Source: www.medscape.com
Author: Nick Mulcahy

In patients with oropharyngeal cancer, modifying radiotherapy to spare swallowing structures appears to be an effective strategy to reduce the long-term dysphagia that accompanies chemoradiotherapy, according to a small longitudinal study.

Importantly, the strategy did not come at the expense of locoregional control, report investigators in a study published online April 26 in the Journal of Clinical Oncology.

Dysphagia has emerged as perhaps the most important late adverse effect in this setting, supplanting xerostomia, said the study’s senior author, Avraham Eisbruch, MD, professor of radiation oncology at the University of Michigan Medical School and Comprehensive Cancer Center in Ann Arbor.

“Aggressive chemoradiotherapy approaches produce more dysphagia than in the past,” he told Medscape Oncology.

Meanwhile, the late adverse effect of xerostomia is on the wane, because the use of intensity-modulated radiotherapy (IMRT) has allowed radiation oncologists to spare most patients’ salivary glands from radiation, he said.

To address the problem of dysphagia, Dr. Eisbruch and colleagues at the University of Michigan used IMRT in combination with chemotherapy.

Their treatment planning for 73 patients with stages III to IV oropharyngeal cancer included sparing any swallowing structure that did not have tumor involvement. The structures included pharyngeal constrictors, glottic and supraglottic larynx, and esophagus.

One year after concurrent chemotherapy and IMRT, all 73 of the patients had either absent or minimal observer-rated dysphagia (scores, 0 to 1), with the exception of 4 people: 1 who was feeding-tube dependent and 3 who required a soft diet.

The results compare favorably with various other study outcomes, said Dr. Eisbruch.

“The rate of long-term feeding-tube dependency is up to 20% in studies of aggressive regimens of chemoradiotherapy,” he said.

However, there is an important qualification with this new approach, said Dr. Eisbruch: “It requires a high degree of certainty in defining targets.”

Dr. Eisbruch said the guiding principle is that “tumor targeting should be in preference to sparing structures.” However, he also believes that sparing swallowing structures should become a standard of care in the treatment of head and neck cancers with IMRT, just as sparing salivary glands has become a standard among clinicians who use IMRT.

Agreed, said K. William Harter, MD, who was approached by Medscape Oncology for outside comment.

Dr. Harter is professor and vice chair of radiation oncology at the Georgetown University Medical Center and Lombardi Comprehensive Cancer Center in Washington, DC.

“We have used this approach for a number of years,” he said, referring to the sparing of both swallowing structures and salivary glands with IMRT.

However, “not everyone has IMRT,” Dr. Harter pointed out.

Another Way to Minimize Dysphagia
Dr. Harter had some practical advice for all clinicians — IMRT users or not — who want to reduce dysphagia in this setting.

“Elective feeding tubes should be avoided unless nutritionally essential,” he said.

Feeding tubes themselves are contributors to long-term dysphagia, he explained. “The presence of a feeding tube tends to reduce use of the swallowing mechanism.”

Dr. Harter’s sole criticism of the dysphagia study was that it “does not address the role of feeding tubes in long-term dysphagia or at least in slow recovery.”

“I don’t know how feeding tubes contributed to dysphagia in this study because I don’t know how many patients had them, or for how long,” he said.

Nevertheless, the study is valuable in a number of ways, including it’s underscoring of the “influence of treatment on swallowing,” said Dr. Harter.

The study also underscores the fact that “precision treatment planning in IMRT should be the cornerstone of head and neck cancer planning programs.”

Local and Regional Control: “High”
The 73 patients with stages III to IV oropharyngeal cancer had a median follow-up of 36 months. The 3-year disease-free and locoregional recurrence-free survivals were 88% and 96%, respectively. The latter rate was described as “high” by the investigators.

In this prospective longitudinal study of chemotherapy plus IMRT, patients were required to have had no previous therapy and a Karnofsky performance status of 60 or higher.

The study included current smokers (22%), past smokers (42%), and never smokers (36%).

Smoking status did not affect the occurrence of dysphagia, said Dr. Eisbruch. “I believe our results are relevant to all oropharyngeal cancer patients, including heavy smokers with a poor prognosis. However, there is a need to validate the data,” he said.

Patients with tumors involving the posterior pharyngeal wall (medial to the carotid arteries) or with radiologic evidence of involvement of the retropharyngeal nodes were excluded because the pharyngeal constrictors, which are part of the swallowing mechanism, would be encompassed completely within the targets, which would prevent partial sparing, note the investigators.

With regard to the IMRT, 70 Gy and 59 to 63 Gy were delivered to the gross and subclinical planning target volumes, respectively, in 35 daily fractions, they note.

With regard to the concurrent chemotherapy, carboplatin and paclitaxel 30 mg/m2 were administered once weekly. Feeding tubes were inserted if weight loss during therapy approached 10%.

At each follow-up visit, observer-rated dysphagia was scored on a scale of 0 to 4, on the basis of the National Cancer Institute Common Terminology Criteria for Adverse Events.

The focus on dysphagia and, therefore, the adverse effect of radiation treatment is part of an evolution of care, suggested Dr. Eisbruch.

“Aggressive treatment of head and neck cancer has greatly improved local and regional control rates. As a result, quality of life has come to the forefront of clinical concerns as more patients survive,” he said.

“We can use technology to help — first with xerostomia and now with dysphagia — without reducing local and regional control,” he said.

Notes:
1. Source: Clin Oncol. Published online April 26, 2010.
2. The study was supported by grants from the National Institutes of Health and the Newman Family Foundation. Dr. Eisbruch and Dr. Harter have disclosed no relevant financial relationships.