Kinomic Profiling Identifies Pathways of HER2 Targeted Therapy Resistance in HER2 Positive Breast Cancer Cell Lines

Common practice is to irradiate at least the ipsilateral IB level. However, elective irradiation of level IB increases dose to the larynx, oral cavity, and mandible, potentially increasing acute and long-term toxicity. This study reports regional control rates and long-term toxicity for employing a policy of withholding radiation to the level IB lymph nodes unless clinically indicated. Materials/Methods: Between 2003 and 2010, 95 patients with stage I IVB oropharyngeal cancer were treated with definitive IMRT with simultaneous-integrated boost technique. The median age was 59. The T and N stage distributions were: 28% T1, 40% T2, 22% T3, 10% T4, 9% N0, 15% N1, 16% N2a, 35% N2b, 11% N2c, and 14% N3. The primary sites were tonsil (52%), base of tongue (45%), and others (3%). Of 55 patients with HPV data, 89% were positive. Median dose to the gross tumor volume was 70 Gy. Ninety-four percent of patients had concurrent chemotherapy, and 12% had pre-radiation (RT) neck dissection. Indications for ipsilateral IB nodal coverage were: (1) a grossly enlarged level IB node, (2) primary or nodal tumor invasion of the ipsilateral level IB or submandibular gland (SMG), and (3) tumor involvement of the oral cavity or other structures that drain primarily to the ipsilateral level IB. Contralateral IB level was not covered in the absence of the above clinical factors in the contralateral neck. Adverse late effects were determined using the Common Terminology Criteria Adverse Event (CTCAE) v4.03. Results: Of 82 patients that did not have a pre-RT neck dissection, 28% (23/82) had ipsilateral level IB coverage and 1 had bilateral IB coverage. Of 23 patients with ipsilateral IB coverage, 13 were for SMG involvement, 5 for IB node involvement, 2 for oral cavity involvement, 2 for oral cavity +/SMG +/IB node involvement, and 1 for unknown reasons due to incomplete data. Of 11 patients that had a pre-RT neck dissection, none had the contralateral IB level covered. With a median follow-up of 2.7 years, only one patient failed in the neck (in the tracheostomy stoma site) at 11.3 months. At 2 years, regional control, local control, disease-free survival and overall survival were 99%, 99%, 89%, and 94%, respectively. No patients developed grade 3 xerostomia or grade 4 osteonecrosis. At 2 years, rates of grade 1-2 xerostomia, gastrostomy tube dependency, and grade 3 osteoradionecrosis were 15%, 4%, and 1%, respectively. Conclusions: Our data supports that in the absence of level IB and oral cavity involvement, the ipsilateral and the contralateral level IB nodal levels do not need to be covered in IMRT plans for oropharyngeal carcinoma. Author Disclosure: J.W. Jang: None. R.J. Parambi: None. L.S. Liliana: None. N.J. Liebsch: None. A.W. Chan: None.