Investigating the potential of proton therapy for hypoxia-targeted dose escalation in non-small cell lung cancer.
Aged
Aged, 80 and over
Carcinoma, Non-Small-Cell Lung
/ radiotherapy
Female
Humans
Linear Energy Transfer
Lung Neoplasms
/ radiotherapy
Male
Middle Aged
Organs at Risk
Proton Therapy
/ adverse effects
Radiotherapy Dosage
Radiotherapy Planning, Computer-Assisted
/ methods
Tumor Hypoxia
/ radiation effects
NSCLC
PET
Proton therapy
Tumor hypoxia
Journal
Radiation oncology (London, England)
ISSN: 1748-717X
Titre abrégé: Radiat Oncol
Pays: England
ID NLM: 101265111
Informations de publication
Date de publication:
11 Oct 2021
11 Oct 2021
Historique:
received:
16
07
2021
accepted:
13
09
2021
entrez:
12
10
2021
pubmed:
13
10
2021
medline:
29
1
2022
Statut:
epublish
Résumé
Hypoxia is known to be prevalent in solid tumors such as non-small cell lung cancer (NSCLC) and reportedly correlates with poor prognostic clinical outcome. PET imaging can provide in-vivo hypoxia measurements to support targeted radiotherapy treatment planning. We explore the potential of proton therapy in performing patient-specific dose escalation and compare it with photon volumetric modulated arc therapy (VMAT). Dose escalation has been calibrated to the patient specific tumor response of ten stage IIb-IIIb NSCLC patients by combining HX4-PET imaging and radiobiological modelling of oxygen enhancement ratio (OER) to target variable tumor hypoxia. In a dose-escalation-by-contour approach, escalated dose levels were simulated to the most hypoxic region of the primary target and its effectiveness in improving loco-regional tumor control was assessed. Furthermore, the impact on normal tissue of proton treatments including dose escalation was evaluated in comparison to the normal tissue complication probability (NTCP) of conventional VMAT plans. Ignoring regions of tumor hypoxia can cause overestimation of TCP values by up to 10%, which can effectively be recovered on average to within 0.9% of the nominal TCP, using patient-specific dose escalations of up to 22% of the prescribed dose to PET defined hypoxic regions. Despite such dose escalations, the use of protons could also simultaneously reduce mean doses to the heart (- 14.3 Gy This study suggests that the administration of proton therapy for dose escalation to patient specific regions of tumor hypoxia in the treatment of NSCLC can mitigate TCP reduction due to hypoxia-induced radio resistance, while simultaneously reducing NTCP levels even when compared to non-escalated treatments delivered with state-of-the-art photon techniques.
Sections du résumé
BACKGROUND
BACKGROUND
Hypoxia is known to be prevalent in solid tumors such as non-small cell lung cancer (NSCLC) and reportedly correlates with poor prognostic clinical outcome. PET imaging can provide in-vivo hypoxia measurements to support targeted radiotherapy treatment planning. We explore the potential of proton therapy in performing patient-specific dose escalation and compare it with photon volumetric modulated arc therapy (VMAT).
METHODS
METHODS
Dose escalation has been calibrated to the patient specific tumor response of ten stage IIb-IIIb NSCLC patients by combining HX4-PET imaging and radiobiological modelling of oxygen enhancement ratio (OER) to target variable tumor hypoxia. In a dose-escalation-by-contour approach, escalated dose levels were simulated to the most hypoxic region of the primary target and its effectiveness in improving loco-regional tumor control was assessed. Furthermore, the impact on normal tissue of proton treatments including dose escalation was evaluated in comparison to the normal tissue complication probability (NTCP) of conventional VMAT plans.
RESULTS
RESULTS
Ignoring regions of tumor hypoxia can cause overestimation of TCP values by up to 10%, which can effectively be recovered on average to within 0.9% of the nominal TCP, using patient-specific dose escalations of up to 22% of the prescribed dose to PET defined hypoxic regions. Despite such dose escalations, the use of protons could also simultaneously reduce mean doses to the heart (- 14.3 Gy
CONCLUSIONS
CONCLUSIONS
This study suggests that the administration of proton therapy for dose escalation to patient specific regions of tumor hypoxia in the treatment of NSCLC can mitigate TCP reduction due to hypoxia-induced radio resistance, while simultaneously reducing NTCP levels even when compared to non-escalated treatments delivered with state-of-the-art photon techniques.
