Phase II Randomized-registry Embedded Study of Lymphoscintigraphy for Oropharyngeal Neoplasms to Enable Risk-adapted Nodal Guidance for Robotic Surgery and/or Radiotherapy (LONE-RANGR2)

Primary Objectives

To determine whether:

• Omission of the contralateral neck cancer treatment is safe and toxicity-sparing for participants with well lateralized oropharyngeal HNSCC undergoing definitive or PORT radiation. This will be demonstrated by acceptably low contralateral neck failures (<15%)

Secondary Objectives

To determine:

• the relative difference in symptom burden, as measured by the MDASI_HN area-under-the-toxicity curve (AUC), for initial surgical and initial non-surgical therapy cohorts.
• Whether omission of the contralateral neck in radiotherapy planning as definitive of PORT treatment for well-lateralized oropharyngeal tumors will impact symptom burden as measured by MDASI AUC, Grade 2 or higher CTCAE v5.0 toxicity, swallow function, and/or feeding tube rates and dependency.
• Risk adapted therapy approaches lead to differences in distant-metastasis-free survival (DMFS), ipsilateral neck failure, primary site failure, and whether salvage therapy for contralateral neck failures is feasible and effective compared to historical controls.

Inclusion criteria

• Newly diagnosed histopathologically-proven p16+ and/or HPV+ HNSCC of the base of tongue or faucial tonsil
• cT1-2N0-1 per AJCC 8th edition staging.
• Tumor does not cross midline, and must be >1cm from midline
• For tonsil tumors, the primary may extend onto the palate or into the BOT but still be >1cm from midline
• No evidence of contralateral neck disease on contrast MRI, CT Head/Neck, PET/CT, or lymphoscintigraphy nor retropharyngeal lymphadenopathy.
• Able to undergo lymphoscintigraphy procedure
• No contraindications for SLNM, adjuvant chemotherapy, RT nor adjuvant/definitive radiotherapy.
• ECOG 0-1
• Age >18 years
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion criteria

• Previous HN Cancer except small skin cancers.
• Any retropharyngeal lymphadenopathy on either MRI, CT, or PET/CT
• Contralateral neck nodal disease radiographically detected per routine diagnostic imaging or SPECT-CT.
• Distant metastatic spread at the time of inclusion
• Chemotherapy or surgery (for the present tumor), prior to inclusion.
• Previous radiation treatment in the head and neck region, for any reason, except for cutaneous lesions that would not lead to overlap with definitive bilateral neck irradiation
• Recurrent or second primary tumor in the head and neck region
• Non-tongue base or non-faucial tonsil primaries
• Prior history of regionally advanced or distant spread cancers
• Pregnancy or no active contraception for pre-menopausal women
• Known hypersensitivity to iodine or nanocolloid injection
• Having any condition (physical, mental, sociological) that interferes with the informed consent procedure and follow-up schedules Has a diagnosis of active scleroderma, lupus, or other rheumatologic disease which in the opinion of the treating radiation oncologist precludes safe radiation therapy