NTCP modeling of subacute/late laryngeal edema scored by fiberoptic examination

Finding best-fit parameters of normal tissue complication probability (NTCP) models for laryngeal edema after radiotherapy for head and neck cancer.

Forty-eight patients were considered for this study who met the following criteria: (1) grossly uninvolved larynx, (2) no prior major surgery except for neck dissection and tonsillectomy, (3) at least one fiberoptic examination of the larynx within 2 years from radiotherapy, (4) minimum follow-up of 15 months. Larynx dose-volume histograms (DVHs) were corrected into a linear quadratic equivalent one at 2 Gy/fr with alpha/beta = 3 Gy. Subacute/late edema was prospectively scored at each follow-up examination according to the Radiation Therapy Oncology Group scale. G2-G3 edema within 15 months from RT was considered as our endpoint. Two NTCP models were considered: (1) the Lyman model with DVH reduced to the equivalent uniform dose (EUD; LEUD) and (2) the Logit model with DVH reduced to the EUD (LOGEUD). The parameters for the models were fit to patient data using a maximum likelihood analysis.

All patients had a minimum of 15 months follow-up (only 8/48 received concurrent chemotherapy): 25/48 (52.1%) experienced G2-G3 edema. Both NTCP models fit well the clinical data: with LOGEUD the relationship between EUD and NTCP can be described with TD50 = 46.7 +/- 2.1 Gy, n = 1.41 +/- 0.8 and a steepness parameter k = 7.2 +/- 2.5 Gy. Best fit parameters for LEUD are n = 1.17 +/- 0.6, m = 0.23 +/- 0.07 and TD50 = 47.3 +/- 2.1 Gy.

A clear volume effect was found for edema, consistent with a parallel architecture of the larynx for this endpoint. On the basis of our findings, an EUD <30-35 Gy should drastically reduce the risk of G2-G3 edema.