
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- 2023
103. supplementary figures from Telatinib Is an Effective Targeted Therapy for Pseudomyogenic Hemangioendothelioma
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Judith V.M.G. Bovée, Karoly Szuhai, Geert J.L.H. van Leenders, Ferry A.L.M. Eskens, Hans Gelderblom, Stefan Sleijfer, and David G.P. van IJzendoorn
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Supplementary figure 1 Tube formation assay after 24 hours on matrigel with overexpression of indicated proteins using a lentiviral system. Truncated FOSB is most efficient at driving tube formation. Bottom right panel: Western blot of FOSB and truncated FOSB overexpression in HUVECs as detected with a Flag antibody showing effective transduction of both plasmids. Supplementary figure 2 (a) Expression levels of FOSB in the PHE tumor biopsy were compared to normal control HUVECs by real-time qPCR. Both show high expression of FOSB. Expression was normalized against HPRT1. (b) Expression levels of the indicated target genes and receptors were determined in the PHE tumor biopsy compared to normal control HUVECs by real-time qPCR. FAS, JAG, HEY1, FLT1 and PDGFRA were upregulated while VWF was downregulated. ADAMTS13 was not detected in the PHE tumor biopsy. Expression was normalized against HPRT1. Supplementary figure 3 Top panels show cell cycle analysis by analysis of DAPI signal intensity. Gating was performed to identify sub-G1, G1, S-phase and G2 cell fractions. Bottom panels show apoptotic cell fraction as determined by analysis of the PI and VB-48 signal intensity. Apoptotic cell fraction was determined by gating cells negative for PI and VB-48. Supplementary figure 4 (a) Top panel shows 3D assay on matrigel with normal HUVECs and with HUVECs overexpressing truncated FOSB. ShRNA for KIT efficiently blocks tube formation in the normal HUVECs only, while knockdown of KDR shows no effect in either condition. Bottom part of the panel shows the calculated number of loops and junctions of the tube formation assay. (b) IHC of the patient tumor biopsy with a KIT antibody. Tumor cells are negative for KIT while the arrow indicates a mast cell functioning as an internal control.
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- 2023
104. Supplementary Table 1 from Patients with Biallelic BRCA1/2 Inactivation Respond to Olaparib Treatment Across Histologic Tumor Types
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Henk M.W. Verheul, Emile E. Voest, Hans Gelderblom, Paul Hamberg, Ann Hoeben, Derk Jan A. de Groot, Mariette Labots, Debbie G.J. Robbrecht, Niven Mehra, Anne M.L. Jansen, Wendy W.J. de Leng, Erik van Werkhoven, Paul Roepman, Laurien J. Zeverijn, Daphne L. van der Velden, J. Maxime van Berge Henegouwen, Louisa R. Hoes, and Hanneke van der Wijngaart
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Supplementary Table 1
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- 2023
105. Supplementary Table 2 from A First Step toward Personalized Medicine in Osteosarcoma: Pharmacogenetics as Predictive Marker of Outcome after Chemotherapy-Based Treatment
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Dunja M.W.M te Loo, Henk-Jan Guchelaar, Peter M. Hoogerbrugge, Frank N. van Leeuwen, Uta Flucke, H.W. Bart Schreuder, Winette T.A. van der Graaf, Eveline S.J.M. de Bont, Hanneke I. Vos, Remco R. Makkinje, Hans Gelderblom, Marieke J.H. Coenen, and Melanie M. Hagleitner
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Supplementary Table 2. Genetic variants associated with histologic response
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- 2023
106. Data from Phase I/Ib Clinical Trial of Sabatolimab, an Anti–TIM-3 Antibody, Alone and in Combination with Spartalizumab, an Anti–PD-1 Antibody, in Advanced Solid Tumors
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Aung Naing, Luigi Manenti, Sabine Gutzwiller, Haiying Sun, Alexandros Xyrafas, Tyler A. Longmire, Catherine A. Sabatos-Peyton, Armando Santoro, Sofie Wilgenhof, F. Stephen Hodi, Chia-Chi Lin, Philippe L. Bedard, John Sarantopoulos, Patrick M. Forde, David Tai, Toshihiko Doi, Nicolas Mach, Hans Gelderblom, and Giuseppe Curigliano
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Purpose:Sabatolimab (MBG453) and spartalizumab are mAbs that bind T-cell immunoglobulin domain and mucin domain-3 (TIM-3) and programmed death-1 (PD-1), respectively. This phase I/II study evaluated the safety and efficacy of sabatolimab, with or without spartalizumab, in patients with advanced solid tumors.Patients and Methods:Primary objectives of the phase I/Ib part were to characterize the safety and estimate recommended phase II dose (RP2D) for future studies. Dose escalation was guided by a Bayesian (hierarchical) logistic regression model. Sabatolimab was administered intravenously, 20 to 1,200 mg, every 2 or 4 weeks (Q2W or Q4W). Spartalizumab was administered intravenously, 80 to 400 mg, Q2W or Q4W.Results:Enrolled patients (n = 219) had a range of cancers, most commonly ovarian (17%) and colorectal cancer (7%); patients received sabatolimab (n = 133) or sabatolimab plus spartalizumab (n = 86). The MTD was not reached. The most common adverse event suspected to be treatment-related was fatigue (9%, sabatolimab; 15%, combination). No responses were seen with sabatolimab. Five patients receiving combination treatment had partial responses (6%; lasting 12–27 months) in colorectal cancer (n = 2), non–small cell lung cancer (NSCLC), malignant perianal melanoma, and SCLC. Of the five, two patients had elevated expression of immune markers in baseline biopsies; another three had >10% TIM-3–positive staining, including one patient with NSCLC who received prior PD-1 therapy.Conclusions:Sabatolimab plus spartalizumab was well tolerated and showed preliminary signs of antitumor activity. The RP2D for sabatolimab was selected as 800 mg Q4W (alternatively Q3W or Q2W schedules, based on modeling), with or without 400 mg spartalizumab Q4W.
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- 2023
107. Data from A First Step toward Personalized Medicine in Osteosarcoma: Pharmacogenetics as Predictive Marker of Outcome after Chemotherapy-Based Treatment
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Dunja M.W.M te Loo, Henk-Jan Guchelaar, Peter M. Hoogerbrugge, Frank N. van Leeuwen, Uta Flucke, H.W. Bart Schreuder, Winette T.A. van der Graaf, Eveline S.J.M. de Bont, Hanneke I. Vos, Remco R. Makkinje, Hans Gelderblom, Marieke J.H. Coenen, and Melanie M. Hagleitner
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Purpose: Overall survival in patients with osteosarcoma is only 60%. Poor response to chemotherapy is the dominant risk factor for poor survival. Pharmacogenetic research can offer possibilities to optimize treatment and improve outcome. We applied a pathway-based approach to evaluate the cumulative effect of genes involved in the metabolism of cisplatin and doxorubicin in relationship to clinical outcome.Experimental Design: We included 126 patients with osteosarcoma. To comprehensively assess common genetic variation in the 54 genes selected, linkage disequilibrium (LD; r2 = 0.8)–based tag-single nucleotide polymorphisms (SNP) strategy was used. A final set of 384 SNPs was typed using Illumina Beadarray platform. SNPs significantly associated with 5-year progression-free survival (PFS) were replicated in another 64 patients with osteosarcoma.Results: We identified five variants in FasL, MSH2, ABCC5, CASP3, and CYP3A4 that were associated with 5-year PFS. Risk stratification based on the combined effects of the risk alleles showed a significant improvement of 5-year PFS. Patients that carried no or only one risk allele had a 5-year PFS of 100% compared with a 5-year PFS of 84.4% for carriers of two or three risk alleles, 66.7% PFS if a patient carried four to five alleles, and a 5-year PFS of 41.8% for patients with >5 risk alleles (P < 0.001).Conclusions: We identified several genes that showed association with PFS in patients with osteosarcoma. These pharmacogenetic risk factors might be useful to predict treatment outcome and to stratify patients immediately after diagnosis and offer the possibility to improve treatment and outcome. Clin Cancer Res; 21(15); 3436–41. ©2015 AACR.
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- 2023
108. supplementary tables from Telatinib Is an Effective Targeted Therapy for Pseudomyogenic Hemangioendothelioma
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Judith V.M.G. Bovée, Karoly Szuhai, Geert J.L.H. van Leenders, Ferry A.L.M. Eskens, Hans Gelderblom, Stefan Sleijfer, and David G.P. van IJzendoorn
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Supplementary table 1 Primers sequences used for Real-Time qPCR. Supplementary table 2 ShRNA used for inhibition of the receptors, for each receptor the most effective shRNA was selected as tested with Real-Time qPCR. Supplementary table 3 Sequence of the primers used for ChIP-qPCR.
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- 2023
109. Supplementary Data from Phase I/Ib Clinical Trial of Sabatolimab, an Anti–TIM-3 Antibody, Alone and in Combination with Spartalizumab, an Anti–PD-1 Antibody, in Advanced Solid Tumors
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Aung Naing, Luigi Manenti, Sabine Gutzwiller, Haiying Sun, Alexandros Xyrafas, Tyler A. Longmire, Catherine A. Sabatos-Peyton, Armando Santoro, Sofie Wilgenhof, F. Stephen Hodi, Chia-Chi Lin, Philippe L. Bedard, John Sarantopoulos, Patrick M. Forde, David Tai, Toshihiko Doi, Nicolas Mach, Hans Gelderblom, and Giuseppe Curigliano
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Supplementary Materials
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- 2023
110. Supplementary Table 1 from A First Step toward Personalized Medicine in Osteosarcoma: Pharmacogenetics as Predictive Marker of Outcome after Chemotherapy-Based Treatment
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Dunja M.W.M te Loo, Henk-Jan Guchelaar, Peter M. Hoogerbrugge, Frank N. van Leeuwen, Uta Flucke, H.W. Bart Schreuder, Winette T.A. van der Graaf, Eveline S.J.M. de Bont, Hanneke I. Vos, Remco R. Makkinje, Hans Gelderblom, Marieke J.H. Coenen, and Melanie M. Hagleitner
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Supplementary Table 1. Set of 381 SNPs
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- 2023
111. Supplementary Figure 1 from Activation of Tumor-Promoting Type 2 Macrophages by EGFR-Targeting Antibody Cetuximab
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Thorbald van Hall, Henk-Jan Guchelaar, Sjoerd H. van der Burg, Hans Morreau, Hans Gelderblom, Renée Baak-Pablo, Ekaterina S. Jordanova, Tahar van der Straaten, Moniek Heusinkveld, and Jan Pander
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PDF file - 304K
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- 2023
112. Supplementary Legend from Patients with Biallelic BRCA1/2 Inactivation Respond to Olaparib Treatment Across Histologic Tumor Types
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Henk M.W. Verheul, Emile E. Voest, Hans Gelderblom, Paul Hamberg, Ann Hoeben, Derk Jan A. de Groot, Mariette Labots, Debbie G.J. Robbrecht, Niven Mehra, Anne M.L. Jansen, Wendy W.J. de Leng, Erik van Werkhoven, Paul Roepman, Laurien J. Zeverijn, Daphne L. van der Velden, J. Maxime van Berge Henegouwen, Louisa R. Hoes, and Hanneke van der Wijngaart
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Supplementary Legend
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- 2023
113. Pexidartinib provides modest pain relief in patients with tenosynovial giant cell tumor
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John H. Healey, William D. Tap, Heather L. Gelhorn, Xin Ye, Rebecca M. Speck, Emanuela Palmerini, Silvia Stacchiotti, Jayesh Desai, Andrew J. Wagner, Thierry Alcindor, Kristen Ganjoo, Javier Martín-Broto, Qiang Wang, Dale Shuster, Hans Gelderblom, and Michiel van de Sande
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Adult ,Treatment Outcome ,Double-Blind Method ,Humans ,Giant Cell Tumor of Tendon Sheath ,Aminopyridines ,Pain ,Female ,Orthopedics and Sports Medicine ,Surgery ,General Medicine ,Middle Aged - Abstract
Background: The double-blind, randomized, placebo-controlled phase 3 study of orally administered PLX3397 in patients with pigmented villonodular synovitis or giant cell tumor of the tendon sheath (ENLIVEN) showed that pexidartinib provides a robust objective tumor response in adults with tenosynovial giant cell tumors (TGCT) not amenable to improvement with surgery. Based on these results, in 2019, pexidartinib received accelerated approval in the United States in this population as a breakthrough therapy under an orphan drug designation. However, the ability of pexidartinib to relieve pain in ENLIVEN was not fully detailed, and the relationship between pain relief and objective tumor response was not described. Questions/purposes: (1) What level of pain relief was achieved by pexidartinib treatment in ENLIVEN? (2) How was pain relief related to objective tumor responses? (3) How durable was pain relief? Methods: The current study included planned primary and exploratory assessments of patient-assessed worst pain at the site of the tumor in the ENLIVEN trial. ENLIVEN was a phase 3 randomized, placebo-controlled clinical trial in which adults with TGCT not amenable to improvement with surgery received pexidartinib or placebo for 24 weeks, after which eligible patients could receive open-label pexidartinib. Of 174 patients assessed for eligibility, 121 were randomized (50% [60] to placebo, 50% [61] to pexidartinib), and 120 were given either placebo or pexidartinib (59 received placebo and 61 received pexidartinib) and were included in an intent-to-treat analysis. Fifty-nine percent (71 of 120) of the overall treated population was female, and 88% (106 of 120) were White. Mean age was 45 +/- 13 years. Tumors were mostly in the lower extremities (92% [110 of 120]), most commonly in the knee (61% [73 of 120]) and ankle (18% [21 of 120]). As a secondary outcome, patients scored worst pain at the site of the tumor in the past 24 hours on an 11-point numeric rating scale (NRS). The primary definition of a pain response was a decrease of at least 30% in the weekly mean worst-pain NRS score and increase of less than 30% in narcotic analgesic use between baseline and week 25. Planned exploratory assessments of pain included the frequency of a pain response using alternative thresholds, including a decrease in worst-pain NRS score of 50% or more and a decrease of at least 2 points (minimum clinically important difference [MCID]), the magnitude of pain reduction between baseline and week 25, correlation between worst-pain NRS score and tumor shrinkage by RECIST 1.1 criteria, and the durability of the pain response during the open-label extension. Pain responses during the randomized portion of the trial were compared according to intention-to-treat analysis, with a one-sided threshold of p < 0.025 to reduce the risk of false-positive results. Pain assessment was complete for 59% (35 of 59) of patients in the placebo group and 54% (33 of 61) of patients in the pexidartinib group. Demographic and disease characteristics did not differ between the two treatment groups. Results: ®A difference in the primary assessment of a pain response was not detected between pexidartinib and placebo (response percentage 31% [19 of 61] [95% CI 21% to 44%] versus 15% [9 of 59] [95% CI 8% to 27%]; one-sided p = 0.03). In the exploratory analyses, pexidartinib provided a modest improvement in pain (response percentage 26% [16 of 61] [95% CI 17% to 38%] versus 10% [6 of 59] [95% CI 5% to 20%]; one-sided p = 0.02 using the 50% threshold and 31% [19 of 61] [95% CI 21% to 44%] versus 14% [8 of 59] [95% CI 7% to 25%]; one-sided p = 0.02 using the MCID threshold). The least-squares mean change in the weekly mean worst-pain NRS score between baseline and week 25 was larger in patients treated with pexidartinib than placebo (-2.5 [95% CI -3.0 to -1.9] versus -0.3 [95% CI -0.9 to 0.3]; p < 0.001), although the mean difference between the two groups (-2.2 [95% CI -3.0 to -1.4]) was just over the MCID. Improvement in the weekly mean worst-pain NRS score correlated with the reduction in tumor size (r = 0.44; p < 0.001) and tumor volume score (r = 0.61; p < 0.001). For patients in the open-label extension, the change in the worst-pain NRS score from baseline was similar to the change at the end of the randomized portion and just above the MCID (mean -2.7 +/- 2.2 after 25 weeks and -3.3 +/- 1.7 after 50 weeks of receiving pexidartinib). Conclusion: Based on the current study, a modest reduction in pain, just larger than the MCID, may be an added benefit of pexidartinib in these patients, although the findings are insufficient to justify the routine use of pexidartinib for pain relief.
