Radiation-induced Necrosis Research Articles

High-dose bevacizumab for radiation-induced brain necrosis: a case report.

Radiation-induced brain necrosis (RIBN) is a common adverse event from radiation therapy. We present a case of a 56-year-old man, diagnosed with non-small-cell lung cancer with brain metastases 2years prior, for which he had received whole brain radiotherapy and brain stereotactic radiosurgery, who presented to the oncology unit with headache, dizziness and abnormal gait. MRI of the brain revealed radiological worsening of a cerebellar mass, including edema and mass effect. After a multidisciplinary tumor board meeting, the patient was diagnosed with RIBN and received 4 cycles of high-dose bevacizumab, with complete symptom resolution and significant radiological response. We report the successful use of a high-dose, shorter-duration treatment protocol of bevacizumab for RIBN.

Prognostic Value of Nutritional Assessments on Overall Survival in Head and Neck Cancer Survivors with Radiation-Induced Brain Necrosis.

Malnutrition is related to worsened prognosis, but the association between nutritional risk status and overall survival in radiation-induced brain necrosis (RN) has never been studied. We included consecutive patients who had received radiotherapy for head and neck cancer (HNC) and subsequently developed RN from 8 January 2005 through to 19 January 2020. The primary outcome was overall survival. We utilized three commonly-used nutritional assessments: the Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), and the COntrolling NUTritional Status (CONUT) measure, to quantify the baseline nutritional risk. A total of 398 eligible patients were included. During a median follow-up of 2.3 years, 42 (10.6%) patients died of any cause. Malnutrition at admission was associated with an increased risk of future death, as assessed by the GNRI (per 1-point decreased, HR 1.05, 95%CI 1.02-1.09, p = 0.001), the PNI (per 1-point decreased, HR 1.07, 95%CI 1.03-1.12, p = 0.002), and the CONUT (per 1-point increased, HR 1.22, 95%CI 1.08-1.37, p = 0.001). There were no nonlinear correlations between all three indices and post-RN survival. Among HNC survivors with RN, the assessment of nutritional risk by composite indices upon admission could help identify patients who might be at high risk of future death and deliver better nutritional management.

A radiomics model for predicting the response to methylprednisolone in brain necrosis after radiotherapy for nasopharyngeal carcinoma

BackgroundMethylprednisolone is recommended as the front-line therapy for radiation-induced brain necrosis (RN) after radiotherapy for nasopharyngeal carcinoma. However, some patients fail to benefit from methylprednisolone or even progress. This study aimed to develop and validate a radiomic model to predict the response to methylprednisolone in RN.MethodsSixty-six patients receiving methylprednisolone were enrolled. In total, 961 radiomic features were extracted from the pre-treatment magnetic resonance imagings of the brain. Least absolute shrinkage and selection operator regression was then applied to construct the radiomics signature. Combined with independent clinical predictors, a radiomics model was built with multivariate logistic regression analysis. Discrimination, calibration and clinical usefulness of the model were assessed. The model was internally validated using 10-fold cross-validation.ResultsThe radiomics signature consisted of 16 selected features and achieved favorable discrimination performance. The radiomics model incorporating the radiomics signature and the duration between radiotherapy and RN diagnosis, yielded an AUC of 0.966 and an optimism-corrected AUC of 0.967 via 10-fold cross-validation, which also revealed good discrimination. Calibration curves showed good agreement. Decision curve analysis confirmed the clinical utility of the model.ConclusionsThe presented radiomics model can be conveniently used to facilitate individualized prediction of the response to methylprednisolone in patients with RN.

Brain magnetic resonance spectroscopy to differentiate recurrent neoplasm from radiation necrosis: A systematic review and meta-analysis.

