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Item Analysis of Virtual Versus In-Person Prospective Peer Review Workflow in a Multisite Academic Radiation Oncology Department(Elsevier, 2021-11) McClelland, Shearwood III; Amy Achiko, Flora; Bartlett, Gregory K.; Watson, Gordon A.; Holmes, Jordan A.; Rhome, Ryan M.; DesRosiers, Colleen M.; Hutchins, Karen M.; Shiue, Kevin; Agrawal, Namita; Radiation Oncology, School of MedicinePurpose In radiation oncology, peer review is a process where subjective treatment planning decisions are assessed by those independent of the prescribing physician. Before March 2020, all peer review sessions occurred in person; however due to the COVID-19 pandemic, the peer-review workflow was transitioned from in-person to virtual. We sought to assess any differences between virtual versus in-person prospective peer review. Methods and Materials Patients scheduled to receive nonemergent nonprocedural radiation therapy (RT) were presented daily at prospective peer-review before the start of RT administration. Planning software was used, with critical evaluation of several variables including treatment intent, contour definition, treatment target coverage, and risk to critical structures. A deviation was defined as any suggested plan revision. Results In the study, 274 treatment plans evaluated in-person in 2017 to 2018 were compared with 195 plans evaluated virtually in 2021. There were significant differences in palliative intent (36% vs 22%; P = .002), but not in total time between simulation and the start of treatment (9.2 vs 10.0 days; P = .10). Overall deviations (8.0% in-person vs 2.6% virtual; P = .015) were significantly reduced in virtual peer review. Conclusions Prospective daily peer review of radiation oncology treatment plans can be performed virtually with similar timeliness of patient care compared with in-person peer review. A decrease in deviation rate in the virtual peer review setting will need to be further investigated to determine whether virtual workflow can be considered a standard of care.Item Baseline Karnofsky performance status is independently predictive of death within 30 days of intracranial radiation therapy completion for metastatic disease(Elsevier, 2020) McClelland, Shearwood, III.; Agrawal, Namita; Elbanna, May F.; Shiue, Kevin; Bartlett, Gregory K.; Lautenschlaeger, Tim; Zellars, Richard C.; Watson, Gordon A.; Ellsworth, Susannah G.; Radiation Oncology, School of MedicineIntroduction: For patients with brain metastases, palliative radiation therapy (RT) has long been a standard of care for improving quality of life and optimizing intracranial disease control. The duration of time between completion of palliative RT and patient death has rarely been evaluated. Methods: A compilation of two prospective institutional databases encompassing April 2015 through December 2018 was used to identify patients who received palliative intracranial radiation therapy. A multivariate logistic regression model characterized patients adjusting for age, sex, admission status (inpatient versus outpatient), Karnofsky Performance Status (KPS), and radiation therapy indication. Results: 136 consecutive patients received intracranial palliative radiation therapy. Patients with baseline KPS <70 (OR = 2.2; 95%CI = 1.6-3.1; p < 0.0001) were significantly more likely to die within 30 days of treatment. Intracranial palliative radiation therapy was most commonly delivered to provide local control (66% of patients) or alleviate neurologic symptoms (32% of patients), and was most commonly delivered via whole brain radiation therapy in 10 fractions to 30 Gy (38% of patients). Of the 42 patients who died within 30 days of RT, 31 (74%) received at least 10 fractions. Conclusions: Our findings indicate that baseline KPS <70 is independently predictive of death within 30 days of palliative intracranial RT, and that a large majority of patients who died within 30 days received at least 10 fractions. These results indicate that for poor performance status patients requiring palliative intracranial radiation, hypofractionated RT courses should be strongly considered.Item Commentary: Fractionated Proton Beam Radiation Therapy and Hearing Preservation for Vestibular Schwannoma: Preliminary Analysis of a Prospective Phase 2 Clinical Trial(Wolters Kluwer, 2022-07) McClelland, Shearwood; Combs, Stephanie E.; Halasz, Lia M.; Lo, Simon S.; Shiue, Kevin; Radiation