First Adaptive Radiotherapy Trial Initiated for Head and Neck Cancer Patients

The trial, sponsored by the US National Cancer Institute (Bethesda, MD, USA), provides indications that ART may benefit patients with less technical problems than previously believed.

The findings of this trial were released online February 2012 in advance of publication in the International Journal of Radiation Oncology Biology Physics. Physicians commonly use radiotherapy to treat squamous cell carcinoma of the oropharynx. Current standard-of-care treatment is called intensity-modulated radiotherapy (IMRT). IMRT allows clinicians to “sculpt” radiation to fit the anatomy of individual patients. Although attractive, this technique has a major problem--it is based entirely on a computed (CT) or magnetic resonance imaging (MRI) scan taken before actual treatment begins. Because a typical course of radiation treatment for oropharynx cancer lasts six to seven weeks, standard IMRT cannot compensate for typical changes that take place in a patient’s body during this time, such as weight loss, shrinkage of tumor, or gradual movement of normal tissues. Recent work suggests that the inability of standard IMRT to keep up with these changes might lead to unanticipated toxicity, or potentially worse, missing of tumor.

For this new trial, which was conducted at the University of Texas M.D. Anderson Cancer Center (Houston, TX, USA), investigators began patients on standard IMRT. They then took CT scans while patients were lying in the radiation treatment room each day so they could track changes in tumor and normal tissues during the entire course of treatment. Through computerized techniques, the investigators adapted treatment if they noticed significant tumor or body changes that could affect quality of treatment. Most interestingly, the researchers found that most patients required only one or at most two adaptions of IMRT to maintain treatment quality.

“This is the first prospective clinical trial of its kind to gauge how ‘refitting’ of IMRT to a patient’s body actually impacts care for a patient who has head and neck cancer,” noted David Schwartz, MD, vice-chair of radiation medicine at the North Shore- Long Island Jewish (LIJ) Health System, associate professor at the Hofstra-North Shore Long Island Jewish LIJ School of Medicine (Hempstead, NY, USA), and a senior investigator at The Feinstein Institute for Medical Research (Manhasset, NY, USA).
“What most encouraged us was that ART appears effective with only one or two additional replans. This means that ART does not have to be overly burdensome or expensive to make a difference. This is something that is feasible, and could eventually make a real-world difference in many clinics. ART keeps radiation treatment tightly fitted to a patient’s body, almost as if it were being shrink-wrapped. It is as individualized as our current treatment can realistically be.”

Twenty-four patients enrolled onto this institutional review board approved trial; data for 22 of these patients were analyzed with at least 12 months follow-up. Treatment was initiated with a baseline IMRT plan, and computed tomography (CT) imaging was performed in the treatment room each day to map tumors and normal anatomy to assess need for ART replanning.

Primary site was base of tongue in 15 patients, tonsil in six patients, and glossopharyngeal sulcus in one patient. Twenty patients (9%) had American Joint Committee on Cancer (AJCC) stage IV disease. T stage distribution was two T1, 12 T2, three T3, and five T4. N stage distribution was one N0, two N1, five N2a, 12 N2b, and two N2c. Of the patients, 21 (95%) received systemic therapy.

All patients required at least one ART replan because of tumor and normal tissue changes; eight patients (36%) required a second ART replan. For the patients who required one adaptive replan, parotid salivary glands had shrunk by an average of 16% and tumors had shrunk by 5% by the time of the replan. For the patients who required a second adaptive replan, parotid glands and tumors had shrunk by 24% and 14%, respectively. Most ART replans were completed within one day.

With a 31-month median follow-up, there has been no primary site failure and one nodal relapse, yielding 100% local and 95% regional disease control at two years. Chronic toxicity and functional outcomes beyond one year remain favorable relative to published results for standard IMRT.

Related Links:
University of Texas M.D. Anderson Cancer Center
Hofstra-North Shore Long Island Jewish School of Medicine
Feinstein Institute for Medical Research