Postradiation treatment necrosis is one of the most serious late sequelae and appears within 6months. The magnetic resonance spectroscopy imaging (MRSI) has been used for the detection of brain tumors. The study aimed to determine the radiological accuracy and efficacy in distinguishing recurrent brain tumor from radiation-induced necrosis by identifying pseudoprogression. The research was performed in accordance with the preferred reporting items for systematic review and meta-analysis guidelines. International electronic databases including 15 English sources were investigated. A total of 4281 papers with 2159 citations from 15 databases from 2011 to 2021 met the search strategies of magnetic resonance (MR) spectroscopy in recurrent brain tumors and postradiation necrosis. Nine studies were enrolled in the meta-analysis with a total of 354 patients (203 male and 151 female) whose average age ranged from 4 to 74years. Anbarloui etal., Elias etal., Nemattalla etal., Smith etal., Zeng etal., and Weybright etal. showed strong evidence of heterogeneity regarding choline/N-acetylaspartate (Cho/NAA) ratio in the evaluation of the nine studies. Elias etal., Nemattalla etal., Bobek-Billewicz etal., and Smith etal. showed a high heterogeneity in Cho/creatine (Cr) ratio. Elias etal., Nemattalla etal., Smith etal., and Weybright etal. revealed high heterogeneity in NAA/Cr ratio estimates. MR spectroscopy is effective in distinguishing recurrent brain tumors from necrosis. Our meta-analysis revealed that Cho/NAA, Cho/Cr, and NAA/Cr ratios were significantly better predictor of detected recurrent tumor. Therefore, the MRSI is an informative tool in the distinction of tumor recurrence versus necrosis.

Results of hypofractionated stereotactic radiotherapy for resected and intact large brain metastases

To compare the results of post-resection or isolated HF-SRT in patients with LBMs. A prospective study included 115 patients with 129 intact LBMs and 133 patients with 149 resected LBMs who underwent HF-SRT. Median baseline focal size was 22.5 and 28 mm, median target volume - 8.3 and 23.7 cm3, respectively. Median follow-up was 13.9 months, median overall survival - 19.1 months. After 12 months, local recurrences developed in 17 and 31% of patients, respectively (p=0.0078). Local recurrence after 12 months developed in 23% of patients with residual tumor in postoperative cavity compared to 16% of patients after total resection (p=0.0073). After 12 months, incidence of leptomeningeal progression was 27 and 11%, respectively (p=0.033), incidence of symptomatic radiation-induced necrosis - 4 and 23%, respectively (p=0.0006). Post-resection HF-SRT demonstrated better local control and less severe symptomatic radiation-induced necrosis compared to patients with intact LBMs. Incidence of leptomeningeal progression is significantly higher after resection of LBMs.

Cancer-Associated Fibroblasts Promote Radioresistance of Breast Cancer Cells via the HGF/c-Met Signaling Pathway

Cancer-associated fibroblasts (CAFs) are an integral part of the tumor microenvironment (TME), which is involved in therapy resistance. This study aimed to investigate the role of CAFs in radiosensitivity of breast cancer cells. The CAFs were isolated from the breast cancer tissues, and the conditioned medium was collected to culture breast cancer cells. Radiation-induced DNA damage was evaluated by immunofluorescence and western blotting. Cytokine array and enzyme-linked immunosorbent assay were performed to analyze the secretion of cytokines and growth factors. An in vitro clonogenic survival assay and in vivo xenograft mouse model were performed to determine the radiosensitivity of breast cancer cells. Finally, the expression of hepatocyte growth factor (HGF) and c-Met in the breast cancer tissues were detected by immunohistochemistry. The CAFs were found to secrete HGF to activate the c-Met signaling pathway, which induced epithelial-to-mesenchymal transition, growth, and radioresistance of breast cancer cells. Furthermore, radiation was observed to enhance HGF secretion by CAFs and increase c-Met expression in breast cancer cells, which led to HGF/c-Met signaling pathway activation. Moreover, radiation-induced tumor necrosis factor α (TNFα) secretion by breast cancer cells promoted CAF proliferation and HGF secretion. Additionally, HGF and c-Met high expression were associated with worse recurrence-free survival in patients with breast cancer who had received radiation therapy. The findings revealed that HGF and TNFα are critical for the crosstalk between breast cancer cells and CAFs in the TME and that the HGF/c-Met signaling pathway is a promising therapeutic target for radiosensitizing breast cancer.

High-Dose-Rate Brachytherapy as an Organ-Sparing Treatment for Early Penile Cancer.