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- 2023
114. Tenosynovial Giant Cell Tumor Observational Platform Project (TOPP) Registry : A 2-Year Analysis of Patient-Reported Outcomes and Treatment Strategies
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Emanuela Palmerini, John H Healey, Nicholas M Bernthal, Sebastian Bauer, Hendrik Schreuder, Andreas Leithner, Javier Martin-Broto, Francois Gouin, Julio Lopez-Bastida, Hans Gelderblom, Eric L Staals, Florence Mercier, Petra Laeis, Xin Ye, and Michiel van de Sande
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Adult ,Cancer Research ,Oncology and Carcinogenesis ,Medizin ,Pain ,Giant Cell Tumor of Tendon Sheath ,patient-reported outcome ,All institutes and research themes of the Radboud University Medical Center ,quality of life (QoL) ,7.1 Individual care needs ,Clinical Research ,Humans ,tenosynovial giant cell tumor observational platform project (TOPP) ,Prospective Studies ,Patient Reported Outcome Measures ,Oncology & Carcinogenesis ,diffuse-TGCT ,Pain Research ,patient-reported outcome (PRO) ,prospective ,tenosynovial giant cell tumor observational platform project ,Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10] ,Good Health and Well Being ,quality of life ,Oncology ,Management of diseases and conditions ,Chronic Pain ,pexidartinib - Abstract
Background: The Tenosynovial giant cell tumor Observational Platform Project (TOPP) registry is an international prospective study that -previously described the impact of diffuse-type tenosynovial giant cell tumour (D-TGCT) on patient-reported outcomes (PROs) from a baseline snapshot. This analysis describes the impact of D-TGCT at 2-year follow-up based on treatment strategies. Material and Methods: TOPP was conducted at 12 sites (EU: 10; US: 2). Captured PRO measurements assessed at baseline, 1-year, and 2-year follow-ups were Brief Pain Inventory (BPI), Pain Interference, BPI Pain Severity, Worst Pain, EQ-5D-5L, Worst Stiffness, and -Patient-Reported Outcomes Measurement Information System. Treatment interventions were no current/planned treatment (Off-Treatment) and systemic treatment/surgery (On-Treatment). Results: A total of 176 patients (mean age: 43.5 years) were included in the full analysis set. For patients without active treatment strategy -(Off-Treatment) at baseline (n = 79), BPI Pain Interference (1.00 vs. 2.86) and BPI Pain Severity scores (1.50 vs. 3.00) were numerically favorable in patients remaining Off-Treatment compared with those who switched to an active treatment strategy at year 1. From 1-year to 2-year -follow-ups, patients who remained Off-Treatment had better BPI Pain Interference (0.57 vs. 2.57) and Worst Pain (2.0 vs. 4.5) scores compared with patients who switched to an alternative treatment strategy. In addition, EQ-5D VAS scores (80.0 vs. 65.0) were higher in patients who remained -Off-Treatment between 1-year and 2-year follow-ups compared with patients who changed treatment strategy. For patients receiving systemic treatment at baseline, numerically favorable scores were seen in patients remaining on systemic therapy at 1-year follow-up: BPI Pain Interference (2.79 vs. 5.93), BPI Pain Severity (3.63 vs. 6.38), Worst Pain (4.5 vs. 7.5), and Worst Stiffness (4.0 vs. 7.5). From 1-year to 2-year follow-up, EQ-5D VAS scores (77.5 vs. 65.0) were higher in patients who changed from systemic treatment to a different treatment strategy. Conclusion: These findings highlight the impact D-TGCT has on patient quality of life, and how treatment strategies may be influenced by these outcome measures. (ClinicalTrials.gov number: NCT02948088)The TOPP registry is an international prospective study that previously described the impact of diffuse-type tenosynovial giant cell tumor on patient-reported outcomes from a baseline snapshot. This article reports a 2-year follow-up based on treatment strategies and could represent a benchmark for future clinical trials.
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- 2023
115. Response to letter entitled re: UGT1A1 genotype-guided dosing of irinotecan: A prospective safety and cost analysis in poor metaboliser patients
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Emma C. Hulshof, Mirjam de With, Geert-Jan Creemers, Henk-Jan Guchelaar, Ron HJ. Mathijssen, Hans Gelderblom, and Maarten J. Deenen
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Cancer Research ,Oncology - Published
- 2022
116. Symptoms reported by gastrointestinal stromal tumour (GIST) patients on imatinib treatment: combining questionnaire and forum data
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Dide den Hollander, Anne R. Dirkson, Suzan Verberne, Wessel Kraaij, Gerard van Oortmerssen, Hans Gelderblom, Astrid Oosten, Anna K. L. Reyners, Neeltje Steeghs, Winette T. A. van der Graaf, Ingrid M. E. Desar, Olga Husson, Medical Oncology, Surgery, Targeted Gynaecologic Oncology (TARGON), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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Symptom measurement ,Gastrointestinal Stromal Tumors ,EUROPEAN-ORGANIZATION ,MESYLATE ,SDG 3 - Good Health and Well-being ,QUALITY-OF-LIFE ,Surveys and Questionnaires ,Humans ,INTERNET ,Protein Kinase Inhibitors ,Fatigue ,Muscle Cramp ,Tyrosine kinase inhibitors ,OUTCOMES ,Patient-reported outcomes ,Gastrointestinal stromal tumours ,humanities ,PREVALENCE ,Cross-Sectional Studies ,Oncology ,Imatinib Mesylate ,Quality of Life ,ADVERSE EVENTS ,Social media mining ,TYROSINE KINASE INHIBITOR ,Patient forum ,CLINICAL-TRIALS ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] - Abstract
Purpose Treatment with the tyrosine kinase inhibitor (TKI) imatinib in patients with gastrointestinal stromal tumours (GIST) causes symptoms that could negatively impact health-related quality of life (HRQoL). Treatment-related symptoms are usually clinician-reported and little is known about patient reports. We used survey and online patient forum data to investigate (1) prevalence of patient-reported symptoms; (2) coverage of symptoms mentioned on the forum by existing HRQoL questionnaires; and (3) priorities of prevalent symptoms in HRQoL assessment. Methods In the cross-sectional population-based survey study, Dutch GIST patients completed items from the EORTC QLQ-C30 and Symptom-Based Questionnaire (SBQ). In the forum study, machine learning algorithms were used to extract TKI side-effects from English messages on an international online forum for GIST patients. Prevalence of symptoms related to imatinib treatment in both sources was calculated and exploratively compared. Results Fatigue and muscle pain or cramps were reported most frequently. Seven out of 10 most reported symptoms (i.e. fatigue, muscle pain or cramps, facial swelling, joint pain, skin problems, diarrhoea, and oedema) overlapped between the two sources. Alopecia was frequently mentioned on the forum, but not in the survey. Four out of 10 most reported symptoms on the online forum are covered by the EORTC QLQ-C30. The EORTC-SBQ and EORTC Item Library cover 9 and 10 symptoms, respectively. Conclusion This first overview of patient-reported imatinib-related symptoms from two data sources helps to determine coverage of items in existing questionnaires, and prioritize HRQoL issues. Combining cancer-generic instruments with treatment-specific item lists will improve future HRQoL assessment in care and research in GIST patients using TKI.
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- 2022
117. UGT1A1 genotype-guided dosing of irinotecan: A prospective safety and cost analysis in poor metaboliser patients
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Emma C. Hulshof, Mirjam de With, Femke M. de Man, Geert-Jan Creemers, Birgit A.L.M. Deiman, Jesse J. Swen, Saskia Houterman, Stijn L.W. Koolen, Sander Bins, Anna M.J. Thijs, Marjan M.J. Laven, Anke M. Hövels, Saskia A.C. Luelmo, Danny Houtsma, Katerina Shulman, Howard L. McLeod, Ron H.N. van Schaik, Henk-Jan Guchelaar, Ron H.J. Mathijssen, Hans Gelderblom, Maarten J. Deenen, Clinical Chemistry, Medical Oncology, and Pharmacy
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Genotyping ,Cancer Research ,Toxicity ,Genotype ,Irinotecan ,digestive system ,UDP-glucuronosyl transferase ,SDG 3 - Good Health and Well-being ,Oncology ,Pharmacogenetics ,Costs and Cost Analysis ,Humans ,Camptothecin ,Prospective Studies ,Glucuronosyltransferase ,UGT ,Febrile Neutropenia - Abstract
Aim: To determine the safety, feasibility, pharmacokinetics, and cost of UGT1A1 genotype-guided dosing of irinotecan.Patients and methods: In this prospective, multicentre, non-randomised study, patients intended for treatment with irinotecan were pre-therapeutically genotyped for UGT1A1*28 and UGT1A1)93. Homozygous variant carriers (UGT1A1 poor metabolisers; PMs) received an initial 30% dose reduction. The primary endpoint was incidence of febrile neutropenia in the first two cycles of treatment. Toxicity in UGT1A1 PMs was compared to a historical cohort of UGT1A1 PMs treated with full dose therapy, and to UGT1A1 non-PMs treated with full dose therapy in the current study. Secondary endpoints were pharmacokinetics, feasi- bility, and costs.Results: Of the 350 evaluable patients, 31 (8.9%) patients were UGT1A1 PM and received a median 30% dose reduction. The incidence of febrile neutropenia in this group was 6.5% compared to 24% in historical UGT1A1 PMs (P = 0.04) and was comparable to the incidence in UGT1A1 non-PMs treated with full dose therapy. Systemic exposure of SN-38 of reduced dosing in UGT1A1 PMs was still slightly higher compared to a standard-dosed irinotecan patient cohort (difference: thorn 32%). Cost analysis showed that genotype-guided dosing was cost-saving with a cost reduction of V183 per patient.Conclusion: UGT1A1 genotype-guided dosing significantly reduces the incidence of febrile neutropenia in UGT1A1 PM patients treated with irinotecan, results in a therapeutically effec- tive systemic drug exposure, and is cost-saving. Therefore, UGT1A1 genotype-guided dosing of irinotecan should be considered standard of care in order to improve individual patient safety. (C) 2022 The Authors. Published by Elsevier Ltd.
