1034 - Impact of Synthetic PET Evaluation prior to PET-Guided Functional Modeling in Optimizing Patient Selection for Biology-Guided Radiotherapy

D. F. Hicks¹, H. Chen¹, J. J. Kim¹, L. Tressel¹, D. G. Wallington², K. Becht³, K. L. Johung¹, M. R. Young¹, K. Feghali⁴, D. de Jong⁴, Z. Chen¹, D. J. Carlson¹, and H. S. M. Park⁵; ¹Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, ²Yale New Haven Hospital, New Haven, CT, ³Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, ⁴RefleXion Medical, Inc., Hayward, CA, ⁵Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale School of Medicine, New Haven, CT

Purpose/Objective(s): Hypothesis: Synthetic assessment of diagnostic PET data is consistent with results of PET functional modeling required for biology-guided radiotherapy, which results in smaller lung target volumes than those used in stereotactic body radiotherapy. PET-guided functional modeling (FM) is a prerequisite for biology-guided radiotherapy (BgRT). Optimizing patient selection for BgRT prior to FM would be ideal. We aimed to determine if (1) synthetic PET evaluation results are concordant with FM results, and (2) BgRT planning target volume (PTV) based on a 5mm uniform expansion of gross tumor volume (GTV) from synthetic PET evaluation and CT simulation is smaller than stereotactic body radiotherapy (SBRT) PTV based on a 5mm uniform expansion of internal target volume (ITV) from CT simulation. Materials/

Methods: Patients were selected for BgRT candidacy based on initial criteria: =8 Gy/fraction planned to lung or bone, 1-5cm tumor size, <2cm of motion, >2cm from PET-avid organs at risk, and SUVmax>6 with homogenous uptake <2cm from the superior-inferior PTV edge. Synthetic PET evaluation was performed by creating mock volumes from diagnostic PET-CT (mGTV, mPTV) with a passing goal of Activity Concentration (mAC) =5 kBq/ml (target AC minus background AC) and Normalized Target Signal (mNTS) =2.7 (target contrast divided by immediate background noise). After CT simulation, the true BgRT GTV and PTV as well as SBRT ITV and PTV were created. FM PET generated the true AC and NTS in preparation for BgRT.

Results: In January-February 2024, 3 patients (primary lung cancer, lung oligometastasis, and iliac bone oligometastasis) successfully completed FM. Case 1 failed both synthetic PET evaluation (mAC 3.1 kBq/ml, mNTS indeterminate) and FM (AC 3.8 kBq/ml, NTS indeterminate). Case 2 passed both synthetic PET evaluation (mAC 10.6 kBq/ml, mNTS 15.7) and FM (AC 10.6 kBq/ml, NTS 7.8), as did Case 3 (mAC 5.3 kBq/ml, mNTS 8.4) and FM (AC 6.6 kBq/ml, NTS 5.7). mPTV and BgRT PTV were smaller than SBRT PTV in the two lung cases (Case 1: 6.8 and 8.8 vs. 13.3 cc, respectively; Case 2: 23.8 and 38.5 vs. 66.8 cc, respectively).

Conclusion: Early experience with synthetic PET evaluation demonstrated general agreement with functional modeling results for BgRT. This may serve as a tool to screen for optimal BgRT cases with smaller target volumes than those of SBRT plans.

	BgRT Target			Synthetic PET Evaluation			Functional Modeling
Case	Site	Size (cm)	SUVmax	mAC (PASS if =5 kBq/ml)	mNTS (PASS if =2.7)	Result	AC (PASS if =5 kBq/ml)	NTS (PASS if =2.7)	Result
1	Lung Primary	1.1	6.2	3.1	n/a	FAIL	3.8	n/a	FAIL
2	Lung Oligometastasis	2.8	9.5	10.6	15.7	PASS	10.6	7.8	PASS
3	Bone Oligometastasis	1.9	7.6	5.3	8.4	PASS	6.6	5.7	PASS
	Diagnostic PET-CT			CT Simulation
Case	PET Volume (cc)	mGTV (cc)	mPTV (cc)	GTV phase selected	BgRT GTV (cc)	BgRT PTV (cc)	Extent of motion (cm)	SBRT ITV (cc)	SBRT PTV (cc)
1	0.6	1.2	6.8	mid-cycle	1.7	8.8	0.6	2.8	13.3
2	5.3	8.4	23.8	mid-cycle	15.8	38.5	1.5	29.4	66.8
3	1.6	2.5	10.9	n/a	4.2	16.1	n/a	n/a	16.1