Radiation-induced Tissue Changes Research Articles

MRI-based radiomic features for identifying recurrent prostate cancer after proton radiation therapy.

Magnetic Resonance Imaging (MRI) evaluation of recurrent prostate cancer (PCa) following proton beam therapy is challenging due to radiation-induced tissue changes. This study aimed to evaluate MRI-based radiomic features so as to identify the recurrent PCa after proton therapy. We retrospectively studied 12 patients with biochemical recurrence (BCR) following proton therapy. Two experienced radiologists identified prostate lesions from multi-parametric MRI (mpMRI) images post-proton therapy and marked control regions of interest (ROIs) on the contralateral side of the prostate gland. A total of 210 radiomic features were extracted from lesions and control regions on the T2-weighted (T2WI) and Apparent Diffusion Coefficient (ADC) image series. Recursive Feature Elimination with Cross-Validation method (RFE-CV) was used for feature selection. A Multilayer Perceptron (MLP) neural network was developed to classify three classes: cancerous, benign, and healthy tissue. The 12-core biopsy results were used as the gold standard for the segmentations. The classifier performance was measured using specificity, sensitivity, the area under receiver operating characteristic curve (AUC), and other statistical indicators. Based on biopsy results, 10 lesions were identified as PCa recurrence while eight lesions were confirmed to be benign. Ten radiomic features (10/210) were selected to build the multi-class classifier. The radiomics classifier gave an accuracy of 0.83 in identifying cancerous, benign, and healthy tissue with a sensitivity of 0.80 and specificity of 0.85. The model yielded an AUC of 0.87, 95% CI [0.72-1.00] in differentiating cancer from the benign and healthy tissues. Our proof-of-concept study demonstrates the potential of using radiomic features as part of the differential diagnosis of PCa on mpMRI following proton therapy. The results need to be validated in a larger cohort.

Identification of Molecular Mechanisms in Radiation Cystitis: Insights from RNA Sequencing.

Pelvic cancer survivors who were treated with radiation therapy are at risk for developing (hemorrhagic) radiation cystitis (RC) many years after completion of radiation therapy. Patients with RC suffer from lower urinary tract symptoms, including frequency, nocturia, pelvic pain, and incontinence. In advanced stages, hematuria can occur, potentially escalating to life-threatening levels. Current therapeutic options for RC are limited, partly due to ethical concerns regarding bladder biopsy in patients with fragile bladder tissue. This study aimed to leverage our established preclinical model to elucidate the molecular pathways implicated in radiation-induced tissue changes in the bladder. Female C57Bl/6 mice received a single dose of 40 Gy using CT-guided imaging and a two-beam irradiation approach using the SARRP irradiator. Bladders from irradiated and age-matched littermate controls were harvested at 1 week [n = 5/group] or 6 months [n = 5/group] after irradiation, RNA was harvested, and mRNA sequencing was performed at paired-end 150bp on the Illumina NovaSeq6000 with a target of 30 million reads per sample. Following RNA sequencing, thorough bioinformatics analysis was performed using iPathwayGuide v2012 (ADVAITA Bioinformatics). Findings of the RNA sequencing were validated using qPCR analysis. At 1 week post-irradiation, altered gene expression was detected in genes involved in DNA damage response, apoptosis, and transcriptional regulation. By 6 months post-irradiation, significant changes in gene expression were observed in inflammation, collagen catabolism, and vascular health. Affected pathways included the p53, JAK-STAT, and PI3K-Akt pathways. These findings were validated in vivo in bladder tissues from our preclinical model. This is the first study to determine the molecular changes in the bladder in response to radiation treatment. We have successfully pinpointed several pathways and specific genes that undergo modification, thereby contributing to the progression of radiation cystitis. These insights enhance our understanding of the pathophysiology of radiation cystitis and may ultimately pave the way to the identification of potential new therapeutic targets.

