Sep 30

QP 08 - Head and Neck 3: Quick Pitch: Prognosis in Focus: Predicting Outcomes in Head and Neck Cancer

1042 - Automated CBCT-Based Tumor Volume Tracking is Prognostic in Virally-Mediated Head and Neck Cancer

08:05am - 08:10am PT

Room 160

Presenter(s)

Eric Stutheit-Zhao, MD, PhD - Princess Margaret Cancer Centre, Toronto, ON

E. Y. Stutheit-Zhao¹, T. Tadic², T. Patel³, A. Bushehri⁴, H. B. Chan⁵, O. Wong⁴, J. Lee⁶, S. H. Huang⁷, Z. Baskurt⁷, J. Cho², E. Hahn⁷, A. McPartlin⁸, A. Hosni⁸, J. H. J. Kim⁷, J. G. Ringash⁹, J. N. Waldron¹⁰, A. L. McNiven¹¹, B. Haibe-Kains⁶, A. J. Hope⁷, and S. V. Bratman¹; ¹Princess Margaret Cancer Centre, Toronto, ON, Canada, ²Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, ³Techna Institute, University Health Network, Toronto, ON, Canada, ⁴Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada, ⁵Department of Radiation Oncology, Princess Margaret Cancer Centre/University of Toronto, Toronto, ON, Canada, ⁶Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada, ⁷Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, ⁸Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada, ⁹Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada, ¹⁰Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada, ¹¹Tom Baker Cancer Centre, Calgary, AB, Canada

Purpose/Objective(s): Radiotherapy (RT) or chemoradiotherapy (CRT) enables curative treatment in many head & neck cancer (HNC) patients, but 20-40% recur. Improved early biomarkers of response could stratify patients for therapy intensification or de-intensification. Cone beam CT (CBCT), routinely acquired for image-guided RT, is underutilized for response assessment. Automated CBCT-based tumor volume tracking may provide a biomarker of response and intrinsic radiosensitivity. We retrospectively evaluated gross primary tumor volume changes (GTVp) during RT/CRT using automated CBCT analysis in patients with nasopharynx (NPC) and oropharynx (OPC) cancer with mature clinical outcomes.

Materials/Methods: We analyzed CBCT images of non-metastatic NPC and OPC treated with curative RT/CRT in 2006–2017. Patients missing >5 CBCT images and OPC with GTVp < 20 cc were excluded (the latter due to poor reproducibility). We used deformable registration to map manually delineated GTVp to CBCTs, with air/bone excluded using Otsu thresholding. Percent change in GTVp per fraction (Fx) was fitted with locally weighted smoothing and the area under the curve (AUC) was computed to summarize rate and extent of GTVp change. Associations with recurrence-free survival (RFS) were analyzed using multivariable Cox models adjusted for baseline GTVp.

Results: We analyzed 23285 CBCTs from 657 patients: 262 NPC (216 EBV+, 17 EBV-, 29 not tested), 395 OPC (271 p16+, 124 p16-). Median follow-up was 6.2 years. GTVp decreased in 93.0% of patients (median -9.97%, range: -59.8, +10.5). Concurrent chemotherapy was associated with greater GTVp shrinkage (log-likelihood ratio [LR]: -0.50 [-0.91, -0.09], p=0.02). Patients with p16- OPC trended towards less GTVp shrinkage (LR: -0.40 [-0.98, 0.18], p=0.17). GTVp shrinkage was not correlated with smoking history or baseline GTVp. Greater GTVp shrinkage during RT/CRT predicted favorable RFS in NPC and p16+ OPC but not p16- OPC, when adjusted for baseline GTVp in a Cox model (Table). Examining earlier treatment response markers, Fx 18 AUC showed the strongest correlation with total AUC (Pearson R=0.916) and was similarly significantly associated with RFS in NPC and p16+ OPC.

Conclusion: In a large retrospective cohort with mature clinical follow-up, automated GTVp tracking on CBCT was prognostic for RFS as early as Fx 18 in virally-mediated HNC treated with definitive RT/CRT. These findings support the further development of CBCT-based biomarkers as a practical biomarker for adaptive risk stratification.

Abstract 1042 - Table 1

Metric	Disease	GTVp change		Baseline GTVp (per 10cc)
Metric	Disease	Hazard ratio [95% CI]	P value	Hazard ratio [95% CI]	P value
AUC	NPC	1.19 [1.02, 1.39]	0.020 *	1.07 [1.01, 1.13]	0.010 *
	OPC, p16+	1.13 [1.01, 1.28]	0.036 *	1.09 [1.02, 1.16]	0.008 **
	OPC, p16-	1.03 [0.93, 1.14]	0.579	1.14 [1.05, 1.24]	0.001 **
AUC, Fx 18	NPC	1.45 [1.01, 2.08]	0.040 *	1.07 [1.02, 1.13]	0.010 *
	OPC, p16+	1.45 [1.11, 1.91]	0.007 **	1.08 [1.02, 1.15]	0.012 *
	OPC, p16-	1.19 [0.93, 1.53]	0.175	1.14 [1.05, 1.23]	0.001 **