Identifiants
pubmed: 34635135
doi: 10.1186/s13014-021-01914-2
pii: 10.1186/s13014-021-01914-2
pmc: PMC8507157
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
199Subventions
Organisme : personalized health and related technologies (phrt)
ID : 2018-223
Informations de copyright
© 2021. The Author(s).
Références
Lancet Oncol. 2005 Feb;6(2):112-7
pubmed: 15683820
Cancer Treat Rev. 2012 Dec;38(8):1027-32
pubmed: 22560366
J Natl Cancer Inst. 2018 Jan 1;110(1):
pubmed: 28922791
World J Clin Oncol. 2014 Dec 10;5(5):824-44
pubmed: 25493221
Int J Radiat Oncol Biol Phys. 2010 Jun 1;77(2):357-66
pubmed: 19660879
Int J Radiat Oncol Biol Phys. 2002 Jun 1;53(2):407-21
pubmed: 12023146
Transl Lung Cancer Res. 2017 Jun;6(3):366-372
pubmed: 28713681
Radiat Oncol. 2013 Jun 15;8:144
pubmed: 23767810
J Clin Oncol. 2020 Mar 1;38(7):706-714
pubmed: 31841363
Semin Radiat Oncol. 2018 Apr;28(2):79-87
pubmed: 29735194
Cancer Metastasis Rev. 2007 Jun;26(2):225-39
pubmed: 17440684
J Clin Oncol. 2018 Jun 20;36(18):1813-1822
pubmed: 29293386
Phys Med. 2020 Aug;76:166-172
pubmed: 32683269
Radiother Oncol. 2015 Aug;116(2):281-6
pubmed: 26238010
Int J Radiat Oncol Biol Phys. 2019 Feb 1;103(2):403-410
pubmed: 30291994
JAMA Oncol. 2017 Aug 10;3(8):e172032
pubmed: 28727865
Radiother Oncol. 2020 May;146:200-204
pubmed: 32220701
Med Phys. 1997 Jan;24(1):103-10
pubmed: 9029544
Radiother Oncol. 2017 Feb;122(2):274-280
pubmed: 28139305
Phys Med Biol. 2008 Jun 21;53(12):R151-91
pubmed: 18495981
Int J Radiat Oncol Biol Phys. 1995 Jul 15;32(4):1227-37
pubmed: 7607946
J Thorac Dis. 2021 Feb;13(2):1270-1285
pubmed: 33717598
Phys Med Biol. 2011 Aug 21;56(16):R113-44
pubmed: 21775795
Int J Radiat Oncol Biol Phys. 2019 Aug 1;104(5):1124-1132
pubmed: 30822531
Int J Radiat Oncol Biol Phys. 2007 May 1;68(1):291-300
pubmed: 17448882
Med Phys. 2004 Nov;31(11):3150-7
pubmed: 15587667
Adv Radiat Oncol. 2016 Nov 16;2(1):37-43
pubmed: 28740914
Radiother Oncol. 2015 Jun;115(3):367-72
pubmed: 26028228
Acta Oncol. 2018 Apr;57(4):485-490
pubmed: 29141489
J Clin Oncol. 2010 May 1;28(13):2181-90
pubmed: 20351327
Br J Radiol. 1996 Sep;69(825):839-46
pubmed: 8983588
Phys Med Biol. 2011 Jun 7;56(11):3251-68
pubmed: 21540489
Acta Oncol. 2014 May;53(5):605-12
pubmed: 23957623
Radiat Oncol. 2016 May 04;11:66
pubmed: 27142674
Radiother Oncol. 2015 Oct;117(1):49-54
pubmed: 26341608
Br J Radiol. 2014 Mar;87(1035):20130676
pubmed: 24588669