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Radiology has an important role in the diagnosis, staging and treatment of lung cancer and can offer minimally invasive therapies for poor surgical candidates. Radiology is also important in the follow up of patients after treatment, the assessment of treatment complications and detection of recurrent disease. Understanding the normal post-operative and post-radiation appearances, and recognizing early and late complications is useful for all clinicians involved in the care of patients with cancer.

PURPOSE: We aimed to evaluate the effect on the radiation dose to the patient by reducing the tube current during the placement of the ablation needles (reduced dose group) compared with the patient doses delivered when scanning at the standard fully diagnostic level (full dose group) in computed tomography (CT)-guided percutaneous cryoablation. METHODS: We conducted a retrospective study of 103 patients undergoing cryoablation in a tertiary cancer center. Overall, 62 patients were scanned with standard exposure parameters (full dose group) set on a 64-slice multidetector CT scanner, while 41 patients were scanned on a reduced dose protocol. Dose levels were retrieved from the hospital picture and archiving communication system including the volumetric CT dose index (CTDIvol), total dose length product (DLP), length of cryoablation procedure, number of cryoablation needles and patient size. Wilcoxon Mann-Whitney (rank-sum) tests were used to compare the median DLP, CTDIvol and skin dose between the two groups. RESULTS: Median total DLP for the full dose group was 6025 mGy·cm (1909–13353 mGy·cm) compared with 3391 mGy·cm (1683–6820 mGy·cm) for the reduced dose group. The reduced dose group had a 44% reduction in total DLP and 42% reduction in total CTDIvol (p < 0.001). The estimated skin doses were 384 mGy for the full dose group and 224 mGy for the reduced dose group (42% reduction) (p < 0.001). At 12-month follow-up, the technical success for the full dose (n=62) was 97% with 2 patients requiring a further cryoablation treatment for residual tumor. The technical success for the reduced dose group (n=41) was 100%. CONCLUSION: CT dose reduction technique during image-guided cryoablation treatment of renal tumors can achieve significant radiation dose reduction whilst maintaining sufficient image quality.

Highlights • Muscle invasive bladder cancer with variant histology has worse outcomes. • Chemoradiation is associated with similar OS to surgery for variant histology. • Adenocarcinoma and SCC have worse OS associated with chemoRT compared to surgery., Purpose For muscle-invasive bladder cancer, bladder preserving chemoradiotherapy (BPCRT) has shown to be a viable alternative for patients with urothelial carcinoma (UCa). Traditionally bladder cancer with variant histology UCa or other tumors types involving the bladder have worse outcomes and BPCRT has been contraindicated. However, there is limited high level evidence for this recommendation. Materials/methods The National Cancer Database (NCDB) was queried for all patients with Bladder cancer treated from 2004 to 2015 restricted to clinical stage T2-4, N0, M0 who had variants of UCa or other tumors types involving the bladder (e.g. adenocarcinoma and squamous cell carcinoma). Only patients treated with definitive intent with either radical cystectomy or BPCRT after maximal transurethral tumor resection were analyzed. Propensity-score matching was used. Results 356 patients had BPCRT and 2093 patients had definitive surgery for muscle-invasive bladder cancer limited to variants of UCa and other tumors types involving the bladder. On multivariable analysis worse prognosis was associated with age >65 years old (HR 1.24, p = 0.004) and T4 disease (HR 1.90, p

Liver transplantation continues to rise in frequency, with over 1,000 procedures performed in the UK in 2018. Complications are increasingly uncommon but when they occur, early recognition and intervention is vital to save grafts. Imaging after the perioperative period is often performed at patients' local hospitals meaning that all radiologists and sonographers need to have an understanding of how to assess a transplant liver. Part I of this series will focus on vascular complications, including the normal postoperative vascular anatomy following liver transplantation, normal post-transplantation vascular imaging findings and abnormal findings that may prompt further investigation. Vascular complications following liver transplantation will be illustrated using a collection of cases.

Introduction The coronavirus disease 2019 (COVID-19) has created unprecedented challenges on the healthcare system. The aim of this multi-centre study was to measure the impact of COVID-19 on IR services in the UK. Material and Methods Retrospective cross-sectional study of IR practice in six UK centres during the COVID-19 pandemic was carried out. All therapeutic IR procedures were identified using the respective hospital radiology information systems and COVID-19 status found on the hospital patient record systems. The total number of therapeutic IR procedures was recorded over two time periods, 25/03/2019–21/04/2019 (control group) and 30/03/2020–26/04/2020 (COVID-19 group). The data points collected were: procedure type, aerosol-generating nature, acute or elective case, modality used, in- or out-of-hours case and whether the procedure was done at the bedside (portable). Results A 31% decrease in overall number of IR procedures was observed during COVID-19 compared to the control group (1363 cases vs 942 cases); however, the acute work decreased by only 0.5%. An increase in out-of-hours work by 10% was observed. COVID-19 was suspected or laboratory proved in 9.9% of cases (n = 93), and 15% of total cases (n = 141) were classed as aerosol-generating procedures. A 66% rise in cholecystostomy was noted during COVID-19. Image-guided ablation, IVC filters, aortic stent grafting and visceral vascular stenting had the greatest % decreases in practice during COVID-19, with 91.7%, 83.3%, 80.8% and 80.2% decreases, respectively. Conclusion During the global pandemic, IR has continued to provide emergency and elective treatment highlighting the adaptability of IR in supporting other specialties.

