Magnetic Resonance Imaging Assesses Radiation Encenhalopathy And Recurrence Pattern Of High-grade Glioma

Radiation encephalopathy is one of common complications in patients with head and neck cancer and brain tumor after radiotherapy.At present,radiation encephalopathy at later stage is generally regarded as a progressive and irreversible process and with a poor prognosis.Several studies had showed that bevacizumab reversed radiation encephalopathy(especially when the disease was at early stage).Therefore,it is important to diagnose radiation encephalopathy at early stage.However,the natural course of radiation encephalopathy remains to be poorly understood.This study aimed to investigate MRI characteristics and natural evolution of radiation encephalopathy.High-grade gliomas(HGG,WHO grade Ⅲ or Ⅳ)are the most common primary malignant brain tumor in adults.Despite aggressive treatment,including surgical resection,radiotherapy and chemotherapy,the survival of HGG is poor.For example,the median overall survival time of glioblastoma patient after diagnosis is only 14.6 months.Recurrence of HGG is unavoidable.However,understanding the recurrence pattern of HGG is good for designing better chemoradiation protocol,especially the radiotherapy delineation.The issue of HGG recurrence pattern of Chinese is rarely investigated.The present study analyzed follow-up MRI examinations of patients with radiation encephalopathy and obtained some useful conlusions.We also observed clinical response and MRI characteristic of 8 patients who received bevacizumab treatment due to radiation encephalopathy to evaluate the clinical effectiveness.We retrospectively evaluated pretreatment and serial posttreatment MR images of HGG patients to assess the recurrence patterns of them.We aimed to obtain evidence to design better chemoradiation protocol,especially the radiotherapy delineation,based on recurrence patterns of HGG.Part 1:A series of 162 follow-up MRI examinations from 68 nasopharyngeal carcinoma patients with radiation encephalopathy in temporal lobes were analyzed retrospectively.This study aimed to investigate the natural course of radiation encephalopathy by MRI evaluation.Results:Contrast enhanced lesions,white matter lesions,gray matter lesions,cyst and hemosiderin deposition were detected in 105(100%),98(93.3%),94(89.5%),2(1.7%)and 2(1.7%)of the 105 initial diagnosed temporal lobes.Twelve new injured temporal lobes were found during the follow-up,4 of them just presented as solid enhanced nodular lesions.Importantly,in 11(11/117,9.4%)injured temporal lobes,solid enhanced nodular lesions were found to be the only initial abnormalities to occur alone.All of the contrast enhanced nodular lesions larger than 2 cm showed necrotic core.At the last follow-up,contrast enhanced lesions and white matter lesions were detected in all of the 117 temporal lobes.Gray matter lesions,temporal lobe atrophy,cysts and hemosiderin deposition were detected in 115(98.3%),24(20.5%),and 6(5.1%)of 117 temporal lobes,respectively.Conclusions:MRI evaluation an effective method to assess and investigate the natural course of radiation encephalopathy.For the first time,solid enhanced nodular lesions were found to be the earliest MRI abnormality of radiation encephalopathy after nasopharyngeal carcinoma radiotherapy.Contrast enhanced lesions are the most commonly seen,followed by,in order,white matter lesions,gray matter lesions,temporal lobe atrophy,cyst and hemosiderin deposition.The maximal diameter of the smallest contrast enhanced lesion with necrosis was 8 mm.All contrast enhanced nodular lesions larger than 2 cm showed necrotic core.Part 2:Pretreatment and posttreatment MR images and clinical response were assessed in 8 patients who received bevacizumab treatment due to radiation encephalopathy.Changes in bi-dimensional measurements of the largest perpendicular diameters of radiation encephalopathy lesions were calculated on post-contrast T1 and T2-weighted images.Moreover,mini-mental status examination(MMSE,total value 30),Karnofsky performance status(KPS,total value 100)and associated clinical outcomes were observeed for each patient.Results:MRI analysis showed that the average reduction was 54%and 40%in post-contrast T1 and T2-weighted sequence analysis,respectively.Obvious clinical neurological improvements were expressed in all patients.Obvious improvements were observed in KPS values of 5 patients:40,40,10,10 and 40;2 patients,from 90 to 90 without improvement;1 patient,from 80 to 80,without improvement.Obvious improvements were observed in MMSE values of 3 patients:5,7 and 8;1 patient,from 28 to 28,without improvement.Conclusions:Patients with radiation encephalopathy experienced obvious improvement of clinical symptom and neurological status examination after bevacizumab treatment.MRI assessment showed contrast enhanced lesion on postcontrast T1-weighted image regressed and recovered more obviously and quickly than hyperintensity on T2/FLAIR.MRI assessment also could offer a quantitative index to show the clinical response.MRI assessment was consistent with clinical neurological improvement.Part 3:Pretreatment and serial posttreatment MR images of high-grade glioma(HGG)patients were retrospectively evaluated.The postcontrast T1-weighted images showing tumor recurrence were fused with the planning computed tomography images.The volume of recurrent tumor(V recur)was delineated.Recurrence patterns were classified according to the relationship of Vrecur to the 60Gy isodose line.The overall survival(OS)and progression-free survival(PFS)time were calculate respectively.Results:At a median follow-up of 14 months,54 HGG patients developed tumor recurrence.The median OS and PFS time were 14 and 10.5 months.Thirty-four patients developed central recurrence at a median of 11 months;8 patients developed in-field recurrence at a median of 9 months;2 patients developed marginal recurrence at 2 and 58 months after pathological diagnosis;2 patients developed distant recurrence at 2 and 35 months after pathological diagnosis.Nine of 20 patients with subventricular zone(SVZ)involvement on postcontrast T1-weighted image before surgical resection or radiotherapy developed cerebrospinal fluid dissemination.Conclusions:The main recurrence patterns of HGG after temozolomide-based chemoradiotherapy are local recurrence(central recurrence and in-field recurrence).The delineation protocol in which GTV consists of the resection cavity and any residual contrast-enhancing tumor but ignoring any edema and GTV adds a 2 cm/1 cm margin to create CTV1/CTV2 is suitable.Additionally,we should pay a special attention to cerebrospinal fluid dissemination of HGG SVZ involvement on postcontrast T1-weighted image before surgical resection or radiotherapy may be a high risk factor of cerebrospinal fluid dissemination.HGG patients with SVZ involvement inclined to develop cerebrospinal fluid dissemination in lateral ventricle(especially in the ipsilateral one).For HGG patients with SVZ involvement,the treatment protocol consisting of the present standard treatment plus radiotherapy to ipsilateral lateral ventricle even the supratentorial ventricles for prevention or intrathecal chemotherapy needs to be observed.