A new NIH-funded phase II study suggests that certain patients with human papilloma virus (HPV)-positive oropharyngeal cancer can safely receive lower- dose radiation therapy, using a new approach that customises radiation dose based on response to induction chemotherapy and other prognostic factors.

Lowering the dose of radiation therapy did not compromise outcomes – 95 percent of patients were alive two years after starting treatment.

“Treatment for head and neck cancer can be quite gruelling, so it’s very encouraging to see we can safely dial back treatment in patients with less aggressive disease and an overall good prognosis, particularly for young patients who have many years to deal with long-term side effects,” said lead study author Anthony Cmelak, MD, a professor of radiation oncology at the Vanderbilt-Ingram Cancer Center in Nashville, TN.

“However, we need longer follow-up, as well as confirmatory phase III data, before we can recommend applying this strategy in practice.”

It is estimated that approximately 70 percent of newly-diagnosed oropharyngeal cancers are related to HPV, and the incidence of HPV-related disease appears to be rising.

Patients with HPV-positive tumours tend to have better outcomes compared to patients with HPV-negative disease.

In this first-of-a-kind study, 90 patients with operable stage III/IVA HPV-positive oropharyngeal squamous carcinoma received induction chemotherapy with paclitaxel, cisplatin, and cetuximab.

Such therapy sensitizers the cancer to further treatment, and has been shown to decrease the risk of cancer spread, predict the tumour’s sensitivity to radiation, and relieve tumour-related side effects.

The 62 patients who had a complete clinical response to induction chemotherapy, meaning they had no signs of cancer on endoscopic exam, received a reduced dose (54 Gy) of intensity-modulated radiation therapy (IMRT), and the rest of the patients received standard dose IMRT (70 Gy).

IMRT uses advanced technology to manipulate beams of radiation to conform to the shape of a tumour.

All patients received standard cetuximab along with radiation.

Among patients who received lower-dose IMRT, the two-year overall and progression-free survival were 93 percent and 80 percent, respectively; survival was slightly higher among patients with less than 10 pack-years of smoking and earlier-stage disease (two-year progression-free and overall survival 96 percent).

As expected, outcomes were worse for the higher-risk patients treated with the standard IMRT dose (two-year overall survival and progression free survival were 87 and 65 percent, respectively).

According to Dr. Cmelak, lower-dose IMRT would not be suitable for patients with HPV-negative disease or larger tumours.

Reducing IMRT dose offers patients a better quality of life by decreasing the risk of debilitating, often long-term, side effects ─ trouble swallowing, dry mouth, loss of taste, neck stiffness, and thyroid problems.

Patients will be followed on this study for five years to capture late recurrences.

Researchers are also planning another randomised phase II study that will explore an even less intensive approach involving so-called reduced-field IMRT to treat only areas of initial gross tumour in patients with low-risk HPV tumours.

It is hoped that this approach would yield similar survival benefits with further reductions in the risk for long-term side effects.

Source: ASCO