Low-dose-rate brachytherapy is an effective organ-sparing treatment for patients with early-stage penile cancer. However, only limited data are available on the role of high-dose-rate brachytherapy (HDR-BT) in this clinical setting. Between 2002 and 2020, 31 patients with early penile cancer were treated at our center with interstitial HDR BT at a dose of 18 × 3 Gy twice daily. A breast brachytherapy template was used for the fixation of stainless hollow needles. The median follow-up was 117.5 months (range, 5-210). Eight patients (25.8%) developed a recurrence; of these, seven were salvaged by partial amputation. Six patients died of internal comorbidities or a second cancer. The probability of local control at 5 and 10 years was 80.7% (95% CI: 63.7-97.7%) and 68.3% (95% CI: 44.0-92.6%), respectively. Cause-specific survival was 100%. Only one case of radiation-induced necrosis was observed. The probability of penile sparing at 5 and 10 years was 80.6% (95% CI: 63.45-97.7%) and 62.1% (95% CI: 34.8-89.4%), respectively. These results show that HDR-BT for penile cancer can achieve results comparable to LDR-BT with organ sparing. Despite the relatively large patient cohort-the second largest reported to date in this clinical setting-prospective data from larger samples are needed to confirm the role of HDR-BT in penile cancer.

NIMG-78. DEVELOPMENT OF A PRECLINICAL GLIOBLASTOMA MURINE MODEL FOR THE ASSESSMENT OF RADIATION NECROSIS USING DIFFUSION KURTOSIS IMAGING

Abstract Glioblastoma (GB) patients often present with either radiation-induced necrosis (RN) or develop tumor recurrence (TR). Radiologically, differentiating between these two disease states is particularly difficult, especially utilizing traditional MRI techniques. Accurately distinguishing these separate states is important, as failure to do so can ultimately lead to unnecessary surgical intervention or early cessation of appropriate radiation therapy. Currently, distinction between these pathologies is made using best clinical judgement by the neuro-oncology team. Therefore, there is a need for developing novel non-invasive techniques that can reliably distinguish between radiation necrosis and tumor recurrence. Primary data was collected utilizing orthotopically transplanted GL261 mouse GB cells in a C57BL/6 mouse. Tumor induction was verified by MRI after two weeks. RN and TR were initiated using an aggressive radiation dose fractionation (12 Gy or 60 Gy). This was completed using a 4 mm radiation cone such that one portion of the tumor received 100% dose of 12 Gy or 60 Gy fraction which is sufficient to cause RN, whereas the tumor edge received only 50% of the dose, allowing for tumor recurrence. Our data demonstrated mice tumor recurrence and radiation necrosis on MRI imaging. Axial T2-weighted MRI and DKI sequence at 2 weeks following implantation demonstrated edema compatible with tumor recurrence. One week later, the T2-weighted MRI and DKI sequences demonstrated continued tumor progression. In a separate mouse with orthotopic glioblastoma implantation with high dose (60 Gy) radiation treatment, T2 imaging and DKI demonstrated areas of tumor and suspected central radiation necrosis. DKI imaging biomarkers was compared by liquid biopsy, H&E staining, and Immunohistochemistry (IHC) analysis of sacrificed mice. Our H&E staining results showed typical pathological features of GB and RN, and TR in each case. This result demonstrated that our proposed model for radiation induction was effective at achieving its goal.

Development of a normal tissue complication probability (NTCP) model using an artificial neural network for radiation-induced necrosis after carbon ion re-irradiation in locally recurrent nasopharyngeal carcinoma

The aim of the present study was to build a normal tissue complication probability (NTCP) model using an artificial neural network (ANN) for radiation-induced necrosis after carbon ion re-irradiation in locally recurrent nasopharyngeal carcinoma (rNPC), and to determine the predictive parameters applied to the model. A total of 150 patients with rNPC treated at Shanghai Proton and Heavy Ion Center during 2015-2019 were selected to determine the dominant factors causing mucosal necrosis after carbon therapy. An ANN was built to study both dose-volume histogram (DVH) and clinical factors. Simple oversampling and data normalization were used in the training process. Ten-fold cross validation was conducted to prevent overfitting. Of the DVH factors, the prediction accuracy ranged from 58.3-65.2%, whereas planning target volume (PTV) receiving dose more than 25 GyE (PTV.V25) yielded the best prediction accuracy. Of the clinical factors, baseline necrosis, sex, and biologically equivalent dose (BED) of initial treatment could increase the accuracy of PTV.V25 by 0.5%, 0.5%, and 1.5%, respectively. An ANN was built to predict radiation-induced necrosis after re-irradiation in rNPC. The best accuracy and area under receiver-operating characteristic (ROC) curve (AUC) were 66.7% and 0.689. The most predictive dosimetric and clinical parameters were PTV.V25 and BED of initial treatment.

