. Author manuscript; available in PMC: 2024 Nov 21.

Published in final edited form as: Int J Radiat Oncol Biol Phys. 2024 Apr 15;120(2):370–408. doi: 10.1016/j.ijrobp.2024.04.001

Table 3.

Comparison of functional parameters, PTV, and OARs for varying RT modalities using functional avoidance planning

Study first author	N	Age	Cancer type	FLI modality: Definition	RT modality comparison	Significant changes in dose-function parameters	Plan quality: Significant results
Christian⁸³	6	N/A	All NSCLC	SPECT Q: Visual threshholding into 2 groups; weighting	Coplanar Noncoplanar	No significant changes	No significant changes
Dougherty⁸⁶	31	64 (med)	26 NSCLC 5 SCLC	CT V (HU): 15% of max, with further processing	IMPT IMPT (dose-escalated) VMAT	IMPT changes vs VMAT fMLD ↓ 7.18^* fV20 ↓ 9.18^* fV30 ↓ 4.41^* IMPT changes vs dose-escalated fV20 ↓ 1.37^* fV30 ↓ 1.03^*	IMPT reductions vs VMAT MLD ↓ 6.5^* V20 ↓ 8.25^* Mean esophagus ↓ 4.54^* Mean heart ↓ 7.11^* Cord max ↓ 23.34^*
Farr⁸⁷	15	71 (med)	12 NSCLC 1 SCLC 2 other	SPECT Q: 20%, 40%, 60%, and 80% of max	IMRT VMAT 3DCRT	3DCRT produced no statistically significant reductions or increases to functional parameters, aside from fV20 at the 40% threshold. VMAT produced statistically significant reductions in fV20 at the 20% threshold, fMLD and fV20 at the 40% threshold, fMLD and fV20 at the 60% threshold, and fMLD at the 80% threshold. IMRT produced statistically significant reductions for all functional parameters except fV5 for the 20% and 40% thresholds, and fV30 for the 60% and 80% thresholds.	Only the functional IMRT plan had statistically significant reductions in OAR-related parameters: V20 ↓ 2.02^* V30 ↓ 1.03^* Esophagus V60 ↓ 1.5^* VMAT had a statistically significant increase in esophagus V60: Esophagus V60 ↑ 1.29^*
Huang⁹²	8	66 (med)	NSCLC	CT V (Jacobian): Thresholded into 2 groups (unspecified)	IMRT Double-scattering proton therapy (DSPT) IMPT	Only 2 IMRT plans were clinically acceptable. Both proton plans were superior in sparing low-dose regions. IMPT specifically did so while maintaining PTV coverage.	Significance not reported. V5 median IMRT > DSPT > IMPT V20 median IMRT = DSPT > IMPT MLD median IMRT > DSPT > IMPT Mean heart median IMRT > DSPT > IMPT Mean esophagus median IMRT = DSPT > IMPT Cord max IMRT > IMPT > DSPT
