Modeling of salivary production recovery after radiotherapy using mixed models: determination of optimal dose constraint for IMRT planning and construction of convenient tools to predict salivary function.
OBJECTIVE
The mathematical relationship between the dose to the parotid glands and salivary gland production needs to be elucidated. This study, which included data from patients included in a French prospective study assessing the benefit of intensity-modulated radiotherapy (RT), sought to elaborate a convenient and original model of salivary recovery.


METHODS
Between January 2001 and December 2004, 44 patients were included (35 with oropharyngeal and 9 with nasopharyngeal cancer). Of the 44 patients, 24 were treated with intensity-modulated RT, 17 with three-dimensional conformal RT, and 2 with two-dimensional RT. Stimulated salivary production was collected for </=24 months after RT. The data of salivary production, time of follow-up, and dose to parotid gland were modeled using a mixed model. Several models were developed to assess the best-fitting variable for the dose level to the parotid gland.


RESULTS
Models developed with the dose to the contralateral parotid fit the data slightly better than those with the dose to both parotids, suggesting that contralateral and ipsilateral parotid glands are not functionally equivalent even with the same dose level to the glands. The best predictive dose-value variable for salivary flow recovery was the volume of the contralateral parotid gland receiving >40 Gy.


CONCLUSIONS
The results of this study show that the recommendation of a dose constraint for intensity-modulated RT planning should be established at the volume of the contralateral parotid gland receiving >40 Gy rather than the mean dose. For complete salivary production recovery after 24 months, the volume of the contralateral parotid gland receiving >40 Gy should be <33%. Our results permitted us to establish two convenient tools to predict the saliva production recovery function according to the dose received by the contralateral parotid gland.
Department of Radiotherapy, Centre Antoine-Lacassagne, Canceropôle PACA, Nice, France.
Cécile
C
Ortholan
Emmanuel
E
Chamorey
Karen
K
Benezery
Juliette
J
Thariat
Olivier
O
Dassonville
Gilles
G
Poissonnet
Alexandre
A
Bozec
Philippe
P
Follana
Frédérique
F
Peyrade
Anne
A
Sudaka
Jean Pierre
JP
Gerard
René Jean
RJ
Bensadoun
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D003198:Computer Simulation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009303:Nasopharyngeal Neoplasms / Q000532:radiotherapy*; D009959:Oropharyngeal Neoplasms / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D012466:Salivary Gland Diseases / Q000209:etiology / Q000517:prevention & control*; D012472:Salivation / Q000528:radiation effects*; D012984:Software