Proton Beam Therapy in the Reirradiation Setting of Brain and Base of Skull Tumour Recurrences

The therapeutic management of local tumour recurrence after a first course of radical radiotherapy is always complex. Surgery and reirradiation carry increased morbidity due to radiation-induced tissue changes. Proton beam therapy (PBT) might be advantageous in the reirradiation setting, thanks to its distinct physical characteristics. Here we systematically reviewed the use of PBT in the management of recurrent central nervous system (CNS) and base of skull (BoS) tumours, as published in the literature. The research question was framed following the Population, Intervention, Comparison and Outcomes (PICO) criteria: the population of the study was cancer patients with local disease recurrence in the CNS or BoS; the intervention was radiation treatment with PBT; the outcomes of the study focused on the clinical outcomes of PBT in the reirradiation setting of local tumour recurrences of the CNS or BoS. The identification stage resulted in 222 records in Embase and 79 in Medline as of March 2023. Sixty-eight duplicates were excluded at this stage and 56 were excluded after screening as not relevant, not in English or not full-text articles. Twelve full-text articles were included in the review and are presented according to the site of disease, namely BoS, brain or both brain and BoS. This review showed that reirradiation of brain/BoS tumour recurrences with PBT can provide good local control with acceptable toxicity rates. However, reirradiation of tumour recurrences in the CNS or BoS setting needs to consider several factors that can increase the risk of toxicities. Therefore, patient selection is crucial. Randomised evidence is needed to select the best radiation modality in this group of patients.

Volumetric tumor delineation and assessment of its early response to radiotherapy with optical coherence tomography.

Texture analyses of optical coherence tomography (OCT) images have shown initial promise for differentiation of normal and tumor tissues. This work develops a fully automatic volumetric tumor delineation technique employing quantitative OCT image speckle analysis based on Gamma distribution fits. We test its performance in-vivo using immunodeficient mice with dorsal skin window chambers and subcutaneously grown tumor models. Tumor boundaries detection is confirmed using epi-fluorescence microscopy, combined photoacoustic-ultrasound imaging, and histology. Pilot animal study of tumor response to radiotherapy demonstrates high accuracy, objective nature, novelty of the proposed method in the volumetric separation of tumor and normal tissues, and the sensitivity of the fitting parameters to radiation-induced tissue changes. Overall, the developed methodology enables hitherto impossible longitudinal studies for detecting subtle tissue alterations stemming from therapeutic insult.

Abstract 181: The Regenerative Effects Of Reconstruction: An Analysis Of Cutaneous Gene Expression Changes In Irradiated Breast Reconstruction Patients

Purpose: The detrimental effects of radiation therapy on the skin and underlying tissues of breast cancer patients are well documented. While acute changes resolve with time, the overall quality of the skin is forever altered. Breast reconstruction in the context of radiation therapy has been shown to have higher rates of complications and failure, as well as unfavorable aesthetic outcomes. While the adverse effects of radiation are well known, the molecular mechanisms and genetic changes of radiation-induced skin injury are not yet described. Additionally, while there is often clinical improvement in the quality of irradiated tissue with the use of certain reconstructive techniques, the genetic alterations underlying these phenotypic changes are unknown. We utilized RNA Sequencing technology to analyze gene expression profiles of irradiated and non-irradiated breast skin to identify the major pathways that are affected by radiation therapy. Additionally, we used this technology to determine the genetic impact of commonly performed reconstructive breast procedures on these identified dysregulated pathways. Methods: Full thickness skin samples were collected from irradiated and non-irradiated breast cancer patients at the time of mastectomy and either autologous or alloplastic reconstruction. Cases performed in either delayed or immediate fashion were included. Additional samples were collected 3-6 months later at the time of secondary revision. Samples from patients undergoing non-oncologic breast surgery or prophylactic mastectomy were included as controls. Internal control samples were collected when symmetry procedures were performed. All samples were analyzed using RNA-Seq to determine the cellular transcriptome for irradiated versus non-irradiated breast skin, both before and after reconstruction. Gene expression was then analyzed via hierarchical clustering to determine the biologic pathways that were altered by radiation and reconstruction. Results: Gene expression profiles of 50 patients were analyzed. Irradiated samples were shown to have distinct profiles from non-irradiated and control samples. Genomic analysis demonstrated multiple dysregulated biologic pathways in irradiated tissue. In irradiated patients who underwent autologous reconstruction, a number of these dysregulated genetic pathways were reversed to near-normal levels post-reconstruction. This regenerative phenomenon was less clear in the alloplastic reconstruction group. Conclusion: We utilized gene expression profiling to identify biologic pathways that are altered by radiation therapy and demonstrated that autologous reconstruction with microvascular free tissue transfer may restore these dysregulated pathways to resemble non-irradiated, control tissue. We have identified future targets for primary inhibition or pharmacologic rescue of radiation-induced tissue changes. Presently, plastic surgeons can use these findings to tailor reconstructive efforts in irradiated patients to reverse these detrimental phenotypic changes and improve overall reconstructive outcomes.