Towards differentiation of brain tumor from radiation necrosis using multi-parametric MRI: Preliminary results at 4.7 T using rodent models

BackgroundIt remains a clinical challenge to differentiate brain tumors from radiation-induced necrosis in the brain. Despite significant improvements, no single MRI method has been validated adequately in the clinical setting. MethodsMulti-parametric MRI (mpMRI) was performed to differentiate 9L gliosarcoma from radiation necrosis in animal models. Five types of MRI methods probed complementary information on different scales i.e., T2 (relaxation), CEST based APT (probing mobile proteins/peptides) and rNOE (mobile macromolecules), qMT (macromolecules), diffusion based ADC (cell density) and SSIFT iAUC (cell size), and perfusion based DSC (blood volume and flow). ResultsFor single MRI parameters, iAUC and ADC provide the best discrimination of radiation necrosis and brain tumor. For mpMRI, a combination of iAUC, ADC, and APT shows the best classification performance based on a two-step analysis with the Lasso and Ridge regressions. ConclusionA general mpMRI approach is introduced to choosing candidate multiple MRI methods, identifying the most effective parameters from all the mpMRI parameters, and finding the appropriate combination of chosen parameters to maximize the classification performance to differentiate tumors from radiation necrosis.

Mortality of early treatment for radiation-induced brain necrosis in head and neck cancer survivors: A multicentre, retrospective, registry-based cohort study

SummaryBackgroundThe evidence of early treatment for radiation-induced brain necrosis (RN) in head and neck cancer survivors remains insufficient. This study aimed to determine whether early anti-RN treatment was associated with lower mortality.MethodsIn this cohort study, we utilized data from the Study in Radiotherapy-related Nervous System Complications (NCT03908502) and Hong Kong Cancer Registry. We included consecutive patients who had received radiotherapy (RT) for head and neck cancers and had subsequently developed RN between Jan 8, 2005 and Jan 19, 2020. Patients who had tumor progression before the diagnosis of RN, underwent surgical brain necrosis lesions resection before corticosteroids and/or bevacizumab treatment, had intracranial metastases before the diagnosis of RN, lacked follow-up data, or had a follow-up period of less than three months were excluded. Individual-level data were extracted from electronic medical records of the above-mentioned registries. The primary outcome was all-cause death. The vital status of each patient was confirmed through a standardized telephone interview. We compared patients who received early treatment (initiating bevacizumab or corticosteroids treatment within three months after RN diagnosis) with patients who did not (following a “watch-and-wait” policy).FindingsOf 641 eligible patients, 451 patients (70·4%) received early treatment after RN diagnosis and 190 patients (29·6%) did not. Overall, 112 patients (17·5%) died, of whom 73 (16·2%) in the early treatment group and 39 (20·5%) in the watch-and-wait group, during a median follow-up of 3·87 years. The early treatment group showed a lower risk of all-cause death compared with the watch-and-wait group after adjusting for age, sex, absence or presence of neurological symptoms at baseline, RN lesion features on brain magnetic resonance imaging, history of stroke, prior tumor-related characteristics (TNM stage, RT dose and techniques, and chemotherapy), and the time interval from RT to RN (HR 0·48, 95%CI 0·30 to 0·77; p = 0·0027), and extensive sensitivity analyses yielded similar results. There was no significant difference in the effect of early treatment on post-RN survival among subgroups stratified by presence or absence of neurological symptoms at diagnosis (p for interaction=0·41).InterpretationAmong head and neck cancer survivors with RN, initiating treatment early after RN diagnosis is associated with a lower risk of all-cause mortality as compared with following the watch-and-wait policy, irrespective of whether patients exhibit symptoms or not. Further prospective randomised studies would be needed to validate our findings since the observational study design might lead to some potential confounding. In the absence of data from randomised trials, our study will have an important implication for clinicians regarding the optimal timing of treatment for RN, and provides the foundation and supporting data for future trials on this topic.FundingNational Natural Science Foundation of China (81925031, 81820108026, 81872549, 81801229, 82003389), the Science and Technology Program of Guangzhou (202007030001), Young Teacher Training Program of Sun Yat-sen University (20ykpy106), Key-Area Research and Development Program of Guangdong Province (2018B030340001), the National Medical Research Council Singapore Clinician Scientist Award (NMRC/CSA-INV/0027/2018, CSAINV20nov-0021), the Duke-NUS Oncology Academic Program Goh Foundation Proton Research Programme, NCCS Cancer Fund, the Kua Hong Pak Head and Neck Cancer Research Programme, and the National Research Foundation Clinical Research Programme Grant (NRF-CRP17-2017-05).