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- 2022
118. Open Knowledge Discovery and Data Mining from Patient Forums.
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Anne Dirkson, Suzan Verberne, Gerard Van Oortmerssen, Hans Gelderblom, and Wessel Kraaij
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- 2018
- Full Text
- View/download PDF
119. Sample Bias in Web-Based Patient-Generated Health Data of Dutch Patients With Gastrointestinal Stromal Tumor: Survey Study: Survey Study
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Anne Dirkson, Dide den Hollander, Suzan Verberne, Ingrid Desar, Olga Husson, Winette T A van der Graaf, Astrid Oosten, Anna K L Reyners, Neeltje Steeghs, Wouter van Loon, Gerard van Oortmerssen, Hans Gelderblom, Wessel Kraaij, Surgery, Medical Oncology, Faculteit Medische Wetenschappen/UMCG, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Targeted Gynaecologic Oncology (TARGON)
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representativeness ,pharmacovigilance ,social media ,rare cancer ,Medicine (miscellaneous) ,Health Informatics ,patient forum ,sample bias ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] - Abstract
Background Increasingly, social media is being recognized as a potential resource for patient-generated health data, for example, for pharmacovigilance. Although the representativeness of the web-based patient population is often noted as a concern, studies in this field are limited. Objective This study aimed to investigate the sample bias of patient-centered social media in Dutch patients with gastrointestinal stromal tumor (GIST). Methods A population-based survey was conducted in the Netherlands among 328 patients with GIST diagnosed 2-13 years ago to investigate their digital communication use with fellow patients. A logistic regression analysis was used to analyze clinical and demographic differences between forum users and nonusers. Results Overall, 17.9% (59/328) of survey respondents reported having contact with fellow patients via social media. Moreover, 78% (46/59) of forum users made use of GIST patient forums. We found no statistically significant differences for age, sex, socioeconomic status, and time since diagnosis between forum users (n=46) and nonusers (n=273). Patient forum users did differ significantly in (self-reported) treatment phase from nonusers (P=.001). Of the 46 forum users, only 2 (4%) were cured and not being monitored; 3 (7%) were on adjuvant, curative treatment; 19 (41%) were being monitored after adjuvant treatment; and 22 (48%) were on palliative treatment. In contrast, of the 273 patients who did not use disease-specific forums to communicate with fellow patients, 56 (20.5%) were cured and not being monitored, 31 (11.3%) were on curative treatment, 139 (50.9%) were being monitored after treatment, and 42 (15.3%) were on palliative treatment. The odds of being on a patient forum were 2.8 times as high for a patient who is being monitored compared with a patient that is considered cured. The odds of being on a patient forum were 1.9 times as high for patients who were on curative (adjuvant) treatment and 10 times as high for patients who were in the palliative phase compared with patients who were considered cured. Forum users also reported a lower level of social functioning (84.8 out of 100) than nonusers (93.8 out of 100; P=.008). Conclusions Forum users showed no particular bias on the most important demographic variables of age, sex, socioeconomic status, and time since diagnosis. This may reflect the narrowing digital divide. Overrepresentation and underrepresentation of patients with GIST in different treatment phases on social media should be taken into account when sourcing patient forums for patient-generated health data. A further investigation of the sample bias in other web-based patient populations is warranted.
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- 2022
120. Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial
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Sebastian Bauer, Robin L. Jones, Jean-Yves Blay, Hans Gelderblom, Suzanne George, Patrick Schöffski, Margaret von Mehren, John R. Zalcberg, Yoon-Koo Kang, Albiruni Abdul Razak, Jonathan Trent, Steven Attia, Axel Le Cesne, Ying Su, Julie Meade, Tao Wang, Matthew L. Sherman, Rodrigo Ruiz-Soto, and Michael C. Heinrich
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Cancer Research ,Indoles ,Gastrointestinal Stromal Tumors ,Medizin ,Antineoplastic Agents ,Proto-Oncogene Proteins c-kit ,Oncology ,Drug Resistance, Neoplasm ,Mutation ,Imatinib Mesylate ,Sunitinib ,Humans ,Pyrroles ,Protein Kinase Inhibitors - Abstract
PURPOSE Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is approved for advanced gastrointestinal stromal tumor (GIST) after imatinib failure. Ripretinib is a switch-control TKI approved for advanced GIST after prior treatment with three or more TKIs, including imatinib. We compared efficacy and safety of ripretinib versus sunitinib in patients with advanced GIST who were previously treated with imatinib (INTRIGUE, ClinicalTrials.gov identifier: NCT03673501 ). PATIENTS AND METHODS Random assignment was 1:1 to once-daily ripretinib 150 mg or once-daily sunitinib 50 mg (4 weeks on/2 weeks off) and stratified by KIT/ platelet-derived growth factor α mutation and imatinib intolerance. The primary end point was progression-free survival (PFS) by independent radiologic review using modified Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included objective response rate by independent radiologic review, safety, and patient-reported outcome measures. RESULTS Overall, 453 patients were randomly assigned to ripretinib (intention-to-treat [ITT], n = 226; KIT exon 11 ITT, n = 163) or sunitinib (ITT, n = 227; KIT exon 11 ITT, n = 164). Median PFS for ripretinib and sunitinib ( KIT exon 11 ITT) was 8.3 and 7.0 months, respectively (hazard ratio, 0.88; 95% CI, 0.66 to 1.16; P = .36); median PFS (ITT) was 8.0 and 8.3 months, respectively (hazard ratio, 1.05; 95% CI, 0.82 to 1.33; nominal P = .72). Neither was statistically significant. Objective response rate was higher for ripretinib versus sunitinib in the KIT exon 11 ITT population (23.9% v 14.6%, nominal P = .03). Ripretinib was associated with a more favorable safety profile, fewer grade 3/4 treatment-emergent adverse events (41.3% v 65.6%, nominal P < .0001), and better scores on patient-reported outcome measures of tolerability. CONCLUSION Ripretinib was not superior to sunitinib in terms of PFS. However, meaningful clinical activity, fewer grade 3/4 treatment-emergent adverse events, and improved tolerability were observed with ripretinib.
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- 2022
121. Response to 'Plasma Uracil as a DPD Phenotyping Test: Pre-analytical Handling Matters'
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Mirjam de With, Jonathan Knikman, Jan H. M. Schellens, Hans Gelderblom, Annemieke Cats, Henk‐Jan Guchelaar, Ron H. J. Mathijssen, Jesse J. Swen, Didier Meulendijks, Medical Oncology, and Clinical Chemistry
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Pharmacology ,Pharmacology (medical) - Published
- 2022
122. Comparison of two chemotherapy regimens in patients with newly diagnosed Ewing sarcoma (EE2012)
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Bernadette Brennan, Laura Kirton, Perrine Marec-Bérard, Nathalie Gaspar, Valerie Laurence, Javier Martín-Broto, Ana Sastre, Hans Gelderblom, Cormac Owens, Nicola Fenwick, Sandra Strauss, Veronica Moroz, Jeremy Whelan, and Keith Wheatley
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Bayes Theorem ,Bone Neoplasms ,General Medicine ,Sarcoma, Ewing ,Disease-Free Survival ,Vincristine ,Doxorubicin ,Antineoplastic Combined Chemotherapy Protocols ,Dactinomycin ,Humans ,Ifosfamide ,Busulfan ,Melphalan ,Cyclophosphamide ,Etoposide - Abstract
Internationally, a single standard chemotherapy treatment for Ewing sarcoma is not defined. Because different chemotherapy regimens were standard in Europe and the USA for newly diagnosed Ewing sarcoma, and in the absence of novel agents to investigate, we aimed to compare these two strategies.EURO EWING 2012 was a European investigator-initiated, open-label, randomised, controlled phase 3 trial done in 10 countries. We included patients aged 2-49 years, with any histologically and genetically confirmed Ewing sarcoma of bone or soft tissue, or Ewing-like sarcomas. The eligibility criteria originally excluded patients with extrapulmonary metastatic disease, but this was amended in the protocol (version 3.0) in September, 2016. Patients were randomly assigned (1:1) to either the European regimen of vincristine, ifosfamide, doxorubicin, and etoposide induction, and consolidation using vincristine, actinomycin D, with ifosfamide or cyclophosphamide, or busulfan and melphalan (group 1); or the US regimen of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide induction, plus ifosfamide and etoposide, and consolidation using vincristine and cyclophosphamide, or vincristine, actinomycin D, and ifosfamide, with busulfan and melphalan (group 2). All drugs were administered intravenously. The primary outcome measure was event-free survival. We used a Bayesian approach for the design, analysis, and interpretation of the results. Patients who received at least one dose of study treatment were considered in the safety analysis. The trial was registered with EudraCT, 2012-002107-17, and ISRCTN, 54540667.Between March 21, 2014, and May 1, 2019, 640 patients were entered into EE2012, 320 (50%) randomly allocated to each group. Median follow-up of surviving patients was 47 months (range 0-84). Event-free survival at 3 years was 61% with group 1 and 67% with group 2 (adjusted hazard ratio [HR] 0·71 [95% credible interval 0·55-0·92 in favour of group 1). The probability that the true HR was less than 1·0 was greater than 0·99. Febrile neutropenia as a grade 3-5 treatment toxicity occurred in 234 (74%) patients in group 1 and in 183 (58%) patients in group 2. More patients in group 1 (n=205 [64%]) required at least one platelet transfusion compared with those in group 2 (n=138 [43%]). Conversely, more patients required blood transfusions in group 2 (n=286 [89%]) than in group 1 (n=277 [87%]).Dose-intensive chemotherapy with vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide is more effective, less toxic, and shorter in duration for all stages of newly diagnosed Ewing sarcoma than vincristine, ifosfamide, doxorubicin, and etoposide induction and should now be the standard of care for Ewing sarcoma.The European Union's Seventh Framework Programme for Research, Technological Development, and Demonstration; The National Coordinating Centre in France, Centre Léon Bérard; SFCE; Ligue contre le cancer; Cancer Research UK.
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- 2022
123. How do others cope?: Extracting coping strategies for adverse drug events from social media
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Anne Dirkson, Suzan Verberne, Gerard van Oortmerssen, Hans Gelderblom, and Wessel Kraaij
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Health Informatics ,Computer Science Applications - Abstract
Patients advise their peers on how to cope with their illness in daily life on online support groups. To date, no efforts have been made to automatically extract recommended coping strategies from online patient discussion groups. We introduce this new task, which poses a number of challenges including complex, long entities, a large long-tailed label space, and cross-document relations. We present an initial ontology for coping strategies as a starting point for future research on coping strategies, and the first end-to-end pipeline for extracting coping strategies for side effects. We also compared two possible computational solutions for this novel and highly challenging task; multi-label classification and named entity recognition (NER) with entity linking (EL). We evaluated our methods on the discussion forum from the Facebook group of the worldwide patient support organization 'GIST support international' (GSI); GIST support international donated the data to us. We found that coping strategy extraction is difficult and both methods attain limited performance (measured with F1 score) on held out test sets; multi-label classification outperforms NER+EL (F1=0.220 vs F1=0.155). An inspection of the multi-label classification output revealed that for some of the incorrect predictions, the reference label is close to the predicted label in the ontology (e.g. the predicted label 'juice' instead of the more specific reference label 'grapefruit juice'). Performance increased to F1=0.498 when we evaluated at a coarser level of the ontology. We conclude that our pipeline can be used in a semi-automatic setting, in interaction with domain experts to discover coping strategies for side effects from a patient forum. For example, we found that patients recommend ginger tea for nausea and magnesium and potassium supplements for cramps.This information can be used as input for patient surveys or clinical studies.
