Lancet: IMRT reduces most common radiotherapy side effect

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The use of (IMRT) to treat head and neck cancer resulted in lower incidence of dry mouth, or xerostomia, thereby improving associated quality of life measures, a study published Jan. 13 in The Lancet concluded.

IMRT is known to reduce irradiation to the parotid glands. With xerostomia as the most common side-effect of radiotherapy, the authors sought to determine whether parotid-sparing IMRT would reduce the occurrence of xerostomia, which can affect speech and swallowing while also accelerating dental carries, the authors noted.

Conventional radiotherapy served as the control, with 34 patients randomly treated with this standard treatment and 39 with IMRT. All patients had been diagnosed with squamous-cell carcinoma of the head and neck (HNSCC) arising from the oropharynx or hypopharynx, with all patients likewise at high-risk of radiation-induced xerostomia given expected radiation doses of greater than 24 Gy to both parotid glands. Primary tumors in both groups were treated with 65 Gy in 30 fractions or 60 Gy in 30 fractions for postoperative patients.

"At each timepoint from three to 24 months, a smaller proportion of IMRT patients reported grade 2 or worse LENT SOMA [Late Effects of Normal Tissues Subjective-Objective Management Analytic] subjective xerostomia compared with conventional radiotherapy," Christopher M. Nutting, MD, of the head and neck unit, Royal Marsden Hospitals NHS Foundation Trust in London, and colleagues observed.

At three-month follow-up, 87 percent of conventional radiotherapy patients reported grade 2 or worse xerostomia, compared with 76 percent in the IMRT group. At the median 12-month follow-up, the IMRT group presented with significantly fewer cases of xerostomia, at 34 percent, compared with 74 percent of the control group. Finally, after two years follow-up, 29 percent of IMRT patients and 83 percent of conventional radiotherapy patients were diagnosed with grade 2 or higher xerostomia.

"The proportion of patients that reported grade 2 or worse xerostomia at 12 months did not differ by tumor site, radiotherapy indication (primary versus postoperative), stage of disease, or use of neoadjuvant chemotherapy," the authors reported.

After 12 months, unstimulated saliva flow from the contralateral parotid gland was recorded in 16 of 34 IMRT patients, compared with none of the 25 conventional radiotherapy patients available for follow-up. At 24 months, seven of 16 IMRT patients and none of the 15 conventional radiotherapy patients evaluated had unstimulated saliva flow. The 12-month measure was statistically significant.

"The only recorded acute adverse event of grade 2 or worse to differ between treatment groups (at the 1 percent significance level) was fatigue," with 41 percent of conventional radiotherapy patients and 74 percent of IMRT patients reporting the symptom, according to Nutting and colleagues. The authors attributed this difference to the IMRT group ostensibly receiving higher radiation doses to surrounding tissues, an argument bolstered by a dosimetry review in a patient subset revealing this discrepancy.

"Our trial showed a significant reduction of radiation-induced xerostomia for patients treated with IMRT compared with conventional radiotherapy," the authors argued. "Furthermore, we showed recovery of saliva flow by quantitative measurements, and improvements on QoL [quality of life] measures associated with xerostomia. To our knowledge our trial is the first to show that parotid-sparing IMRT reduces xerostomia in HNSCC."

The authors recognized that a substantially larger patient sample was required to detect significant differences in locoregional progression-free survival or overall survival between the two therapies.

Nutting and colleagues concluded that "[s]paring the parotid glands with IMRT significantly reduces the incidence of xerostomia and leads to recovery of saliva secretion and improvements in associated quality of life, and thus strongly supports a role for IMRT in squamous-cell carcinoma of the head and neck."