Novel stereotactic body radiation therapy (SBRT)-based partial tumor irradiation targeting hypoxic segment of bulky tumors (SBRT-PATHY): improvement of the radiotherapy outcome by exploiting the bystander and abscopal effects.


Journal

Radiation oncology (London, England)
ISSN: 1748-717X
Titre abrégé: Radiat Oncol
Pays: England
ID NLM: 101265111

Informations de publication

Date de publication:
29 Jan 2019
Historique:
received: 19 12 2018
accepted: 20 01 2019
entrez: 31 1 2019
pubmed: 31 1 2019
medline: 14 3 2019
Statut: epublish

Résumé

Despite the advances in oncology, patients with bulky tumors have worse prognosis and often receive only palliative treatments. Bulky disease represents an important challenging obstacle for all currently available radical treatment options including conventional radiotherapy. The purpose of this study was to assess a retrospective outcome on the use of a newly developed unconventional stereotactic body radiation therapy (SBRT) for PArtial Tumor irradiation of unresectable bulky tumors targeting exclusively their HYpoxic segment (SBRT-PATHY) that exploits the non-targeted effects of radiotherapy: bystander effects (local) and the abscopal effects (distant). Twenty-three patients with bulky tumors received partial bulky irradiation in order to induce the local non-targeted effect of radiation (bystander effect). The hypoxic tumor segment, called the bystander tumor volume (BTV), was defined using PET and contrast-enhanced CT, as a hypovascularized-hypometabolic junctional zone between the central necrotic and peripheral hypervascularized-hypermetabolic tumor segment. Based on tumor site and volume, the BTV was irradiated with 1-3 fractions of 10-12 Gy prescribed to 70% isodose-line. The pathologic lymph nodes and metastases were not irradiated in order to assess the distant non-targeted effects of radiation (abscopal effect). No patient received any systemic therapy. At the time of analysis, with median follow-up of 9.4 months (range: 4-20), 87% of patients remained progression-free. The bystander and abscopal response rates were 96 and 52%, respectively. Median shrinkage of partially irradiated bulky tumor expressing intensity of the bystander effect was 70% (range 30-100%), whereas for the non-irradiated metastases (intensity of the abscopal effect), it was 50% (range 30-100%). No patient experienced acute or late toxicity of any grade. SBRT-PATHY showed very inspiring results on exploitation of the radiation-hypoxia-induced non-targeted effects that need to be confirmed through our ongoing prospective trial. Present study has been retrospectively registered by the local ethic committee under study number A 26/18.

Sections du résumé

BACKGROUND BACKGROUND
Despite the advances in oncology, patients with bulky tumors have worse prognosis and often receive only palliative treatments. Bulky disease represents an important challenging obstacle for all currently available radical treatment options including conventional radiotherapy. The purpose of this study was to assess a retrospective outcome on the use of a newly developed unconventional stereotactic body radiation therapy (SBRT) for PArtial Tumor irradiation of unresectable bulky tumors targeting exclusively their HYpoxic segment (SBRT-PATHY) that exploits the non-targeted effects of radiotherapy: bystander effects (local) and the abscopal effects (distant).
MATERIALS AND METHODS METHODS
Twenty-three patients with bulky tumors received partial bulky irradiation in order to induce the local non-targeted effect of radiation (bystander effect). The hypoxic tumor segment, called the bystander tumor volume (BTV), was defined using PET and contrast-enhanced CT, as a hypovascularized-hypometabolic junctional zone between the central necrotic and peripheral hypervascularized-hypermetabolic tumor segment. Based on tumor site and volume, the BTV was irradiated with 1-3 fractions of 10-12 Gy prescribed to 70% isodose-line. The pathologic lymph nodes and metastases were not irradiated in order to assess the distant non-targeted effects of radiation (abscopal effect). No patient received any systemic therapy.
RESULTS RESULTS
At the time of analysis, with median follow-up of 9.4 months (range: 4-20), 87% of patients remained progression-free. The bystander and abscopal response rates were 96 and 52%, respectively. Median shrinkage of partially irradiated bulky tumor expressing intensity of the bystander effect was 70% (range 30-100%), whereas for the non-irradiated metastases (intensity of the abscopal effect), it was 50% (range 30-100%). No patient experienced acute or late toxicity of any grade.
CONCLUSIONS CONCLUSIONS
SBRT-PATHY showed very inspiring results on exploitation of the radiation-hypoxia-induced non-targeted effects that need to be confirmed through our ongoing prospective trial. Present study has been retrospectively registered by the local ethic committee under study number A 26/18.

