Temporal Lobe Necrosis Following Radiotherapy in Nasopharyngeal Carcinoma: New Insight Into the Management

Cerebral radiation necrosis (CRN) is one of the most prominent sequelae following radiation therapy for nasopharyngeal carcinoma (NPC), which might have devastating effects on patients’ quality of life (QOL). Advances in histopathology and neuro-radiology have shed light on the management of CRN more comprehensively, yet effective therapeutic interventions are still lacking. CRN was once regarded as progressive and irreversible, however, in the past 20 years, with the application of intensity-modulated radiation therapy (IMRT), both the incidence and severity of CRN have declined. In addition, newly developed medical agents including bevacizumab-a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), nerve growth factor (NGF), monosialotetrahexosylganglioside (GM1), etc., have shown great potency in successfully reversing radiation-induced CRN. As temporal lobes are most frequently compromised in NPC patients, this review will summarize the state-of-the-art progress regarding the incidence, pathophysiology, prevention, treatment, and prognosis of temporal lobe necrosis (TLN) after IMRT in NPC.

Temporal Lobe Necrosis in Head and Neck Cancer Patients after Proton Therapy to the Skull Base

Purpose To demonstrate temporal lobe necrosis (TLN) rate and clinical/dose-volume factors associated with TLN in radiation-naïve patients with head and neck cancer treated with proton therapy where the field of radiation involved the skull base. Materials and Methods Medical records and dosimetric data for radiation-naïve patients with head and neck cancer receiving proton therapy to the skull base were retrospectively reviewed. Patients with <3 months of follow-up, receiving <45 GyRBE or nonconventional fractionation, and/or no follow-up magnetic resonance imaging (MRI) were excluded. TLN was determined using MRI and graded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Clinical (gender, age, comorbidities, concurrent chemotherapy, smoking, radiation techniques) and dose-volume parameters were analyzed for TLN correlation. The receiver operating characteristic curve and area under the curve (AUC) were performed to determine the cutoff points of significant dose-volume parameters. Results Between 2013 and 2019, 234 patients were included. The median follow-up time was 22.5 months (range = 3.2–69.3). Overall TLN rates of any grade, ≥ grade 2, and ≥ grade 3 were 5.6% (N = 13), 2.1%, and 0.9%, respectively. The estimated 2-year TLN rate was 4.6%, and the 2-year rate of any brain necrosis was 6.8%. The median time to TLN was 20.9 months from proton completion. Absolute volume receiving 40, 50, 60, and 70 GyRBE (absolute volume [aV]); mean and maximum dose received by the temporal lobe; and dose to the 0.5, 1, and 2 cm3 volume receiving the maximum dose (D0.5cm3, D1cm3, and D2cm3, respectively) of the temporal lobe were associated with greater TLN risk while clinical parameters showed no correlation. Among volume parameters, aV50 gave maximum AUC (0.921), and D2cm3 gave the highest AUC (0.935) among dose parameters. The 11-cm3 cutoff value for aV50 and 62 GyRBE for D2cm3 showed maximum specificity and sensitivity. Conclusion The estimated 2-year TLN rate was 4.6% with a low rate of toxicities ≥grade 3; aV50 ≤11 cm3, D2cm3 ≤62 GyRBE and other cutoff values are suggested as constraints in proton therapy planning to minimize the risk of any grade TLN. Patients whose temporal lobe(s) unavoidably receive higher doses than these thresholds should be carefully followed with MRI after proton therapy.