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- 2022
124. 2022-RA-1571-ESGO ‘Mirror conversation’ as part of the quality assurance of a regional gynaecological comprehensive cancer care network in the Netherlands
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Cor D de Kroon, Caroline Grimbergen, Caroline de Vogel, Natascha Walpot, Anne-Marie den Boer, Tapasya Vreeken – van Tol, Hans Gelderblom, Carina Hilders, and Marjolein Kagie
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- 2022
125. 2022-RA-1395-ESGO Quality assessment as part of the quality assurance of a regional gynecological comprehensive cancer care network in the Netherlands
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Cor D de Kroon, Natascha Walpot, Ria van Mierlo, Maaike vd Aa, Brigitte Gijsen, Anne-Marie den Boer, Hans Gelderblom, Carina Hilders, and Marjolein Kagie
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- 2022
126. Clinical Activity of Ripretinib in Patients with Advanced Gastrointestinal Stromal Tumor Harboring Heterogeneous KIT/PDGFRA Mutations in the Phase III INVICTUS Study
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Sebastian Bauer, Steven Attia, Hans Gelderblom, Peter Reichardt, Gina Z. D'Amato, Michael Heinrich, Julie Meade, Patrick Schöffski, Suzanne George, John Zalcberg, Margaret von Mehren, Jean-Yves Blay, Rodrigo Ruiz-Soto, Ping Chi, César Serrano, Robin L. Jones, Ying Su, Institut Català de la Salut, [Bauer S] Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany. German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany. [Heinrich MC] VA Portland Veterans Health Care System, Portland, Oregon. OHSU Knight Cancer Institute, Portland, Oregon. [George S] Dana-Farber Cancer Institute, Boston, Massachusetts. [Zalcberg JR] Monash University School of Public Health and Preventive Medicine and Alfred Health, Melbourne, Victoria, Australia. [Serrano C] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Gelderblom H] Leiden University Medical Center, Leiden, the Netherlands, and Vall d'Hebron Barcelona Hospital Campus
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Oncology ,Cancer Research ,medicine.medical_specialty ,Medizin ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,PDGFRA ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,medicine.disease_cause ,Placebo ,Exon ,Environmental Health::Science::Contamination::Physical Contamination::Radioactive Pollution::Environmental Health::Science::Mutation [PUBLIC HEALTH] ,Internal medicine ,Medicine ,Liquid biopsy ,Stromal tumor ,enfermedades del sistema digestivo::neoplasias del sistema digestivo::neoplasias gastrointestinales::enfermedades del sistema digestivo::tumores del estroma gastrointestinal [ENFERMEDADES] ,fenómenos genéticos::variación genética::mutación [FENÓMENOS Y PROCESOS] ,Aparell digestiu - Càncer - Tractament ,Mutation ,GiST ,business.industry ,Mutació (Biologia) ,diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,digestive system diseases ,Avaluació de resultats (Assistència sanitària) ,Digestive System Diseases::Digestive System Neoplasms::Gastrointestinal Neoplasms::Digestive System Diseases::Gastrointestinal Stromal Tumors [DISEASES] ,business ,Tyrosine kinase - Abstract
Purpose: Most patients with gastrointestinal stromal tumor (GIST) have activating mutations in KIT/PDGFRA and are initially responsive to tyrosine kinase inhibitors (TKI). The acquisition of secondary mutations leads to refractory/relapsed disease. This study reports the results of an analysis from the phase III INVICTUS study (NCT03353753) characterizing the genomic heterogeneity of tumors from patients with advanced GIST and evaluating ripretinib efficacy across KIT/PDGFRA mutation subgroups. Patients and Methods: Tumor tissue and liquid biopsy samples that captured circulating tumor DNA were collected prior to study enrollment and sequenced using next-generation sequencing. Subgroups were determined by KIT/PDGFRA mutations and correlation of clinical outcomes and KIT/PDGFRA mutational status was assessed. Results: Overall, 129 patients enrolled (ripretinib 150 mg once daily, n = 85; placebo, n = 44). The most common primary mutation subgroup detected by combined tissue and liquid biopsies were in KIT exon 11 (ripretinib, 61.2%; placebo, 77.3%) and KIT exon 9 (ripretinib, 18.8%; placebo, 15.9%). Patients receiving ripretinib demonstrated progression-free survival (PFS) benefit versus placebo regardless of mutation status (HR 0.16) and in all assessed subgroups in Kaplan–Meier PFS analysis (exon 11, P < 0.0001; exon 9, P = 0.0023; exon 13, P < 0.0001; exon 17, P < 0.0001). Among patients with wild-type KIT/PDGFRA by tumor tissue, PFS ranged from 2 to 23 months for ripretinib versus 0.9 to 10.1 months for placebo. Conclusions: Ripretinib provided clinically meaningful activity across mutation subgroups in patients with advanced GIST, demonstrating that ripretinib inhibits a broad range of KIT/PDGFRA mutations in patients with advanced GIST who were previously treated with three or more TKIs.
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- 2021
127. Limited evolution of the actionable metastatic cancer genome under therapeutic pressure
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Egbert F. Smit, Henk M.W. Verheul, Martijn P. Lolkema, Lodewyk F. A. Wessels, Paul Roepman, Edwin Cuppen, Hans Gelderblom, Adrianus J. de Langen, Joris van de Haar, L.R. Hoes, Emile E. Voest, and Medical Oncology
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Oncology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Concordance ,Cancer ,Treatment options ,General Medicine ,Disease ,medicine.disease ,Genome ,General Biochemistry, Genetics and Molecular Biology ,Clinical trial ,Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] ,SDG 3 - Good Health and Well-being ,Internal medicine ,Cancer genome ,Biopsy ,medicine ,business - Abstract
Genomic profiling is critical for the identification of treatment options for patients with metastatic cancer, but it remains unclear how frequently this procedure should be repeated during the course of the disease. To address this, we analyzed whole-genome sequencing (WGS) data of 250 biopsy pairs, longitudinally collected over the treatment course of 231 adult patients with a representative variety of metastatic solid malignancies. Within the biopsy interval (median, 6.4 months), patients received one or multiple lines of (mostly) standard-of-care (SOC) treatments, with all major treatment modalities being broadly represented. SOC biomarkers and biomarkers for clinical trial enrollment could be identified in 23% and 72% of biopsies, respectively. For SOC genomic biomarkers, we observed full concordance between the first and the second biopsy in 99% of pairs. Of the 219 biomarkers for clinical trial enrollment that were identified in the first biopsies, we recovered 94% in the follow-up biopsies. Furthermore, a second WGS analysis did not identify additional biomarkers for clinical trial enrollment in 91% of patients. More-frequent genomic evolution was observed when considering specific genes targeted by small-molecule inhibitors or hormonal therapies (21% and 22% of cases, respectively). Together, our data demonstrate that there is limited evolution of the actionable genome of treated metastases. A single WGS analysis of a metastatic biopsy is generally sufficient to identify SOC genomic biomarkers and to identify investigational treatment opportunities.Whole-genome sequencing of metastatic biopsies longitudinally sampled during the course of anticancer treatment reveals that the actionable metastatic cancer genome remains relatively stable over time.
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- 2021
128. Ripretinib intrapatient dose escalation after disease progression provides clinically meaningful outcomes in advanced gastrointestinal stromal tumour
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Rodrigo Ruiz-Soto, Filip Janku, Suzanne George, Neeta Somaiah, Robin L. Jones, Albiruni Ryan Abdul Razak, Ying Su, Hans Gelderblom, Michael S. Gordon, Kristen N. Ganjoo, Julia Jennings, Julie Meade, Ping Chi, Jonathan C. Trent, Margaret von Mehren, K. Shi, and Michael Heinrich
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Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Stromal cell ,Gastrointestinal Stromal Tumors ,medicine.drug_class ,Ripretinib ,Article ,Tyrosine-kinase inhibitor ,Internal medicine ,medicine ,Humans ,Urea ,Dosing ,Progression-free survival ,Naphthyridines ,Adverse effect ,Protein Kinase Inhibitors ,Pharmacology ,Gastrointestinal stromal tumours ,medicine.diagnostic_test ,GiST ,business.industry ,Progression-Free Survival ,Regimen ,Treatment Outcome ,Positron emission tomography ,Disease Progression ,Female ,business - Abstract
Purpose: Ripretinib is a switch-control tyrosine kinase inhibitor that broadly inhibits KIT and platelet-derived growth factor receptor a kinase signalling. Ripretinib showed preliminary efficacy in patients with advanced gastrointestinal stromal tumour (GIST) in a phase I study across a range of doses. Results were confirmed in the phase III INVICTUS study, and ripretinib 150 mg once daily (QD) was subsequently approved as a >fourth-line therapy. Here, we report the phase I study results of intrapatient dose escalation (IPDE) in patients with GIST treated across second, third and later lines of therapy. Methods: Patients with advanced GIST who experienced disease progression (PD) at ripretinib 150 mg QD could dose escalate to 150 mg twice daily (BID). Progression-free survival (PFS) 1 was calculated from the date of the first dose of ripretinib 150 mg QD to PD (as per Response Evaluation Criteria in Solid Tumours 1.1); PFS2 was from the date of IPDE (150 mg BID) to PD or death. Treatment-emergent adverse events (TEAEs) were summarised by dosing periods and compared descriptively. Results: Of 142 patients with GIST receiving ripretinib 150 mg QD, 67 underwent IPDE. IPDE provided benefit across all lines of therapy; the median PFS2 was 5.6, 3.3 and 4.6 months for patients on second-, third-and >fourth-line therapy, respectively. A partial metabolic response after IPDE was demonstrated in 13 of 37 patients with available positron emission tomography scans. TEAEs reported at both doses were similar. Conclusion: Ripretinib IPDE after PD provided continued clinical benefit in advanced GIST across second, third and later lines of therapy with a similar safety profile to that observed with the QD regimen. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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- 2021
129. Clinicopathological features and treatment outcome of oesophageal gastrointestinal stromal tumour (GIST)
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Yvonne Schrage, Astrid W. Oosten, Alessandro Gronchi, Sheima Farag, Peter Hohenberger, Neeltje Steeghs, Hans Gelderblom, Mahmoud Mohammadi, Ingrid M.E. Desar, An K.L. Reyners, Patrick Schöffski, Piotr Rutkowski, J.W. van Sandick, Nikolaos Vassos, Esther Bastiaannet, Nikki S. IJzerman, Robin L. Jones, Marco Baia, Javier Martin-Broto, Medical Oncology, Targeted Gynaecologic Oncology (TARGON), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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Male ,PROGNOSIS ,Esophageal Neoplasms ,Survival ,Anastomotic Leak ,LEIOMYOMAS ,Gastroenterology ,Postoperative Complications ,0302 clinical medicine ,Neoplasm Metastasis ,Treatment outcome ,RISK ,medicine.diagnostic_test ,GiST ,Margins of Excision ,General Medicine ,Middle Aged ,Neoadjuvant Therapy ,Progression-Free Survival ,Tumor Burden ,Europe ,Fine-needle aspiration ,Oncology ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Imatinib Mesylate ,Female ,030211 gastroenterology & hepatology ,Esophagoscopy ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] ,medicine.medical_specialty ,Stromal cell ,RESECTION ,Gastrointestinal Stromal Tumors ,Biopsy, Fine-Needle ,Enucleation ,Antineoplastic Agents ,Disease-Free Survival ,CLASSIFICATION ,03 medical and health sciences ,Median follow-up ,Internal medicine ,Biopsy ,Mitotic Index ,medicine ,Adjuvant therapy ,Humans ,Aged ,Retrospective Studies ,Gastrointestinal stromal tumours ,business.industry ,ADENOCARCINOMA ,Plastic Surgery Procedures ,Esophagectomy ,Oesophagus ,PATHOLOGY ,Localized disease ,Surgery ,business - Abstract
Contains fulltext : 235268.pdf (Publisher’s version ) (Open Access) BACKGROUND: Oesophageal gastrointestinal stromal tumours (GISTs) account for ≤1% of all GISTs. Consequently, evidence to guide clinical decision-making is limited. METHODS: Clinicopathological features and outcomes in patients with primary oesophageal GIST from seven European countries were collected retrospectively. RESULTS: Eighty-three patients were identified, and median follow up was 55.0 months. At diagnosis, 59.0% had localized disease, 25.3% locally advanced and 13.3% synchronous metastasis. A biopsy (Fine Needle aspiration n = 29, histological biopsy n = 31) was performed in 60 (72.3%) patients. The mitotic count was low (5/5hpf) mitotic count were associated with worse disease free survival. CONCLUSION: Based on the current study, enucleation can be recommended for oesophageal GIST smaller than 4 cm, while oesophagectomy should be preserved for larger tumours. Patients with larger tumours (>4 cm) and/or high mitotic count should be treated with adjuvant therapy.
