LASSO-based NTCP model for radiation-induced temporal lobe injury developing after intensity-modulated radiotherapy of nasopharyngeal carcinoma

Abstract

We investigated the incidence of temporal lobe injury (TLI) in 132 nasopharyngeal carcinoma (NPC)patients who had undergone intensity-modulated radiotherapy (IMRT) in our hospital between March 2005 and November 2009; and identified significant dosimetric predictors of TLI development. Contrastenhanced lesions or cysts in the temporal lobes, as detected by magnetic resonance imaging (MRI), were regarded as radiation-induced TLIs. We used the least absolute shrinkage and selection operator (LASSO) method to select D max (the maximum point dose) and the D 1cc (the top dose delivered to a 1-mL volume) from 15 dose-volume-histogram-associated and four clinically relevant candidate factors; the D max and the D 1cc were the most significant predictors of TLI development. We drew dose-response curves for D max and D 1cc . The tolerance dose (TD) for the 5% and 50% probabilities of TLI development were 69.0 ± 1.6 and 82.1 ± 2.4 Gy for D max and 62.8 ± 2.2 and 80.9 ± 3.4 Gy for D 1cc , respectively. The incidence of TLI in NPC patients after IMRT was higher than expected because the therapeutic window is narrow. High-quality longitudinal studies are needed to gain further insight into the complex spatiotemporal effects of non-uniform irradiation on TLI development in NPC patients.Temporal lobe necrosis is one of the most serious late complications developing after definitive radiotherapy of nasopharyngeal carcinoma (NPC) patients. Such injury has a tremendous impact on both quality-of-life (QoL) and survival in the era of conventional two-dimensional radiotherapy (2D-RT) 1-3 . Currently, the use of intensity-modulated radiotherapy (IMRT) (in preference to 2D-RT or forward-planned 3D-RT) to treat NPC has greatly reduced the occurrence of late toxicities, as IMRT improves sparing of adjacent normal tissues. However, in patients with locally advanced NPC, tumor infiltration into the skull base and intracranial tissue is common. The surrounding normal organs (anteriorly: the optic nerve and chiasm; posteriorly: the brain stem) have relatively low tolerances to radiation, and strict dose constraints must be put in place to preserve their critical physiological functions. High doses to the temporal lobes (TLs), a common undesirable side-effect of treatment, may trigger RT-induced TL injury (TLI). Calculation of appropriate dose thresholds improves treatment planning, thereby mitigating TLI development and preventing the negative impacts thereof on the QoL of locally advanced NPC patients [4][5][6] .In recent years, the clinical characteristics of, risk factors for, and dose-volume tolerances appropriate to prevent, TLI after IMRT have been preliminarily explored in several retrospective studies 4,5,[7][8][9][10] . However, significant methodological heterogeneities are evident among these studies, rendering it impossible to compare the results, and the actual tolerance dose (TD) used to avoid the development of TLI after IMRT remains ambiguous.

Radiation associated brain image changes after proton therapy for skull base head and neck cancers

“…Analysis of dosimetric correlations with RAIC suggest that risk can be kept below 5% when doses of 63 Gy is delivered to small volumes of the brain (≤ 2cc), but increases towards 50% with doses of 70 Gy to 80 Gy (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12).…”

Nomogram for radiation-induced hypothyroidism prediction in nasopharyngeal carcinoma after treatment

“…29 LASSO has recently been utilized to select optimal predictors from data that are multicollinear for other radiation-induced complications. 30,31 However, no studies have investigated RHT with this sophisticated statistical method. In this study, we used LASSO to identify predictors of Cox regression and present a nomogram for the prediction of RHT in patients with NPC.…”

The relations of dosimetric parameters with long‐term outcomes and late toxicities in advanced T‐stage nasopharyngeal carcinoma with IMRT

“…Assessing quality of life for patients with NPC has become an important issue. Cheng et al 25 reported that the crude TLI rate after IMRT was 12.9%; they used the least absolute shrinkage and selection operator method to select Dmax and D1cc, which were the most significant predictors of TLI development. 20,21 The incidence of radiation-induced TLI was 1.9%-13.1% after IMRT, 15,22 which most likely occurs in patients with advanced T-stage disease.…”

“…They used 0.5 cc of temporal lobe volume that received 69 Gy as a cutoff. Cheng et al 25 reported that the crude TLI rate after IMRT was 12.9%; they used the least absolute shrinkage and selection operator method to select Dmax and D1cc, which were the most significant predictors of TLI development. A study involving 749 patients with NPC demonstrated that the risk of TLI increased at D0.5cc ≥ 73.66Gy.…”