Investigating the potential of proton therapy for hypoxia-targeted dose escalation in non-small cell lung cancer.
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BORIS DOI
Date of Publication
October 11, 2021
Publication Type
Article
Division/Institute
Contributor
Köthe, Andreas | |
Bizzocchi, Nicola | |
Safai, Sairos | |
Lomax, Antony John | |
Fattori, Giovanni |
Subject(s)
Series
Radiation oncology
ISSN or ISBN (if monograph)
1748-717X
Publisher
BioMed Central
Language
English
Publisher DOI
PubMed ID
34635135
Uncontrolled Keywords
Description
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
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
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 GyRBE), lung (- 8.3 GyRBE), esophagus (- 6.9 GyRBE) and spinal cord (- 3.8 Gy) compared to non-escalated VMAT plans. These reductions are predicted to lead to clinically relevant decreases in NTCP for radiation-induced pneumonitis (- 11.3%), high grade heart toxicity (- 7.4%) and esophagitis (- 7.5%).
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.
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
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
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 GyRBE), lung (- 8.3 GyRBE), esophagus (- 6.9 GyRBE) and spinal cord (- 3.8 Gy) compared to non-escalated VMAT plans. These reductions are predicted to lead to clinically relevant decreases in NTCP for radiation-induced pneumonitis (- 11.3%), high grade heart toxicity (- 7.4%) and esophagitis (- 7.5%).
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.
File(s)
| File | File Type | Format | Size | License | Publisher/Copright statement | Content | |
|---|---|---|---|---|---|---|---|
| s13014-021-01914-2.pdf | text | Adobe PDF | 1.3 MB | published |