Identifying risk factors for L'Hermitte's sign after IMRT for head and neck cancer

Abstract

Background: L'Hermitte's sign (LS) after chemoradiotherapy for head and neck cancer appears related to higher spinal cord doses. IMRT plans limit spinal cord dose, but the incidence of LS remains high.

Methods: One hundred seventeen patients treated with TomoTherapy™ between 2008 and 2015 prospectively completed a side-effect questionnaire (VoxTox Trial Registration: UK CRN ID 13716). Baseline patient and treatment data were collected. Radiotherapy plans were analysed; mean and maximum spinal cord dose and volumes receiving 10, 20, 30 and 40 Gy were recorded. Dose variation across the cord was examined. These data were included in a logistic regression model.

Results: Forty two patients (35.9%) reported LS symptoms. Concurrent weekly cisplatin did not increase LS risk (p = 0.70, OR = 1.23 {95% CI 0.51-2.34}). Of 13 diabetic participants (9 taking metformin), only 1 developed LS (p = 0.025, OR = 0.13 {95% CI 0.051-3.27}). A refined binary logistic regression model showed that patients receiving unilateral radiation (p = 0.019, OR = 2.06 {95% CI 0.15-0.84}) were more likely to develop LS. Higher V_40Gy (p = 0.047, OR = 1.06 {95% CI 1.00-1.12}), and younger age (mean age 56.6 vs 59.7, p = 0.060, OR = 0.96 {95% CI 0.92-1.00}) were associated with elevated risk of LS, with borderline significance.

Conclusions: In this cohort, concomitant cisplatin did not increase risk, and LS incidence was lower in diabetic patients. Patient age and dose gradients across the spinal cord may be important factors.

Keywords: Chemoradiotherapy; Cisplatin; Head and neck neoplasms; Spinal cord; Transverse myelitis.

Fig. 1

Spinal cord dosimetry a ‘whole cord’ shown in blue, ‘short cord’ in pink. b axial dose gradient across the cervical cord; max. Left - right gradient 8.3Gy (36.9–28.6Gy). Dose wash; 95% isodose for 60Gy (57.9Gy) dark red, 50Gy light red, 45Gy orange, 40Gy amber, 35Gy green, 30Gy light blue, 25Gy royal blue

Fig. 2

Number of cycles of cisplatin received vs incidence of LS a number of cisplatin cycles received by patients with and without LS (absolute numbers above bars). b - Receiver Operator Characteristic curve - number of cisplatin cycles received for prediction of LS (AUC = 0.525, 95% CI = 0.416 to 0.634)

Fig. 3

Dose inhomogeneity in patients with and without LS a Box and whisker plots showing higher homogeneity index in LS patients b higher homogeneity index in patients receiving unilateral neck radiation.