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Feasibility of chemosensitivity testing in soft tissue sarcomas

BACKGROUND: Soft tissue sarcomas comprise less than 1% of all solid malignancies. The presentation and behavior of these tumors differs depending on location and histological characteristics. Standard therapy consists of complete surgical resection in combination with adjuvant radiotherapy. The role...

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Autores principales: Lehnhardt, Marcus, Muehlberger, Thomas, Kuhnen, Cornelius, Brett, Daniel, Steinau, Hans U, Jafari, Hamid Joneidi, Steinstraesser, Lars, Müller, Oliver, Homann, Heinz H
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1087896/
https://www.ncbi.nlm.nih.gov/pubmed/15836792
http://dx.doi.org/10.1186/1477-7819-3-20
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author Lehnhardt, Marcus
Muehlberger, Thomas
Kuhnen, Cornelius
Brett, Daniel
Steinau, Hans U
Jafari, Hamid Joneidi
Steinstraesser, Lars
Müller, Oliver
Homann, Heinz H
author_facet Lehnhardt, Marcus
Muehlberger, Thomas
Kuhnen, Cornelius
Brett, Daniel
Steinau, Hans U
Jafari, Hamid Joneidi
Steinstraesser, Lars
Müller, Oliver
Homann, Heinz H
author_sort Lehnhardt, Marcus
collection PubMed
description BACKGROUND: Soft tissue sarcomas comprise less than 1% of all solid malignancies. The presentation and behavior of these tumors differs depending on location and histological characteristics. Standard therapy consists of complete surgical resection in combination with adjuvant radiotherapy. The role of chemotherapy is not clearly defined and is largely restricted to clinical trials. Only a limited number of agents have proved to be effective in soft tissue sarcomas. The use of doxorubicin, epirubicin and ifosfamide allowed response rates of more than 20%. In addition, recent chemotherapy trials did not demonstrate any significant differences in efficacy for various histological subtypes. METHODS: The objective of this study was to gain additional information about the chemosensitivity of soft tissue sarcomas to seven 7 different chemotherapy agents as single drugs and 4 combinations. Therefore we used an established ATP based in-vitro testing system and examined 50 soft tissue sarcomas. Chemosensitivity was assessed using a luciferin-luciferase-based luminescence assay providing individual chemosensitivity indices for each agent tested. RESULTS: The sensitivity varied widely according to the histological subtypes. The tumors state of cellular dedifferentiation played a crucial role for the efficiency of the chemotherapeutic agents. The sensitivity also depended on the presentation of the sarcoma as a primary or recurrent tumor. The highest sensitivity was demonstrated for actinomycin D as a single agent, with 74% of the tumor samples exhibiting a high-grade sensitivity (20% low sensitivity, no resistance). The combination of actinomycin D and ifosfamide yielded a high sensitivity in 76% (2% resistance). Doxorubicin as a mono-therapy or in combination with ifosfamide achieved high sensitivity in 70% and 72%, respectively, and resistance in 6% of the samples. CONCLUSION: Chemosensitivity testing is feasible in soft tissue sarcomas. It can be used to create sensitivity and resistance profiles of established and new cytotoxic agents and their combinations in soft tissue sarcomas. Our data demonstrate measurable discrepancies of the drug efficiency in soft tissue sarcomas, sarcoma subtypes and tumor recurrencies. However, current therapeutic regime does not take this in consideration, yet.
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spelling pubmed-10878962005-04-30 Feasibility of chemosensitivity testing in soft tissue sarcomas Lehnhardt, Marcus Muehlberger, Thomas Kuhnen, Cornelius Brett, Daniel Steinau, Hans U Jafari, Hamid Joneidi Steinstraesser, Lars Müller, Oliver Homann, Heinz H World J Surg Oncol Research BACKGROUND: Soft tissue sarcomas comprise less than 1% of all solid malignancies. The presentation and behavior of these tumors differs depending on location and histological characteristics. Standard therapy consists of complete surgical resection in combination with adjuvant radiotherapy. The role of chemotherapy is not clearly defined and is largely restricted to clinical trials. Only a limited number of agents have proved to be effective in soft tissue sarcomas. The use of doxorubicin, epirubicin and ifosfamide allowed response rates of more than 20%. In addition, recent chemotherapy trials did not demonstrate any significant differences in efficacy for various histological subtypes. METHODS: The objective of this study was to gain additional information about the chemosensitivity of soft tissue sarcomas to seven 7 different chemotherapy agents as single drugs and 4 combinations. Therefore we used an established ATP based in-vitro testing system and examined 50 soft tissue sarcomas. Chemosensitivity was assessed using a luciferin-luciferase-based luminescence assay providing individual chemosensitivity indices for each agent tested. RESULTS: The sensitivity varied widely according to the histological subtypes. The tumors state of cellular dedifferentiation played a crucial role for the efficiency of the chemotherapeutic agents. The sensitivity also depended on the presentation of the sarcoma as a primary or recurrent tumor. The highest sensitivity was demonstrated for actinomycin D as a single agent, with 74% of the tumor samples exhibiting a high-grade sensitivity (20% low sensitivity, no resistance). The combination of actinomycin D and ifosfamide yielded a high sensitivity in 76% (2% resistance). Doxorubicin as a mono-therapy or in combination with ifosfamide achieved high sensitivity in 70% and 72%, respectively, and resistance in 6% of the samples. CONCLUSION: Chemosensitivity testing is feasible in soft tissue sarcomas. It can be used to create sensitivity and resistance profiles of established and new cytotoxic agents and their combinations in soft tissue sarcomas. Our data demonstrate measurable discrepancies of the drug efficiency in soft tissue sarcomas, sarcoma subtypes and tumor recurrencies. However, current therapeutic regime does not take this in consideration, yet. BioMed Central 2005-04-18 /pmc/articles/PMC1087896/ /pubmed/15836792 http://dx.doi.org/10.1186/1477-7819-3-20 Text en Copyright © 2005 Lehnhardt et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Lehnhardt, Marcus
Muehlberger, Thomas
Kuhnen, Cornelius
Brett, Daniel
Steinau, Hans U
Jafari, Hamid Joneidi
Steinstraesser, Lars
Müller, Oliver
Homann, Heinz H
Feasibility of chemosensitivity testing in soft tissue sarcomas
title Feasibility of chemosensitivity testing in soft tissue sarcomas
title_full Feasibility of chemosensitivity testing in soft tissue sarcomas
title_fullStr Feasibility of chemosensitivity testing in soft tissue sarcomas
title_full_unstemmed Feasibility of chemosensitivity testing in soft tissue sarcomas
title_short Feasibility of chemosensitivity testing in soft tissue sarcomas
title_sort feasibility of chemosensitivity testing in soft tissue sarcomas
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1087896/
https://www.ncbi.nlm.nih.gov/pubmed/15836792
http://dx.doi.org/10.1186/1477-7819-3-20
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