Oncology, School of MedicineItem Dosimetric Impact of Source Displacement in GammaTile Surgically Targeted Radiation Therapy for Gliomas(Springer Nature, 2023-05-02) Ng, Sook Kien; Yue, Yong; Shiue, Kevin; Shah, Mitesh V.; Le, Yi; Radiation Oncology, School of MedicineBackground: This study aims to evaluate dosimetric changes that happened during the first month after GammaTile surgically targeted radiation therapy (STaRT) for gliomas due to Cesium-131 (Cs-131) seed displacement caused by cavity shrinkage in brain brachytherapy. Methodology: In this study, 10 glioma patients had 4-11 GammaTiles placed along the resection bed after maximal safe resection during craniotomy. Each GammaTile is composed of four Cs-131 seeds embedded in a biodegradable collagen sponge to minimize seed movement and maintain seed-to-cavity surface distance. The Cs-131 seed positions were identified using VariSeed on day one. On day 30, post-implant computed tomography (CT) images and dosimetry parameters were calculated. An iterative closest point (ICP) algorithm was used to compute rigid transformation between the day one and day 30 seed clouds. The seed displacement was calculated after registration. The volume receiving 100% of the prescription dose (V100), the dose received by 90% of the planning target volume (D90_PTV), the planning target volume receiving 100% of the prescription dose (V100_PTV), and the dose to organs at risk (OARs) were calculated for both CT images to determine the dosimetric changes from any seed displacement. Results: The mean seed displacement of 1.8 ± 1.0 mm for all patients was observed between day one and day 30. The maximum seed displacement for each patient ranged from 2.3 mm to 7.3 mm. The mean V100 difference between day one and day 30 was 2.5 cc (range = 0.5-6.5 cc). The mean D90_PTVs were 95.5% (range = 69.0%-131.0%) and 98.1% (range = 19.9%-149.0%) on day one and day 30, respectively. The mean V100_PTVs were 88.4% (range = 81.3%-99.1%) and 87.9% (range = 47.0%-99.7%) on day one and day 30, respectively. On day one, the brainstem dose was 63.5 Gy for one case and 28.1 Gy for another case; while on day 30, the brainstem dose was 55.8 Gy and 20.6 Gy for the same patients, contributing to 7.7 Gy (12.8%) and 7.5 Gy (12.5%) dose reductions to brainstem for these patients, respectively. Only two patients received a dose to the optic nerves (34.1 Gy and 5.2 Gy). There were small changes (1.8 Gy and 0.5 Gy, respectively) in the dose to optic nerves when comparing the dose calculated on day one and the dose calculated on day 30 CT images. The same two patients received 30.4 Gy and 6.8 Gy to the chiasm, respectively. Small changes in the dose to the chiasm (≤1.1 Gy) were noted between day one and day 30. Conclusions: A maximum seed displacement of up to 7.3 mm and a mean seed displacement of 1.8 mm caused by cavity shrinkage were observed during the first month after GammaTile STaRT for gliomas. There were noticeable changes in dosimetry parameters. Changes in the doses to OARs, particularly the brainstem, were large (up to 12.8% of the prescription dose). These changes in dosimetry should be considered when evaluating treatment outcomes and planning future GammaTile treatments.Item Genomic Analysis of Human Brain Metastases Treated with Stereotactic Radiosurgery Under the Phase-II Clinical Trial (NCT03398694) Reveals DNA Damage Repair at the Peripheral Tumor Edge(medRxiv, 2023-04-24) Shireman, Jack M.; White, Quinn; Agrawal, Namita; Ni, Zijian; Chen, Grace; Zhao, Lei; Gonugunta, Nikita; Wang, Xiaohu; Mccarthy, Liam; Kasulabada, Varshitha; Pattnaik, Akshita; Ahmed, Atique U.; Miller, James; Kulwin, Charles; Cohen-Gadol, Aaron; Payner, Troy; Lin, Chih-Ta; Savage, Jesse J.; Lane, Brandon; Shiue, Kevin; Kamer, Aaron; Shah, Mitesh; Iyer, Gopal; Watson, Gordon; Kendziorski, Christina; Dey, Mahua; Radiation Oncology, School of MedicineStereotactic Radiosurgery (SRS) is one of the leading treatment modalities for oligo brain metastasis (BM), however no comprehensive genomic data assessing the effect of radiation on BM in humans exist. Leveraging a unique opportunity, as part of the clinical trial (NCT03398694), we collected post-SRS, delivered via Gamma-knife or LINAC, tumor samples from core and peripheral-edges of the resected tumor to characterize the genomic effects of overall SRS as well as the SRS delivery modality. Using these rare patient samples, we show that SRS results in significant