Less Toxic Radiotherapy Designed for HPV-Positive Oropharynx Cancer

Early findings of the study were presented by Dr. Shanthi Marur, first author on the study and an oncologist from the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (Baltimore, MD, USA), at the 49th annual meeting of the American Society of Clinical Oncology, held in Chicago (IL, USA), in May 31 to June 4, 2013.

Patients enrolled in the trial received an initial course of chemotherapy followed by treatment with the targeted therapy cetuximab, a monoclonal antibody. In the study, a patient’s response to those initial treatments determined the dose during radiation treatment. “Those patients who had a really good response to chemotherapy might also be more responsive to radiation,” stated Dr. Barbara Burtness, senior author on the study and chief of head and neck medical oncology at Fox Chase Cancer Center (Philadelphia, PA, USA). “Therefore, the use of a full dose of radiation for those patients might represent overtreatment.” Dr. Burtness is also chair of the Eastern Cooperative Oncology Group (ECOG), which sponsors this ongoing trial. ECOG is a US National Cancer Institute-funded team of researchers who organize and perform clinical trials.

According to the US National Cancer Institute, more than 40,000 people will be diagnosed with cancer of the oropharynx in 2013, and nearly 8,000 will die from the disease. Between 60%–80% of cases are associated with infection by HPVs. “Patients with HPV-associated oropharyngeal cancer tend to be younger than other oropharyngeal cancer patients, and would be living with the aftereffects of treatment for more years,” noted Dr. Burtness. A patient who undergoes traditional radiation to the back of the throat—typically 66–70 Gy—may suffer serious side effects such as dry mouth and problems with swallowing.

The investigators suspected a subset of HPV-associated oropharyngeal cancer patients, identified by their response to chemotherapy, may be suitable for trials of lower radiation. Dr. Burtness and her coinvestigators enrolled 90 patients in the trial, 80 of whom were analyzable. Of those patients, 95% were men, and the median age was 57. The researchers reported that most patients tolerated the induction chemotherapy and treatment with cetuximab, and 96% completed all three cycles. Forty-six patients had a complete clinical response, which meant all signs of the primary tumor had disappeared following treatment. These patients went on to receive a lower than standard dose of radiation, at 54 Gy.

The researchers reported that most patients tolerated the treatment with low incidence of high-grade side effects, but other data are premature. The primary endpoint of the study is two-year progression-free survival, the fraction of patients whose diseases have not worsened after two years. The investigators reported that if the two-year progression-free survival rate is at least 85%, further studies on lower-dose radiation are necessary. “We do not expect that anyone would want to lower the dose of radiation based on this study, which is very much a developmental study,” said Dr. Burtness. “We’ve never had a comparative trial of low dose versus standard dose IMRT.”

Dr. Burtness noted among patients who received a lower dose of radiation, “what seemed to predict for a slightly worse outcome was either a heavy smoking history [more than 10 pack years], or those with larger tumors.” She also reported that although it is too early to draw definitive conclusions, the early results “may justify further study of de-intensifying radiation among nonsmokers with HPV-associated oropharyngeal cancers.”


Related Links:

Fox Chase Cancer Center
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center