Hans Gelderblom

Bio: Hans Gelderblom is an academic researcher from Leiden University Medical Center. The author has contributed to research in topics: Medicine & GiST. The author has an hindex of 81, co-authored 591 publications receiving 27541 citations. Previous affiliations of Hans Gelderblom include Leiden University & Maastricht University Medical Centre.

Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial

Abstract: Summary Background Effective targeted treatment is unavailable for most sarcomas and doxorubicin and ifosfamide—which have been used to treat soft-tissue sarcoma for more than 30 years—still have an important role Whether doxorubicin alone or the combination of doxorubicin and ifosfamide should be used routinely is still controversial We assessed whether dose intensification of doxorubicin with ifosfamide improves survival of patients with advanced soft-tissue sarcoma compared with doxorubicin alone Methods We did this phase 3 randomised controlled trial (EORTC 62012) at 38 hospitals in ten countries We included patients with locally advanced, unresectable, or metastatic high-grade soft-tissue sarcoma, age 18–60 years with a WHO performance status of 0 or 1 They were randomly assigned (1:1) by the minimisation method to either doxorubicin (75 mg/m 2 by intravenous bolus on day 1 or 72 h continuous intravenous infusion) or intensified doxorubicin (75 mg/m 2 ; 25 mg/m 2 per day, days 1–3) plus ifosfamide (10 g/m 2 over 4 days with mesna and pegfilgrastim) as first-line treatment Randomisation was stratified by centre, performance status (0 vs 1), age ( vs ≥50 years), presence of liver metastases, and histopathological grade (2 vs 3) Patients were treated every 3 weeks till progression or unacceptable toxic effects for up to six cycles The primary endpoint was overall survival in the intention-to-treat population The trial is registered with ClinicalTrialsgov, number NCT00061984 Findings Between April 30, 2003, and May 25, 2010, 228 patients were randomly assigned to receive doxorubicin and 227 to receive doxorubicin and ifosfamide Median follow-up was 56 months (IQR 31–77) in the doxorubicin only group and 59 months (36–72) in the combination group There was no significant difference in overall survival between groups (median overall survival 12·8 months [95·5% CI 10·5–14·3] in the doxorubicin group vs 14·3 months [12·5–16·5] in the doxorubicin and ifosfamide group; hazard ratio [HR] 0·83 [95·5% CI 0·67–1·03]; stratified log-rank test p=0·076) Median progression-free survival was significantly higher for the doxorubicin and ifosfamide group (7·4 months [95% CI 6·6–8·3]) than for the doxorubicin group (4·6 months [2·9–5·6]; HR 0·74 [95% CI 0·60–0·90], stratified log-rank test p=0·003) More patients in the doxorubicin and ifosfamide group than in the doxorubicin group had an overall response (60 [26%] of 227 patients vs 31 [14%] of 228; p vs 40 [18%] of 223 patients), neutropenia (93 [42%] vs 83 [37%]), febrile neutropenia (103 (46%) vs 30 [13%]), anaemia (78 [35%] vs 10 [5%]), and thrombocytopenia (75 [33%]) vs one [ Interpretation Our results do not support the use of intensified doxorubicin and ifosfamide for palliation of advanced soft-tissue sarcoma unless the specific goal is tumour shrinkage These findings should help individualise the care of patients with this disease Funding Cancer Research UK, EORTC Charitable Trust, UK NHS, Canadian Cancer Society Research Institute, Amgen

Radiomics: Images Are More than Pictures, They Are Data.

Abstract: In the past decade, the field of medical image analysis has grown exponentially, with an increased number of pattern recognition tools and an increase in data set sizes. These advances have facilitated the development of processes for high-throughput extraction of quantitative features that result in the conversion of images into mineable data and the subsequent analysis of these data for decision support; this practice is termed radiomics. This is in contrast to the traditional practice of treating medical images as pictures intended solely for visual interpretation. Radiomic data contain first-, second-, and higher-order statistics. These data are combined with other patient data and are mined with sophisticated bioinformatics tools to develop models that may potentially improve diagnostic, prognostic, and predictive accuracy. Because radiomics analyses are intended to be conducted with standard of care images, it is conceivable that conversion of digital images to mineable data will eventually become routine practice. This report describes the process of radiomics, its challenges, and its potential power to facilitate better clinical decision making, particularly in the care of patients with cancer.

Inhibition of mutated, activated BRAF in metastatic melanoma.

Abstract: Methods We conducted a multicenter, phase 1, dose-escalation trial of PLX4032 (also known as RG7204), an orally available inhibitor of mutated BRAF, followed by an extension phase involving the maximum dose that could be administered without adverse effects (the recommended phase 2 dose). Patients received PLX4032 twice daily until they had disease progression. Pharmacokinetic analysis and tumor-response assessments were conducted in all patients. In selected patients, tumor biopsy was performed before and during treatment to validate BRAF inhibition. Results A total of 55 patients (49 of whom had melanoma) were enrolled in the dose-escalation phase, and 32 additional patients with metastatic melanoma who had BRAF with the V600E mutation were enrolled in the extension phase. The recommended phase 2 dose was 960 mg twice daily, with increases in the dose limited by grade 2 or 3 rash, fatigue, and arthralgia. In the dose-escalation cohort, among the 16 patients with melanoma whose tumors carried the V600E BRAF mutation and who were receiving 240 mg or more of PLX4032 twice daily, 10 had a partial response and 1 had a complete response. Among the 32 patients in the extension cohort, 24 had a partial response and 2 had a complete response. The estimated median progression-free survival among all patients was more than 7 months. Conclusions Treatment of metastatic melanoma with PLX4032 in patients with tumors that carry the V600E BRAF mutation resulted in complete or partial tumor regression in the majority of patients. (Funded by Plexxikon and Roche Pharmaceuticals.)