Is it worth to perform salvage radical prostatectomy for radio-recurrent prostate cancer? A literature review.

Salvage radical prostatectomy (sRP) represents a curative option for prostate cancer (PCa) biochemical recurrence (BCR) after radiation therapy (RT). In this review, we aimed to outline the contemporary results and use of sRP. A web search was performed on the Ovid platform using Embase and Medline databases from January 2010 using pre-defined search terms. Web search was implemented by manual search. Oncological and functional outcomes and complications were summarized using standard classification systems, when feasible. sRP is currently underused, being chosen for radio-recurrent PCa treatment in around 1% of the cases. Surgery is complex due to radiation-induced tissue changes making posterior planes and apex dissection particularly challenging. Patient selection is paramount to maximize the oncological benefit. Most series report a BCR-free survival > 60%, mainly at the end of a short- to intermediate-term follow-up. Five-year progression-free survival is nearly 50% and 5-year cancer-specific survival rates are around 90%. Major peri-operative complications, anastomotic leaks and strictures, still more frequent than in a primary RP setting, have been steering towards more acceptable rates in recent years, when compared to historical series. Continence rates are widely variable, often in between 39 and 60%. Potency remains difficult to recover. sRP represents a curative option with promising short- to medium-term oncological results and acceptable side effects, in high-volume institutions. In appropriately selected patients, the procedure should not be underused due to the fear of poor functional outcomes and/or complications. Prospective studies are needed to assess the long-term outcomes and to further refine patient selection criteria.

Correlation of Appearance of MRI Perinidal T2 Hyperintensity Signal and Eventual Nidus Obliteration Following Photon Radiosurgery of Brain AVMs: Combined Results of LINAC and Gamma Knife Centers

A wide variety of radiologic changes occur within and adjacent to the nidus of arteriovenous malformations (AVMs) after stereotactic radiosurgery (SRS). Our objective was to study the magnetic resonance imaging(MRI)-defined changes following photon radiosurgery of AVMs and specifically to correlate the appearance of a perinidal T2 hyperintensity signal with the eventual angiographic obliteration of an AVM nidus in response to SRS treatment. This retrospective study was conducted on 62 patients with brain AVMs who received photon SRS treatments between 2004 and 2017, using either a technique based on a linear accelerator at the Alexandria LINAC Radiosurgery Center in Egypt (21 patients/AVMs) or a technique based on a gamma unit at the Koto Memorial Gamma Knife Center in Japan (41 patients/AVMs). All patients included in the study had serial clinical and radiologic follow-ups for ≥ 2 years after SRS treatments. In the combined study series of 62 patients/AVMs treated with photon SRS, the follow-up MRIs revealed that 50 AVMs (80.6%) showed nonvisualized nidus and 12 AVMs (19.4%) showed decreased nidus size. Radiation-induced changes, defined as appearance of perinidal T2 hyperintensities in post-SRS MRIs, occurred in 34 patients (54.8%). Of the 35 patients with available follow-up angiographic studies, 30 AVMs (85.7%) demonstrated complete nidus obliteration at a mean of 36 months (range: 8-66 months) after SRS. Of the 30 AVMs with both MRI evidence of a nonvisualized nidus and angiographic verification of complete nidus obliteration, 20 AVMs (66.7%) were associated with prior MRI evidence of the appearance of a perinidal T2 hyperintensity signal at an average of 12 months (range: 6-45 months) after SRS. Of the five AVMs with both MRI evidence of decreased nidus size and angiographic verification of partial nidus obliteration, four AVMs (80%) showed perinidal T2 hyperintensity signal on post-SRS follow-up MRIs. Lower Spetzler-Martin grade (p = 0.013), smaller AVM volume (p = 0.017), and appearance of post-SRS perinidal T2 hyperintensity signal (p = 0.007) were the statistically significant independent predictors of AVM obliteration. The appearance of perinidal T2 hyperintensity signal in the post-SRS MRIs had a sensitivity of 66.7%, a specificity of 20%, and an overall accuracy of 60% in predicting the eventual obliteration of the AVM nidus. The present study may help improve our current understanding of the mechanisms behind the radiation-induced tissue changes following AVM SRS. Because the SRS-induced hemodynamic changes within the AVM nidus initiate the cascade of the subsequent formation of perinidal vasogenic brain edema, the appearance of perinidal high T2 signal in the follow-up MRIs after SRS would be a valuable indicator of the AVM response to SRS. The development of perinidal hyperintensity was the strongest predictive factor of AVM obliteration (p = 0.007), with relatively high sensitivity (66.7%) and accuracy (60%) and fairly low specificity (20%), as a prognostic sign of eventual complete angiographic obliteration of the AVM nidus following SRS.