Ieko⁹³	13	75.1 (mean)	All NSCLC	CT V (HU): 20th percentile	VMAT (SBRT) 3DCRT (SBRT) Proton (SBRT)	VMAT changes vs 3DCRT: fV10 ↓ 3.3^* (threshold) fV10 ↓ 3^* (weighting) Proton changes vs 3DCRT: fV5 ↓ 16^* (threshold) fV5 ↓ 15.3^* (weighting) fV10 ↓ 6.2^* (threshold) fV10 ↓ 5.4^* (weighting) fMLD ↓ 1.7^* (threshold) fMLD ↓ 1.8^* (weighting) Proton changes vs VMAT: fV5 ↓ 12.2^* (threshold) fV5 ↓ 11.2^* (weighting) fV10 ↓ 2.9^* (threshold) fV10 ↓ 2.4^* (weighting) fMLD ↓ 1.3^* (threshold) fMLD ↓ 1.4^* (weighting)	VMAT changes vs 3DCRT: V10 ↓ 3.2^* contra-MLD ↑ 0.6^* Cord max ↑ 3^* Proton changes vs 3DCRT: PTV D₁ ↓ 2.9^* PTV D₉₉ ↓ 1.4^* MLD ↓ 1.7^* V5 ↓ 15.7^* V10 ↓ 6.2^* contra-MLD ↓ 1.2^* contra-V5 ↓ 8.9^* contra-V20 ↓ 0.6^* Cord max ↓ 9.1^* Heart max ↓ 8.1^* Proton changes vs VMAT: PTV D₁ ↓ 2.3^* PTV D₉₉ ↓ 1^* MLD ↓ 1.3^* V5 ↓ 12.3^* V10 ↓ 3^* contra-MLD ↓ 1.8^* contra-V5 ↓ 13^* contra-V10 ↓ 0.7^* Cord max ↓ 12.1^* Heart max ↓ 8.5^*
Kimura⁶⁹	8	72.5 (med)	All lung cancer	CT (direct thresholding): > −860 HU	IMRT VMAT	IMRT changes VS VMAT: fV5 ↓^* fV10 ↓^* fV20 ↑^*	IMRT changes vs VMAT: CI ↑ 0.64^* Mean esophagus ↓ 0.7^* PTV > 250 cc V5 ↓^* PTV > 250 cc fV5 ↓^*
Lavrenkov⁹⁴	17	N/A	All NSCLC	SPECT Q: 60% of max	IMRT 3DCRT	IMRT changes vs 3DCRT stage III: fV20 ↓ 7.7^* fMLD ↓ 2.7^* IMRT changes vs 3DCRT nonuniform heterogeneous hypoperfusion: fV20 ↓ 11.5^* fMLD ↓ 3.6^*	IMRT changes vs 3DCRT stage III: PTV₉₀/fV20 ↑ 2.1^* IMRT changes vs 3DCRT nonuniform heterogeneous hypoperfusion: PTV₉₀/fV20 ↑ 2.3^*
Lavrenkov⁹⁵	25	N/A	All NSCLC	SPECT Q: 60% of max	IMRT 3DCRT	IMRT changes vs 3DCRT stage III and nonuniform heterogeneous hypoperfusion: fV20 ↓ 10.6^* fMLD ↓ 3.2^*	IMRT changes vs 3DCRT stage III and nonuniform heterogeneous hypoperfusion: PTV₉₀/fV20 ↑ 2.4^*
Lee²¹	8	N/A	All NSCLC	SPECT Q: Threshold into 7 equidistant bins; 70% of max threshold used for dose-function parameters	VMAT proton VMAT and proton	(VMAT + proton) changes vs VMAT fMLD ↓^* (median) (VMAT + proton) changes vs proton fMLD ↓^* (median)	(VMAT + proton) changes vs VMAT PTV V60 ↑^* (median) SUV_peak mean ↑^* (median) MLD ↓^* (median) V5 ↓^* (median) V10 ↓^* (median) V20 ↓^* (median) Mean heart ↓^* (median) Cord D_0.03 ↓^* (median) (VMAT + proton) changes vs proton PTV V60 ↑^* (median) SUV_peak mean ↑^* (median) MLD ↑^* (median) Mean heart ↑^* (median) Cord D_0.03 ↑^* (median)
McGuire¹²⁷	5	N/A	All lung	SPECT Q: Threshold into 4 regions, with subsequent weighting	IMRT: 7 and 4 beams	Four beams vs 7 beams fV5 ↓ 8.6^* fV13 ↓ 3.3^* fV20 ↓ 1.4 fV30 ↑ 1.8	No significant differences
Mounessi¹¹⁴	13	N/A	NSCLC	SPECT Q: 30% of max	IMRT VMAT	Only IMRT gives a significant reduction in fV30 for localized hypoperfusion patients. Only VMAT gives a significant reduction in fV30 for diffuse hypoperfusion patients. Only IMRT gives a significant increase in V20 to nonfunctional lung. Only VMAT gives a significant increase to mean dose to nonfunctional lung.	No significant difference
