Physics-based in silico modelling of microvascular pulmonary perfusion in COVID-19.

Due to its ability to induce heterogenous, patient-specific damage in pulmonary alveoli and capillaries, COVID-19 poses challenges in defining a uniform profile to elucidate infection across all patients. Computational models that integrate changes in ventilation and perfusion with heterogeneous damage profiles offer valuable insights into the impact of COVID-19 on pulmonary health. This study aims to develop an in silico hypothesis-testing platform specifically focused on studying microvascular pulmonary perfusion in COVID-19-infected lungs. Through this platform, we explore the effects of various acinar-level pulmonary perfusion abnormalities on global lung function. Our modelling approach simulates changes in pulmonary perfusion and the resulting mismatch of ventilation and perfusion in COVID-19-afflicted lungs. Using this coupled modelling platform, we conducted multiple simulations to assess different scenarios of perfusion abnormalities in COVID-19-infected lungs. The simulation results showed an overall decrease in ventilation-perfusion (V/Q) ratio with inclusion of various types of perfusion abnormalities such as hypoperfusion with and without microangiopathy. This model serves as a foundation for comprehending and comparing the spectrum of findings associated with COVID-19 in the lung, paving the way for patient-specific modelling of microscale lung damage in emerging pulmonary pathologies like COVID-19.

First application of GammaTile cesium-131 brachytherapy with maximal safe resection of a glioma in a patient with limited scleroderma.

The purpose of this report is to present the first documented application of GammaTile to an intra-cranial tumor of a patient with a symptomatic radiosensitive connective tissue disorder, a case where there were significant concerns with standard oncologic strategies. We hypothesized that GammaTile® (GT Medical Technologies, Tempe, Arizona, USA) would also be advantageous in the application of intra-cranial tumors in patients with conditions of increased radiosensitivity. We generated a standard external beam radiation therapy (EBRT) plan consisting of an overall 1.5 cm expansion to 59.4 Gy in 1.8 Gy fractions. Also, we developed a CyberKnife (Accuray, Sunnyvale, CA, USA) plan with a 5 mm expansion on the surgical cavity prescribed to 60 Gy in 30 fractions, to make an EBRT comparison using the same prescription volume as GammaTile. We report the first published application of GammaTile® brachytherapy to an intra-cranial malignancy in a patient with limited scleroderma. The dose delivered by GammaTile was compared to the dose that would be delivered with both typical volumes and small volumes of EBRT. The maximum dose delivered to the scar and scalp by GammaTile was reduced to half of that from other external beam techniques (~25 Gy vs. ~55 Gy). MRI imaging at 6 months and 12 months post-resection demonstrated no evidence of disease recurrence nor radiation necrosis. At the 12-month follow-up visit, the surgical scar was well-healed with no skin changes to the surrounding scalp. Dosimetrically and clinically, this report highlights the successful application of GammaTile to an intra-cranial tumor bed in a patient with scleroderma.

Novel combination of GammaTile cesium-131 brachytherapy with 5-aminolevulinic acid fluorescence-guided resection in the re-irradiation of pediatric recurrent high-grade glioma: illustrative case.

BACKGROUND: Herein, the authors describe the successful utilization of 5-aminolevulinic acid (5-ALA) and the first case of GammaTile cesium-131 therapy in a pediatric patient with recurrent high-grade glioma. 5-ALA was utilized to optimize gross-total resection prior to GammaTile implantation. After conversion to an equivalent dose in 2-Gy fractions (EQD2), a composite was made of the GammaTile dose with the initial external beam radiotherapy. Two hypothetical plans consisting of a standard hypofractionated strategy for glioma reirradiation and a CyberKnife plan using GammaTile's planning target volume were developed and likewise underwent EQD2 conversion and composite plan generation with the initial radiotherapy. OBSERVATIONS: 5-ALA was useful in achieving gross-total resection with no acute toxicity from the surgery or GammaTile irradiation. When compared with the hypothetical composite doses, GammaTile's composite, axium point dose (D0.03cc) to the brainstem was 32.9 Gy less than the hypofractionated and the CyberKnife composite plans at 38.7 Gy and 40.2 Gy, respectively. The right hippocampus demonstrated a substantially reduced composite plan dose with GammaTile with a D0.03cc of 62.4 Gy versus 71.7 and 80.7 Gy for the hypofractionated and CyberKnife composite plans, respectively. LESSONS: Utilization of 5-ALA and GammaTile therapy yielded clinically superior tumor debulking and effective radiotherapy dose localization with sparing of organs at risk, respectively.