CLRM-06 PROSPECTIVE CLINICAL STUDY OF CONVENTIONALLY FRACTIONATED CONCURRENT CHEMORADIOTHERAPY AND HYPOFRACTIONATED CONCURRENT CHEMORADIOTHERAPY AFTER THE SURGERY OF HIGH-GRADE GLIOMAS

PURPOSETo observe and evaluate the efficacy and safety of conventional fractionated concurrent chemoradiotherapy and hypofractionated concurrent chemoradiotherapy for adjuvant treatment of newly treated high-grade glioma. METHODFor newly treated patients with high-grade gliomas with WHO grade III-IV, all patients started concurrent chemoradiotherapy within 1 month after surgery, and received concurrent temozolomide 75 mg/m2 during radiotherapy until the end of radiotherapy. Sequential temozolomide chemotherapy at 200 mg/m2 for at least 6 cycles. All patients were randomly divided into groups, one group was given conventional fractional irradiation, 60Gy/30f in high-risk areas, 46Gy/23f in low-risk areas, and the other group was given low-fractionated irradiation, 53Gy/15f in high-risk areas, and 53Gy/15f in low-risk areas 43Gy/15f. The overall survival (OS), progression-free survival (PFS), radiation-induced cerebral edema and radiation-induced brain necrosis were evaluated. RESULTAs of December 31, 2022, a total of 60 patients were enrolled, including 30 in the conventional fractionation treatment group and 30 in the hypofractionated treatment group. At present, 58 patients survived and 2 died, 2 in the conventional fractionation group, one due to tumor recurrence and one due to cardiac accident; 7 patients recurred, including 4 in the conventional fractionation group and 3 in the low fractionation group. Radiation cerebral edema occurred in 9 cases, 6 cases in the hypofractionated group and 3 cases in the conventional fractionation group, all of which were completely relieved after dehydration with mannitol, which did not affect the progress of radiotherapy. No radiation necrosis occurred during follow-up. CONCLUSIONCompared with the standard stupp regimen, using 53Gy/15f in the high-risk area and 43Gy/15f in the low-risk area as an adjuvant therapy with concurrent temozolomide and sequential temozolomide, there was no increased risk of disease recurrence, no increased risk of death, and no increased risk of death.

The safety and efficacy of anlotinib in combination with stereotactic radiotherapy for the treatment of brain metastases from non-small cell lung cancer

Objective: To investigate the efficacy and safety of anti-vascular drug anlotinib in combination with stereotactic radiosurgery (SRS) for the treatment of brain metastases from non-small cell lung cancer (NSCLC). Methods: A total of 46 patients diagnosed with NSCLC brain metastases and treated with SRS in Peking University Third Hospital were included from October 2017 to June 2019. Of these, 21 patients (33 lesions) received anlotinib combined with SRS (combined treatment group), while 25 patients (35 lesions) only received SRS (SRS-alone group). The data of combined treatment group and SRS-alone group were compared, including remission rate of intracranial hypertension, response rate (RR) of local control of intracranial lesions, incidence of radiation-induced brain necrosis and intracranial progression-free survival (iPFS). The medication and adverse reactions of anlotinib in the combined treatment group were recorded. Results: The remission rate of intracranial hypertension in the combined treatment group was 71.4% (15/21), which was significantly higher than that in the SRS-alone group [12.0% (3/25), P<0.001). However, the RR of combined treatment group and SRS-alone group was 80.9% (17/21) and 60.0% (15/25), respectively, with no statistically significant difference (P=0.289). The incidence of radiation-induced brain necrosis in the combined treatment group was 3.0% (1/33), which was significantly lower than that in the SRS-alone group [20.0% (7/35), P=0.030]. The iPFS of the combination treatment group was (13.9±2.4) months, which was significantly longer than that in the SRS-alone group [(11.4±1.8) months, P<0.001]. The medication time of anlotinib in the combined treatment group was 6 (6, 18) weeks. One patient developed grade Ⅰ hypertension and one patient developed grade Ⅰ hand-foot syndrome. The incidence of drug-related adverse reactions was 9.5% (2/21). Conclusions: Anlotinib in combination with SRS may relieve brain edema, reduce the rate of radiation-induced brain necrosis, and the rate of drug-related adverse reactions were low.

