Is It Time to De-Escalate Radiation Therapy in Patients with HPV+ HNC?

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How Radiotherapy Works

Radiotherapy works by damaging the DNA in cells. It can potentially kill all cells, but there is increased killing in malignant cells due to the fact that their DNA repair mechanisms often don’t function normally. When cancer cells with a significant DNA injury start to divide, they fall apart and die. “Because cancer cells divide more rapidly than normal cells and aren’t able to repair DNA damage as well, they are more likely to die than normal cells close to the cancer,” said Dr. Ramey.

For head and neck cancers, photons are generated within a machine called a linear accelerator and modulated as they leave the machine with a technique called intensity modulated radiation therapy (IMRT). “As the photon interacts with the patient, its DNA damage is either ignited directly by interacting with the dividing cells or via indirect actions with water within the body,” said David Clump, MD, PhD, assistant professor in the department of radiation oncology, UPMC Hillman Cancer Center, Pittsburgh, Pa. “As the photon interacts with water within the body, the water molecule is split to create a free radical that subsequently damages the DNA of dividing cells.”

The process is optimized by using technology to deliver a quality-assured, reproducible dosing of radiation that aims to minimize toxicity to normal tissues while targeting a tumor and its expected drainage pattern. “Treatments are then delivered over a series of weeks using a specific dose of radiation per treatment as well as a specific number of treatments called fractions,” Dr. Clump said.

Radiotherapy works best on cells in the active replication phase, outside of the G0 (resting) stage of the cell cycle. “As a result, actively replicating cancer cells are the best targets of radiotherapy and tend to respond more quickly,” said Dr. Page. “Normal tissue will exhibit some signs of radiotherapy response sooner or later in a course of therapy, depending on its radiation sensitivity.”

In addition to damaging dividing cells, radiotherapy also works by stimulating an immune response against the tumor. “The interaction of radiation with the immune system is complicated, and radiation can both suppress and enhance anti-tumor immunity depending on how it is delivered and what other treatments the patient receives,” said Dr. Sikora—KA