Bacterial epiglottitis superimposed on oropharyngeal cancer: A case report.

BACKGROUND: Patients undergoing chemotherapy and radiotherapy are placed in an immunocompromised state worth consideration in the event of potential airway compromise, especially when superimposed on an airway-obstructing tumor. We report a case of bacterial epiglottitis in a patient with active oropharyngeal cancer (OPC), who presented in such a way that an infectious etiology was not initially considered in the patient's care. To our knowledge, such a circumstance has not been reported in the literature. CASE: Here, we report a case of a 68-year-old male with advanced-stage OPC who developed respiratory distress and underwent emergent tracheostomy. The patient was diagnosed postoperatively with Haemophilus influenza and Pseudomonas aerugeniosa. Following antibiotic treatment, the patient recovered to the point in which he could then undergo concomitant chemoradiation. The patient later had a recurrence of P. aerugeniosa during their radiotherapy that was also treated with antibiotics. The patient experienced continued symptoms related to their OPC and underwent pharyngectomy. Despite the initial success of this procedure, the patient experienced tumor recurrence and succumbed to his disease. CONCLUSION: This case underscores the importance of considering multiple etiologies concerning airway compromise, as the consequence of delayed cancer treatment may be loss of local cancer control.

Radiation-induced myofibroblastoma within the nasal sinus requiring maxillectomy and ethmoidectomy: A case report and literature review.

We report a case of radiation-induced myofibroblastoma of the right nasal cavity in a patient with a remote history of radiotherapy for pediatric retinoblastoma. The patient required maxillectomy and ethmoidectomy. To our knowledge, a rare number of cases have been reported in this location.

Survival Is Worse in Patients Completing Immunotherapy Prior to SBRT/SRS Compared to Those Receiving It Concurrently or After.

Purpose/Objectives: The abscopal effect could theoretically be potentiated when combined with immunomodulating drugs through increased antigen production. The optimal dosing and schedule of radiotherapy with immunotherapy are unknown, although they are actively investigated in laboratory and clinical models. Clinical data in patients treated for metastatic disease with both modalities may guide future studies. Materials and Methods: This is a single-institution retrospective review of all patients treated with stereotactic body radiotherapy (SBRT)/stereotactic radiosurgery (SRS) and immunomodulating therapy within 6 months before or after SBRT/SRS for metastatic cancer. Clinical and tumor characteristics were recorded, as well as SBRT/SRS details, immunotherapy details, and survival. Log-rank tests on Kaplan-Meier curves for overall survival (OS) that were calculated from the end of SBRT/SRS were used in univariate analysis and Cox proportional hazards regression for multivariate analysis. Results: A total of 125 patients were identified who met the inclusion criteria; 70 received SBRT, and 57 received SRS. Eighty-three patients were treated for non-small cell lung cancer, 7 patients for small cell lung cancer, and 35 patients for other cancers, with the most common one being melanoma. Fifty-three percent of patients received nivolumab, 29% pembrolizumab, 13% atezolizumab, 5% other. Twenty percent received immunotherapy before SBRT/SRS, 39% during SBRT/SRS, 41% after. Eighty-six patients had died by the time of the analysis; the median OS for the whole cohort was 9.7 months. Patients who had completed immunotherapy prior to SBRT/SRS had worse OS than those who received concurrent therapy or immunotherapy after SBRT/SRS, with a difference in median OS of 3.6 months vs. 13.0 months (p = 0.010) that was retained on multivariate analysis (p = 0.011). There was no significant difference in OS between patients receiving SRS vs. SBRT (p = 0.20), sex (p = 0.53), age >62 years (p = 0.76), or lung primary vs. others (p = 0.73) on univariate or multivariate analysis. When comparing before/concurrent to after/concurrent administration, there is a difference in survival with after/concurrent survival of 8.181 months and before survival of 13.010 months, but this was not significant (p = 0.25). Conclusions: OS appears to be worse in patients who complete immunotherapy prior to SBRT/SRS compared to those receiving it concurrently or after. The design of this retrospective review may be prone to lead time bias, although the difference in median survival is longer than the 6-month window before SBRT/SRS and could only account for part of this difference. Further analysis into causes of death and toxicity and prospective studies are needed to confirm the results of this analysis.

