Neoadjuvant irradiation of extremity soft tissue sarcoma with ions (Extrem-ion): study protocol for a randomized phase II pilot trial.
Carbon ion therapy
Extremity soft tissue sarcoma
Heavy ion therapy
Hypofractionation
Irradiation
Proton therapy
Randomized trial
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
12 May 2022
12 May 2022
Historique:
received:
09
01
2022
accepted:
17
04
2022
entrez:
13
5
2022
pubmed:
14
5
2022
medline:
20
5
2022
Statut:
epublish
Résumé
The standard of care treatment for soft tissue sarcoma of the extremities is a wide resection in combination with pre- or postoperative radiotherapy with high local control rates, sparing patients the necessity of amputation without compromising on overall survival rates. The currently preferred timing of radiotherapy is under debate. Albeit having higher rates of acute wound complications, late side effects like fibrosis, joint stiffness or edema are less frequent in preoperative compared to postoperative radiotherapy. This can be explained in smaller treatment volumes and a lower dose in the preoperative setting. Particles allow better sparing of surrounding tissues at risk, and carbon ions additionally offer biologic advantages and are preferred in less radiosensitive tumors. Hypofractionation allows for a significantly shorter treatment duration. Extrem-ion is a prospective, randomized, monocentric phase II trial. Patients with resectable or marginally resectable, histologically confirmed soft tissue sarcoma of the extremities will be randomized between neoadjuvant proton or neoadjuvant carbon ion radiotherapy in active scanning beam application technique (39 Gy [relative biological effectiveness, RBE] in 13 fractions [5-6 fractions per week] in each arm). The primary objective is the proportion of therapies without wound healing disorder the first 120 days after surgery or discontinuation of treatment for any reason related to the treatment. The secondary endpoints of the study consist of local control, local progression-free survival, disease-free survival, overall survival, and quality of life. The aim of this study is to confirm that hypofractionated, preoperative radiotherapy is safe and feasible. The potential for reduced toxicity by the utilization of particle therapy is the rational of this trial. A subsequent randomized phase III trial will compare the hypofractionated proton and carbon ion irradiation in regards to local control. ClinicalTrials.gov Identifier: NCT04946357 ; Retrospectively registered June 30, 2021.
Sections du résumé
BACKGROUND
BACKGROUND
The standard of care treatment for soft tissue sarcoma of the extremities is a wide resection in combination with pre- or postoperative radiotherapy with high local control rates, sparing patients the necessity of amputation without compromising on overall survival rates. The currently preferred timing of radiotherapy is under debate. Albeit having higher rates of acute wound complications, late side effects like fibrosis, joint stiffness or edema are less frequent in preoperative compared to postoperative radiotherapy. This can be explained in smaller treatment volumes and a lower dose in the preoperative setting. Particles allow better sparing of surrounding tissues at risk, and carbon ions additionally offer biologic advantages and are preferred in less radiosensitive tumors. Hypofractionation allows for a significantly shorter treatment duration.
METHODS
METHODS
Extrem-ion is a prospective, randomized, monocentric phase II trial. Patients with resectable or marginally resectable, histologically confirmed soft tissue sarcoma of the extremities will be randomized between neoadjuvant proton or neoadjuvant carbon ion radiotherapy in active scanning beam application technique (39 Gy [relative biological effectiveness, RBE] in 13 fractions [5-6 fractions per week] in each arm). The primary objective is the proportion of therapies without wound healing disorder the first 120 days after surgery or discontinuation of treatment for any reason related to the treatment. The secondary endpoints of the study consist of local control, local progression-free survival, disease-free survival, overall survival, and quality of life.
DISCUSSION
CONCLUSIONS
The aim of this study is to confirm that hypofractionated, preoperative radiotherapy is safe and feasible. The potential for reduced toxicity by the utilization of particle therapy is the rational of this trial. A subsequent randomized phase III trial will compare the hypofractionated proton and carbon ion irradiation in regards to local control.
TRIAL REGISTRATION
BACKGROUND
ClinicalTrials.gov Identifier: NCT04946357 ; Retrospectively registered June 30, 2021.
Identifiants
pubmed: 35550036
doi: 10.1186/s12885-022-09560-x
pii: 10.1186/s12885-022-09560-x
pmc: PMC9097299
doi:
Substances chimiques
Ions
0
Protons
0
Carbon
7440-44-0
Banques de données
ClinicalTrials.gov
['NCT04946357']
Types de publication
Clinical Trial Protocol
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
538Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : UH 270/2-1; AOBJ: 674373
Informations de copyright
© 2022. The Author(s).
Références
Biom J. 2018 Jan;60(1):196-206
pubmed: 29076185
Ann Surg Oncol. 2018 Mar;25(3):754-767
pubmed: 28895107
Eur J Surg Oncol. 2014 Dec;40(12):1641-7
pubmed: 25282099
J Clin Oncol. 1998 Jan;16(1):197-203
pubmed: 9440743
J Clin Oncol. 2015 Jul 10;33(20):2231-8
pubmed: 25667281
Anticancer Res. 2017 Dec;37(12):6959-6964
pubmed: 29187480
Int J Radiat Oncol Biol Phys. 2000 Nov 1;48(4):1051-8
pubmed: 11072162
Eur Radiol. 2009 Jun;19(6):1499-511
pubmed: 19266204
Ann Surg. 1982 Sep;196(3):305-15
pubmed: 7114936
J Clin Oncol. 1996 Mar;14(3):859-68
pubmed: 8622034
Lancet. 2002 Jun 29;359(9325):2235-41
pubmed: 12103287
Ann Surg Oncol. 2017 Oct;24(11):3252-3263
pubmed: 28741123
Am J Clin Oncol. 2018 Dec;41(12):1154-1161
pubmed: 29664796
Control Clin Trials. 1989 Mar;10(1):1-10
pubmed: 2702835
Cancer J. 2009 Jul-Aug;15(4):325-32
pubmed: 19672150
Acta Oncol. 2013 May;52(4):793-802
pubmed: 22877243
CA Cancer J Clin. 2018 Jan;68(1):7-30
pubmed: 29313949
J Natl Compr Canc Netw. 2020 Dec 02;18(12):1604-1612
pubmed: 33285515
Radiother Oncol. 2017 Aug;124(2):271-276
pubmed: 28697854
Acta Oncol. 2010 Oct;49(7):1132-40
pubmed: 20831505
Cancer J. 2014 Nov-Dec;20(6):433-9
pubmed: 25415691
Int J Radiat Oncol Biol Phys. 2008 Jul 15;71(4):1196-203
pubmed: 18207661
Eur J Cancer. 1994;30A(6):746-51
pubmed: 7917531
Radiother Oncol. 2005 Apr;75(1):48-53
pubmed: 15948265
Stat Med. 2017 Nov 10;36(25):3935-3947
pubmed: 28783881
Trials. 2021 Feb 12;22(1):134
pubmed: 33579340
Radiat Oncol. 2018 May 16;13(1):96
pubmed: 29769103