1022 - ACRIN 6685 PET-CT Threshold to Reinterpret Pre-Treatment Head and Neck Cancer (HNC) Imaging? Stage Migration and Treatment Outcomes

N. Mohsin¹, H. N. Yankey¹, T. J. Galloway², K. Ruth¹, and J. Q. M. Yu¹; ¹Fox Chase Cancer Center, Philadelphia, PA, ²Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA

Purpose/Objective(s): ACRIN 6685 established a positron emission tomography with computed tomography (PET-CT) based maximum standardized uptake value of 1.8 to have a negative predictive value of 0.942 for lymph node (LN) detection in clinical N0 necks. We report the rate of N-stage migration, number of “involved” LNs per 6685 versus standard clinical PET evaluation interpretation, and outcomes in patients treated with definitive (chemo)radiation [(C)RT]. Materials/

Methods: This single-institution IRB approved retrospective study reviews HNC squamous cell carcinoma patients (T1-T4 N0-N3 disease) treated 2015-2022 with a staging PET-CT obtained prior to definitive (C)RT to document stage and LN involvement. (C)RT regimen and dosing were per standard practice. PET imaging was reinterpreted by a nuclear medicine radiologist (JQY) per 6685 criteria and the difference from the original standard clinical interpretation that was used to make treatment decisions was compared by Chi-square tests and logistic regression. Survival and recurrence outcomes were compared by disease site using Cox and competing risks methods.
Results: Of 179 patients (median age 61, 86% male) who met inclusion criteria, 133 (74%) had oropharynx [OPC], of which 86% were p16+. Nodal status distribution, determined by pre-treatment PET, was N0=14%, N1=44%, N2/N2a-c=37%, and N3/N3a-b=5%. T stage included 19% T1, 40% T2, and 41% T3-T4 disease. PET scans were obtained a median of 27 days [IQR 29,39] prior to the initiation of (C)RT. With reinterpretation of imaging, 88% patients had an increase in positive LN from a mean of 2.7 (0-10) to 4.4 (0-13), with 79 patients interpreted to have new contralateral involvement. 50% patients were upstaged (80% N0, 71% N1, 15% N2/N2a-c, and 0% N3/N3a-b patients), as shown in Table 1. Over follow up, 34 patients died. The mean follow up for surviving patients was 36.8 months (17.6-52.4). 11 patients (91% OPC) had 14 nodal recurrences. 11 recurrences were in nodal levels read positive on both interpretations (original+/6685+), 1 was in an original-/6685+ node level that was prescribed 56 Gy, and 2 were in original-/6685- levels that were prescribed 56-63 Gy. All 3 recurrences in original- regions had multi-station LN recurrences in areas both original+ and original-. At 36 months, PFS, OS, LRF is shown in Table 1.
Conclusion: Re-interpretation with ACRIN 6685 criteria yielded increasing positive LNs and subsequent upstaging. Recurrences in areas interpreted as originally uninvolved but upstaged by 6685 criteria were rare (<1% of patients). Most nodal recurrences occurred in regions initially read as positive and treated to carcinoma dose.

Table 1. Outcomes by diagnosis
Disease Site	% of patients with an increase in positive LNs	% of patients with upstaging of N stage	PFS	OS	LRF
			At 36 months
OPC p16+	89%	45%	84%	86%	94%
OPC p16-	95%	39%	37%	40%	55%
Non-OPC	83%	67%	69%	83%	80%
p-value	0.31	0.040	<0.001	<0.001	<0.001