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- 2021
130. Patterns of Perioperative Treatment and Survival of Localized, Resected, Intermediate- or High-Grade Soft Tissue Sarcoma: A 2000–2017 Netherlands Cancer Registry Database Analysis
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Judith V.M.G. Bovée, Milan van Meekeren, Hans Gelderblom, Marta Fiocco, Vincent K Y Ho, and Rick L. Haas
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0301 basic medicine ,medicine.medical_specialty ,Article Subject ,medicine.medical_treatment ,Database analysis ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,RC254-282 ,Survival analysis ,Tumor size ,Proportional hazards model ,business.industry ,Soft tissue sarcoma ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Perioperative ,medicine.disease ,Surgery ,Cancer registry ,Radiation therapy ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,business ,Research Article - Abstract
Background. Standard therapy for localized soft tissue sarcoma (STS) is wide, limb-sparing resection. For intermediate- or high-grade tumors, (neo)adjuvant therapies are frequently added to the treatment plan. In this study, data from a Dutch nationwide database are used to (1) assess whether perioperative management of STS follows ESMO guidelines, (2) characterize prognostic factors for overall survival (OS), and (3) assess the association between perioperative treatment and survival. Methods. All intermediate- or high-grade, localized STS cases, who have undergone surgery and diagnosed between 2000 and 2017, were identified in the Netherlands Cancer Registry (NCR) database. Variables with demographic, treatment, and survival data were obtained. Survival curves were estimated by Kaplan–Meier’s method, and the effect of prognostic factors on OS was assessed in a multivariable Cox regression analysis. Results. A total of 4957 patients were identified. There were slightly more males (54.7%). Median age at diagnosis was 64 years, and 53.6% of the tumors were located in the extremities. Radiotherapy (RT) was administered to 2481 (50.1%) patients, and 252 (5.1%) patients were treated with perioperative systemic chemotherapy. The total use of perioperative RT did not significantly change in the last 20 years, but the timing followed clinical guidelines: preoperative RT increased significantly (2000–2008: 3.7%, 2009–2017: 22.3%; p < 0.001 ), whereas the use of postoperative RT diminished (2000–2008: 45.9%, 2009–2017: 26.1%; p < 0.001 ). The use of perioperative chemotherapy slightly decreased (2000–2008: 5.9%, 2009–2017: 4.4%; p = 0.015). 5-year OS was 59.6% (95% CI: 58.2–61.0). Sex, age, year of diagnosis, tumor location, tumor size, histological grade, depth, histological subtype, surgical margins, and the use of perioperative RT were identified as independent predictors for OS. Conclusion. Preoperative RT is gradually replacing postoperative RT for localized STS in the Netherlands. The use of perioperative chemotherapy is rare and has slightly decreased in recent years. Identified baseline characteristics and treatment factors predicting OS may aid in future treatment decisions.
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- 2021
131. Supporting Patients with Cancer after Dobbs v. Jackson Women's Health Organization
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Andrew G Shuman, Matti S Aapro, Benjamin Anderson, Katherine Arbour, Pedro C Barata, Aditya Bardia, Eduardo Bruera, Bruce A Chabner, Herbert Chen, Edwin Choy, Pierfranco Conte, Giuseppe Curigliano, Don Dizon, Eileen O’Reilly, Antonio Tito Fojo, Hans Gelderblom, Timothy A Graubert, Jayne S Gurtler, Evan Hall, Fred R Hirsch, Ahmed Idbaih, David H Ilson, Michael Kelley, Carlo La Vecchia, Heinz Ludwig, Beverly Moy, Hyman Muss, Frans Opdam, Rebecca D Pentz, Marshall R Posner, Jeffrey S Ross, Adrian Sacher, Suresh Senan, Enrique Soto-Perez-de-Celis, Kenneth K Tanabe, Jan B Vermorken, Eric Wehrenberg-Klee, Susan E Bates, Radiation Oncology, CCA - Cancer Treatment and quality of life, and CCA - Cancer biology and immunology
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Cancer Research ,Oncology ,Human medicine - Abstract
In the context of cancer, whether or not to choose pregnancy termination represents a difficult and multifaceted decision. In this editorial, members of The Oncologist editorial team attempt to contextualize the potential implications of the recent Supreme Court decision in Dobbs v. Jackson Women’s Health Organizationfor patients with cancer.
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- 2022
132. Retrospective observational studies in ultra-rare sarcomas: A consensus paper from the Connective Tissue Oncology Society (CTOS) community of experts on the minimum requirements for the evaluation of activity of systemic treatments
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Silvia Stacchiotti, Anna Maria Frezza, George D. Demetri, Jean-Yves Blay, Jyoti Bajpai, Giacomo G. Baldi, Elizabeth H. Baldini, Robert S. Benjamin, Sylvie Bonvalot, Judith V.M.G. Bovée, Dario Callegaro, Paolo G. Casali, Sandra P. D'Angelo, Elizabeth J. Davis, Angelo P. Dei Tos, Elizabeth G. Demicco, Jayesh Desai, Palma Dileo, Mikael Eriksson, Hans Gelderblom, Suzanne George, Rebecca A. Gladdy, Mrinal M. Gounder, Abha A. Gupta, Rick Haas, Andrea Hayes, Peter Hohenberger, Kevin B. Jones, Robin L. Jones, Bernd Kasper, Akira Kawai, David G. Kirsch, Eugenie S. Kleinerman, Axel Le Cesne, Roberta Maestro, Javier Martin Broto, Robert G. Maki, Aisha B. Miah, Emanuela Palmerini, Shreaskumar R. Patel, Chandrajit P. Raut, Albiruni R.A. Razak, Damon R. Reed, Piotr Rutkowski, Roberta G. Sanfilippo, Marta Sbaraglia, Inga-Marie Schaefer, Dirk C. Strauss, Sandra J. Strauss, William D. Tap, David M. Thomas, Annalisa Trama, Jonathan C. Trent, Winette T.A. van der Graaf, Winan J. van Houdt, Margaret von Mehren, Breelyn A. Wilky, Christopher D.M. Fletcher, Alessandro Gronchi, Rosalba Miceli, and Andrew J. Wagner
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Consensus ,Methodology ,Ultra-rare sarcoma ,Sarcoma ,Soft Tissue Neoplasms ,General Medicine ,Retrospective study ,Observational Studies as Topic ,Oncology ,Connective Tissue ,Observational study ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Reactive Oxygen Species ,Retrospective Studies - Abstract
Background: In ultra-rare sarcomas (URS) the conduction of prospective, randomized trials is challenging. Data from retrospective observational studies (ROS) may represent the best evidence available. ROS implicit limitations led to poor acceptance by the scientific community and regulatory authorities. In this context, an expert panel from the Connective Tissue Oncology Society (CTOS), agreed on the need to establish a set of minimum requirements for conducting high-quality ROS on the activity of systemic therapies in URS. Methods: Representatives from > 25 worldwide sarcoma reference centres met in November 2020 and identified a list of topics summarizing the main issues encountered in ROS on URS. An online survey on these topics was distributed to the panel; results were summarized by descriptive statistics and discussed during a second meeting (November 2021). Results: Topics identified by the panel included the use of ROS results as external control data, the criteria for contributing centers selection, modalities for ensuring a correct pathological diagnosis and radiologic assessment, consistency of surveillance policies across centers, study end-points, risk of data duplication, results publication. Based on the answers to the survey (55 of 62 invited experts) and discussion the panel agreed on 18 statements summarizing principles of recommended practice. Conclusions: These recommendations will be disseminated by CTOS across the sarcoma community and incorporated in future ROS on URS, to maximize their quality and favor their use as control data when results from prospective studies are unavailable. These recommendations could help the optimal conduction of ROS also in other rare tumors.
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- 2022
133. Preoperative Radiotherapy in Patients With Primary Retroperitoneal Sarcoma
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Dario Callegaro, Chandrajit P. Raut, Taiwo Ajayi, Dirk Strauss, Sylvie Bonvalot, Deanna Ng, Eberhard Stoeckle, Mark Fairweather, Piotr Rutkowski, Winan J. van Houdt, Hans Gelderblom, Claudia Sangalli, Andrew Hayes, Charles Honoré, Rebecca A. Gladdy, Magali Fau, Rick Haas, Dimitri Tzanis, Aisha B. Miah, Peter Chung, Elizabeth H. Baldini, Sandrine Marreaud, Saskia Litiere, Carol J. Swallow, and Alessandro Gronchi
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Surgery - Abstract
The aim of the present study was to compare the effect of radiotherapy (RT) on abdominal recurrence-free survival (ARFS) in patients with primary retroperitoneal sarcoma treated in the EORTC-STBSG-62092 (STRASS) phase 3 randomized controlled trial (STRASS cohort) and off-trial (STREXIT cohort) and to pool STRASS and STREXIT data to test the hypothesis that RT improves ARFS in patients with liposarcoma.The STRASS trial did not show any difference in ARFS between patients treated with preoperative radiotherapy+surgery (RT+S) versus surgery alone (S).All consecutive adult patients not enrolled in STRASS and underwent curative-intent surgery for a primary retroperitoneal sarcoma with or without preoperative RT between 2012 and 2017 (STRASS recruiting period) among ten STRASS-recruiting centres formed the STREXIT cohort. The effect of RT in STREXIT was explored with a propensity score (PS)-matching analysis. Primary endpoint was ARFS defined as macroscopically incomplete resection or abdominal recurrence or death of any cause, whichever occurred first.STRASS included 266 patients, STREXIT included 831 patients (727 after excluding patients who received preoperative chemotherapy, 202 after 1:1 PS-matching). The effect of RT on ARFS in STRASS and 1:1 PS-matched STREXIT cohorts, overall and in patients with liposarcoma, was similar. In the pooled cohort analysis, RT administration was associated with better ARFS in patients with liposarcoma [N=321, hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.42-0.89]. In particular, patients with well-differentiated liposarcoma and G1-2 dedifferentiated liposarcoma (G1-2 DDLPS, n=266) treated with RT+S had better ARFS (HR, 0.63; 95% CI, 0.40-0.97) while patients with G3 DDLPS and leiomyosarcoma had not. At the current follow-up, there was no association between RT and overall survival or distant metastases-free survival.In this study, preoperative RT was associated with better ARFS in patients with primary well-differentiated liposarcoma and G1-2 DDLPS.
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- 2022
134. Microsatellite instability in rectal cancer: what does it mean? A study of two randomized trials and a systematic review of the literature
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Marloes Swets, Cristina Graham Martinez, Shannon van Vliet, Arjan van Tilburg, Hans Gelderblom, Corrie A M Marijnen, Cornelis J H van de Velde, and Iris D Nagtegaal
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Histology ,Rectal Neoplasms ,Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14] ,Humans ,microsatellite instability ,Prospective Studies ,General Medicine ,prognosis ,Colorectal Neoplasms ,rectal cancer ,Neoplasm Staging ,Randomized Controlled Trials as Topic ,Pathology and Forensic Medicine - Abstract
Contains fulltext : 283497.pdf (Publisher’s version ) (Open Access) AIM: Currently, compelling evidence illustrates the significance of determining microsatellite instability (MSI) in colorectal cancer (CRC). The association of MSI with proximal CRC is well established, however, its implications in patients with rectal cancer remain undefined. We therefore aimed to determine the role of MSI with respect to incidence and outcome in patients with rectal cancer. METHODS AND RESULTS: For this we examined patients from two prospective phase III trials: TME trial and PROCTOR-SCRIPT trial (n = 1250). In addition, we performed a literature review to evaluate the overall prevalence, the effect on survival and the response to neo-adjuvant treatment in patients with MSI rectal cancer compared with microsatellite stable (MSS) rectal cancer. Our TME and PROCTOR-SCRIPT cohort showed no differences in terms of overall survival (OS) (hazard ratio [HR] 1.00, 95% confidence interval [CI] 0.69-1.47) and disease-free survival (DFS) (HR 1.00, 95% CI 0.68-1.45) in patients with MSI compared to MSS rectal cancer. The total number of MSI cases in all included studies (including our own) was 1220 (out of 16,526 rectal cancer patients), with an overall prevalence of 6.7% (standard error 1.19%). Both for OS as for DFS there was no impact of MSI status on prognosis (HR 1.00, 95% CI 0.77-1.29 and HR 0.86, 95% CI 0.60-1.22, respectively). The risk ratio (RR) for downstaging and pathological complete response showed also no impact of MSI status (RR 1.15, 95% CI 0.86-1.55 and RR 0.81, 95% CI 0.54-1.22, respectively). CONCLUSION: Rectal cancer patients with MSI form a distinct and rare subcategory, however, there is no prognostic effect of MSI in rectal cancer patients.
