Effect of Dosimetric Factors on Occurrence and Volume of Temporal Lobe Necrosis Following Intensity Modulated Radiation Therapy for Nasopharyngeal Carcinoma: A Case-Control Study

Abstract

To determine the dosimetric risk factors for the occurrence of temporal lobe necrosis (TLN) among nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiation therapy (IMRT), and to investigate the impact of dose-volume parameters on the volume of TLN lesions. Between January 2008 and June 2011, 2130 patients with NPC underwent definitive IMRT at out center. A case-control study was conducted between 43 patients who had developed TLN and 43 control subjects free of TLN following IMRT. Clinical features of patients and dose-volume parameters of irradiated temporal lobes (TLs), including maximum (Dmax) and minimum dose (Dmin), Mean dose (Dmean), absolute volumes receiving specific dose (Vds) from 20 to 76 Gy (V20-V76), doses covering certain volume (Dvs) from 0.25 to 6.0 cm3 (D0.25-D6.0), were retrospectively analyzed. Multivariate logistic regression models were fitted to determine risk factors for the occurrence of TLN. Trend test followed by linear regression analysis was performed to test the correlation between TLN volume (V-N) and dosimetric factors. Receiver operating characteristics analysis was conducted to acquire a dose constraint for preventing large TLN lesions. TLN lesions with V-N > 5 cm3 were considered large. The actuarial incidence of TLN was 3.48%, 7.01% at 3 and 4 years. Dosimetric parameters except Dmin were ubiquitously higher in TLs with necrosis than in healthy TLs. Multivariate regression analyses showed all the dosimetric factors significantly associated with TLN occurrence (P < 0.05), except for Dmin and V76. The highest odds ratios were seen with Vds at dose ≥70 Gy. Concurrent use of Cetuximab is a potential independent clinical risk factor for TLN occurrence (odds ratio 8.200, 95% confidence interval 0.962-69.925, P = 0.053). Test for trend showed a common trend of increase with V-N and dosimetric parameters (P < 0.05) except Dmax, Dmin, and V75. Stepwise multivariate linear regression suggested V45 to be the most powerful predictor for V-N (adjusted R2 = 0.305, P < 0.0001). Using V45 = 15.1 cm3 as a cut point, the sensitivity, specificity, positive predicting value and negative predicting value for large TLN lesions was 94.1%, 63.9%, 57.1%, and 96.0%, respectively. Dosimetric parameters are significantly associated with TLN occurrence and the extent of TL injury. V45 < 15.1 cm3 is a relatively safe dose constraint for limiting TLN volume within 5cm3. To better manage TLN, it would be important to avoid both high dose delivered to small volume and moderate dose delivered to large volume in TLs. The impact of concurrent Cetuximab on TLN occurrence awaits further validation.