The Critical Components for Effective Adaptive Radiotherapy in Patients with Unresectable Non-Small-Cell Lung Cancer: Who, When and How

Figures & data

Table 1. Studies relating to the ‘who’ of adaptive radiotherapy in patients with non-small-cell lung cancer.

	Sample size (n)	Treatment	Result	Ref.
Who	64	CCRT	Patients with stage III unresectable NSCLC receiving radical radiotherapy could benefit from ART	[23]
	41	CCRT (n = 21) or SCRT (n = 20)	Patients with initial large GTV receiving CCRT could benefit from ART	[24]
	32	IMRT (with/without ART = 8/8), PSPT (with/without ART = 8/8)	Mean target volume variation from the planning position could be applied to identify lung cancer patients who need ART	[25]
	240	Treated with 55 Gy in 20 fractions of radiotherapy	An automatic algorithm based on the shape and volume of tumors from CBCT could predict the patients who need ART	[26]
	25	Helical tomotherapy	A Bayesian model adaptation algorithm based on GTV change could predict response to radiotherapy in NSCLC patients who had locally advanced (stage III–IV) disease	[27]
	28	Functional avoidance radiation therapy during weeks 1–3	FDG PET radiomics could predict tumor response to radiotherapy in patients with stage IIB–IIIB NSCLC	[28]
	25	Hi-Art helical tomotherapy over 8 weeks	PSI-related mathematical modeling could be used to personalize and adapt radiotherapy in NSCLC patients	[29]
	92	Radical radiotherapy	One SNP signature was found to predict dose–response in stage III NSCLC patients	[30]

ART: Adaptive radiotherapy; CBCT: Cone-beam computed tomography; CCRT: Concurrent chemoradiotherapy; FDG: Fluorodeoxyglucose; GTV: Gross tumor volume; IMRT: Intensity-modulated radiation therapy; NSCLC: Non-small-cell lung cancer; PSI: Proliferation saturation index; PSPT: Passive-scattering proton therapy; SCRT: Sequential chemoradiotherapy; SNP: Single-nucleotide polymorphism.

Table 2. Studies relating to the ‘when’ of adaptive radiotherapy in patients with non-small-cell lung cancer.

	Sample size (n)	Treatment	Result	Ref.
When	17	Helical tomotherapy	ART should be arranged when the GTV decreases by >30% during the first 20 fractions of radiotherapy	[31]
	60	CCRT	ART should be suggested after 15 fractions of radiotherapy	[32]
	32	CCRT	ART should be performed during fractions 15–20 of radiotherapy	[33]
	41	CCRT (n = 21) or SCRT (n = 20)	To receive ART at fraction 15 of radiotherapy	[24]
	22	CCRT	The period of 30–50 Gy in 20 fractions of radiotherapy might be the optimum time point for ART	[34]
	64	CCRT	ART routinely scheduled after 42–44 Gy in 20 fractions of radiotherapy	[23]

ART: Adaptive radiotherapy; CCRT: Concurrent chemoradiotherapy; GTV: Gross tumor volume; SCRT: Sequential chemoradiotherapy.

Table 3. Studies relating to the ‘how’ of adaptive radiotherapy in patients with non-small-cell lung cancer.

	Sample size	Treatment	Result	Ref.
How	n1 = 177; n2 = 63; n3 = 17	Radical radiotherapy; CCRT; helical tomotherapy	CBCT-guided ART	[14,18,31]
	n1 = 217; n2 = 64	CCRT; CCRT	Mid-CT-guided ART	[19,23]
	n1 = 14; n2 = 63; n3 = 17	CCRT; CCRT; CCRT	Mid-PET/CT-guided ART	[35–37]
	n1 = 19; n2 = 316; n3 = 5; n4 = 25; n5 = 50; n6 = 23	SABR; 3DCRT, IMRT, SBRT; SBRT; SABR; SABR; CCRT or SCRT	Online MRI-guided ART	[38–43]

3DCRT: 3D Conformal radiotherapy; ART: Adaptive radiotherapy; CBCT: Cone-beam computed tomography; CCRT: Concurrent chemoradiotherapy; CT: Computed tomography; IMRT: Intensity-modulated radiation therapy; SABR: Stereotactic ablative radiotherapy; SBRT: Stereotactic body radiation therapy.

Table 4. Comparison of different forms of image guidance.

	Advantage	Disadvantage
CBCT	Early detection of anatomical changes by daily/weekly CBCT	Image quality is poor for the quantitative analysis of tumor and anatomical changes Increased burden on radiation oncologists and technicians Extends the time of maintaining passive position in patients treated with radiotherapy CBCT images are inadequate for the adaptive plan, and new CT simulations need to be arranged after changes observed by CBCT
Mid-CT	A scheduled plan greatly assists in implementing resource preallocation and ART effectively CT images can be directly applied to the design of new adaptive plans	Impossible to track the changes of tumor and anatomical structures in time The scheduled time point is not suitable for every patient because of differences in tumor response to the same radiation dose
Mid-PET/CT	PET/CT-guided GTV delineation is conducive to boosting GTV dose	Extra medical treatment consumed (except for CT simulations) New GTV delineation is dependent on the results of PET/CT and CT simulation image fusion, which is normally a subjective decision by different doctors
Online MRI	Good for reviewing changes of tumor and anatomical structures and motility changes in a timely manner	This technology has not yet been popularized High cost Safety and reliability remain unclear

ART: Adaptive radiotherapy; CBCT: Cone-beam computed tomography; CT; Computed tomography; GTV: Gross tumor volume.

Figure 1. A schematic representation of three crucial elements to successfully perform adaptive radiotherapy in non-small-cell lung cancer.

Non-small-cell lung cancer patients with large tumor volume, earlier tumor response to radiotherapy and significantly decreased tumor volume are the eligible patients for adaptive radiotherapy (ART). The accomplishment of 30–50 Gy/15–25 fractions of radiation is the appropriate period for ART in non-small-cell lung cancer patients. Different forms of image guidance, including CBCT, MRI and PET-CT can be applied in the implementation of ART, and various image guidance techniques can be used separately or jointly. In the future, predictive and monitoring models based on circulating biomarkers and the radiomics characteristics will be useful to screen appropriate patients and determine the correct time for the ART schedule.

CBCT: Cone-beam computed tomography; CT: Computed tomography; F: Fraction; FDG: Fluorodeoxyglucose; MR: Magnetic resonance.

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