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- 2022
135. Corrigendum to ‘Age-related differences of oncological outcomes in primary extremity soft tissue sarcoma: a multistate model including 6260 patients’ [Eur J Cancer 141 (2020) 128-136]
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Ibtissam Acem, Cornelis Verhoef, Anja J. Rueten-Budde, Dirk J. Grünhagen, Winan J. van Houdt, Michiel A.J. van de Sande, Will Aston, Han Bonenkamp, Ingrid M.E. Desar, Peter C. Ferguson, Marta Fiocco, Hans Gelderblom, Robert J. van Ginkel, Winette van der Graaf, Anthony M. Griffin, Rick L. Haas, Jos A. van der Hage, Andrew J. Hayes, Lee M. Jeys, Johnny Keller, Minna K. Laitinen, Andreas Leithner, Katja Maretty-Kongstad, Toshifumi Ozaki, Rob Pollock, Veroniek M. van Praag, Myles J. Smith, Maria A. Smolle, Emelie Styring, Joanna Szkandera, Kazuhiro Tanaka, Per-Ulf Tunn, Madeleine Willegger, Reinard Windhager, Jay S. Wunder, and Olga Zaikova
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Cancer Research ,Oncology - Published
- 2022
136. Mutational heterogeneity of imatinib resistance and efficacy of ripretinib vs sunitinib in patients with gastrointestinal stromal tumor: ctDNA analysis from INTRIGUE
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Sebastian Bauer, Robin Lewis Jones, Suzanne George, Hans Gelderblom, Patrick Schöffski, Margaret von Mehren, John Raymond Zalcberg, Yoon-Koo Kang, Albiruni Ryan Abdul Razak, Jonathan C. Trent, Steven Attia, Axel Le Cesne, William Reichmann, Kam Sprott, Haroun Achour, Matthew L. Sherman, Rodrigo Ruiz-Soto, Jean-Yves Blay, and Michael C. Heinrich
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Cancer Research ,Oncology - Abstract
397784 Background: Ripretinib, a switch-control tyrosine kinase inhibitor (TKI), is indicated for patients (pts) with gastrointestinal stromal tumor (GIST) who received prior treatment with ≥3 TKIs, including imatinib. Sunitinib is approved for advanced GIST after imatinib failure. Circulating tumor DNA (ctDNA) analysis may provide insight into the efficacy of these agents in second-line advanced GIST. Here, we present exploratory baseline ctDNA results from INTRIGUE. Methods: INTRIGUE is an open-label, phase 3 study that enrolled adult pts with advanced GIST who progressed on or had intolerance to imatinib (NCT03673501). Randomization was 1:1 to ripretinib 150 mg once daily (QD) or sunitinib 50 mg QD (4 wks on/2 wks off). Baseline peripheral whole blood was analyzed by Guardant360, a 74-gene ctDNA next-generation sequencing (NGS)-based assay. Only KIT mutations are reported here. Results: Of 453 pts in the overall intent-to-treat (ITT) population, 362 (80%) samples were analyzed. ctDNA was detected in 280/362 (77%), with KIT mutations detected in 213/280 (76%). Common resistance mutations were in the KIT activation loop (AL; exons 17/18; 89/213, 42%) and ATP-binding pocket (ATP-BP; exons 13/14; 81/213, 38%). Efficacy in pts with detectable ctDNA in the KIT exon 11 and overall ITT populations was consistent with the primary analysis based on tumor data used for randomization. Pts with KIT exon 11 + 17/18 (−9/13/14) mutations had superior progression-free survival (PFS), objective response rate (ORR), and overall survival (OS) with ripretinib vs sunitinib, whereas pts with exon 11 + 13/14 (−9/17/18) mutations had better PFS, ORR, and OS with sunitinib vs ripretinib (Table). Subgroup safety profiles were consistent with the primary analysis. Conclusions: While KIT ATP-BP mutations predicted clinical benefit from sunitinib vs ripretinib, pts harboring resistance mutations in the KIT AL derived meaningful clinical benefit from ripretinib but not sunitinib. This study demonstrates the value of ctDNA NGS-based sequencing of the complex landscape of KIT mutations to predict the clinical benefit of ripretinib or sunitinib as second-line therapy in pts with advanced GIST. Clinical trial information: NCT03673501 . [Table: see text]
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- 2023
137. Management of tenosynovial giant cell tumour of the foot and ankle
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Hans Gelderblom, Geert Spierenburg, Lizz van der Heijden, Sarah Tamar Lancaster, Sarah Pratap, Monique J L Mastboom, C. L. Max H. Gibbons, and Michiel A. J. van de Sande
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Giant Cell Tumor of Tendon Sheath ,Soft Tissue Neoplasms ,Synovectomy ,Arthroscopy ,medicine ,Humans ,Orthopedics and Sports Medicine ,Child ,Mri scan ,Aged ,Foot ,business.industry ,Forefoot ,Middle Aged ,medicine.disease ,Tenosynovial giant cell tumour ,medicine.anatomical_structure ,Pigmented villonodular synovitis ,Female ,Surgery ,Sarcoma ,Radiology ,Ankle ,Neoplasm Recurrence, Local ,business ,Foot (unit) - Abstract
Aims Tenosynovial giant cell tumour (TGCT) is one of the most common soft-tissue tumours of the foot and ankle and can behave in a locally aggressive manner. Tumour control can be difficult, despite the various methods of treatment available. Since treatment guidelines are lacking, the aim of this study was to review the multidisciplinary management by presenting the largest series of TGCT of the foot and ankle to date from two specialized sarcoma centres. Methods The Oxford Tumour Registry and the Leiden University Medical Centre Sarcoma Registry were retrospectively reviewed for patients with histologically proven foot and ankle TGCT diagnosed between January 2002 and August 2019. Results A total of 84 patients were included. There were 39 men and 45 women with a mean age at primary treatment of 38.3 years (9 to 72). The median follow-up was 46.5 months (interquartile range (IQR) 21.3 to 82.3). Localized-type TGCT (n = 15) predominantly affected forefoot, whereas diffuse-type TGCT (Dt-TGCT) (n = 9) tended to panarticular involvement. TGCT was not included in the radiological differential diagnosis in 20% (n = 15/75). Most patients had open rather than arthroscopic surgery (76 vs 17). The highest recurrence rates were seen with Dt-TGCT (61%; n = 23/38), panarticular involvement (83%; n = 5/8), and after arthroscopy (47%; n = 8/17). Three (4%) fusions were carried out for osteochondral destruction by Dt-TGCT. There were 14 (16%) patients with Dt-TGCT who underwent systemic treatment, mostly in refractory cases (79%; n = 11). TGCT initially decreased or stabilized in 12 patients (86%), but progressed in five (36%) during follow-up; all five underwent subsequent surgery. Side effects were reported in 12 patients (86%). Conclusion We recommend open surgical excision as the primary treatment for TGCT of the foot and ankle, particularly in patients with Dt-TGCT with extra-articular involvement. Severe osteochondral destruction may justify salvage procedures, although these are not often undertaken. Systemic treatment is indicated for unresectable or refractory cases. However, side effects are commonly experienced, and relapses may occur once treatment has ceased. Cite this article: Bone Joint J 2021;103-B(4):788–794.
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- 2021
138. Surgical management of 144 diffuse-type TGCT patients in a single institution: A 20-year cohort study
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Geert Spierenburg, Lizz van der Heijden, Monique J. L. Mastboom, Kirsten van Langevelde, Robert J. P. van der Wal, Hans Gelderblom, and Michiel A. J. van de Sande
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Cohort Studies ,Male ,surgery ,sarcoma ,Oncology ,Testicular Neoplasms ,tenosynovial giant cell tumor ,diffuse type ,Giant Cell Tumor of Tendon Sheath ,Humans ,General Medicine ,pigmented villonodular synovitis ,Neoplasms, Germ Cell and Embryonal - Abstract
Background and Objectives Surgery is the mainstay of treatment for tenosynovial giant cell tumors (TGCTs). However, achieving a cure through surgery alone remains challenging, especially for the diffuse-type (D-TGCT). Methods Our goal was to describe the surgical management of patients with D-TGCT related to large joints, treated between 2000 and 2020. We analyzed the effect of (in)complete resections and the presence of postoperative tumor (POT) on magnetic resonance imaging (MRI) on radiological and clinical outcomes. Results A total of 144 patients underwent open surgery for D-TGCT, of which 58 (40%) had treatment before. The median follow-up was 65 months. One hundred twenty-five patients underwent isolated open surgeries, in which 25 (20%) patients' D-TGCT was intentionally removed incompletely. POT presence on the first postoperative MRI was observed in 64%. Both incomplete resections and POT presence were associated with higher rates of radiological progression (73% vs. 44%; Kaplan-Meier [KM] analysis p = 0.021) and 59% versus 7%; KM analysis p < 0.001), respectively. Furthermore, patients with POT presence clinically worsened more often than patients without having POT (49% vs. 24%; KM analysis p = 0.003). Conclusions D-TGCT is often resected incompletely and tumor presence is commonly observed on the first postoperative MRI, resulting in worse radiological and clinical outcomes. Therefore, surgeons should try to remove D-TGCT in toto and consider other multimodal therapeutic strategies.
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- 2022
139. Short-term and long-term prognostic value of histological response and intensified chemotherapy in osteosarcoma: a retrospective reanalysis of the BO06 trial
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Eni Musta, Nan van Geloven, Jakob Anninga, Hans Gelderblom, Marta Fiocco, and Algebra, Geometry & Mathematical Physics (KDV, FNWI)
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Osteosarcoma ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Bone Neoplasms ,General Medicine ,Prognosis ,Retrospective Studies - Abstract
Objectives Cure rate models accounting for cured and uncured patients, provide additional insights into long and short-term survival. We aim to evaluate the prognostic value of histological response and chemotherapy intensification on the cure fraction and progression-free survival (PFS) for the uncured patients. Design Retrospective analysis of a randomised controlled trial, MRC BO06 (EORTC 80931). Setting Population-based study but proposed methodology can be applied to other trial designs. Participants A total of 497 patients with resectable highgrade osteosarcoma, of which 118 were excluded because chemotherapy was not started, histological response was not reported, abnormal dose was reported or had disease progression during treatment. Intervention(s) Two regimens with the same anticipated cumulative dose (doxorubicin 6×75 mg/m2/week; cisplatin 6×100 mg/m2/week) over different time schedules: every 3 weeks in regimen-C and every 2 weeks in regimen-DI. Primary and secondary outcome measures The primary outcome is PFS computed from end of treatment because cure, if it occurs, may happen at any time during treatment. A mixture cure model is used to study the effect of histological response and intensified chemotherapy on the cure status and PFS for the uncured patients. Results Histological response is a strong prognostic factor for the cure status (OR 3.00, 95% CI 1.75 to 5.17), but it has no clear effect on PFS for the uncured patients (HR 0.78, –95% CI 0.53 to 1.16). The cure fractions are 55% (46%–63%) and 29% (22%–35%), respectively, among patients with good and poor histological response (GR, PR). The intensified regimen was associated with a higher cure fraction among PR (OR 1.90, 95% CI 0.93 to 3.89), with no evidence of effect for GR (OR 0.78, 95% CI 0.38 to 1.59). Conclusions Accounting for cured patients is valuable in distinguishing the covariate effects on cure and PFS. Estimating cure chances based on these prognostic factors is relevant for counselling patients and can have an impact on treatment decisions. Trial registration number NCT86294690.
