Main Session
Sep 30
SS 37 - Head and Neck 4: Refining Radiation: What Clinical Trials Can Tell Us

316 - High Bleeding Rates in a Randomized Phase 2 Trial of SBRT with Concurrent and Adjuvant Cetuximab +/- Docetaxel in Previously-Irradiated HNSCC

01:25pm - 01:35pm PT
Room 314

Presenter(s)

Alberto Vera, MD - UPMC Cancer Center, Pittsburgh, PA

A. A. Vera1, C. T. Wilke1, J. A. A. Vargo IV2, M. L. Bulat1, J. Ohr3, D. P. Zandberg3, Z. Rahman3, S. Kim4, J. T. Johnson4, D. Petro5, S. Marks5, L. Francis5, V. Gorantla5, J. Mountz6, H. Wang7, D. A. Clump II8, D. E. Heron9, C. Snyderman10, H. D. Skinner1, and Y. M. Mowery1; 1Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, 2UPMC Cancer Center, Pittsburgh, PA, 3Department of Hematology and Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, 4Department of Otolaryngology, Division of Head and Neck Surgery, UPMC, Pittsburgh, PA, 5Division of Hematology and Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, 6Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 7University of Pittsburgh School of Medicine, Pittsburgh, PA, 8Department of Radiation Oncology, West Virginia University Cancer Institute, Morgantown, WV, 9Department of Radiation Oncology, Bon Secours Mercy Health System, Youngstown, OH, 10Department of Otolaryngology, Division of Head and Neck Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA

Purpose/Objective(s): Recurrent head & neck squamous cell carcinoma (rHNSCC) presents a major challenge in previously-irradiated patients. Stereotactic body radiation therapy (SBRT) offers ablative, highly conformal RT doses while minimizing dose to adjacent normal tissue. Toxicity data are limited for head & neck SBRT reirradiation with concurrent systemic therapy. Here we report grade 4+ bleeding adverse events (AEs) for patients receiving SBRT reirradiation with cetuximab +/- docetaxel.

Materials/Methods: This phase 2 randomized controlled trial evaluated SBRT with concurrent & adjuvant cetuximab (Arm 1) vs. cetuximab/docetaxel (Arm 2). Key inclusion criteria included age =18 yr, ECOG 0-1, and rHNSCC in a region of prior RT (=50 Gy). SBRT was 44–50 Gy in 5 fractions (every other day). 1° endpoint was 1-year locoregional PFS. 2° endpoints included AEs, which were prospectively collected (CTCAE v4.0) & verified on retrospective chart review. Dosimetric data (ipsilateral internal carotid artery [ICA] max dose, D0.03 cc, and D2 cc) were analyzed to explore correlations with bleeds. Association between arterial bleed & anatomic factors (air-tumor-artery interface and >180° artery encasement), prior neck dissection (Fisher’s exact test), and number of head & neck RT courses (Mann-Whitney test) were also evaluated.

Results: Due to poor accrual, the trial closed after randomizing 38 patients (19/arm). Median follow-up was 10 months. Eleven patients in Arm 1 & 13 in Arm 2 had prior neck dissection. Six patients (16%) received 3 total RT courses. Seven patients (18%; n=3 on Arm 1; n=4 on Arm 2) had grade 4+ arterial bleeds (5 ICA, 1 external carotid artery [ECA], 1 lingual artery), which was higher than the 2% arterial bleed rate reported in our prior institutional trial with concurrent cetuximab (NCT01104922). Six of 7 bleeds were fatal, with 5 likely related to tumor progression. Median time from SBRT to bleed was 6.1 months (IQR 4.3 – 18.8). Treatment arm, ipsilateral ICA dose parameters, prior neck dissection, and time between 1st & 2nd RT courses did not correlate with bleeds. There was a trend towards association between arterial bleed and number of head & neck RT courses (p = 0.056). Bleeds were significantly associated with >180° tumor encasement of the artery that bled (RR 2.66, 95% CI 1.31-4.82; p=0.03) and tumor located between air & artery without intervening normal tissue (RR 3.10, 95% CI 1.76 – 3.71; p=0.0097).

Conclusion: Grade 4+ arterial bleeds were observed after SBRT reirradiation with concurrent and adjuvant cetuximab +/- docetaxel, particularly with uncontrolled disease, no normal tissue separating air/tumor/artery, and/or tumor involving >180° of a major artery (ICA, ECA, or lingual artery). Patient selection is critically important in re-irradiation strategies for rHNSCC to optimize tumor control and to avoid high-grade normal tissue complications.