genomic changes at DNA and RNA levels throughout the tumor. Mutations and expression profiles of peripheral tumor samples indicated interaction with surrounding brain tissue as well as elevated DNA damage repair. Central samples show GSEA enrichment for cellular apoptosis while peripheral samples carried an increase in tumor suppressor mutations. There are significant differences in the transcriptomic profile at the periphery between Gamma-knife vs LINAC.Item Histology, Tumor Volume, and Radiation Dose Predict Outcomes in NSCLC Patients After Stereotactic Ablative Radiotherapy(Elsevier, 2018) Shiue, Kevin; Cerra-Franco, Alberto; Shapiro, Ronald; Estabrook, Neil; Mannina, Edward M.; Deig, Christopher R.; Althouse, Sandra; Liu, Sheng; Wan, Jun; Zang, Yong; Agrawal, Namita; Ioannides, Pericles; Liu, Yongmei; Zhang, Chen; DesRosiers, Colleen; Bartlett, Greg; Ewing, Marvene; Langer, Mark P.; Watson, Gordon; Zellars, Richard; Kong, Feng-Ming; Lautenschlaeger, Tim; Radiation Oncology, School of MedicineIntroduction It remains unclear if histology should be independently considered when choosing stereotactic ablative body radiotherapy dose prescriptions for NSCLC. Methods The study population included 508 patients with 561 lesions between 2000 and 2016, of which 442 patients with 482 lesions had complete dosimetric information. Eligible patients had histologically or clinically diagnosed early-stage NSCLC and were treated with 3 to 5 fractions. The primary endpoint was in-field tumor control censored by either death or progression. Involved lobe control was also assessed. Results At 6.7 years median follow-up, 3-year in-field control, involved lobe control, overall survival, and progression-free survival rates were 88.1%, 80.0%, 49.4%, and 37.2%, respectively. Gross tumor volume (GTV) (hazard ratio [HR] = 1.01 per mL, p = 0.0044) and histology (p = 0.0225) were independently associated with involved lobe failure. GTV (HR = 1.013, p = 0.001) and GTV dose (cutoff of 110 Gy, biologically effective dose with α/β = 10 [BED10], HR = 2.380, p = 0.0084) were independently associated with in-field failure. For squamous cell carcinomas, lower prescription doses were associated with worse in-field control (12 Gy × 4 or 10 Gy × 5 versus 18 Gy or 20 Gy × 3: HR = 3.530, p = 0.0447, confirmed by propensity score matching) and was independent of GTV (HR = 1.014 per mL, 95% confidence interval: 1.005–1.022, p = 0.0012). For adenocarcinomas, there were no differences in in-field control observed using the above dose groupings (p = 0.12 and p = 0.31, respectively). Conclusions In the absence of level I data, GTV and histology should be considered to personalize radiation dose for stereotactic ablative body radiotherapy. We suggest lower prescription doses (i.e., 12 Gy × 4 or 10 G × 5) should be avoided for squamous cell carcinomas if normal tissue tolerances are met.Item Impact of Lung Parenchymal-Only Failure on Overall Survival in Early-Stage Lung Cancer Patients Treated With Stereotactic Ablative Radiotherapy(Elsevier, 2021) Elbanna, May; Shiue, Kevin; Edwards, Donna; Cerra-Franco, Alberto; Agrawal, Namita; Hinton, Jason; Mereniuk, Todd; Huang, Christina; Ryan, Joshua L.; Smith, Jessica; Aaron, Vasantha D.; Burney, Heather; Zang, Yong; Holmes, Jordan; Langer, Mark; Zellars, Richard; Lautenschlaeger, Tim; Radiation Oncology, School of MedicineIntroduction: The impact of lung parenchymal-only failure on patient survival after stereotactic ablative body radiotherapy (SABR) for early-stage non-small-cell lung cancer (NSCLC) remains unclear. Patients and methods: The study population included 481 patients with early-stage NSCLC who were treated with 3- to 5-fraction SABR between 2000 and 2016. The primary study objective was to assess the impact of out-of-field lung parenchymal-only failure (OLPF) on overall survival (OS). Results: At a median follow-up of 5.9 years, the median OS was 2.7 years for all patients. Patients with OLPF did not have a significantly different OS compared to patients without failure (P = .0952, median OS 4.1 years with failure vs. 2.6 years never failure). Analysis in a 1:1 propensity score-matched cohort for Karnofsky performance status, comorbidity score, and smoking status showed no differences in OS between patients without failure and those with OLPF (P = .8). In subgroup analyses exploring the impact of time of failure on OS, patients with OLPF 6 months or more after diagnosis