Landmark Trials in Selected Head and Neck Cancers

Abstract

This chapter contains a summary of some key findings from a selection of 18 trials related to oral cavity, nasopharynx, oropharynx, larynx, and hypopharynx cancer.

The RTOG 90-03 trial compared four radiation therapy fractionation schemes for locoregionally advanced patients undergoing radiation therapy alone and is discussed. The VA Larynx study, RTOG 91-11, a study by Bonner et al. that compared radiation therapy plus or minus cetuximab, and RTOG 0522 are included as landmark trials in the development of an organ preservation approach for the management of locoregionally advanced disease. The TAX 324 trial compared two different induction chemotherapy regimens in patients undergoing chemoradiotherapy, and the PARADIGM and DECIDE trials studied the role of induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone. A meta-analysis by Pignon et al. is included that studied the role of chemotherapy in patients undergoing definitive locoregional treatment.

Three trials dealing with nasopharynx cancer are discussed including the Intergroup 0099 trial and the MAC-NPC Collaborative Group meta-analysis which studied the role of chemotherapy. A study by Lin et al. evaluated the role of measuring plasma EBV DNA and is included.

A trial done by Tata Memorial Centre is included that randomized patients with mostly oral tongue carcinoma to elective neck dissection at the time of primary cancer surgery or watchful waiting with therapeutic neck dissection for nodal relapse.

The EORTC 22931 and RTOG 9501 trials were published in 2004 and demonstrated that the addition of concurrent cisplatin chemotherapy to radiation therapy in the postoperative setting improved outcomes for selected (based on pathologic features) patients with squamous cell carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx. A pooled analysis of data from these two postoperative trials is included, which was designed to analyze the selection criteria, clinical and pathologic risk factors, and outcomes and to establish precisely which patients benefit from the addition of cisplatin to postoperative radiation therapy.

A study by Yamazaki et al. is discussed which was the first prospective randomized trial to study hypofractionation versus standard fractionation in early-stage larynx cancer.

Three trials are discussed that studied various forms of treatment de-intensification in patients with HPV-positive oropharyngeal carcinoma, including a phase 2 study by ECOG, RTOG 1016, and the De-ESCALaTE trial.

There are hundreds of trials to choose from, and therefore, no claim toward completeness can be made in the current format. These trials relate to the multidisciplinary management of head and neck cancer from the perspective of a radiation oncologist. Readers are encouraged to refer to the full manuscript of these trials for a greater understanding. This material is provided for educational purposes only and with the goal of encouraging further study about the landmark trials that have impacted oncology.