Accurate Differentiation of Recurrent Gliomas from Radiation Injury by Kinetic Analysis of α-11C-Methyl-l-Tryptophan PET

PET of amino acid transport and metabolism may be more accurate than conventional neuroimaging in differentiating recurrent gliomas from radiation-induced tissue changes. α-(11)C-methyl-l-tryptophan ((11)C-AMT) is an amino acid PET tracer that is not incorporated into proteins but accumulates in gliomas, mainly because of tumoral transport and metabolism via the immunomodulatory kynurenine pathway. The aim of this study was to evaluate the usefulness of (11)C-AMT PET supplemented by tracer kinetic analysis for distinguishing recurrent gliomas from radiation injury. Twenty-two (11)C-AMT PET scans were obtained in adult patients who presented with a lesion suggestive of tumor recurrence on conventional MRI 1-6 y (mean, 3 y) after resection and postsurgical radiation of a World Health Organization grade II-IV glioma. Lesional standardized uptake values were calculated, as well as lesion-to-contralateral cortex ratios and 2 kinetic (11)C-AMT PET parameters (volume of distribution [VD], characterizing tracer transport, and unidirectional uptake rate [K]). Tumor was differentiated from radiation-injured tissue by histopathology (n = 13) or 1-y clinical and MRI follow-up (n = 9). Accuracy of tumor detection by PET variables was assessed by receiver-operating-characteristic analysis. All (11)C-AMT PET parameters were higher in tumors (n = 12) than in radiation injury (n = 10) (P ≤ 0.012 in all comparisons). The lesion-to-cortex K-ratio most accurately identified tumor recurrence, with highly significant differences both in the whole group (P < 0.0001) and in lesions with histologic verification (P = 0.006); the area under the receiver-operating-characteristic curve was 0.99. A lesion-to-cortex K-ratio threshold of 1.39 (i.e., a 39% increase) correctly differentiated tumors from radiation injury in all but 1 case (100% sensitivity and 91% specificity). In tumors that were high-grade initially (n = 15), a higher lesion-to-cortex K-ratio threshold completely separated recurrent tumors (all K-ratios ≥ 1.70) from radiation injury (all K-ratios < 1.50) (100% sensitivity and specificity). Kinetic analysis of dynamic (11)C-AMT PET images may accurately differentiate between recurrent World Health Organization grade II-IV infiltrating gliomas and radiation injury. Separation of unidirectional uptake rates from transport can enhance the differentiating accuracy of (11)C-AMT PET. Applying the same approach to other amino acid PET tracers might also improve their ability to differentiate recurrent gliomas from radiation injury.

