Early-stage squamous cell carcinoma of the oropharynx: Radiotherapy vs. Trans-Oral Robotic Surgery (ORATOR) – study protocol for a randomized phase II trial

Abstract

BackgroundThe incidence of oropharyngeal squamous cell carcinoma (OPSCC) has markedly increased over the last three decades due to newly found associations with human papillomavirus (HPV) infection. Primary radiotherapy (RT) is the treatment of choice for OPSCC at most centers, and over the last decade, the addition of concurrent chemotherapy has led to a significant improvement in survival, but at the cost of increased acute and late toxicity. Transoral robotic surgery (TORS) has emerged as a promising alternative treatment, with preliminary case series demonstrating encouraging oncologic, functional, and quality of life (QOL) outcomes. However, comparisons of TORS and RT in a non-randomized fashion are susceptible to bias. The goal of this randomized phase II study is to compare QOL, functional outcomes, toxicity profiles, and survival following primary RT (± chemotherapy) vs. TORS (± adjuvant [chemo] RT) in patients with OPSCC.Methods/DesignThe target patient population comprises OPSCC patients who would be unlikely to require chemotherapy post-resection: Tumor stage T1-T2 with likely negative margins at surgery; Nodal stage N0-2, ≤3 cm in size, with no evidence of extranodal extension on imaging. Participants will be randomized in a 1:1 ratio between Arm 1 (RT ± chemotherapy) and Arm 2 (TORS ± adjuvant [chemo] RT). In Arm 1, patients with N0 disease will receive RT alone, whereas N1-2 patients will receive concurrent chemoradiation. In Arm 2, patients will undergo TORS along with selective neck dissections, which may be staged. Pathologic high-risk features will be used to determine the requirement for adjuvant radiotherapy +/- chemotherapy. The primary endpoint is QOL score using the M.D. Anderson Dysphagia Inventory (MDADI), with secondary endpoints including survival, toxicity, other QOL outcomes, and swallowing function. A sample of 68 patients is required.DiscussionThis study, if successful, will provide a much-needed randomized comparison of the conventional strategy of primary RT vs. the novel strategy of primary TORS. The trial is designed to provide a definitive QOL comparison between the two arms, and to inform the design of an eventual phase III trial for survival outcomes.Trial registrationNCT01590355

The Epidemic of Human Papillomavirus and Oropharyngeal Cancer in a Canadian Population

“…In the United States and Europe, there is compelling evidence that opc is on the rise, and that the increase is primarily a result of increasing rates of In Canada, population-based studies have provided indirect evidence of the phenomenon by demonstrating that the incidence of head-and-neck cancers at hpv-related anatomic sites (oropharynx) are rising and that those of smoking-related sites (for example, oral cavity) are declining 2,11,12 . However, no previous study has performed hpv testing of tumour samples, and thus we have attempted to provide the first direct evidence of this dramatic shift in disease prevalence and demographics.…”

Oropharyngeal Cancer

“…A trans-oral approach or endoscopic mucosal resection is considered an adequate option for localized small primary lesions without nodal spread because suffi cient outcomes for effi cacy and function can be achieved [ 36 ]. Postoperative RT should be added if a positive surgical margin is revealed in the pathological specimen; however, this has been associated with a higher risk of adverse events than single modality treatment [ 37 -39 ].…”

Definitive radiotherapy for head and neck squamous cell carcinoma: update and perspectives on the basis of EBM

“…They also emphasized that clinical and instrumental assessments were essential, and also proposed the endpoint of disease free with a functional larynx, such as laryngo-esophageal dysfunction-free survival. Minimum invasive surgery has recently evolved, and objective and functional estimations are needed for comparisons between different treatment modalities including surgical series (60,65).…”