Towards a multi-scale computer modeling workflow for simulation of pulmonary ventilation in advanced COVID-19.

Physics-based multi-scale in silico models offer an excellent opportunity to study the effects of heterogeneous tissue damage on airflow and pressure distributions in COVID-19-afflicted lungs. The main objective of this study is to develop a computational modeling workflow, coupling airflow and tissue mechanics as the first step towards a virtual hypothesis-testing platform for studying injury mechanics of COVID-19-afflicted lungs. We developed a CT-based modeling approach to simulate the regional changes in lung dynamics associated with heterogeneous subject-specific COVID-19-induced damage patterns in the parenchyma. Furthermore, we investigated the effect of various levels of inflammation in a meso-scale acinar mechanics model on global lung dynamics. Our simulation results showed that as the severity of damage in the patient's right lower, left lower, and to some extent in the right upper lobe increased, ventilation was redistributed to the least injured right middle and left upper lobes. Furthermore, our multi-scale model reasonably simulated a decrease in overall tidal volume as the level of tissue injury and surfactant loss in the meso-scale acinar mechanics model was increased. This study presents a major step towards multi-scale computational modeling workflows capable of simulating the effect of subject-specific heterogenous COVID-19-induced lung damage on ventilation dynamics.

Cardiac toxicity in patients with lung cancer receiving thoracic radiotherapy and immunotherapy.

Background: Immune checkpoint inhibitors (ICIs) are used to treat locally-advanced and metastatic lung cancer, which can lead to severe immunogenic-related cardiotoxicities. We assessed the risk of cardiotoxicity in ICI-treated lung cancer patients with or without cardiac radiation from thoracic radiotherapy. Methods: Retrospective data was collected on Stage III-IV lung cancer patients who received ICIs between 2015 and 2018. All cardiotoxicities associated with ICI were assessed in correlation with the timing of radiotherapy (RT) in relation to ICI, and the mean RT heart dose. The rate of cardiac events in relation to RT timing and heart dose was compared using multiple logistic regression including the Framingham risk score and steroid use prior to ICI therapy. Results: Of 194 ICI-treated patients evaluated, 55.2% (n=107/194) patients had received thoracic RT at a median dose of 60.4 Gy (range, 15-75). Cardiotoxicities such as non-ST elevated myocardial infarction and new onset supraventricular tachycardias were observed in 13 (12.2%) of those who had thoracic RT versus 9 (10.3%) who did not (p=0.87). 38 patients who received RT concurrently with ICI did not develop any cardiotoxicity whereas 14.1% (n=22/156) of those who did not receive concurrent RT developed cardiotoxicities (univariate, p=0.030; multivariate, p=0.055). There were no significant differences in the mean heart RT dose, Framingham risk score, and steroid treatment between patients that received concurrent RT with ICI versus non-concurrent RT/ICI. Conclusion: ICI-related cardiotoxicities were not significantly associated with patients who received concurrent thoracic radiotherapy in this retrospective review. Further validation of prospective studies is needed to confirm these results.