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- 2022
140. First-line chemotherapy in advanced intra-abdominal well-differentiated/dedifferentiated liposarcoma: An EORTC Soft Tissue and Bone Sarcoma Group retrospective analysis
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Silvia Stacchiotti, Winette T. A. Van der Graaf, Roberta G. Sanfilippo, Sandrine I. Marreaud, Winan J. Van Houdt, Ian R. Judson, Alessandro Gronchi, Hans Gelderblom, Saskia Litiere, Bernd Kasper, and Medical Oncology
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Adult ,Lipopolysaccharides ,Cancer Research ,Osteosarcoma ,Antibiotics, Antineoplastic ,Bone Neoplasms ,Sarcoma ,Liposarcoma ,anthracycline ,chemotherapy ,epirubicin ,Oncology ,SDG 3 - Good Health and Well-being ,Doxorubicin ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Ifosfamide ,Retrospective Studies - Abstract
BACKGROUND: No prospective trial with anthracycline-based chemotherapy has individually assessed response in a well-differentiated (WD)/dedifferentiated (DD) liposarcoma patient cohort. We conducted a retrospective analysis of first-line chemotherapy in liposarcoma of intra-abdominal origin (IA-LPS) in patients who had entered the European Organisation for Research and Treatment of Cancer (EORTC)/Soft Tissue and Bone Sarcoma Group (STBSG) trials. METHODS: We searched for all adult patients treated with first-line chemotherapy for advanced IA-LPS in the EORTC STBSG phase 2 and 3 trials from 1978. Treatment was aggregated into 5 groups: anthracycline alone, ifosfamide alone, doxorubicin plus ifosfamide (D+IFO), doxorubicin/cyclophosphamide/vincristine/dacarbazine, and “other” (brostallicin, trabectedin). Response was assessed prospectively by Response Evaluation Criteria in Solid Tumors or World Health Organization criteria. Progression-free survival (PFS) and overall survival (OS) were computed by Kaplan-Meier method. RESULTS: A total of 109 patients with IA-LPS from 13 trials were identified (104 evaluable for response). Overall, there were 10/109 (9.2%) responders: 3/48 (6.3%) in the anthracycline alone group, 2/15 (13%) in the ifosfamide alone group, and 4/18 (22%) in the D+IFO group. At the 10-month median follow-up (interquartile range, 6-24), the median OS was 19 months (95% CI, 15-21) and median PFS 4 months (95% CI, 3-6). D+IFO achieved a not statistically significant longer median PFS (12 months) and median OS (31 months) than observed with other regimens. Univariate/multivariate analysis did not identify prognostic factors. CONCLUSIONS: Cytotoxic chemotherapy, in particular anthracycline alone, had marginal activity in advanced IA-LPS. Ifosfamide-containing regimens showed higher activity, although it was not statistically significant and in a small number of cases, with the combination of doxorubicin and ifosfamide appearing to be the more active regimen available in fit patients. This series provides a benchmark for future trials on new drugs in WD/DD liposarcoma.;.
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- 2022
141. Comparable effectiveness of 45-min and 20-min post-infusion scalp cooling time in preventing paclitaxel-induced alopecia – a randomized controlled trial
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Rieneke T Lugtenberg, Corina JG van den Hurk, Carolien H Smorenburg, Linda Mosch, Danny Houtsma, Margaret AG den Hollander - van Deursen, Ad A Kaptein, Hans Gelderblom, and Judith R Kroep
- Abstract
Purpose Scalp cooling can prevent chemotherapy-induced alopecia (CIA). Previously, the post-infusion cooling time (PICT) could be successfully reduced in docetaxel-treated patients from 90 to 45 and 20 minutes. Therefore it seems plausible that the PICT can be shortened for paclitaxel-treated patients as well. Methods Patients treated with weekly paclitaxel were included in this multi-center trial and randomly assigned to a PICT of 45 or 20 minutes. The results were compared to a standard PICT of 90 minutes, derived from prospective collected data from the Dutch Scalp Cooling Registry. The primary endpoint was the percentage of patients who decide to not wear a wig or head covering. Secondary endpoints were the degree of CIA assessed with the Dean scale for assessment of hair loss; alopecia graded according to NCI CTC toxicity version 4.03 (CTCAE4.03); tolerance of scalp cooling and perceived distress of CIA. Results 91 patients were enrolled in this study, 74 patients were evaluable for hair loss. Hair preservation was successful in 27 patients (75%) with a PICT of 45 minutes and in 31 patients (82%) with a PICT of 20 minutes. There was no difference in success rate with the standard PICT of 90 minutes (85%, p = 0.29). Similar success rates were seen when using the Dean sale and CTCAE assessment, with no differences between groups (p = 0.12 and p = 0.38). Conclusions A 20 minute PICT is as effective as 45 and 90 minutes to prevent weekly paclitaxel-induced alopecia and should be the new standard of care.
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- 2022
142. Tenosynovial giant cell tumors (TGCT): molecular biology, drug targets and non-surgical pharmacological approaches
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Judith Bovee, Hans Gelderblom, Kirsten Van Langevelde, Michiel Van de Sande, Karoly Szuhai, Geert Spierenburg, and Lizz Van der Heijden
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Pharmacology ,Colony-stimulating factor 1 ,tenosynovial giant cell tumor ,Macrophages ,Clinical Biochemistry ,Giant Cell Tumor of Tendon Sheath ,CSF1R ,drug development ,systemic therapy ,CSF1 ,Drug Discovery ,drug targets ,colony-stimulating factor 1 receptor ,Humans ,Molecular Medicine ,Molecular Biology - Abstract
Introduction Tenosynovial giant cell tumor (TGCT) is a mono-articular, benign or locally aggressive and often debilitating neoplasm. Systemic therapies are becoming part of the multimodal armamentarium when surgery alone will not confer improvements. Since TGCT is characterized by colony-stimulating factor-1 (CSF1) rearrangements, the most studied molecular pathway is the CSF1 and CSF1 receptor (CSF1R) axis. Inhibiting CSF1-CSF1R interaction often yields considerable radiological and clinical responses; however, adverse events may cause treatment discontinuation because of an unfavorable risk-benefit ratio in benign disease. Only Pexidartinib is approved by the US FDA; however, the European Medicines Agency has not approved it due to a uncertain risk-benefit ratio. Thus, there is a need for safer and effective therapies. Areas covered Light is shed on disease mechanisms and potential drug targets. The safety and efficacy of different systemic therapies are evaluated. Expert opinion The CSF1-CSF1R axis is the principal drug target; however, the effect of CSF1R inhibition on angiogenesis and the role of macrophages, which are essential in the postoperative course, needs further elucidation. Systemic therapies have a promising role in treating mainly diffuse-type, TGCT patients who are not expected to clinically improve from surgery. Future drug development should focus on targeting neoplastic TGCT cells.
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- 2022
143. Prediction models with survival data: a comparison between machine learning and the Cox proportional hazards model
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Audinga-Dea Hazewinkel, Hans Gelderblom, and Marta Fiocco
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Recent years have seen increased interest in using machine learning (ML) methods for survival prediction, chiefly using big datasets with mixed datatypes and/or many predictors Model comparisons have frequently been limited to performance measure evaluation, with the chosen measure often suboptimal for assessing survival predictive performance. We investigated ML model performance in an application to osteosarcoma data from the EURAMOS-1 clinical trial (NCT00134030). We compared the performance of survival neural networks (SNN), random survival forests (RSF) and the Cox proportional hazards model. Three performance measures suitable for assessing survival model predictive performance were considered: the C-index, and the time-dependent Brier and Kullback-Leibler scores. Comparisons were also made on predictor importance and patient-specific survival predictions. Additionally, the effect of ML model hyper-parameters on performance was investigated. All three models had comparable performance as assessed by the C-index and Brier and Kullback-Leibler scores, with the Cox model and SNN also comparable in terms of relative predictor importance and patient-specific survival predictions. RSFs showed a tendency for according less importance to predictors with uneven class distributions and predicting clustered survival curves, the latter a result of tuning hyperparameters that influence forest shape through restrictions on terminal node size and tree depth. SNNs were comparatively more sensitive to hyperparameter misspecification, with decreased regularization resulting in inconsistent predicted survival probabilities. We caution against using RSF for predicting patient-specific survival, as standard model tuning practices may result in aggregated predictions, which is not reflected in performance measure values, and recommend performing multiple reruns of SNNs to verify prediction consistency.
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- 2022
144. Best clinical management of tenosynovial giant cell tumour (TGCT): A consensus paper from the community of experts
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Silvia Stacchiotti, Hans Roland Dürr, Inga-Marie Schaefer, Klaus Woertler, Rick Haas, Annalisa Trama, Augusto Caraceni, Jyoti Bajpai, Giacomo Giulio Baldi, Nicholas Bernthal, Jean-Yves Blay, Kjetil Boye, Javier-Martin Broto, Wei-Wu Tom Chen, Paolo Angelo Dei Tos, Jayesh Desai, Stephan Emhofer, Mikael Eriksson, Alessandro Gronchi, Hans Gelderblom, Jendrik Hardes, Wolfgang Hartmann, John Healey, Antoine Italiano, Robin L. Jones, Akira Kawai, Andreas Leithner, Herbert Loong, Eric Mascard, Carlo Morosi, Nadine Otten, Emanuela Palmerini, Shreyaskumar R. Patel, Peter Reichardt, Brian Rubin, Piotr Rutkowski, Claudia Sangalli, Kathrin Schuster, Beatrice M. Seddon, Morena Shkcodra, Eric L. Staals, William Tap, Matt van de Rijn, Kirsten van Langevelde, Filip M.M. Vanhoenacker, Andrew Wagner, Lisette Wiltink, Sydney Stern, Michiel Van de Sande, and Sebastian Bauer
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Oncology ,Medizin ,Radiology, Nuclear Medicine and imaging ,Human medicine ,General Medicine - Abstract
Weitere Nicht-UDE Autoren sind nicht mit aufgeführt. enosynovial giant cell tumour (TGCT) is a rare, locally aggressive, mesenchymal tumor arising from the joints, bursa and tendon sheaths. TGCT comprises a nodular- and a diffuse-type, with the former exhibiting mostly indolent course and the latter a locally aggressive behavior. Although usually not life-threatening, TGCT may cause chronic pain and adversely impact function and quality of life (QoL). CSFR1 inhibitors are effective with benefit on symptoms and QoL but are not available in most countries. The degree of uncertainty in selecting the most appropriate therapy and the lack of guidelines on the clinical management of TGCT make the adoption of new treatments inconsistent across the world, with suboptimal outcomes for patients. A global consensus meeting was organized in June 2022, involving experts from several disciplines and patient representatives from SPAGN to define the best evidence-based practice for the optimal approach to TGCT and generate the recommendations presented herein.
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- 2023
145. Prospective practice survey of management of cetuximab-related skin reactions
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Petronella O. Witteveen, C.M.L. van Herpen, C. del Grande, A.N.M. Wymenga, B. van Doorn, J. J. Koldenhof, Hans Gelderblom, Chantal M. L. Driessen, Ann Hoeben, Christine B. Boers-Doets, J. W. B. de Groot, R. T. Lugtenberg, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and MUMC+: MA Medische Oncologie (9)
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Male ,medicine.medical_specialty ,medicine.drug_class ,Colorectal cancer ,Antibiotics ,Cetuximab ,Skin reaction ,Skin Diseases ,TOXICITY ,03 medical and health sciences ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Quality of life ,QUALITY-OF-LIFE ,Internal medicine ,Surveys and Questionnaires ,medicine ,Clinical endpoint ,Humans ,HEAD ,Prospective Studies ,Head and neck cancer ,030304 developmental biology ,PLUS CETUXIMAB ,0303 health sciences ,business.industry ,Middle Aged ,medicine.disease ,Management ,METASTATIC COLORECTAL-CANCER ,Oncology ,030220 oncology & carcinogenesis ,Observational study ,TRIAL ,Original Article ,Female ,business ,medicine.drug ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] - Abstract
Purpose Evidence-based guidelines on how to prevent or treat cetuximab-related skin reactions are lacking and multiple care and management strategies are used. The main purpose of the present study is to gain information about the different skincare products being used against skin reactions in metastatic colorectal cancer (mCRC) and recurrent/metastatic (R/M) or locally advanced (LA) squamous cell cancer of the head and neck (SCCHN) patients treated with cetuximab. Methods An open-label, prospective observational study conducted in the Netherlands. The occurrence of skin reactions and the care and management options taken were documented for 16 weeks, starting from the first administration of cetuximab. Results A total of 103 patients were included in 7 hospitals. 38 patients (37%) developed a grade ≥ 2 skin reaction. Eighty-six patients could be analysed for the primary endpoint (73.3% males, mean age 62.4 years, n = 44 LA SCCHN, n = 16 R/M SCCHN, n = 26 mCRC). The most frequently used skin products at some point during the observation period were moisturizing products (70%), systemic antibiotics (64%), topical antibiotics (58%), lipid-regenerating (28%) and other topical products (28%). The overall use of products gradually increased from baseline to week 6–10, reducing by week 16. Hospital protocols were the primary reason (> 50%) for choice of the skincare products and medications. Conclusion A variety of skin care products and antibiotics were commonly used. Only few patients developed severe cutaneous reactions. For patients, the occurrence of skin reactions did not influence their willingness to continue cetuximab therapy.
