Abstract
Enhanced acute mucositis is the limiting factor for accelerated, hyperfractionated radiotherapy in head and neck (H&N) Squamous cell carcinomas (SCCs). We have developed a simple, new form of conformal radiotherapy, accelerated multiple arc radiotherapy (AcMAR), which covers the target volume by combined, segmental, and rotational arc fields. Two to three rotational fields were placed with CT guidance, each covering the primary tumor and lymph nodes separately. The optimal inter-isocenter distance was determined by 3D dose calculation. The surface area of oro-pharyngeal mucosa irradiated by more than a 50% dose by this method was reduced by 37-73% compared to that with a conventional parallel opposing technic. Dose searching, randomized two-dose study was initiated in Kitami Red-cross General Hospital (KRCGH) in January 1995, and 101 patients were registered and completed AcMAR in Oct 2000. All the patients were followed for up to 96 months (24-96 mo, Median 48 mo) at the time of analysis. Fifty-one out of 101 patients were Stage III (17) and IV (34). Primary site of tumors were; 38 larynx, 25 oropharynx, 15 hypopharynx, 13 oral cavity, and 10 other miscellaneous sites. Patients were randomly allocated either to Group (A) 60 Gy/24 fr/ bid/3 wks to gross tumor volume (GTV), or Group (B) 66 Gy/33 fr/bid/4 wks to GTV. Forty Gy/16 frlbid/2 wks was given to the volume of “prophylactic” irradiation in both groups of patients. Results were as follows: 1) All the patients, except for one, completed AcMAR without treatment interruption. Acute mucositis at the site of high-dose irradiation was intense; 72% of Group (A) and 62.5% of Group (B) experienced WHO Grade 3 (confluent) mucositis focally. Fifty-one out of 53 in Group (A) and 48/48 in Group (B), however, could maintain oral food intake (WHO Grade 1 or 2) even at the peak of their mucositis, because of the limited area of severe mucositis. 2) With regard to late morbidity, however, 6/46 (followed >24 mo) in Group (A) suffered from mucosal ulceration, two of which resulted in patients' death. No late ulceration nor laryngeal edema was observed in Group (B) patients.(3) Tumor control was impressive and promising; Nine out of 88 (followed >24 mo)“in-field” recurrence, only 3 “outside” failure (two of them were successfully “salvaged” by second RT), and 8 distant failures. Three-year loco-regional control rate was 86.4%, and three-year causespecific, disease-free survival was 77.3%. Our results strongly suggest that an improved tumor control could be obtained when the accelerated fractionation is combined with conformal radiotherapy. The dose limiting acute symptoms was volume-dependent (hence improved by AcMAR), but the late ulceration was not. The size of single fraction should, therefore, be kept with in a certain range.