Munawar¹¹⁷	10	N/A	NSCLC	SPECT V: Threshold at 50% and 70% of max; weighting	IMRT: 9 and 3 field	3-field change vs 9-field All patients No significant difference Group 1: Clinically acceptable fMLD ↓ 1.078^* Group 2: Not acceptable No significant difference	3-field change vs 9-field All patients No significant difference Group 1: Clinically acceptable No significant difference Group 2: Not acceptable No significant difference
Tian¹²²	10	N/A	NSCLC	SPECT Q: 4, 5, 7 beam: threshold (unspecified)	IMRT	4 beam changes vs 5 beam fV5 ↓ 10.28^* fV30 ↑ 1.22^* 4 beam changes vs 7 beam fV5 ↓ 15.24^* fV20 ↑ 2.2^* fV30 ↑ 1.6^* fMLD ↓ 0.62^* 5 beam changes vs 7 beam fV5 ↓ 4.96^* fV20 ↑ 1.74^* fV30 ↑ 0.48^*	4 beam changes vs 5 beam CI ↓ 0.09^* 4 beam changes vs 7 beam CI ↓ 0.1^* 5 beam changes vs 7 beam HI ↑ 0.12^*
Vicente⁵⁷	12	64	All lung cancer	CT V (HU-Jacobian hybrid): Thresholding at average of pretreatment scan CT V (airway segmentation)	IMRT VMAT vs 3DCRT conventional plan All plans were SBRT	IMRT vs 3DCRT fD_mean ↓ 32% fV13.5 ↓ 39% VMAT vs 3DCRT fD_mean ↓ 14% fV13.5 ↓ 5%	Not reported
Wang¹¹⁵	16	55 (med)	All NSCLC	CT V (Jacobian): Top 30%	IMRT: Equally spaced beams IMRT: Manual beams	Manual change vs equal fV5 ↓ 13.2^* fV10 ↓ 14.1^* fV20 ↓4.4^* fV30 ↓ 2	Manual change vs equal Mean cord ↓ 6.5^* Max cord ↓ 4.4^* Heart V60 ↑ 3.9^*
Yamamoto¹⁰⁹	15	75.1 (mean)	All NSCLC	CT V (Jacobian): Thresholded into 3 equal volumes (unspecified)	VMAT IMRT	Only IMRT had a significant decrease in fMLD and fV20 to moderately ventilated lung for the functional plan compared with anatomic.	Only IMRT had a significant reduction in mean lung dose in the functional plan compared with anatomic.
Yin¹³¹	10	N/A	NSCLC	SPECT Q: Visual thresholding	IMRT 3DCRT	IMRT changes vs 3DCRT fV5 ↑^* fV40 ↓^*	Significance not reported. IMRT changes vs 3DCRT PTV V66 ↑ Heart V30 ↑

Abbreviations: 3DCRT = 3-dimensional conformal radiation therapy; CT = computed tomography; FLI = functional lung imaging; fMLD = mean dose to functional lung; fVx = dose parameter (x) to functional lung, defined as in the modality column; HU = Hounsfield unit; IMPT = intensity modulated proton therapy; IMRT = intensity modulated radiation therapy; MLD = mean dose to non-PTV lung; Vx = dose parameter (x) to non-PTV lung; NSCLC = non-small cell lung cancer; OAR = organs at risk; PTV = planning target volume; Q = perfusion; RT = radiation therapy; SBRT = stereotactic body radiation therapy; SCLC = small cell lung cancer; SPECT = single-photon emission computed tomography; SUV = standardized update volume; V/VENT = ventilation; VMAT = volumetric modulated arc therapy.

Statistically significant; anatomic plans not compared.