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- 2020
146. Multicenter Comparison of Molecular Tumor Boards in The Netherlands
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Nienke Solleveld, Arja ter Elst, Hans Gelderblom, Jan H. von der Thüsen, Ernst-Jan M. Speel, Ed Schuuring, Harry J.M. Groen, Berber Piet, Wendy W.J. de Leng, Anthonie J. van der Wekken, Katrien Grünberg, Stefan M. Willems, Leonie I. Kroeze, Tom E. J. Theunissen, Adrianus J. de Langen, Léon C van Kempen, Lizza E.L. Hendriks, Sayed M S Hashemi, Bart Koopman, Marthe S. Paats, Anne S R van Lindert, Ruud W. J. Meijers, Niven Mehra, Kim Monkhorst, Daniëlle A M Heideman, Winand N.M. Dinjens, Mirjam C. Boelens, Marjolijn J. L. Ligtenberg, Tom van Wezel, Wim Timens, Teodora Radonic, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Pulmonologie, MUMC+: MA Med Staf Spec Longziekten (9), RS: GROW - R2 - Basic and Translational Cancer Biology, Pathologie, Pathology, Pulmonary medicine, CCA - Cancer Treatment and quality of life, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Groningen Research Institute for Asthma and COPD (GRIAC), Targeted Gynaecologic Oncology (TARGON), Pulmonary Medicine, and Immunology
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Cancer Diagnostics and Molecular Pathology ,Referral ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,medicine.medical_treatment ,Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] ,Molecular tumor board ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,Multidisciplinary approach ,Neoplasms ,Physicians ,Rare mutations ,Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14] ,Molecular diagnostics ,Humans ,Medicine ,Tumor board ,Target therapy ,Pathology, Molecular ,Composition methods ,Netherlands ,Multidisciplinary ,business.industry ,Cancer ,medicine.disease ,CANCER ,PATHOLOGY ,030104 developmental biology ,Workflow ,Oncology ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,030220 oncology & carcinogenesis ,Family medicine ,business ,Decision making ,GENOMICS - Abstract
Background Molecular tumor boards (MTBs) provide rational, genomics‐driven, patient‐tailored treatment recommendations. Worldwide, MTBs differ in terms of scope, composition, methods, and recommendations. This study aimed to assess differences in methods and agreement in treatment recommendations among MTBs from tertiary cancer referral centers in The Netherlands. Materials and Methods MTBs from all tertiary cancer referral centers in The Netherlands were invited to participate. A survey assessing scope, value, logistics, composition, decision‐making method, reporting, and registration of the MTBs was completed through on‐site interviews with members from each MTB. Targeted therapy recommendations were compared using 10 anonymized cases. Participating MTBs were asked to provide a treatment recommendation in accordance with their own methods. Agreement was based on which molecular alteration(s) was considered actionable with the next line of targeted therapy. Results Interviews with 24 members of eight MTBs revealed that all participating MTBs focused on rare or complex mutational cancer profiles, operated independently of cancer type–specific multidisciplinary teams, and consisted of at least (thoracic and/or medical) oncologists, pathologists, and clinical scientists in molecular pathology. Differences were the types of cancer discussed and the methods used to achieve a recommendation. Nevertheless, agreement among MTB recommendations, based on identified actionable molecular alteration(s), was high for the 10 evaluated cases (86%). Conclusion MTBs associated with tertiary cancer referral centers in The Netherlands are similar in setup and reach a high agreement in recommendations for rare or complex mutational cancer profiles. We propose a “Dutch MTB model” for an optimal, collaborative, and nationally aligned MTB workflow. Implications for Practice Interpretation of genomic analyses for optimal choice of target therapy for patients with cancer is becoming increasingly complex. A molecular tumor board (MTB) supports oncologists in rationalizing therapy options. However, there is no consensus on the most optimal setup for an MTB, which can affect the quality of recommendations. This study reveals that the eight MTBs associated with tertiary cancer referral centers in The Netherlands are similar in setup and reach a high agreement in recommendations for rare or complex mutational profiles. The Dutch MTB model is based on a collaborative and nationally aligned workflow with interinstitutional collaboration and data sharing., Worldwide, molecular tumor boards (MTBs) differ in terms of scope, composition, methods, and recommendations. This article assesses differences in methods and agreement in treatment recommendations among MTBs from tertiary cancer referral centers in The Netherlands.
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- 2020
147. Comparable effectiveness of 45- and 20-min post-infusion scalp cooling time in preventing paclitaxel-induced alopecia - a randomized controlled trial
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Rieneke T, Lugtenberg, Corina J G, van den Hurk, Carolien H, Smorenburg, Linda, Mosch, Danny, Houtsma, Margaret A G den Hollander-van, Deursen, Ad A, Kaptein, Hans, Gelderblom, and Judith R, Kroep
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Scalp ,Paclitaxel ,Hypothermia, Induced ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Alopecia ,Antineoplastic Agents ,Breast Neoplasms ,Female ,Taxoids ,Prospective Studies - Abstract
Scalp cooling can prevent chemotherapy-induced alopecia (CIA). Previously, the post-infusion cooling time (PICT) could be successfully reduced in docetaxel-treated patients from 90 to 45 and 20 min. Therefore, it seems plausible that the PICT can be shortened for paclitaxel-treated patients as well.Patients treated with weekly paclitaxel were included in this multi-centre trial and randomly assigned to a PICT of 45 or 20 min. The results were compared to a standard PICT of 90 min, derived from prospective collected data from the Dutch Scalp Cooling Registry. The primary endpoint was the percentage of patients who decide to not wear a wig or head covering. Secondary endpoints were the degree of CIA assessed with the Dean scale for assessment of hair loss; alopecia graded according to NCI CTC toxicity version 4.03 (CTCAE4.03); tolerance of scalp cooling and perceived distress of CIA.Ninety-one patients were enrolled in this study; 74 patients were evaluable for hair loss. Hair preservation was successful in 27 patients (75%) with a PICT of 45 min and in 31 patients (82%) with a PICT of 20 min. There was no difference in success rate with the standard PICT of 90 min (85%, p = 0.29). Similar success rates were seen when using the Dean scale and CTCAE assessment, with no differences between groups (p = 0.12 and p = 0.38).A 20 min PICT is as effective as 45 and 90 min to prevent weekly paclitaxel-induced alopecia and should be the new standard of care.ClinicalTrials.gov Identifier: NCT03266185.
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- 2022
148. Disease progression in osteosarcoma: a multistate model for the EURAMOS-1 (European and American Osteosarcoma Study) randomised clinical trial
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Audinga-Dea Hazewinkel, Carlo Lancia, Jakob Anninga, Michiel van de Sande, Jeremy Whelan, Hans Gelderblom, and Marta Fiocco
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Osteosarcoma ,clinical trials ,sarcoma ,bone diseases ,Adolescent ,paediatric oncology ,Disease Progression ,Humans ,Bone Neoplasms ,General Medicine ,Risk Assessment - Abstract
ObjectivesInvestigating the effect of prognostic factors in a multistate framework on survival in a large population of patients with osteosarcoma. Of interest is how prognostic factors affect different disease stages after surgery, with stages of local recurrence (LR), new metastatic disease (NM), LR+NM, secondary malignancy, a second NM, and death.DesignAn open-label, international, phase 3 randomised controlled trial.Setting325 sites in 17 countries.ParticipantsThe subset of 1631 metastases-free patients from 1965 patients with high-grade resectable osteosarcoma, from the European and American Osteosarcoma Study.Main outcome measuresThe effect of prognostic factors on different disease stages, expressed as HRs; predictions of disease progression on an individual patient basis, according to patient-specific characteristics and history of intermediate events.ResultsOf 1631 patients, 526 experienced an intermediate event, and 305 died by the end of follow-up. An axial tumour site substantially increased the risk of LR after surgery (HR=10.84, 95% CI 8.46 to 13.86) and death after LR (HR=11.54, 95% CI 6.11 to 21.8). A poor histological increased the risk of NM (HR=5.81, 95% CI 5.31 to 6.36), which sharply declined after 3 years since surgery. Young patients (18 had a decreased risk of death after event (eg, for death after LR: HR=2.40, 95% CI 1.52 to 3.90; HR=0.35, 95% CI 0.21 to 0.56, respectively).ConclusionsOur findings suggest that patients with axial tumours should be monitored for LR and patients with poor histological response for NM, and that for young patients (Trial registration numberNCT00134030.
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- 2022
149. Harmonising patient-access programmes:the Dutch DRUG Access Protocol platform
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Laurien J Zeverijn, Sahar Barjesteh van Waalwijk van Doorn-Khosrovani, Anke A M G Pisters van Roy, Lonneke Timmers, T H Ly Tran, Jolanda E de Boer, Gijsbrecht F de Wit, Birgit S Geurts, Hans Gelderblom, Henk M W Verheul, Nicole Blijlevens, A N Machteld Wymenga, Ferry A L M Eskens, Egbert F Smit, Haiko J Bloemendal, Emile E Voest, Medical Oncology, Internal medicine, AII - Cancer immunology, and CCA - Cancer Treatment and quality of life
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Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] ,Oncology ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,Humans ,Antineoplastic Agents ,Health Services Accessibility ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] ,Netherlands - Abstract
Item does not contain fulltext
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- 2022
150. RANKL inhibition for giant cell lesions of the jaw: A retrospective cohort analysis
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Willem H. Schreuder, Astrid Lipplaa, Arjen H.G. Cleven, Henk van den Berg, Peter H. Bisschop, Renate T. de Jongh, Max J.H. Witjes, Peter A.W.H. Kessler, Matthias A.W. Merkx, Esther Edelenbos, Cornelis Klop, Ruud Schreurs, Anneke M. Westermann, Jacqueline M. Tromp, Henriette Levenga, Hans Gelderblom, Jan de Lange, MUMC+: MA Mondzorg Kaak Aangezicht Chirurgie (3), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Oral and Maxillofacial Surgery, Other Research, CCA - Cancer biology and immunology, Endocrinology, AMS - Ageing & Vitality, AMS - Musculoskeletal Health, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Graduate School, AMS - Rehabilitation & Development, Oncology, CCA -Cancer Center Amsterdam, AMS - Tissue Function & Regeneration, Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Academic Centre for Dentistry Amsterdam, Maxillofacial Surgery (AMC), Maxillofacial Surgery (VUmc), Oral Kinesiology, Maxillofacial Surgery (AMC + VUmc), Internal medicine, Amsterdam Gastroenterology Endocrinology Metabolism, and Pediatrics
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Giant Cell Tumor of Bone ,Male ,Cancer Research ,Bone Density Conservation Agents ,RANKL ,Bone Neoplasms ,Giant Cells ,Cohort Studies ,Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10] ,Oncology ,SDG 3 - Good Health and Well-being ,Humans ,Female ,Giant cell lesions of the jaw (GCLJ) ,Neoplasm Recurrence, Local ,Denosumab ,Retrospective Studies ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] - Abstract
Contains fulltext : 288341.pdf (Publisher’s version ) (Open Access) BACKGROUND: In all giant-cell-rich lesions (GCRL) occurring in bone, a common underlying excessive RANKL expression is held responsible for the osteolytic activity. Apart from giant cell tumour of bone (GCTB), systematic outcome analysis of RANKL inhibition in other GCRL is unavailable. The aim of this study is to assess the efficacy and safety of a 1-year denosumab protocol in giant cell lesions of the jaw (GCLJ). METHODS: A retrospective cohort study was conducted compromising patients treated with a 1-year protocol of monthly subcutaneously administered 120 mg denosumab. Objective tumour response based on histology and imaging was used to calculate objective tumour response rate, progression-free survival (PFS) and time to progression. Type, severity and frequency of adverse events were recorded in a standardised way to assess safety. RESULTS: Twenty patients, predominantly female (90%), were included. Fifty-five per cent of lesions were located in the mandible; most classified as aggressive lesions (90%). Thirty-five per cent (7/20) of cases were either recurrent after prior treatment or progressive, while on other drug treatment. Objective tumour response rate was 100% after 12 months of treatment. Median PFS was 50.4 months (95% CI 38.0-62.8) with a cumulative PFS rate of 22.6% (95% CI 1.8-43.4) at 5 years follow-up. Median time to progression was 38.4 months (95% CI 26.0-50.8). Treatment was well tolerated, and none of the patients had to interrupt therapy for toxicity. CONCLUSION: High-dose denosumab is effective and safe in achieving a complete response in GCLJ within 12 months. The high long-term relapse rate after treatment cessation is the main obstacle for denosumab to become standard treatment for GCLJ.
- Published
- 2022
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