Date of Award

January 2019

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Henry S. Park

Second Advisor

Zain A. Husain

Abstract

Hypothesis/Specific Aims:

There is a paucity of pathologic neck dissection data in oropharyngeal carcinoma (OPC), particularly in the modern era, due to the rise in definitive chemoradiation. Additionally, most of these studies do not address human papillomavirus (HPV) status, which has a tendency for further nodal spread; therefore, the natural course of nodal spread in HPV-associated OPC is unclear. We sought to evaluate nodal disease in the context of de-intensification radiation therapy regimens to determine if it is safe and appropriate for clinical trials to take place.

Methods:

Using a retrospective database, we reviewed the records of patients with OPSCC who underwent neck dissection from 2010 to 2016. Patients were included if they had OPSCC with surgery as primary treatment, no previous diagnosis of head and neck cancer, a neck dissection, and no previous curative oncologic treatment.

Results:

In the first part of our study, we determined that there is a 5.3% rate of level IB involvement in HPV+ OPSCC and a 0% rate of occult level IB involvement in cT1-2N0-2b OPSCC per the American Joint Committee on Cancer 7th Edition (AJCC 7). In the second part of our study, 43% of patients had an increase in pathologic node number relative to that predicted on imaging; in 21 patients (21%), occult nodal disease was found on neck dissection in an additional nodal station beyond what was predicted on pre-operative imaging. Based on these imaging and pathologic nodal patterns, if an approach using coverage of involved nodes as well as the next uninvolved nodal echelon were used, all pathologic sites of disease would be covered in 97% of the patients in this study. In the third part of our study, we determined that distant metastasis was the predominant mechanism of failure in HPV+ OPSCC with ≥5 involved lymph nodes; conversely, patients with <5 involved lymph nodes had low rates of locoregional recurrence, distant metastasis, and death.

Conclusions:

Our work has 1) led to changes in the way radiation therapy is delivered to level IB at Yale-New Haven Hospital, 2) has laid the groundwork for HPV+ OPSCC submandibular sparing clinical trials, 3) demonstrated biologic feasibility of a volume de-escalation trial in HPV+ OPSCC, and 4) identified a subset of patients with < 5 involved lymph nodes that have the lowest risk of recurrence (locoregional or distant) that are ideal for de-intensification treatment and trials.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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