Lhermitte Sign After Chemo-IMRT of Head-and-Neck Cancer: Incidence, Doses, and Potential Mechanisms

Abstract

Purpose We have observed a higher rate of Lhermitte's syndrome (LS) after chemo-IMRT of head and neck cancer than the published rates after conventional radiotherapy. We hypothesized that the inhomogeneous spinal cord dose distributions produced by IMRT caused a “bath and shower” effect, characterized by low doses in the vicinity of high doses, reducing spinal cord tolerance. Methods and Materials 73 patients with squamous cell carcinoma of the oropharynx participated in a prospective study of IMRT concurrent with weekly carboplatin and taxol. 15 (21%) reported LS in at least 2 consecutive follow-up visits. Mean dose, maximum dose, partial (Vd) as well as the absolute volume (cc) of spinal cord receiving specified doses (≥10 Gy, 20 Gy, 30 Gy, 40 Gy), and the pattern of dose distributions at the “anatomical” (from the base of the skull to the aortic arch) and “plan-related” (from the top through the bottom of the PTV's) spinal cords were compared between LS and 34 non-LS patients. Results LS patients had significantly higher spinal cord mean doses, V30, V40, and volumes receiving ≥30 and ≥ 40 Gy compared to the non-LS patients (p < 0.05). Strongest predictors of LS were higher V40 and higher cord volumes receiving ≥40 Gy (p ≤ 0.007). There was no evidence of larger spinal cord volumes receiving low doses in the vicinity of higher doses (“bath and shower”) in LS compared to non-LS patients. Conclusions Greater mean dose, V30, V40, and cord volumes receiving ≥30 and ≥40 Gy characterized LS compared to non-LS patients. “Bath and shower” effects could not be validated in this study as a potential contributor to LS. The higher than expected rates of LS may be due to the specific concurrent chemotherapy agents, or to more accurate identification of LS in the setting of a prospective study.

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

“…On this basis, patients were categorised as either having LS or not. Previous studies show that the average duration of LS is 4-6 months [10,11,13]. We therefore took a single positive response as sufficient to define patients as having developed LS.…”

“…To minimise bias from inter-observer contouring variability, the spinal cord was re-contoured for all cases by one observer (DJN). To replicate the methodology of a similar study [13], two separate volumes were created; 'whole cord' and 'short cord' (Fig. 1a).…”

“…Historical series, in which patients were treated with conformal, field-based techniques, report a risk of LS following RT for HNC between 3 and 13% [9][10][11]. More recent work on LS following Intensity Modulated RT (IMRT) for thoracic and head and neck malignancy describes an incidence between 15 and 29% [5,12,13]. Since IMRT permits superior sparing of critical organs at risk (OARs), and given our previous understanding of the dose-response relationship of the spinal cord [1,14], these results are surprising.…”

“…Since IMRT permits superior sparing of critical organs at risk (OARs), and given our previous understanding of the dose-response relationship of the spinal cord [1,14], these results are surprising. Recent research has indicated that younger age and higher maximum dose are risk factors, and inferred that concomitant chemotherapy may also be implicated [13,15].…”

“…This often results in inhomogeneous dose distributions across OARs, and work on rat models has suggested that such inhomogeneity may be a risk factor for LS [16]. Whilst some clinical data appears to support this notion [12], no convincing evidence of a 'bath and shower' effect has yet been seen [13].…”