did not have significantly different OS compared to those without failure, when accounting for immortal time bias (P = .3, median OS 4.3 years vs. 3.5 years never failure). Only 7 patients in our data set experienced failure within 6 months of treatment, of which only 4 were confirmed to be true failures; therefore, limited data are available in our cohort on the impact of OLPF for ≤ 6 months on OS. Conclusion: OLPF after SABR for early-stage NSCLC does not appear to adversely affect OS, especially if occurring at least 6 months after SABR. More studies are needed to understand if OLPF within 6 months of SABR is associated with adverse OS. These data are useful when discussing prognosis of lung parenchymal failures after initial SABR.Item Literature review of management of brain metastases from germ cell tumors(AME, 2022-04-30) Le , Amy; Arbab , Mona; Adra , Nabil; Miller , James C.; Watson , Gordon A.; Shiue, Kevin; Radiation Oncology, School of MedicineObjective: In this review article, we discuss the role of chemotherapy, surgery, and radiation therapy in the treatment of brain metastases from germ cell tumors (GCT). Background: GCT rarely metastasize to the brain and there is limited data to guide management. Most instances of brain metastases occur in patients with non-seminomatous germ cell tumors (NSGCT). Methods: We searched PubMed using the terms 'central nervous system (CNS) metastases' or 'brain metastases' and 'germ cell' from 2011 through August 2021. Review articles and prospective trials related to the treatment of brain metastases in GCT were included in addition to articles obtained by hand search of the references and clinical practice guidelines. Conclusions: We highlight the importance of using chemotherapy as first-line therapy in most situations. We discuss the very minimal data regarding surgery and its primary role when there is significant mass effect or brain shift. We also compare whole brain radiation therapy (WBRT) with the use of radiosurgery. We then provide overall recommendations based on the reviewed data and our experience as a referral center for GCT.Item Local and distant brain control in melanoma and NSCLC brain metastases with concurrent radiosurgery and immune checkpoint inhibition(Springer, 2022-07) Le, Amy; Mohammadi, Homan; Mohammed, Toka; Burney, Heather; Zang, Yong; Frye, Douglas; Shiue, Kevin; Lautenschlaeger, Tim; Miller, James; Radiation Oncology, School of MedicineIntroduction The treatment of brain metastases with stereotactic radiosurgery (SRS) in combination with immune checkpoint inhibitors (ICI) has become more common in recent years, but there is a lack of prospective data on cancer control outcomes when these therapies are administered concurrently. Methods Data were retrospectively reviewed for patients with non-small cell lung cancer (NSCLC) and melanoma brain metastases treated with SRS at a single institution from May 2008 to January 2017. A parametric proportional hazard model is used to detect the effect of concurrent ICI within 30, 60, or 90 days of ICI administration on local control and distant in-brain control. Other patient and lesion characteristics are treated as covariates and adjusted in the regression. A frailty term is added in the baseline hazard to capture the within-patient correlation. Results We identified 144 patients with 477 total lesions, including 95 NSCLC patients (66.0%), and 49 (34.0%) melanoma patients. On multivariate analysis, concurrent SRS and ICI (SRS within 30 days of ICI administration) was not associated with local control but was associated with distant brain control. When controlling for prior treatment to lesion, number of lesions, and presence of extracranial metastases, patients receiving this combination had a statistically significant decrease in distant brain failure compared to patients that received non-concurrent ICI or no ICI (HR 0.15; 95% CI 0.05–0.47, p = 0.0011). Conclusion Concurrent ICI can enhance the efficacy of SRS. Prospective studies would allow for stronger evidence to support the impact of concurrent SRS and ICI on disease outcomes.Item Nearly Half of Metastatic Brain Disease Patients Prescribed 10 Fractions of Whole-Brain Radiation Therapy Die Without Completing Treatment(Elsevier, 2019) McClelland, Shearwood, III; Agrawal, Namita; Shiue, Kevin; Bartlett, Gregory K.; Zellars, Richard C.; Watson, Gordon A.; Ellsworth, Susannah G.; Radiation Oncology, School of Medicine