Subcontinuous epileptiform activity after failed hippocampal radiosurgery

Although gamma-knife radiosurgery (GKS) has proved efficacious in temporal lobe epilepsy (TLE), its antiepileptic mechanism of action remains elusive. Human and experimental data suggest that subnecrotic radiation-induced tissue changes might contribute to the antiepileptic effect of GKS. However, there are no data regarding the evolution of electroencephalography (EEG) activity within GKS-treated hippocampus, information that aid in better understanding both the mechanism of action and the reason for failure of GKS treatment. Two patients with disabling seizures 4 and 6 years after mesial temporal GKS with a marginal dose of 24 Gy were investigated with stereotactic intracerebral EEG recordings. Both patients had right TLE with hippocampal atrophy, but with past history of Coxsackie virus meningoencephalitis and congenital toxoplasmosis, respectively. Ten to 12 electrodes were implanted, including seven to eight electrodes within the epileptic temporal lobe. In both patients, depths electrodes placed within the irradiated mesial temporal structures disclosed a remarkable pattern of subcontinuous spiking activity intermingled with asymptomatic rhythmic discharges up to 1 min in duration. This activity differed from the abnormalities usually captured in mesial TLE (mTLE) and suggested radiosurgery-induced brain changes. Both patients underwent anterior temporal lobectomy and achieved a class I outcome after a follow-up of 18 and 40 months, respectively. Pathologic examination of the surgical specimens showed variable degrees of radiation-effect changes. Our study shows that mesial temporal structures previously treated with GKS can demonstrate a persistent high degree of epileptiform activity in patients who failed to respond to that treatment. Although this persistent EEG activity appears likely to reflect GKS-induced brain changes, its relation to GKS seizure outcome remains unclear.

Carotid Tortuosity in Patients With Prior Cervical Radiation

Anatomic distortion associated with radiation-induced tissue changes may pose challenges for patients with prior cervical irradiation undergoing carotid stenting. We sought to evaluate the effect of these changes on carotid intervention. Carotid angioplasty and stenting (CAS) for high-grade stenosis was performed in 203 patients. In all, 12 consecutive patients with prior ipsilateral cervical irradiation were age-/sex-matched to 24 controls. Degree of internal carotid (IC) tortuosity was assessed by 4 methods: (a) deviation of IC from common carotid (CCA) axis, (b) number of intersections between this axis and the course of the IC, (c) total degrees of angulation along the course of the extracranial IC, and (d) the IC length to straight-line distance ratio. Carotid angioplasty and stenting was successful in all patients. Mean age was 72.8 ± 10 years; 58.4% were male. Twenty-nine percent were symptomatic (14.4% transient ischemic attack [TIA], 8.5% cardiovascular accident [CVA], and 6.5% amaurosis). Comorbidities were similar between the entire cohort and the subgroups of irradiated/control patients. The IC revealed a higher degree of deviation from the axis of the CCA in the previously irradiated patients compared to those without radiation (29.2° ± 4.5° vs 13.0° ± 2.0°, P = .001) and was more likely to intersect this axis in those with a history of cervical irradiation (83.3% vs 14.3%, P < .05). Irradiated patients also exhibited a significantly greater degree of tortuosity versus nonirradiated patients when assessed by total angulation along the course of the carotid (171.8° ± 26.0° vs 74.2° ± 20.2°, P = .014) and by the IC length:distance ratio (1.14 ± 0.05 vs 1.04 ± 0.03, P = .020). Despite increased IC tortuosity in patients with prior irradiation, all procedures were successfully completed and there did not appear to be a predilection for a specific filter type. A history of cervical irradiation is associated with increased tortuosity of the IC, leading to potential challenges for filter and stent deployment. However, this increased procedural complexity did not affect technical success rate or device selection in this series.

Stereotactic biopsy combined with stereotactic 125iodine brachytherapy for diagnosis and treatment of locally recurrent single brain metastases

This paper reports on stereotactic biopsy combined with stereotactic (125)iodine brachytherapy (SBT) for locally recurrent, previously irradiated cerebral metastases, focusing on feasibility, complications, cerebral disease control, and survival. All patients with suspected locally recurrent metastases detected by MRI were selected for this combined procedure. After stereotactic biopsy, all patients with a verified vital tumor underwent SBT (50 Gy surface dose applied for 42 days) during the same surgical procedure. Histological results of biopsy, complications, treatment response, local and distant disease control, and survival were evaluated. Thirty patients underwent stereotactic biopsy, and 27 were treated with SBT for histologically proved tumor recurrence. There was no treatment-related mortality, and morbidity was transient and low (6.6%). Median survival was 14.8 months. After one year the actuarial incidence of local and distant relapse was 6.7 and 45.5%, respectively. There was no grade 3 or 4 CNS toxicity, even among the 18.5% of patients with tumors >30 mm. For these patients stereotactic biopsy seems to be a safe and valuable means of differentiating between radiation-induced tissue changes and tumor recurrence/progression. SBT is a safe, minimally invasive, and highly effective treatment option for cerebral disease control and survival. Furthermore, it can be performed during the same stereotactic operation.

