PRIMARY OBJECTIVE:
I. To measure the proportion of participants alive without progression of disease two years following induction therapy (IT) response-guided IMRT.
SECONDARY OBJECTIVES:
I. To assess the 1-year rate of progression-free survival (PFS) after IT response-guided IMRT.
II. To assess the 1- and 2-year cumulative incidence of locoregional recurrence (LRR) after IT response-guided IMRT.
III. To assess the 1- and 2-year cumulative incidence of distant metastasis (DM) after IT response-guided IMRT.
IV. To assess the 1- and 2-year rates of overall survival (OS) after IT response-guided IMRT.
V. To compare the rates of severe acute toxicities between standard and de-escalated IMRT.
VI. To compare the rates of severe late toxicities between standard and response-guided IMRT over a period of 2 years.
EXPLORATORY OBJECTIVES:
I. To compare the frequency of radiation treatment breaks between standard and de-escalated IMRT.
II. To compare the frequency of hospitalizations between standard and de-escalated IMRT.
III. To compare pre-treatment and short- and long-term post-treatment quality of life (QoL) after standard versus de-escalated IMRT.
IV. To compare pre-treatment and short- and long-term post-treatment levels of fatigue after standard versus de-escalated IMRT.
V. To compare radiation dosimetric parameters between standard and de-escalated IMRT.
VI. To explore differences in efficacy endpoints by sex, age, English language status, and race/ethnicity.
VII. To explore heterogeneity of treatment effects (HTEs) of efficacy endpoints by variables, such as sex, age, English language status, and race/ethnicity.
VIII. To explore the association between EBV deoxyribonucleic acid (DNA) levels and disease response on imaging upon completion of IT.
IX. To explore longitudinal EBV DNA levels after completion of IT response-guided IMRT.
X. To compare the rates of severe very late toxicities (from years 2 to 10 after completion of IMRT) between standard and response-guided IMRT.
XI. To explore the association between adjuvant (post-chemoradiation) systemic therapy use and oncologic outcomes (PFS, locoregional recurrence, distant metastasis, and overall survival), quality of life, and fatigue.
XII. To assess frequency of intra-treatment tumor hypoxia in participants undergoing standard and de-escalated radiotherapy.
XII. To explore the association between the presence of intra-treatment tumor hypoxia and baseline demographic and clinical characteristics.
XIV. To explore the association between the presence of intra-treatment tumor hypoxia and oncologic outcomes, toxicity, quality of life, and fatigue.
XV. To evaluate the relationship between intra-treatment tumor hypoxia and pre-treatment EBV DNA levels.
XVI. To evaluate the relationship between intra-treatment tumor hypoxia and end-of-treatment EBV DNA levels.
OUTLINE: Patients with partial radiographic response to IT in the primary tumor and lymph nodes are assigned to Arm I. Patients with stable or progressive disease are assigned to Arm II.
ARM I (DE-ESCALATED INTENSITY): Patients undergo de-escalated IMRT once daily (QD) 5 days a week for up to 7 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT)/magnetic resonance imaging (MRI), positron emission tomography (PET), PET/CT, CT, and/or bone scans throughout the trial
ARM II (STANDARD): Patients undergo standard IMRT QD on 5 days a week for up to 7 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT/MRI, PET, PET/CT, CT, and/or bone scans throughout the trial.
After completion of study treatment, patients are followed up at 3 months then every 6 months for up to 10 years.
