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Cytoprotection Studied for Comprehensive Salivary Gland Sparing During IMRT for HNC

Cytoprotection Studied for Comprehensive Salivary Gland Sparing During IMRT for HNC

HOUSTON-In head and neck cancer, intensity-modulated radiotherapy (IMRT) may reduce some, but does not eliminate treatment toxicity, according to studies comparing IMRT vs standard radiotherapy in this patient population. Investigators have found reduced rates of xerostomia but little difference in acute grade 3 mucositis, reported David I. Rosenthal, MD, associate professor of radiation oncology at The University of Texas M. D. Anderson Cancer Center. Dr. Rosenthal is therefore undertaking a phase II study to determine whether cytoprotection with amifostine can reduce those side effects. "IMRT leaves 70% of patients with at least some symptoms of dry mouth ," he said. He added that IMRT can reduce xerostomia for many patients but is still associated with mucositis. Late grade 2 to 3 xerostomia was reported as 84% with conventional RT vs 30% with IMRT, but grade 3 or 4 mucositis was more common with IMRT vs conventional RT (42% vs 25%), and more IMRT patients required G-tubes (25% vs 18%); these differences are not statistically significant.[1] Dr. Rosenthal said that some of these effects might be explained by the fact that while IMRT provides relative sparing of the parotid gland, it does not reliably spare the submandibular gland. 25 Gy Threshold
"There appears to be a steep section of the dose-response curve for xerostomia at about 25 Gy, that some have referred to as a threshold. Patients who get more dose have little recovery of salivary gland function at 12 months," he noted. "If the planned mean dose to the parotid gland is more than 24 to 26 Gy, then IMRT may have little if any benefit compared with conventional radiotherapy, and there is considerable increased cost."[2] He explained that two-thirds of stimulated salivary flow is from the parotid gland, and said the majority of unstimulated salivary flow comes from the submandibular gland. "The majority of xerostomia symptoms are related to lack of basal unstimulated salivary gland flow that is primarily from the submandibular gland, and not related to the parotids," he said. In the normal setting, stimulated flow occurs for less than 1 hour per day, during eating. Some studies suggest that the submandibular gland may contribute as much as 90% of total salivary output when patients are not eating. Phase II Study
Dr. Rosenthal's phase II study in head and neck cancer patients will assess whether amifostine (500 mg SC daily prior to radiation) can reduce IMRT-associated xerostomia and mucositis and preserve function of the submandibular and sublingual salivary glands. The treatment regimen includes definitive treatment with 66 Gy of radiation in 30 fractions or postoperative treatment with 60 Gy in 30 fractions. The primary endpoint is the preservation of submandibular and sublingual salivary flow, plus subjective xerostomia scores. Secondary endpoints include the parotid dose-volume histogram, mucositis in lower-dose RT areas, scalp hair-loss patterns, and dysphagia as measured by the Performance Status Score. "Our hypothesis is that combined physical radiotherapy dose-sparing by IMRT and amifostine cytoprotection will improve global salivary sparing and decrease xerostomia," Dr. Rosenthal said.

References

1. Chao KS, Majhail N, Huang C, et al: Intensity-modulated radiation therapy reduces late salivary toxicity without compromising tumor control in patients with orapharyngeal carcinoma: A comparison with conventional techniques. Radiother Oncol 61:275- 280, 2001.
2. Eisbruch A, Ten Kaen RK, Kim HM, et al: Dose, volume and function relationships in parotid salivary glands following conformal and intensitymodulated irradiation of head and neck cancer. Int J Radiation Oncol Bio Phys 45:577-587, 1999.
 
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