MRI before and after external beam intensity-modulated radiotherapy of patients with prostate cancer: The feasibility of monitoring of radiation-induced tissue changes using a dynamic contrast-enhanced inversion-prepared dual-contrast gradient echo sequence

Purpose To identify and quantify suitable pharmacokinetic MRI parameters for monitoring tissue changes after external beam intensity-modulated radiotherapy of prostate cancer. Material and methods Six patients with biopsy-proven prostate cancer (initial PSA, 6.0–81.4 ng/ml) underwent MRI at 1.5 T using a combined endorectal/body phased-array coil and a dynamic contrast-enhanced inversion-prepared dual-contrast gradient echo sequence (T1/T2 ∗w; 1.65 s temporal resolution). MRI was performed before and immediately after radiotherapy, at 3 months and at 1 year. Perfusion, blood volume, mean transit time, delay, dispersion, interstitial volume, and extraction coefficient were calculated in prostate cancer and normal prostate for all four time points using a sequential 3-compartment model. Results Prostate cancer and normal prostate tissue showed a statistically significant decrease in perfusion ( p = 0.006, p = 0.001) and increase in extraction coefficient ( p = 0.004, p < 0.001). For prostate cancer, there was also a decrease in vascular volume ( p = 0.034). The other parameters investigated showed no statistically significant changes. Statistically significant differences between prostate cancer and normal prostate tissue were only observed before radiotherapy, when prostate cancer showed significantly higher perfusion (1.84 vs. 0.12 ml/cm 3 min, p = 0.028) and a smaller extraction coefficient (0.42 vs. 0.64, p = 0.028). Conclusions Two pharmacokinetic parameters, perfusion and extraction coefficient, appear to be suitable candidates for monitoring the response to percutaneous intensity-modulated radiotherapy of prostate cancer.

Radiation-induced changes of brain tissue after radiosurgery in patients with arteriovenous malformations: correlation with dose distribution parameters

purpose To investigate the correlation of radiation-induced changes of brain tissue after radiosurgery in patients with cerebral arteriovenous malformations (AVMs) with treatment planning and dose distribution parameters. Methods and materials The data from 73 AVM patients with complete follow-up information who underwent stereotactic linear accelerator radiosurgery at our institution between 1993 and 1998 were analyzed. Patients were treated with 11–14 noncoplanar fields shaped by a micromultileaf collimator. A median dose of 19 Gy (range, 13.3–22 Gy) was prescribed to the 80% isodose, which completely encompassed the target. Patients were followed at 3-month intervals the first year and then every 6 months with MRI and neurologic examinations. No patient developed radiation necrosis. The end point of radiation-induced tissue changes on follow-up neuroimaging (i.e., edema, blood–brain barrier breakdown [BBBB], and edema and/or BBBB combined) was evaluated. Each end point was further differentiated into four levels with respect to the extent of the image change (i.e., small, intermediate, large, and very large). The correlation of each end point was investigated for several treatment planning parameters, including prescribed dose and the absolute size of the AVM target volume. In addition, a number of dose–volume variables were calculated from each patient's dose distribution in the brain, including the mean dose to a specified volume of 16 and 20 cm 3 that was given the highest dose (Dmean16 and Dmean20, respectively), and the absolute and percentage of brain volume (including the AVM target) receiving a dose of at least 8, 10, and 12 Gy (V8–V12, and V8 rel–V12 rel, respectively). These parameters were also determined excluding the AVM target volume from the considered volume (subscript “excl”). The correlation of all treatment planning and dose–volume parameters with outcome was assessed in univariate Cox proportional hazards models. The results were assessed by p values (statistical significance for p ≤0.05), residual deviance (ResDev) of the fits, and odds ratios. Results The prescribed dose was not predictive of outcome ( p >0.05 for all end points). The AVM target volume correlated significantly with large edema, as well as large edema and/or BBBB. V12 and Dmean20 were significantly associated with all end points, except very large edema and large BBBB. Patients with V12 of 27.6 cm 3 (Dmean20 of 18.9 Gy) had a 2.8-fold (fourfold) higher risk of developing edema and/or BBBB with large extent than those with V12 of 4.2 cm 3 (Dmean20 of 8.4 Gy). For all end points, V12 rel correlated worse with outcome compared with V12 (e.g., end point of large edema and/or BBBB: ResDev = 85.8 and 86.5 for V12 and V12 rel, respectively). Excluding the AVM target volume from the considered irradiated volume led to only small changes in the resulting correlations (e.g., end point of small edema and/or BBBB: ResDev = 99.0 and 98.7 for V12 and V12 excl, respectively, and ResDev = 96.1 and 96.1 for Dmean20 and Dmean20 excl, respectively). Throughout the analysis, V8-V12, Dmean20, and Dmean16 yielded similar results and none of these parameters could be favored over the others. Conclusion Radiation-induced changes of brain tissue after AVM radiosurgery can be well predicted by single dose distribution parameters that are a function of both dose and volume. These can be used to quantify dose–volume response relations. Studies of this nature will eventually help to improve our current understanding of the mechanisms leading to radiation-induced tissue changes after AVM radiosurgery and to optimize radiosurgery treatment planning.

Risk analysis of LINAC radiosurgery in patients with arteriovenous malformation (AVM).

The purposes of this analysis were the evaluation of the toxicity of stereotactic single dose irradiation in patients with an arteriovenous malformation (AVM) and the comparison of the authors' own results with already existing risk prediction models. Computed-tomography (CT) or magnetic-resonance (MR) images, and clinical data of patients treated with linear accelerator radiosurgery for an AVM were analysed retrospectively. Using the Cox proportional hazards model (1), the relevance of treatment parameters and dose-volume relationships to the occurrence of radiation-induced tissue changes (oedema and localised blood-brain-barrier breakdown) were assessed. The 81 patients selected for analysis had a mean follow-up of 28.9 months (range: 9.0-65.7 months). Radiation-induced tissue changes (22 out of 81 i.e. 27.2%) were documented on CT or MR images 6.3-33.8 months after radiosurgery (median time: 12.8 months). The actuarial risk at 2 years was 32.1% for the development of neuroradiological changes and 20.1% for the development of symptomatic tissue alteration. The coefficient of total volume receiving a minimum dose of 10 Gy (VTREAT10) reached statistical significance in a Cox proportional hazards model. These results demonstrate the particular vulnerability of normal brain tissue to single dose irradiation. Optimal conformation of the therapeutic isodose line to the 3D configuration of the target volume may help to reduce side effects.

Risk analysis of linear accelerator radiosurgery

Purpose: To evaluate the toxicity of steriotactic single-dose irradiation and to compare the own results with already existing risk prediction models.Methods and Materials: Computed tomography (CT) or magnetic-resonance (MR) images, and clinical data of 133 consecutive patients treated with linear accelerator radiosurgery were analyzed retrospectively. Using the Cox proportional hazards model the relevance of treatment parameters and dose-volem relationships on the occurrence of radiation-induced tissue changes (edema, localized blood-brain barrier breakdown) were assessed.Results: Sixty-two intraparenchymal lesions (arteriovenous malformation (AVM): 56 patients, meningioma: 6 patients) and 73 skull base tumors were selected for analysis. The median follow-up was 28.1 months (range: 9.0–58.9 months). Radiation-induced tissue changes (32 out of 135, 23.7%) were documented on CT or MR images 3.6–58.7 months after radiosurgery (median time: 17.8 months). The actuarial risk at 2 years for the development of neuroradiological changes was 25.8% for all evaluated patients, 38.4% for intraparenchymal lesions, and 14.6% for skull base tumors. The coefficient: total volume receiving a minimum dose of 10 Gy (VTREAT10) reached statistical significance in a Cox proportional hazards model calculated for all patients, intraparenchymal reached statistical significance in a Cox proportional hazards model calculated for all patients, intraparenchymal lesions, and AVMs. Is skull base tumors, the volume of normal brain tissue covered by the 10 Gy isodose line (VBRAIN10) was the only significant variable.Conclusions: These results demonstrate the particular vulnerability of normal brain tissue to single dose irradiation. Optimal conformation of the therapeutic isodose line to the 3D configuration of the target volume may help to reduce side effects.