Combined Diagnostic Accuracy of Diffusion and Perfusion MR Imaging to Differentiate Radiation-Induced Necrosis from Recurrence in Glioblastoma.

We aimed to use quantitative values derived from perfusion and diffusion-weighted MR imaging (PWI and DWI) to differentiate radiation-induced necrosis (RIN) from tumor recurrence in Glioblastoma (GBM) and investigate the best parameters for improved diagnostic accuracy and clinical decision-making. Methods: A retrospective analysis of follow-up MRI with new enhancing observations was performed in histopathologically confirmed subjects of post-treated GBM, who underwent re-surgical exploration. Quantitative estimation of rCBV (relative cerebral blood volume) from PWI and three methods of apparent diffusion coefficient (ADC) estimation were performed, namely ADC R1 (whole cross-sectional area of tumor), ADC R2 (only solid enhancing lesion), and ADC R3 (central necrosis). ROC curve and logistic regression analysis was completed. A confusion matrix table created using Excel provided the best combination parameters to ameliorate false-positive and false-negative results. Results: Forty-four subjects with a mean age of 46 years (range, 19–70 years) underwent re-surgical exploration with RIN in 28 (67%) and recurrent tumor in 16 (33%) on histopathology. rCBV threshold of >3.4 had the best diagnostic accuracy (AUC = 0.93, 81% sensitivity and 89% specificity). A multiple logistic regression model showed significant contributions from rCBV (p < 0.001) and ADC R3 (p = 0.001). After analysis of confusion matrix ADC R3 > 2032 × 10−6 mm2 achieved 100% specificity with gain in sensitivity (94% vs. 56%). Conclusions: A combination of parameters had better diagnostic performance, and a stepwise combination of rCBV and ADC R3 obviated unnecessary biopsies in 10% (3/28), leading to improved clinical decision-making.

Hemodynamic Imaging in Cerebral Diffuse Glioma-Part B: Molecular Correlates, Treatment Effect Monitoring, Prognosis, and Future Directions.

Simple SummaryCerebral diffuse gliomas present peculiar molecular features tightly linked to phenotypic characteristics that are not readily appreciated by means of standard neuroimaging. In the present Part B of our two-review series, the potential of exploiting glioma vascular and hemodynamic alterations for a better characterization of tumor subtype, differentiation of tumor recurrence from treatment effects, and prognosis prediction is critically discussed together with the advancements related to radiomics and machine learning for innovative imaging biomarkers development.Gliomas, and glioblastoma in particular, exhibit an extensive intra- and inter-tumoral molecular heterogeneity which represents complex biological features correlating to the efficacy of treatment response and survival. From a neuroimaging point of view, these specific molecular and histopathological features may be used to yield imaging biomarkers as surrogates for distinct tumor genotypes and phenotypes. The development of comprehensive glioma imaging markers has potential for improved glioma characterization that would assist in the clinical work-up of preoperative treatment planning and treatment effect monitoring. In particular, the differentiation of tumor recurrence or true progression from pseudoprogression, pseudoresponse, and radiation-induced necrosis can still not reliably be made through standard neuroimaging only. Given the abundant vascular and hemodynamic alterations present in diffuse glioma, advanced hemodynamic imaging approaches constitute an attractive area of clinical imaging development. In this context, the inclusion of objective measurable glioma imaging features may have the potential to enhance the individualized care of diffuse glioma patients, better informing of standard-of-care treatment efficacy and of novel therapies, such as the immunotherapies that are currently increasingly investigated. In Part B of this two-review series, we assess the available evidence pertaining to hemodynamic imaging for molecular feature prediction, in particular focusing on isocitrate dehydrogenase (IDH) mutation status, MGMT promoter methylation, 1p19q codeletion, and EGFR alterations. The results for the differentiation of tumor progression/recurrence from treatment effects have also been the focus of active research and are presented together with the prognostic correlations identified by advanced hemodynamic imaging studies. Finally, the state-of-the-art concepts and advancements of hemodynamic imaging modalities are reviewed together with the advantages derived from the implementation of radiomics and machine learning analyses pipelines.