GammaTile Brachytherapy Combined With External Beam Radiation Therapy for the Treatment of a Partially Resected Secondary Glioblastoma (WHO Grade 4 IDH-Mutant Astrocytoma): Matching External Beam Dose Gradient to Brachytherapy Dose Fall-Off.

Reirradiation of recurrent glioblastomas is most commonly managed with hypofractionated external beam radiation with a modest overall effect. GammaTile, which is a Cesium-131 source embedded in collagen mesh, is an approach that allows the surgical bed of resectable intracranial tumors to receive a greater biological dose than is possible with any form of external beam radiation therapy (EBRT). In this case report, a 28-year-old male presents with a WHO grade 4 isocitrate dehydrogenase (IDH)-mutant astrocytoma (formerly secondary glioblastoma) of the left occipital/parietal lobe after receiving 45 Gy and two cycles of adjuvant temozolomide four years prior for a grade 3 IDH-mutant astrocytoma. The patient proceeded to undergo craniotomy with maximal safe resection and application of GammaTile to a dose of 60 Gy at 5mm depth. Shortly afterward, he developed symptomatic progression of disease in the bilateral splenium and left thalamus/basal ganglia. We irradiated the undertreated residual disease with EBRT to a dose of 35 Gy in 10 fractions without introducing excessive dose to the GammaTile irradiated volume. This was achieved by creating one portion of the planning target volume with a homogeneous dose and another part where the delivered dose decreased with the GammaTile dose buildup. Treatment planning utilized the Gradient Optimization feathering technique with non-coplanar volumetric modulated arc therapy. The resulting composite between the hypofractionated EBRT and GammaTile dose distribution created an approximate dose equivalent of 50 Gy in 2 Gy fractions to the residual disease with no hot spots or areas of under coverage. This is the first report showing the feasibility of combining GammaTile with dose-matched EBRT volumes in a reproducible manner to sub-totally resected, recurrent intracranial neoplasms.

The Impact of Smoking, Alcohol Use, Recurrent Disease, and Age on the Development of Neck Fibrosis in Head and Neck Cancer Patients Following Radiation Therapy.

There is a paucity of information regarding the demographic factors associated with the development of neck fibrosis in head and neck cancer (HNC) patients following radiotherapy. A retrospective review of all patients being treated for HNC at a tertiary care center between 2013 and 2017 was performed. Chi-squared and Mann-Whitney U tests were used to identify differences in incidence and grade of fibrosis, respectively, between populations. A total of 90 patients aged 19 to 99 years were included. Factors associated with an increased incidence of fibrosis included smoking during radiotherapy (p < 0.001), alcohol use (p = 0.026), recurrent disease (p = 0.042), and age less than 60 (p < 0.001) on univariate analysis. Factors associated with increased grade of fibrosis in HNC patients included recurrent HNC (p = 0.033), alcohol use (p = 0.013), patient age younger than 60 years (p = 0.018), smoking during radiotherapy (p < 0.001), and non-Caucasian race (p = 0.012). Identification and intervention directed at patients that possess risk factors associated with fibrosis prior to treatment has the potential to improve the long-term quality of life for HNC patients.

A Single-Institution Analysis of 126 Patients Treated with Stereotactic Radiosurgery for Brain Metastases.

BACKGROUND: The objective of this study was to report our institutional experience with Gamma Knife® Radiosurgery (GKRS) in the treatment of patients with brain metastases. METHODS: Retrospectively collected demographic and clinical data on 126 patients with intracranial metastases were reviewed. The patients in our study underwent GKRS at Vidant Medical Center between 2009 and 2014. Kaplan-Meier curves were used to compare survival based on clinical characteristics for univariate analysis, and a Cox proportional hazards model was used for multivariate analysis. RESULTS: The median age of the patient population was 62 years. Medicare patients constituted 51% of our patient cohort and Medicaid patients 15%. The most common tumor histologies were non-small cell lung cancer (50%), breast cancer (12.7%), and melanoma (11.9%). The median overall survival time for all patients was 5.8 months. Patients with breast cancer had the longest median survival time of 9.15 months, while patients with melanoma had the shortest median survival time of 2.86 months. On univariate analysis, the following factors were predictors for improved overall survival, ECOG score 0 or 1 vs. 2 or greater (17.0 vs. 1.8 months, p < 0.001), controlled extracranial disease vs. progressive extracranial disease (17.4 vs. 4.6 months, p = 0.0001), recursive partitioning analysis Stage I vs. II-III (18.2 vs. 6.2 months, p < 0.007), multiple GKRS treatments (p = 0.002), prior brain metastasectomy (p = 0.012), and prior chemotherapy (p = 0.021). Age, ethnicity, gender, previous external beam radiation therapy, number of brain metastases, and hemorrhagic vs. non-hemorrhagic tumors were not predictors of longer median survival time. Number of metastatic brain lesions of 1-3 vs. ≥4 (p = 0.051) and insurance status of Medicare/Medicaid vs. commercial insurance approached significance (13.7 vs. 6.8 months, p = 0.08). On multivariate analysis, ECOG performance status 0-1 (p < 0.001), multiple GKRS treatments (p = 0.003), and control of extracranial disease (p = 0.001) remained significant predictors of survival. CONCLUSION: ECOG score, control of extracranial disease, and multiple GKRS treatments are predictors of longer median survival following GKRS in our patient population. GKRS is an effective treatment for brain metastases, but these factors may be considered in patient selection for GKRS.

Proctitis following stereotactic body radiation therapy for prostate cancer.

BACKGROUND: Proctitis after radiation therapy for prostate cancer remains an ongoing clinical challenge and critical quality of life issue. SBRT could minimize rectal toxicity by reducing the volume of rectum receiving high radiation doses and offers the potential radiobiologic benefits of hypofractionation. This study sought to evaluate the incidence and severity of proctitis following SBRT for prostate cancer. METHODS: Between February 2008 and July 2011, 269 men with clinically localized prostate cancer were treated definitively with SBRT monotherapy at Georgetown University Hospital. All patients were treated to 35-36.25Gy in 5 fractions delivered with the CyberKnife Radiosurgical System (Accuray). Rectal bleeding was recorded and scored using the CTCAE v.4. Telangiectasias were graded using the Vienna Rectoscopy Score (VRS). Proctitis was assessed via the Bowel domain of the Expanded Prostate Index Composite (EPIC)-26 at baseline and at 1, 3, 6, 9, 12, 18 and 24 months post-SBRT. RESULTS: The median age was 69 years with a median prostate volume of 39 cc. The median follow-up was 3.9 years with a minimum follow-up of two years. The 2-year actuarial incidence of late rectal bleeding ≥ grade 2 was 1.5%. Endoscopy revealed VRS Grade 2 rectal telangiectasias in 11% of patients. All proctitis symptoms increased at one month post-SBRT but returned to near-baseline with longer follow-up. The most bothersome symptoms were bowel urgency and frequency. At one month post-SBRT, 11.2% and 8.5% of patients reported a moderate to big problem with bowel urgency and frequency, respectively. The EPIC bowel summary scores declined transiently at 1 month and experienced a second, more protracted decline between 6 months and 18 months before returning to near-baseline at two years post-SBRT. Prior to treatment, 4.1% of men felt their bowel function was a moderate to big problem which increased to 11.5% one month post-SBRT but returned to near-baseline at two years post-SBRT. CONCLUSIONS: In this single institution cohort, the rate and severity of proctitis observed following SBRT is low. QOL decreased on follow-up; however, our results compare favorably to those reported for patients treated with alternative radiation modalities. Future prospective randomized studies are needed to confirm these observations.

Rectal endoscopy findings following stereotactic body radiation therapy for clinically localized prostate cancer.

BACKGROUND: Treating prostate cancer with SBRT could potentially minimize radiation proctitis by reducing high-dose rectal irradiation. In addition, it offers the potential radiobiologic benefits of hypofractionation. This study reports the endoscopic changes and the associated clinical rectal toxicity in these patients. METHODS: We reviewed the records of patients treated from 2008-2011 for localized prostate cancer who had rectal endoscopy following SBRT. SBRT was delivered either as primary treatment in 5 fractions of 7-7.25 Gy, or as an initial boost in 3 fractions of 6.5 Gy followed by conventionally fractionated radiotherapy to 45-50.4 Gy. Endoscopic changes were graded using the Vienna Rectoscopy Score (VRS). Rectal toxicity was graded via CTCAEv.4. Rectal quality of life (QOL) was assessed via the bowel domain of the EPIC-26 questionnaire. RESULTS: Fifty-one patients with a median 23 months follow-up were analyzed. Thirty-five patients completed SBRT monotherapy and 16 patients received SBRT as a boost to conventionally fractionated IMRT. The median interval from SBRT to rectal endoscopy was 13 months. Endoscopy revealed VRS Grade 1-2 telangiectasias for 10 patients and VRS Grade 1-2 mucosal edema for 12 patients. No rectal ulcerations, strictures or necrosis were observed. Grade 1-2 late rectal bleeding occurred in 10 patients. There were no CTCAEv.4 Grade ≥3 toxicities. Mean EPIC bowel scores decreased from a baseline value of 96.9 to 82.3 at 1-month, but subsequently increased to 91.0 at 24 months. CONCLUSIONS: In this cohort that is skewed towards patients with rectal complaints, the rate and severity of endoscopic changes following SBRT is low. Rectal toxicity and QOL were comparable to patients treated with other radiation modalities. Prospective trials examining the endoscopic outcomes following SBRT for prostate cancer are needed for confirmation of the findings of this study. TRIAL REGISTRATION: The Georgetown Institutional Review Board has approved this retrospective study (IRB 2009-510).

Stereotactic body radiation therapy (SBRT) for clinically localized prostate cancer: the Georgetown University experience.

BACKGROUND: Stereotactic body radiation therapy (SBRT) delivers fewer high-dose fractions of radiation which may be radiobiologically favorable to conventional low-dose fractions commonly used for prostate cancer radiotherapy. We report our early experience using SBRT for localized prostate cancer. METHODS: Patients treated with SBRT from June 2008 to May 2010 at Georgetown University Hospital for localized prostate carcinoma, with or without the use of androgen deprivation therapy (ADT), were included in this retrospective review of data that was prospectively collected in an institutional database. Treatment was delivered using the CyberKnife® with doses of 35 Gy or 36.25 Gy in 5 fractions. Biochemical control was assessed using the Phoenix definition. Toxicities were recorded and scored using the CTCAE v.3. Quality of life was assessed before and after treatment using the Short Form-12 Health Survey (SF-12), the American Urological Association Symptom Score (AUA) and Sexual Health Inventory for Men (SHIM) questionnaires. Late urinary symptom flare was defined as an AUA score ≥ 15 with an increase of ≥ 5 points above baseline six months after the completion of SBRT. RESULTS: One hundred patients (37 low-, 55 intermediate- and 8 high-risk according to the D'Amico classification) at a median age of 69 years (range, 48-90 years) received SBRT, with 11 patients receiving ADT. The median pre-treatment prostate-specific antigen (PSA) was 6.2 ng/ml (range, 1.9-31.6 ng/ml) and the median follow-up was 2.3 years (range, 1.4-3.5 years). At 2 years, median PSA decreased to 0.49 ng/ml (range, 0.1-1.9 ng/ml). Benign PSA bounce occurred in 31% of patients. There was one biochemical failure in a high-risk patient, yielding a two-year actuarial biochemical relapse free survival of 99%. The 2-year actuarial incidence rates of GI and GU toxicity ≥ grade 2 were 1% and 31%, respectively. A median baseline AUA symptom score of 8 significantly increased to 11 at 1 month (p=0.001), however returned to baseline at 3 months (p=0.60). Twenty one percent of patients experienced a late transient urinary symptom flare in the first two years following treatment. Of patients who were sexually potent prior to treatment, 79% maintained potency at 2 years post-treatment. CONCLUSIONS: SBRT for clinically localized prostate cancer was well tolerated, with an early biochemical response similar to other radiation therapy treatments. Benign PSA bounces were common. Late GI and GU toxicity rates were comparable to conventionally fractionated radiation therapy and brachytherapy. Late urinary symptom flares were observed but the majority resolved with conservative management. A high percentage of men who were potent prior to treatment remained potent two years following treatment.

Hypofractionated stereotactic body radiation therapy as monotherapy for intermediate-risk prostate cancer.

BACKGROUND: Hypofractionated stereotactic body radiation therapy (SBRT) has been advanced as monotherapy for low-risk prostate cancer. We examined the dose distributions and early clinical outcomes using this modality for the treatment of intermediate-risk prostate cancer. METHODS: Forty-one sequential hormone-naïve intermediate-risk prostate cancer patients received 35-36.25 Gy of CyberKnife-delivered SBRT in 5 fractions. Radiation dose distributions were analyzed for coverage of potential microscopic ECE by measuring the distance from the prostatic capsule to the 33 Gy isodose line. PSA levels, toxicities, and quality of life (QOL) measures were assessed at baseline and follow-up. RESULTS: All patients completed treatment with a mean coverage by the 33 Gy isodose line extending >5 mm beyond the prostatic capsule in all directions except posteriorly. Clinical responses were documented by a mean PSA decrease from 7.67 ng/mL pretreatment to 0.64 ng/mL at the median follow-up of 21 months. Forty patients remain free from biochemical progression. No Grade 3 or 4 toxicities were observed. Mean EPIC urinary irritation/obstruction and bowel QOL scores exhibited a transient decline post-treatment with a subsequent return to baseline. No significant change in sexual QOL was observed. CONCLUSIONS: In this intermediate-risk patient population, an adequate radiation dose was delivered to areas of expected microscopic ECE in the majority of patients. Although prospective studies are needed to confirm long-term tumor control and toxicity, the short-term PSA response, biochemical relapse-free survival rate, and QOL in this interim analysis are comparable to results reported for prostate brachytherapy or external beam radiotherapy. TRIAL REGISTRATION: The Georgetown Institutional Review Board has approved this retrospective study (IRB 2009-510).

Six-Dimensional Correction of Intra-Fractional Prostate Motion with CyberKnife Stereotactic Body Radiation Therapy.

Large fraction radiation therapy offers a shorter course of treatment and radiobiological advantages for prostate cancer treatment. The CyberKnife is an attractive technology for delivering large fraction doses based on the ability to deliver highly conformal radiation therapy to moving targets. In addition to intra-fractional translational motion (left-right, superior-inferior, and anterior-posterior), prostate rotation (pitch, roll, and yaw) can increase geographical miss risk. We describe our experience with six-dimensional (6D) intra-fraction prostate motion correction using CyberKnife stereotactic body radiation therapy (SBRT). Eighty-eight patients were treated by SBRT alone or with supplemental external radiation therapy. Trans-perineal placement of four gold fiducials within the prostate accommodated X-ray guided prostate localization and beam adjustment. Fiducial separation and non-overlapping positioning permitted the orthogonal imaging required for 6D tracking. Fiducial placement accuracy was assessed using the CyberKnife fiducial extraction algorithm. Acute toxicities were assessed using Common Toxicity Criteria v3. There were no Grade 3, or higher, complications and acute morbidity was minimal. Ninety-eight percent of patients completed treatment employing 6D prostate motion tracking with intra-fractional beam correction. Suboptimal fiducial placement limited treatment to 3D tracking in two patients. Our experience may guide others in performing 6D correction of prostate motion with CyberKnife SBRT.