Abstract PURPOSE: Melanoma brain metastases (MBM) are among the most common solid tumors associated with intracranial hemorrhage (ICH). Our objective is to investigate risk factors for post-radiosurgery intracranial hemorrhage (PRH). METHODS: We collected demographic, clinical, treatment, toxicity, survival, and imaging data for patients with solid MBM who underwent SRS between 2000 and 2016 at our institution. Bleed free survival (BFS) and overall survival (OS) analyses were performed using Kaplan–Meier methods. Logistic regression was used to identify PRH risk factors. RESULTS: From 2000 to 2016, 107 patients with a total of 548 solid MBM received SRS. Median patient age at time of SRS was 63.2 years. Median MBM volume was 2.8 cm3 (range 0.01–21.3 cm3). MBM were in the cortex (n = 431), cerebellum (n= 85), basal ganglia (n= 23), and brain stem (n= 9). MBM were treated to a median dose of 20 Gy (range 14–20 Gy). Seventeen patients received immunotherapy (IT) within 1 year of SRS, 7 patients received concurrent immunotherapy (XR-IT). Median follow-up and OS was 13.5 months and 10.8 months, respectively. Median BFS was 8.3 months. PRH occurred in 123 MBM (22%). MBM volume (p= 0.0001), total MBM volume (p= 0.0006), IT (p= 0.04), and XR-IT (p= 0.03) were associated with increased PRH. PRH cumulative incidence within 24 mo of SRS was increased in MBM > 2.8 cm3 compared with patients with smaller MBM: 27.5% verse 5.3%, respectively. Age, sex, hypertension, MBM location, total MBM number, and marginal dose (p > 0.05) did not significantly impact risk of PRH. No significant difference in 6, 12, or 24 mo actuarial OS rates were observed in patients with PRH (p > 0.05). CONCLUSIONS: Patients with larger MBM volume and IT within 1 year of SRS have the greatest risk of PRH. PRH did not significantly impact OS in this study.

Patients receiving radiotherapy (RT) for oropharyngeal carcinoma are at risk of mandibular toxicity. Risk factors include RT dose exceeding 60 Gy, local trauma, and uncontrolled periodontal disease. Treatment-related osteonecrosis is likely due to changes in bone remodeling. We aim to identify longitudinal changes in mandibular cortical thickness (C.Th) of patients treated with definitive RT for oropharyngeal cancer using quantitative computed tomography (CT). Forty-four patients with squamous cell carcinoma of the oropharynx treated with definitive chemoradiotherapy between 2016-2017 were included in this Institutional Review Board-approved study. A validated bone mapping technique was used to examine the cortical bone changes in the mandible. Briefly, the mandible was segmented from baseline and follow-up clinical CT data using Mimics and C.Th was calculated using Stradwin at thousands of points across the mandibular surface. Iterative closed point (ICP) registration was performed in a computer algorithm software and cortical changes between baseline and follow-up were calculated for corresponding points. The significance of the changes for each point on the surface between the baseline and follow-up scans was calculated. Statistical analyses on the surface maps were performed using a computer software toolbox for the statistical analysis of univariate and multivariate data using linear mixed effects models. The majority of patients had stage III-IV disease (98%) and a tonsil or base of tongue primary (93%). The median age was 60 years and 91% were male. All patient received concurrent chemotherapy and 11% received additional induction chemotherapy. Dental extractions were performed prior to RT in 63%; 4 patients were edentulous. Median time between baseline and follow-up imaging was 90.5 days (range, 25-190). Median volumes receiving 60 Gy for the symphysis, body, angle, and ramus were 0.8%, 29%, 76%, and 43% respectively. Mean C.Th at baseline and follow-up were 2.6 mm (95% CI 2.5-2.7) and 2.4 mm (95% CI 2.3-2.5) respectively, with an overall mean difference of 0.2 mm (95% CI 0.1-0.2, p<0.001). Significant C.Th loss was observed bilaterally at all anatomic locations, however symphyseal and proximal regions (-8.9%) incurred the greatest loss across patients. Greater C.Th loss was observed in patients that underwent pre-RT dental extractions (-7.0%, p<0.001) than those that did not (-4.6%, p=0.11). This study provides new insights into the early effects of head and neck RT on the mandible and suggest an increased bone remodeling following treatment throughout the mandible. Dental extractions prior to RT increase the extent of bone loss. No dose response was observed in this study, however further evaluation of a dose-response relationship are warranted.

The treatment of melanoma brain metastases with stereotactic radiosurgery (SRS) remains a challenge, in part due to the relative radioresistance of melanoma, which recent evidence suggests may be related at least in part to BRAF status. In this study we attempt to discern the clinical, dosimetric, and radiographic factors predictive of relative radioresistance in melanoma brain metastases. From January 2000 to December 2015, a total of 107 patients with 540 melanoma brain metastases were treated with SRS. Patient characteristics were stratified by BRAF mutation status. Time-to-event outcomes were summarized using the Kaplan-Meier estimator. Probability of local failure was estimated with the cumulative incidence method. For spatial analysis, each patient’s magnetic resonance imaging (MRI) DICOM files were converted to NIfTI format and then registered to MNI-152 template space using ANTs affine registration. The transformations used for this registration were then applied to each segmented lesion. Lesions were categorized by local failure status, after which Fisher exact tests were performed for each voxel to determine regions with higher likelihood of local failure. For dosimetric analysis, dose-volume data was analyzed for all lesions, and logistic regressions for local failure were performed at discrete intervals for both dose received by a given volume (VD(Gy)) and volume receiving a given dose (DV(%)). Median overall survival (OS) for all patients was 7.7 mo (CI: 5.3-11.0 mo). OS at 6,12, and 24 months for all patients was 56.3%, 35.8%, and 21.6%, respectively. The cumulative incidence of local failure at one and two years for all patients was 2.3% and 3.3%. The cumulative incidence of local failure at 1 and 2 years was 5.8% and 8.6% for BRAF wildtype (WT) vs. 1.5% and 1.5% for BRAF mutated (Gray’s p-value = 0.002). Tumor volume (cm3; continuous) was also predictive of local failure (HR: 1.13, 95% CI: 1.08-1.19, p <0.001). Voxelwise spatial analysis revealed that lesions in the superior frontal gyrus had a significantly higher likelihood of experiencing local failure (p = 0.001). There was also a higher likelihood of metastasis from BRAF WT versus BRAF mutated in the right superior frontal gyrus (p = 0.03). Dosimetric analysis revealed the most statistically significant predictors of local failure to be the V23.1Gy for BRAF mutated (p=0.001) and the V25.1Gy for BRAF WT(p = 0.004). Fitted logistic regression models were created to determine the probability of local failure associated with several representative discrete doses (Gy) and relative volumes (%) based on BRAF status. Tumor volume, BRAF status, and lesion location predict for local control in melanoma brain metastases. BRAF WT requires higher SRS doses for comparable local control compared to BRAF mutated. Additionally, it appears there may be a spatial component contributing to local failure patterns which would benefit from further investigation.

BACKGROUND:Treatment options are limited for large, unresectable brain metastases.OBJECTIVE:To report a single institution series of staged stereotactic radiosurgery (SRS) that allows for tumor response between treatments in order to optimize the therapeutic ratio.METHODS:Patients were treated with staged SRS separated by 1 mo with a median dose at first SRS of 15 Gy (range 10-21 Gy) and a median dose at second SRS of 14 Gy (range 10-18 Gy). Overall survival was evaluated using the Kaplan-Meier method. Cumulative incidences were estimated for neurological death, radiation necrosis, local failure (marginal or central), and distant brain failure. Absolute cumulative dose-volume histogram was created for each treated lesion. Logistic regression and competing risks regression were performed for each discrete dose received by a certain volume.RESULTS:Thirty-three patients with 39 lesions were treated with staged radiosurgery. Overall survival at 6 and 12 mo was 65.0% and 60.0%, respectively. Cumulative incidence of local failure at 6 and 12 mo was 3.2% and 13.3%, respectively. Of the patients who received staged therapy, 4 of 33 experienced local failure. Radiation necrosis was seen in 4 of 39 lesions. Two of 33 patients experienced a Radiation Therapy Oncology Group toxicity grade > 2 (2 patients had grade 4 toxicities). Dosimetric analysis revealed that dose (Gy) received by volume of brain (ie, VDose(Gy)) was associated with radiation necrosis, including the range V44.5Gy to V87.8Gy.CONCLUSION:Staged radiosurgery is a safe and effective option for large, unresectable brain metastases. Prospective studies are required to validate the findings in this study.

Background and purpose: Anal cancer patients treated with radiation therapy (RT) have an increased risk of hip fractures after treatment. The mechanism of these fractures is unknown; however, femoral fractures have been correlated with cortical bone thinning. The objective of this study was to assess early changes in cortical bone thickness at common sites of femoral fracture in anal cancer patients treated with intensity modulated radiation therapy (IMRT).Materials and methods: RT treatment plans and computed tomography (CT) scans from 23 anal cancer patients who underwent IMRT between November 2012 and December 2014 were retrospectively reviewed. Cortical thickness (Ct.Th) was mapped at homologous vertices within the proximal femur using pre-RT and post-RT (<= 4 months) CT scans. The bone attenuation measurements were collected at homologous locations within the trabecular bone of the right femoral neck (FN). The percent change in Ct.Th and trabecular bone mineral density (trBMD) were assessed. FN cortical thinning was correlated to RT dose using linear regression. A logistic model for dose dependent cortical thinning was constructed.Results: Twenty-two patients were analyzed. Significant post-treatment cortical thinning was observed in the intertrochanteric crest, subcapital and inferior FN (p < 0.05). FN volume receiving >= 40Gy (V40Gy) was a significant predictor of focal cortical thinning >= 30% (p = 0.03). A significant decrease in FN trBMD was observed (-6.4% [range -34.4 to 33%]; p = 0.01).Conclusion: Significant early decrease in Ct.Th and trBMD occurs at the FN in patients treated with RT for anal cancer. FN V40Gy was predictive of clinically significant focal FN cortical thinning. (C) 2016 Elsevier Inc. All rights reserved.

Purpose: Radiation-induced cognitive decline is relatively common after treatment for primary and metastatic brain tumors; however, identifying dosimetric parameters that are predictive of radiation-induced cognitive decline is difficult due to the heterogeneity of patient characteristics. The memory function is especially susceptible to radiation effects after treatment. The objective of this study is to correlate volumetric radiation doses received by critical neuroanatomic structures to post–radiation therapy (RT) memory impairment. Methods and materials: Between 2008 and 2011, 53 patients with primary brain malignancies were treated with conventionally fractionated RT in prospectively accrued clinical trials performed at our institution. Dose-volume histogram analysis was performed for the hippocampus, parahippocampus, amygdala, and fusiform gyrus. Hopkins Verbal Learning Test-Revised scores were obtained at least 6 months after RT. Impairment was defined as an immediate recall score ≤15. For each anatomic region, serial regression was performed to correlate volume receiving a given dose (VD(Gy)) with memory impairment. Results: Hippocampal V53.4Gy to V60.9Gy significantly predicted post-RT memory impairment (P < .05). Within this range, the hippocampal V55Gy was the most significant predictor (P = .004). Hippocampal V55Gy of 0%, 25%, and 50% was associated with tumor-induced impairment rates of 14.9% (95% confidence interval [CI], 7.2%-28.7%), 45.9% (95% CI, 24.7%-68.6%), and 80.6% (95% CI, 39.2%-96.4%), respectively. Conclusions: The hippocampal V55Gy is a significant predictor for impairment, and a limiting dose below 55 Gy may minimize radiation-induced cognitive impairment.

Stereotactic body radiation therapy (SBRT) is associated with an increased risk of vertebral compression fracture. While bone is typically considered radiation resistant, fractures frequently occur within the first year of SBRT. The goal of this work was to determine if rapid deterioration of bone occurs in vertebrae after irradiation. Sixteen male rhesus macaque non-human primates (NHPs) were analyzed after whole-chest irradiation to a midplane dose of 10 Gy. Ages at the time of exposure varied from 45–134 months. Computed tomography (CT) scans were taken 2 months prior to irradiation and 2, 4, 6 and 8 months postirradiation for all animals. Bone mineral density (BMD) and cortical thickness were calculated longitudinally for thoracic (T) 9, lumbar (L) 2 and L4 vertebral bodies; gross morphology and histopathology were assessed per vertebra. Greater mortality (related to pulmonary toxicity) was noted in NHPs <50 months at time of exposure versus NHPs >50 months (P = 0.03). Animals older than 50 months at time of exposure lost cortical thickness in T9 by 2 months postirradiation (P = 0.0009), which persisted to 8 months. In contrast, no loss of cortical thickness was observed in vertebrae out-of-field (L2 and L4). Loss of BMD was observed by 4 months postirradiation for T9, and 6 months postirradiation for L2 and L4 (P < 0.01). For NHPs younger than 50 months at time of exposure, both cortical thickness and BMD decreased in T9, L2 and L4 by 2 months postirradiation (P < 0.05). Regions that exhibited the greatest degree of cortical thinning as determined from CT scans also exhibited increased porosity histologically. Rapid loss of cortical thickness was observed after high-dose chest irradiation in NHPs. Younger age at time of exposure was associated with increased pneumonitis-related mortality, as well as greater loss of both BMD and cortical thickness at both in- and out-of-field vertebrae. Older NHPs exhibited rapid loss of BMD and cortical thickness from in-field vertebrae, but only loss of BMD in out-of-field vertebrae. Bone is sensitive to high-dose radiation, and rapid loss of bone structure and density increases the risk of fractures.

Purpose of Review Normal bone is commonly irradiated during radiation therapy (RT). The true impact of focal radiation on bone tissue remains unclear. The goal of this paper is to present the current understanding of radiation effects on the bone as it pertains to clinically observed radiation side effects. Recent Findings An increased risk of local fracture has been associated with RT-induced bone loss in the pelvis, vertebrae, and ribs. This bone loss appears to occur early after and/or during treatment, which suggests that reactive remodeling of the bone via osteoclast activity is a primary contributor to bone loss and fractures. Summary Several reports have quantified the structural and histological changes observed after bone irradiation. These include changes in bone density and cortical thickness, as well as alterations in both the number and activity of the cells responsible for bone turnover that arise from hematopoietic and mesenchymal lineages: namely, osteoclasts and osteoblasts. All of these changes likely play an important role in the increased risk of fracture reported with RT. However, more research is needed to fully understand the mechanisms of bone damage and its relationship to modifiable factors such as beam energy, dose, photon or charged particle radiation, linear energy transfer (LET), fractionation, and field size.

Introduction The roles of early whole brain radiotherapy (WBRT) and upfront stereotactic radiosurgery (SRS) alone in the treatment of melanoma patients with brain metastasis remain uncertain. We investigated the volumetric kinetics of brain metastasis development and associations with clinical outcomes for melanoma patients who received upfront SRS alone. Methods Volumetric brain metastasis velocity (vBMV) was defined as the volume of new intracranial disease at the time of distant brain failure (DBF) for the first DBF (DBF1) and second DBF (DBF2) averaged over the time since initial or most recent SRS. Non-volumetric brain metastasis velocity (BMV) was calculated for comparison. Results Median overall survival (OS) for all patients was 7.7 months. Increasing vBMVDBF1 was associated with worsened OS (hazard ratio (HR): 1.10, confidence interval (CI): 1.02 - 1.18, p = .01). Non-volumetric BMVDBF1 was not predictive of OS after DBF1 (HR: 1.00, CI: 0.97 - 1.02, p = .77). Cumulative incidence of DBF2 at three months after DBF1 was 50.0% for vBMVDBF1 > 4 cc/yr versus (vs) 15.1% for vBMVDBF1 ≤ 4 cc/yr, (Gray's p-value = .02). Cumulative incidence of salvage WBRT at three months after DBF1 was 50.0% for vBMVDBF1 > 4 cc/yr vs 2.3% for vBMVDBF1 ≤ 4 cc/yr (Gray's p-value < .001). Conclusion In melanoma patients with brain metastasis, volumetric BMV was predictive of survival, shorter time to second DBF, and the need for salvage WBRT. Non-volumetric BMV, however, did not predict for these outcomes, suggesting that vBMV is a stronger predictor in melanoma.

OBJECTIVE There are a variety of salvage options available for patients with brain metastases who experience local failure after stereotactic radiosurgery (SRS). These options include resection, whole-brain radiation therapy, laser thermoablation, and repeat SRS. There is little data on the safety and efficacy of repeat SRS following local failure of a prior radiosurgical procedure. This study evaluates the clinical outcomes and dosimetric characteristics of patients who experienced tumor recurrence and were subsequently treated with repeat SRS. METHODS Between 2002 and 2015, 32 patients were treated with repeat SRS for local recurrence of ≥ 1 brain metastasis following initial SRS treatment. The Kaplan-Meier method was used to estimate time-to-event outcomes including overall survival (OS), local failure, and radiation necrosis. Cox proportional hazards analysis was performed for predictor variables of interest for each outcome. Composite dose-volume histograms were constructed for each reirradiated lesion, and these were then used to develop a predictive dosimetric model for radiation necrosis. RESULTS Forty-six lesions in 32 patients were re-treated with a second course of SRS after local failure. A median dose of 20 Gy (range 14-22 Gy) was delivered to the tumor margin at the time of repeat SRS. Local control at 1 year was 79% (95% CI 67%-94%). Estimated 1-year OS was 70% (95% CI 55%-88%). Twelve patients had died at the most recent follow-up, with 8/12 patients experiencing neurological death (as described in Patchell et al.). Eleven of 46 (24%) lesions in 11 separate patients treated with repeat SRS were associated with symptomatic radiation necrosis. Freedom from radiation necrosis at 1 year was 71% (95% CI 57%-88%). Analysis of dosimetric data revealed that the volume of a lesion receiving 40 Gy (V40Gy) was the most predictive factor for the development of radiation necrosis (p = 0.003). The following V40Gy thresholds were associated with 10%, 20%, and 50% probabilities of radiation necrosis, respectively: 0.28 cm3 (95% CI 3%-28%), 0.76 cm3 (95% CI 9%-39%), 1.60 cm3 (95% CI 26%-74%). CONCLUSIONS Repeat SRS appears to be an effective salvage option for patients with brain metastases experiencing local failure following initial SRS treatment. This series demonstrates durable local control and, although rates of radiation necrosis are significant, repeat SRS may be indicated for select cases of local disease recurrence. Because the V40Gy is predictive of radiation necrosis, limiting this value during treatment planning may allow for a reduction in radiation necrosis rates.

Background and Purpose: High rates of spontaneous rib fractures are associated with thoracic stereotactic body radiation therapy (SBRT). These fractures likely originate within the cortical bone and relate to the cortical thickness (Ct.Th). We report the development and application of a novel Ct.Th and radiation dose mapping technique to assess early site-specific changes of cortical bone in ribs.Materials and methods: Rib Ct.Th maps were constructed from pre-SBRT and 3 month post-SBRT CT scans for 28 patients treated for peripheral lung lesions. The Ct.Th at approximately 50,000 homologous points within the entire rib cage was determined pre- and post-SBRT. Each rib was then divided into 30 homologous regions. The mean dose and thinning were determined per section.Results: Regions of ribs that received >= 10 Gy exhibited significant thinning of cortical bone (p = 0.001). The mean Ct.Th percent difference (95% CI) in regions receiving 10-20 Gy, 20-30 Gy, 30-40 Gy, and >= 40 Gy were -7% (-4%,-11%), 14% (-18%,-11%), 15% (-19%,-11%), and 18% (-22%,-15%) respectively. Regions receiving >20 Gy experienced significantly more thinning than regions receiving lower doses.Conclusions: Substantial early cortical bone thinning was observed post-SBRT in regions of ribs that received >= 10 Gy. The rapid thinning of ribs may predispose ribs to fracture after SBRT. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Cancer-related cognitive impairment (CRCI) is relatively common after treatment of primary and metastatic brain tumors, however the temporality of cognitive decline after radiation therapy (RT) is not well defined, with reports of both early (<4 months) and late onset (>12 months) symptoms. Identifying dosimetric parameters predictive of CRCI is difficult due to the heterogeneity of patient characteristics, as well as inadequate documentation of confounding factors. Memory function is especially susceptible to radiation effect after treatment. The objective of this study is to correlate volumetric radiation doses received by critical neuroanatomic structures to post-RT memory impairment. Between 2008 and 2011, 53 patients with primary brain malignancies were treated with conventionally fractionated RT on a prospectively accrued clinical trial performed at our institution (WFU97100/91105). Tumor types included glioblastoma (13%), primitive neuroectodermal tumors (21%), and low grade/benign tumors (66%).Ten patients received whole brain RT with region boost, all other patients received partial brain RT. The median radiation dose was 54.0 Gy (range = 40.0-60.6 Gy) delivered in 1.8 Gy/fraction (range = 1.5-2.5 Gy/fraction). Dose-volume histogram analysis was performed for the hippocampus, parahippocampus, amygdala, and fusiform gyrus. Hopkins Verbal Learning Test-Revised (HVLT-R) scores were obtained at least 6 months after RT. Impairment was defined as a HVLT-R immediate recall score ≤15, based upon studies reporting optimal sensitivity and specificity for detecting impairment using HVLT-R cut-off scores of 14.5-15.5. For each anatomic region, serial regression was performed to correlate volume receiving a given dose (VD(Gy)) with memory impairment. Hippocampal V53.4Gy - V60.9Gy significantly predicted post-RT memory impairment (P < 0.05). Within this range, the hippocampal V55Gy was the most significant predictor (P = 0.004). Hippocampal V55Gy of 0%, 25%, and 50% were associated with post-RT impairment rates of 14.9% (95% CI = 7.2% - 28.7%), 45.9% (95% CI = 24.7% - 68.6%), and 80.6% (95% CI = 39.2% - 96.4%), respectively. Dose received by the fusiform gyrus was a significant predictor of impairment, with the most significant relationship at V46.5Gy (P = 0.003). No statistically significant relationship was observed for the amygdala or parahippocampus. Injury to the hippocampus plays a fundamental role in CRCI. This analysis provides dosimetric guidelines to limit cognitive decline after cranial RT. The hippocampal V55Gy is a significant predictor for impairment and limiting dose below 55 Gy may minimize treatment related neuro-cognitive toxicity.

Thoracic stereotactic body radiation therapy (SBRT) leads to an increased incidence of spontaneous rib fractures often occurring early after treatment. The etiology of radiation induced rib fracture (RIRF) is unclear, but likely results from bone damage and deterioration. Spontaneous fractures are believed to initiate within cortical bone; cortical thickness (C.Th) is a major determinant of the bone strength. Unfortunately, thin laminar structures comprising the bone cortex of ribs are poorly visualized on clinical CT images due to limited spatial resolution. The objective of this study was to assess early radiation effects on the C.Th of ribs after SBRT using a novel C.Th mapping technique capable of resolving thickness differences >30 μm. Rib cortical thickness maps were constructed from pretreatment and follow-up CT scans acquired 4 months after SBRT for 40 patients treated for primary and metastatic lung malignancies. Patients were treated with several dose fractionation schedules: 50 Gy × 10 fractions (fr) (n = 5), 50 Gy × 5 fr (n = 13), 45 Gy × 3 fr (n = 5), and 54 Gy × 3 fr (n = 7). Post-treatment scans were registered to corresponding pretreatment scans using rigid body transformation. Regions of interest (ROI) along the length of each rib were defined in 10 Gy increments (0 – 50 Gy) and clustered into the following groupings for analysis based on absorbed dose: 0–10 Gy; 20–30 Gy; 30–40 Gy; and >40 Gy. Regions receiving dose on the internal and external surface were analyzed independently, and irradiated regions with volumes <0.5 cm3 were excluded. The mean C.Th within each ROI was determined pre-SBRT and post-SBRT, and the percent difference was calculated. Data were compared using Kruskal-Wallace ANOVA to identify main effects of dose on C.Th, with Dunn's post-hoc analysis for between group differences. Exposure to radiation at doses >20 Gy resulted in significant thinning of cortical bone at the both the internal (P = .029) and external (P = .008) rib surfaces. While no significant cortical thinning was observed at either the internal (+0.5%) or external (-2.9%) surfaces in ribs absorbing 0–10 Gy; significant thinning occurred at, i] the internal surface at locations absorbing 20–30 Gy (-12.7%; P = .013), 30–40 Gy (-12.3%; P = .017); and marginally lower at 40+ Gy (-9.5%; P = 0.08); and ii] the external surface at ROIs absorbing 20–30 Gy (-12.0%; P = .004), 30–40 Gy (-15.4%, P = .003), and 40+ Gy (-9.6%, P = .024). This substantial thinning of cortical bone at both external and internal surfaces could greatly increase the risk of spontaneous fracture. Stereotactic body radiation therapy induced rapid thinning of the cortical bone throughout ribs that absorb >20 Gy. The thinning of cortical bone in irradiated regions of the rib likely contributes to the occurrence of RIRF in patients treated with SBRT.

Purpose/Objective(s)Pelvic insufficiency fractures (PIF) occur in 15-45% of patients following radiation therapy. Studies have demonstrated regions of cortical bone thinning by 30% at common fracture sites in the pelvis. New image processing techniques facilitate the accurate detection of cortical thickness (CTh) using standard CT scans. Acute changes occurring within 1-2 months of treatment have not been assessed. The objective of this study was to evaluate acute changes of CTh in the proximal femur following external beam radiation therapy (EBRT).Materials/MethodsFemoral head CTh maps were constructed from a control scan (1-3 months prior to radiation), the CT simulation scan, and the CT scan performed within 1-2 months following treatment in patients treated for pelvic malignancies. The CTh values from the control scan and simulation scan were compared to establish baseline pretreatment values. Using the radiation treatment plans, dose regions were created in 10 Gy increments ranging from 0 Gy to 60 Gy. Regions of interest (ROI) were defined as the intersection of the dose regions and femoral head. The pretreatment scans were registered to the posttreatment scan using rigid body transformation, and analogous ROIs were identified. A similar process was performed to obtain the ROI for the control subjects. The mean CTh within each ROI was determined posttreatment and compared to the baseline thickness using a repeated measures ANCOVA model that included patient age, gender, chemotherapy treatment, and radiation exposure as main effects.ResultsFifty-one femoral heads were analyzed from 27 patients (15 female). Median patient age was 54 years (range 30 to 87). Radiation treatment techniques included VMAT, 3-field, and 4-field arrangements. Treatments were performed primarily using 6 or 10 MV photons. Dose to the femoral head ranged from 0-59.2 Gy. Median date to follow-up scans was 15 days (range 0 to 52) from the last radiation treatment. The effect of radiation exposure on CTh was significant (P=.050). Significant cortical bone thinning versus control was observed in all ROIs that absorbed >20 Gy, with a mean loss of 15.4% (P=.006), 14.1% (P=.017), and 14.4% (P=.011) in the 20-30 Gy, 30-40 Gy, and > 40 Gy ROIs, respectively. Conversely, the overall effect of age, gender, and use of chemotherapy were not significant.ConclusionThe significant reduction of femoral head CTh of up to 15% seen in patients receiving EBRT in the acute setting presents a possible mechanism for radiation induced fracture. This suggests CTh may be a potential marker for radiation induced PIF. Early CTh loss appears to be primarily affected by radiation exposure. Further research is needed evaluating the correlation between CTh and incidence of fracture. Purpose/Objective(s)Pelvic insufficiency fractures (PIF) occur in 15-45% of patients following radiation therapy. Studies have demonstrated regions of cortical bone thinning by 30% at common fracture sites in the pelvis. New image processing techniques facilitate the accurate detection of cortical thickness (CTh) using standard CT scans. Acute changes occurring within 1-2 months of treatment have not been assessed. The objective of this study was to evaluate acute changes of CTh in the proximal femur following external beam radiation therapy (EBRT). Pelvic insufficiency fractures (PIF) occur in 15-45% of patients following radiation therapy. Studies have demonstrated regions of cortical bone thinning by 30% at common fracture sites in the pelvis. New image processing techniques facilitate the accurate detection of cortical thickness (CTh) using standard CT scans. Acute changes occurring within 1-2 months of treatment have not been assessed. The objective of this study was to evaluate acute changes of CTh in the proximal femur following external beam radiation therapy (EBRT). Materials/MethodsFemoral head CTh maps were constructed from a control scan (1-3 months prior to radiation), the CT simulation scan, and the CT scan performed within 1-2 months following treatment in patients treated for pelvic malignancies. The CTh values from the control scan and simulation scan were compared to establish baseline pretreatment values. Using the radiation treatment plans, dose regions were created in 10 Gy increments ranging from 0 Gy to 60 Gy. Regions of interest (ROI) were defined as the intersection of the dose regions and femoral head. The pretreatment scans were registered to the posttreatment scan using rigid body transformation, and analogous ROIs were identified. A similar process was performed to obtain the ROI for the control subjects. The mean CTh within each ROI was determined posttreatment and compared to the baseline thickness using a repeated measures ANCOVA model that included patient age, gender, chemotherapy treatment, and radiation exposure as main effects. Femoral head CTh maps were constructed from a control scan (1-3 months prior to radiation), the CT simulation scan, and the CT scan performed within 1-2 months following treatment in patients treated for pelvic malignancies. The CTh values from the control scan and simulation scan were compared to establish baseline pretreatment values. Using the radiation treatment plans, dose regions were created in 10 Gy increments ranging from 0 Gy to 60 Gy. Regions of interest (ROI) were defined as the intersection of the dose regions and femoral head. The pretreatment scans were registered to the posttreatment scan using rigid body transformation, and analogous ROIs were identified. A similar process was performed to obtain the ROI for the control subjects. The mean CTh within each ROI was determined posttreatment and compared to the baseline thickness using a repeated measures ANCOVA model that included patient age, gender, chemotherapy treatment, and radiation exposure as main effects. ResultsFifty-one femoral heads were analyzed from 27 patients (15 female). Median patient age was 54 years (range 30 to 87). Radiation treatment techniques included VMAT, 3-field, and 4-field arrangements. Treatments were performed primarily using 6 or 10 MV photons. Dose to the femoral head ranged from 0-59.2 Gy. Median date to follow-up scans was 15 days (range 0 to 52) from the last radiation treatment. The effect of radiation exposure on CTh was significant (P=.050). Significant cortical bone thinning versus control was observed in all ROIs that absorbed >20 Gy, with a mean loss of 15.4% (P=.006), 14.1% (P=.017), and 14.4% (P=.011) in the 20-30 Gy, 30-40 Gy, and > 40 Gy ROIs, respectively. Conversely, the overall effect of age, gender, and use of chemotherapy were not significant. Fifty-one femoral heads were analyzed from 27 patients (15 female). Median patient age was 54 years (range 30 to 87). Radiation treatment techniques included VMAT, 3-field, and 4-field arrangements. Treatments were performed primarily using 6 or 10 MV photons. Dose to the femoral head ranged from 0-59.2 Gy. Median date to follow-up scans was 15 days (range 0 to 52) from the last radiation treatment. The effect of radiation exposure on CTh was significant (P=.050). Significant cortical bone thinning versus control was observed in all ROIs that absorbed >20 Gy, with a mean loss of 15.4% (P=.006), 14.1% (P=.017), and 14.4% (P=.011) in the 20-30 Gy, 30-40 Gy, and > 40 Gy ROIs, respectively. Conversely, the overall effect of age, gender, and use of chemotherapy were not significant. ConclusionThe significant reduction of femoral head CTh of up to 15% seen in patients receiving EBRT in the acute setting presents a possible mechanism for radiation induced fracture. This suggests CTh may be a potential marker for radiation induced PIF. Early CTh loss appears to be primarily affected by radiation exposure. Further research is needed evaluating the correlation between CTh and incidence of fracture. The significant reduction of femoral head CTh of up to 15% seen in patients receiving EBRT in the acute setting presents a possible mechanism for radiation induced fracture. This suggests CTh may be a potential marker for radiation induced PIF. Early CTh loss appears to be primarily affected by radiation exposure. Further research is needed evaluating the correlation between CTh and incidence of fracture.