Dosimetric analysis of radiation-induced brainstem necrosis for nasopharyngeal carcinoma treated with IMRT

BackgroundRadiation-induced brainstem necrosis (RIBN) is a late life-threatening complication that can appear after treatment in patients with nasopharyngeal carcinoma (NPC). However, the relationship between RIBN and radiation dose is not still well-defined.MethodsDuring January 2013 and December 2017, a total of 1063 patients with NPC were treated at Sichuan cancer hospital with IMRT. A total of 479 patients were eligible for dosimetric analysis. Dosimetric parameters of the RIBN, Dmax(the maximum dose), D0.1c (maximum average dose delivered to a 0.1-cc volume), D1cc, D2cc, D3cc, D5cc, D10cc and Dmean (mean does) were evaluated and recorded. ROC curve was used to analyze the area under curve (AUC) and cutoff points. Logistic regression for screening dose-volume parameter and logistic dose response model were used to predict the incidence of brainstem necrosis.ResultsAmong the 479 patients with NPC, 6 patients were diagnosed with RIBN, the incidence of RIBN was 1.25% (6/479), and the median time to RIBN after treatment was 28.5 months (range 18–48 months). The dose of the brainstem in patients with RIBN were higher than that in patients without necrosis. ROC curve showed that the area under the curve (AUC) of Dmax was the largest (0.987). Moreover, logistic stepwise regression indicated that Dmax was the most important dose factor. The RIBN incidence at 5% over 5 years (TD5/5) and 50% incidence over 5 years (TD50/5) was 69.59 Gy and76.45 Gy, respectively.ConclusionsBrainstem necrosis is associated with high dose irritation. Dmax is the most significant predictive dosimetric factor for RIBN. Dmax of brainstem should be considered as the dose limitation parameter. We suggest that the limitation dose for brainstem was Dmax < 69.59 Gy.

A novel nomogram to predict overall survival in head and neck cancer survivors with radiation-induced brain necrosis

Background and purposeThe study aimed to develop and validate a novel nomogram to predict overall survival in head and neck cancer survivors following the diagnosis of radiation-induced brain necrosis (RN). Materials and methodsWe included head and neck cancer survivors with RN from a radiation complications registry study. A total of 495 eligible patients were 7:3 randomly allocated to a training cohort and an internal validation cohort. The Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select significant predictors of post-RN survival in the training cohort, and a multivariable Cox model was used to develop the nomogram. The performance of the nomogram was assessed using the internal validation cohort and externally validated using additional 88 RN patients. ResultsWe identified five predictors of post-RN survival using the training data: age, tumor progression before RN, lower cranial nerves injury, bilateral necrosis, and history of stroke. The nomogram showed favorable performance in the internal validation cohort (C-index 0.761, 95% CI 0.676 to 0.847) and in the external validation cohort (C-index 0.795, 95% CI 0.717 to 0.874). The decision curve analysis indicated that the nomogram was clinically useful when the probabilities of death ranging from 1% to 48% at 1 year, from 3% to 50% at 3 years, and exceeding 2% at 5 years after being diagnosed with RN. ConclusionIn this LASSO-Cox model-based nomogram study, we developed and validated an easily applied model to predict overall survival in head and neck cancer survivors following an RN diagnosis.

Histopathologic and MR Imaging Appearance of Spontaneous and Radiation-Induced Necrosis in Uveal Melanomas: Initial Results.

Simple SummaryUveal melanomas may undergo necrosis, both spontaneously or following radiotherapy. Nowadays radiotherapy is the preferred treatment, whereas enucleation of the eye is used in selected cases. In order to differentiate the effects of radiotherapy from spontaneous degenerative changes in uveal melanomas, we compared the appearance of necrosis, both from a histopathological point of view and from the perspective of MR imaging, in two groups of patients with uveal melanoma: a group who had undergone previous proton beam radiotherapy (secondary enucleation); a control group who had undergone enucleation without any previous radiotherapy treatment (primary enucleation). Irradiated and nonirradiated uveal melanomas differ on the basis of the histological appearance, the MR imaging appearance and the distribution of necrosis. We hope that the findings we observed could be extended to all patients with uveal melanomas treated with radiotherapy, and may enhance the accuracy of radiologists in evaluating MR examinations after radiotherapy.Necrosis in uveal melanomas can be spontaneous or induced by radiotherapy. The purpose of our study was to compare the histopathologic and MRI findings of radiation-induced necrosis of a group of proton beam-irradiated uveal melanomas with those of spontaneous necrosis of a control group of patients undergoing primary enucleation. 11 uveal melanomas who had undergone proton beam radiotherapy, MRI and secondary enucleation, and a control group of 15 untreated uveal melanomas who had undergone MRI and primary enucleation were retrospectively identified. Within the irradiated and nonirradiated group, 7 and 6 eyes with histological evidence of necrosis respectively, were furtherly selected for the final analysis; the appearance of necrosis was assessed at histopathologic examination and MRI. Irradiated melanomas showed a higher degree of necrosis as compared with nonirradiated tumors. Irradiated and nonirradiated lesions differed based on the appearance and distribution of necrosis. Irradiated tumors showed large necrotic foci, sharply demarcated from the viable neoplastic tissue; nonirradiated tumors demonstrated small, distinct foci of necrosis. Radiation-induced necrosis, more pigmented than surrounding viable tumor, displayed high signal intensity on T1-weighted and low signal intensity on T2-weighted images. The hemorrhagic/coagulative necrosis, more prevalent in nonirradiated tumors (4 out of 6 vs. 1 out of 7 cases), appeared hyperintense on T2-weighted and hypointense on T1-weighted images. Our study boosts the capability to recognize radiation-induced alterations in uveal melanomas at MRI and may improve the accuracy of radiologists in the evaluation of follow-up MR examination after radiotherapy.

Leptomeningeal disease and brain control after postoperative stereotactic radiosurgery with or without immunotherapy for resected brain metastases

PurposeImmunotherapy has shown activity in patients with brain metastases (BM) and leptomeningeal disease (LMD). We have evaluated LMD and intraparenchymal control rates for patients with resected BM receiving postoperative stereotactic...

Blood-Brain Barrier Repair of Bevacizumab and Corticosteroid as Prediction of Clinical Improvement and Relapse Risk in Radiation-Induced Brain Necrosis: A Retrospective Observational Study.

BackgroundBlood–brain barrier (BBB) disruption after endothelial damage is a crucial part of radiation-induced brain necrosis (RN), but little is known of BBB disruption quantification and its role in the evaluation of therapeutic effect and prognosis for drug treatment. In this retrospective study, BBB repair by bevacizumab and corticosteroid and the correlation between BBB permeability and treatment response and relapse were evaluated by dynamic contrast-enhanced MRI (DCE-MRI).MethodsForty-one patients with RN after radiotherapy for nasopharyngeal carcinoma (NPC) (28 treated with bevacizumab and 13 with corticosteroid), 12 patients with no RN after NPC radiotherapy, and 12 patients with no radiotherapy history were included as RN, non-RN, and normal groups, respectively. DCE-MRI assessed BBB permeability in white matter of bilateral temporal lobe. DCE parameters were compared at baseline among the three groups. DCE parameters after treatment were compared and correlated with RN volume decrease, neurological improvement, and relapse.ResultsThe extent of BBB leakage at baseline increased from the normal group and non-RN group and to RN necrosis lesions, especially K trans (Kruskal–Wallis test, P < 0.001). In the RN group, bevacizumab-induced K trans and v e decrease in radiation necrosis lesions (both P < 0.001), while corticosteroid showed no obvious effect on BBB. The treatment response rate of bevacizumab was significantly higher than that of corticosteroid [30/34 (88.2%) vs. 10/22 (45.4%), P < 0.001]. Spearman analysis showed baseline K trans, K ep, and v p positively correlated with RN volume decrease and improvement of cognition and quality of life in bevacizumab treatment. After a 6-month follow-up for treatment response cases, the relapse rate of bevacizumab and corticosteroid was 10/30 (33.3%) and 2/9 (22.2%), respectively, with no statistical difference. Post-bevacizumab K trans level predicted relapse in 6 months with AUC 0.745 (P < 0.05, 95% CI 0.546–0.943, sensitivity = 0.800, specificity = 0.631).ConclusionsBevacizumab improved BBB leakage in RN necrosis. DCE parameters may be useful to predict therapeutic effect and relapse after bevacizumab.