Catherine Okoukoni
Wake Forest University
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Publication
Featured researches published by Catherine Okoukoni.
Journal of Neurosurgery | 2017
Will H. McKay; E. McTyre; Catherine Okoukoni; Natalie K. Alphonse-Sullivan; Jimmy Ruiz; Michael T. Munley; Shadi Qasem; Hui-Wen Lo; Fei Xing; Adrian W. Laxton; Stephen B. Tatter; Kounosuke Watabe; Michael D. Chan
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.
Radiotherapy and Oncology | 2016
Catherine Okoukoni; Sarah K. Lynch; E. McTyre; David M. Randolph; Ashley A. Weaver; A. William Blackstock; Brian E. Lally; Michael T. Munley; Jeffrey S. Willey
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 3month 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 ⩾10Gy exhibited significant thinning of cortical bone (p=0.001). The mean Ct.Th percent difference (95% CI) in regions receiving 10-20Gy, 20-30Gy, 30-40Gy, and ⩾40Gy were -7% (-4%,-11%), -14% (-18%,-11%), -15% (-19%,-11%), and -18% (-22%,-15%) respectively. Regions receiving >20Gy 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 ⩾10Gy. The rapid thinning of ribs may predispose ribs to fracture after SBRT.
Bone | 2017
Catherine Okoukoni; David M. Randolph; E. McTyre; Andy Kwok; Ashley A. Weaver; A. William Blackstock; Michael T. Munley; Jeffrey S. Willey
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 (≤4months) 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 3.3%]; 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.
Stem cell reports | 2017
Catherine Okoukoni; Michael Farris; R.T. Hughes; E. McTyre; Corbin A. Helis; Michael T. Munley; Jeffrey S. Willey
Purpose of ReviewNormal 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 FindingsAn 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.SummarySeveral 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.
Advances in radiation oncology | 2017
Catherine Okoukoni; E. McTyre; Diandra N. Ayala Peacock; Ann M. Peiffer; Roy E. Strowd; C.K. Cramer; William H. Hinson; Steve Rapp; Linda J. Metheny-Barlow; Edward G. Shaw; Michael D. Chan
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.
Radiation Research | 2018
Michael Farris; E. McTyre; Catherine Okoukoni; Greg Dugan; Brendan J. Johnson; A. William Blackstock; Michael T. Munley; J. Daniel Bourland; J. Mark Cline; Jeffrey S. Willey
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.
Cureus | 2017
Michael C LeCompte; E. McTyre; Adrianna Henson; Michael Farris; Catherine Okoukoni; C.K. Cramer; P. Triozzi; Jimmy Ruiz; Kounosuke Watabe; Hui-Wen Lo; Michael T. Munley; Adrian W. Laxton; Stephen B. Tatter; Xiaobo Zhou; Michael Chan
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.
Neurosurgery | 2018
Ammoren Dohm; E. McTyre; Catherine Okoukoni; Adrianna Henson; C.K. Cramer; Michael C LeCompte; Jimmy Ruiz; Michael T. Munley; Shadi Qasem; Hui-Wen Lo; Fei Xing; Kounosuke Watabe; Adrian W. Laxton; Stephen B. Tatter; Michael D. Chan
International Journal of Radiation Oncology Biology Physics | 2018
A.H. Masters; E. McTyre; M.C. LeCompte; Catherine Okoukoni; R. Barcus; P. Triozzi; Michael D. Chan; Christopher T. Whitlow
International Journal of Radiation Oncology Biology Physics | 2017
M.C. LeCompte; E. McTyre; A. Henson; Michael Farris; Catherine Okoukoni; C.K. Cramer; P. Triozzi; Michael T. Munley; S. Qasem; F. Xing; K. Watabe; Adrian W. Laxton; Stephen B. Tatter; Michael D. Chan