Identifiants

pubmed: 30696472
doi: 10.1186/s13014-019-1227-y
pii: 10.1186/s13014-019-1227-y
pmc: PMC6352381
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

21

Références

Int J Radiat Oncol Biol Phys. 1999 Oct 1;45(3):721-7
pubmed: 10524428
Cancer Res. 2001 May 15;61(10):3932-6
pubmed: 11358808
Radiology. 1952 Mar;58(3):338-42
pubmed: 14900413
Int J Radiat Oncol Biol Phys. 2004 May 1;59(1):21-7
pubmed: 15093895
Cancer Cell. 2004 May;5(5):429-41
pubmed: 15144951
Cancer. 1990 Jul 1;66(1):114-8
pubmed: 1693874
Technol Cancer Res Treat. 2006 Dec;5(6):607-12
pubmed: 17121437
Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):388-97
pubmed: 17255259
Eur J Cancer. 2007 Jun;43(9):1392-8
pubmed: 17512190
Int J Radiat Oncol Biol Phys. 2010 Apr;76(5):1369-75
pubmed: 19625138
Lancet Oncol. 2009 Sep;10(9):877-84
pubmed: 19656725
Med Phys. 2010 Aug;37(8):4078-101
pubmed: 20879569
Jpn J Clin Oncol. 2011 Apr;41(4):537-42
pubmed: 21242183
Biochem J. 2011 Jun 1;436(2):399-407
pubmed: 21382012
IUBMB Life. 2011 Apr;63(4):221-32
pubmed: 21438113
J Nucl Med. 2011 May;52(5):705-11
pubmed: 21498541
J Surg Res. 2011 Nov;171(1):1-5
pubmed: 21571304
Br J Cancer. 2011 Jun 28;105(1):93-103
pubmed: 21629244
Cancer Res. 2011 Sep 1;71(17):5601-5
pubmed: 21846822
Head Neck. 2012 Oct;34(10):1395-402
pubmed: 22052623
Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Apr;113(4):464-71
pubmed: 22676927
Radiother Oncol. 2012 Sep;104(3):294-9
pubmed: 22998947
Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):654-9
pubmed: 23267058
J Exp Clin Cancer Res. 2013 May 29;32:34
pubmed: 23718763
J Clin Invest. 2013 Jul;123(7):2756-63
pubmed: 23863633
Cancers (Basel). 2011 Sep 15;3(3):3610-31
pubmed: 24212970
Ann Oncol. 2014 Mar;25(3):611-8
pubmed: 24401929
Pathologe. 2014 Nov;35(6):574-7
pubmed: 25319225
Cancer Treat Rev. 2015 Jun;41(6):503-10
pubmed: 25872878
PLoS One. 2015 Apr 30;10(4):e0125351
pubmed: 25927527
Lancet Oncol. 2015 Jul;16(7):795-803
pubmed: 26095785
Curr Probl Cancer. 2016 Jan-Feb;40(1):25-37
pubmed: 26582738
Cureus. 2015 Nov 24;7(11):e389
pubmed: 26719832
CA Cancer J Clin. 2017 Jan;67(1):65-85
pubmed: 27570942
Acta Oncol. 2017 Oct;56(10):1333-1339
pubmed: 28686524
Int J Radiat Biol. 2018 Mar;94(3):199-211
pubmed: 29293036
Virchows Arch. 2018 Apr;472(4):589-598
pubmed: 29520483
Proc Natl Acad Sci U S A. 1995 May 9;92(10):4606-10
pubmed: 7538678
Int J Radiat Oncol Biol Phys. 1995 Sep 30;33(2):281-7
pubmed: 7673015

Auteurs

Slavisa Tubin (S)

KABEG Klinikum Klagenfurt, Institute of Radiation Oncology, Feschnigstraße 11, 9020, Klagenfurt am Wörthersee, Austria. slavisa.tubin@kabeg.at.

Helmut H Popper (HH)

Medical University of Graz, Diagnostic and Research Institute of Pathology, Neue Stiftingtalstrasse 6, 8036, Graz, Austria.

Luka Brcic (L)

Medical University of Graz, Diagnostic and Research Institute of Pathology, Neue Stiftingtalstrasse 6, 8036, Graz, Austria.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH