A Phase II Randomized Sham-Controlled Trial With Allocation Concealment and Blinded Patients and Assessors, Investigating Hyperbaric Oxygen as a Radiation Sensitizer for Locally Advanced Squamous Cell Carcinoma of the Oropharynx and Larynx

The goal of this research is to address the question:

"Does the addition of hyperbaric oxygen to radiation and chemotherapy improve outcomes in locally advanced oropharyngeal or laryngeal squamous cell carcinoma?"

There is reason to believe that hyperbaric oxygen administered immediately prior to radiotherapy will prove beneficial for this cancer type and stage. The basis for this hypothesis is a review of several decades of published work, the conclusion of a recent (2018) Cochrane Review, and results of a Phase I trial. A summary of this body of work follows.

During the 1950's, several reports laid the groundwork for hyperbaric oxygen's potential as an effective radiation sensitizer. Gray and colleagues observed that curability of small animal tumors with radiotherapy was limited by the radio-resistance of the portion of cells that retain their reproductive integrity.(1) Tumor cell sensitivity to irradiation was seen to increase when tumor-bearing mice breathed oxygen under hyperbaric conditions. Gray's group further observed that radiobiological damage demonstrates dependence on the concentration of oxygen in the immediate vicinity of tumor cells at the time of radiation.( 2) It became evident that many solid tumor cell populations exist within a wide range of oxygen tensions.(3) These findings were sufficiently encouraging to warrant a small clinical study to determine if this anticipated radio-sensitization effect could be demonstrated histologically.(4) A small diver recompression chamber was acquired from the Royal Navy and modified to accommodate a recessed acrylic window.(5)

The trial involved eight patients whose breast or lung tumor sites would lie directly below the window, above which a radiation delivery source was mounted. To assess any difference afforded by hyperbaric oxygen, tumors had to be large enough so they could addressed in two aspects. Irradiation of the inferior aspect occurred conventionally, with the superior aspect shielded. Shielding was then reversed and the superior aspect irradiated while patients breathed oxygen to 3.0 atmospheres absolute.(4) Preliminary findings of increased tumor destruction secondary to hyperbaric oxygen exposure promoted investigators to treat another 35 patients in this manner. Despite their uniformly poor prognosis, the hyperbaric effect was again significant and outcomes were deemed "much better than anticipated".(6)