Maier J.,University of Leipzig |
Lange T.,University of Leipzig |
Kerle I.,Medizinische Klinik und Poliklinik |
Specht K.,TU Munich |
And 7 more authors.
Clinical Cancer Research | Year: 2013
Purpose: In gastrointestinal stromal tumor (GIST), there is no biomarker available that indicates success or failure of therapy. We hypothesized that tumor-specific v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (CKIT)- or platelet-derived growth factor receptor-α (PDGFRA)-mutant DNA fragments can be detected and quantified in plasma samples of patients with GIST. Experimental Design: We prospectively collected 291 plasma samples from 38 subjects with GIST harboring activating mutations of CKIT or PDGFRA detected in tumor tissue, irrespective of current disease status or treatment. We used allele-specific ligation PCR to detect mutant free circulating DNA (fcDNA). Results: We were able to detect fcDNA harboring the tumor mutation in 15 of 38 patients. Patients with active disease displayed significantly higher amounts of mutant fcDNA compared with patients in complete remission (CR). The amount of mutant fcDNA correlated with disease course. We observed repeated positive test results or an increase of mutant fcDNA in five patients with progressive disease or relapse. A decline of tumor fcDNA or conversion from positive to negative was seen in five patients responding to treatment. A negative to positive conversion was seen in two patients with relapse and one patient with progression. In two cases, we aimed to identify additional mutations and found four additional exchanges, including mutations not known from sequentially conducted tumor biopsies. Conclusions: Our results indicate that fcDNA harboring tumor-specific mutations in the plasma of patients with GIST can be used as tumor-specific biomarker. The detection of resistance mutations in plasma samples might allow earlier treatment changes and obviates the need for repeated tumor biopsies. ©2013 AACR.
De Wit M.,Klinik fur Innere Medizin Hamatologie und Onkologie |
Ortner P.,POMME med GmbH |
Lipp H.-P.,Apotheke des Universitatsklinikums Tubingen |
Sehouli J.,Klinik fur Frauenheilkunde und Geburtshilfe |
And 5 more authors.
Onkologie | Year: 2013
Background: Cytotoxic extravasation is a rare but potentially serious and painful complication of intravenous drug administration in oncology. Literature is anecdotal, and systematic clinical trials are scarce. The German working group for Supportive Care in Cancer (ASORS) has prepared an expert opinion for the diagnosis, prophylaxis and management of cytotoxic extravasation based on an interdisciplinary expert panel. Material and Methods: A Pubmed search was conducted for diagnosis, risk factors, symptoms, prophylaxis, and treatment of extravasation by the respective responsible expert. A writing committee compiled the manuscript and proposed the level of recommendation. In a consensus meeting, 13 experts reviewed and discussed the current practice in diagnosis and management of cytotoxic extravasation. In a telephone voting among the experts, the level of recommendation by ASORS was determined. Results: Every effort should be made to reduce the risk of extravasation. Staff training, patient education, usage of right materials and infusion techniques have been identified to be mandatory to minimalize the risk of extravasation. Extravasation must be diagnosed as soon as possible, and specific therapy including antidotes dependent on the extravasated drug should be initiated immediately. An extravasation emergency set should be available wherever intravenous cytotoxics are applied. Documentation and post-treatment follow-up are recommended. Conclusion: We have developed a literature- and expert-based consensus recommendation to avoid cytotoxic extravasation. It also provides practical management instructions which should help to avoid surgery and serious late effects. Copyright © 2013 S. Karger AG, Basel.