Accelerated radiation therapy for locally advanced squamous cell carcinomas of the oral cavity and oropharynx selected according to tumor cell kinetics--a phase II multicenter study.
OBJECTIVE
A Phase II multicenter trial testing an accelerated regimen of radiotherapy in locally advanced and inoperable cancers of the head and neck, in patients selected on the basis of 5-bromo-2-deoxyuridine/DNA flow cytometry-derived tumor potential doubling time (Tpot).


METHODS
From September 1992 to September 1993, 23 patients consecutively diagnosed to have locally advanced, inoperable carcinomas of the oral cavity and the oropharynx, with Tpot of < or = 5 days, received an accelerated radiotherapy regimen (AF) based on a modification of the concomitant boost technique: 2 Gy/fraction once a day, delivered 5 days a week up to 26 Gy, followed by 2 Gy/fraction twice a day, with a 6-h interval, one of the two fractions being delivered as a concomitant boost to reduced fields, up to 66 Gy total dose (off-cord reduction at 46 Gy), shortening the overall treatment time to 4.5 weeks. A contemporary control group of 46 patients with Tpot of >5 days or unknown was treated with conventional fractionation (CF): 2 Gy/fraction once a day, 5 days a week, up to 66 Gy in 6.5 weeks, with fields shrinkage after 46 Gy.


RESULTS
All patients completed the accelerated regimen according to protocol and in the prescribed overall treatment time. Immediate tolerance was fairly good: 65% of the patients in the AF group experienced Grade 3 mucositis vs. 45% in the CF group (p = n.s.). Symptoms related to mucosal reactions seemed to persist longer in AF than in CF patients. The crude proportion of mild (Grades 1 and 2) late effects on skin (p < 0.01) and salivary glands (p < 0.05) was higher in AF than in CF patients, although these reactions did not exceed the limits of tolerance. Three patients in the AF and 1 in the CF arm experienced a late Grade 4 bone complication. Actuarial estimates of severe (Grades 3 and 4) late complications showed a 2-year hazard of 33.3% in the AF arm and 49.7% in CF (p = NS). The actuarial 2-year local control rate of the AF patients was 49.4%, while actuarial 2-year overall survival for the same patients was 43.5%.


CONCLUSIONS
The results suggested that this accelerated regimen is worth testing in a controlled randomized trial to compare different accelerated schedules. Our findings also confirmed the 5-bromo-2-deoxyuridine/DNA flow cytometry technique as a suitable method of evaluating tumor cell kinetics in multicenter clinical studies, on condition that all measurements are carried out by one most experienced laboratory.
Antognoni
P
P
Divisione di Radioterapia, Ospedale Multizonale, Varese, Italy.
Bignardi
M
M
Cazzaniga
L F
LF
Poli
A M
AM
Richetti
A
A
Bossi
A
A
Rampello
G
G
Barbera
F
F
Soatti
C
C
Bardelli
D
D
Giordano
M
M
Danova
M
M
D000328:Adult; D000368:Aged; D001973:Bromodeoxyuridine / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002423:Cause of Death; D004247:DNA / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D009959:Oropharyngeal Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D015996:Survival Rate
D004247:DNA; D001973:Bromodeoxyuridine