Radiation therapy to treat cancer has evolved significantly since the discovery of x-rays. Yet, radiation therapy still has room for improvement in reducing side effects and improving control of cancer. Safer and more effective delivery of radiation has led us to novel techniques and use of biomaterials. Biomaterials in combination with radiation and chemotherapy have started to appear in pre-clinical explorations and clinical applications, with many more on the horizon. Biomaterials have revolutionized the field of diagnostic imaging, and now are being cultivated into the field of theranostics, combination therapy, and tissue protection. This review summarizes recent development of biomaterials in radiation therapy in several application areas., Graphical abstract Image 1

Prospective studies have demonstrated increased local control with the addition of a radiosurgery (SRS) boost to whole-brain irradiation (WBRT) in patients with brain metastases. However, the clinical application of SRS boost can be limited by several factors, including tumor size, numbers of lesions, and high cost of care. Here, we investigate the use of WBRT with a simultaneous integrated boost (SIB) to visible lesions in patients with brain metastases. From 2011 to 2016, patients were prospectively enrolled and prescribed a dose of 25 or 37.5 Gray (Gy) WBRT with a SIB dose of 45 or 52.5 Gy to the gross lesions in 10 or 15 fractions, respectively. All plans were optimized for dose coverage of the whole brain and lesions using volumetric arc therapy (VMAT). Comprehensive neurocognitive and quality of life assessments were conducted at baseline and at follow-up. Thirteen patients were treated on this protocol. The 1-year local control rates were 92% at the patient level, and 98.6% at the lesion level. The overall 1-year intracranial control was 46%. Patients had no significant declines in Mini-Mental State Examination (MMSE), Hopkins Verbal Learning Test-Revised (HVLT-R), and Medical Outcomes Study (MOS) Cognitive Functional status scores pre- and post-treatment. WBRT with SIB to gross lesions using VMAT planning appears to be safe and effective in the treatment of brain metastases without significant cognitive decline. This treatment strategy should be considered in those patients with a high number of metastases or ones not amenable for radiosurgery. NCT01218542

Simple Summary Ablation techniques use extremely hot or cold temperatures to kill small cancers. It is now known that in addition to killing the cancer cells, the ablation treatment may stimulate an immune response in patients against the cancer cells, acting like a vaccine. As a result, there is now interest in combining ablation together with drugs that target the immune system of patients with cancer to enhance the effects of both treatments. In order to develop such combined treatments and test them in clinical trials, we need to understand more about their effects so trials can be optimally designed to be most effective. We have analysed 164 circulating proteins in the blood from patients with small renal tumours undergoing ablation treatment to understand more about the effects of ablation on the patient, both at the level of the effects on the cancer cells and the response of the patients. Abstract Further biological understanding of the immune and inflammatory responses following ablation is critical to the rational development of combination ablation-immunotherapies. Our pilot exploratory study evaluated the circulating plasma protein profiles after image-guided ablation (IGA) of small renal masses to determine the resultant systemic effects and provide insight into impact both on the tumour and immune system. Patients undergoing cryotherapy (CRYO), radiofrequency ablation (RFA) or microwave ablation (MWA) for small renal tumours were recruited. Blood samples were obtained at four timepoints; two baselines prior to IGA and at 24 h and 1–3 months post-IGA, and a panel of 164 proteins measured. Of 55 patients recruited, 35 underwent ablation (25 CRYO, 8 RFA, 2 MWA) and biomarker measurements. The most marked changes were 24 h post-CRYO, with 29 proteins increasing and 18 decreasing significantly, principally cytokines and proteins involved in regulating inflammation, danger-associated molecular patterns (DAMPs), cell proliferation, hypoxic response, apoptosis and migration. Intra-individual variation was low but inter-individual variation was apparent, for example all patients showed increases in IL-6 (1.7 to 29-fold) but only 50% in CD27. Functional annotation analysis highlighted immune/inflammation and cell proliferation/angiogenesis-related clusters, with interaction networks around IL-6, IL-10, VEGF-A and several chemokines. Increases in IL-8, IL-6, and CCL23 correlated with cryoprobe number (p = 0.01, rs = 0.546; p = 0.009, rs = 0.5515; p = 0.005, rs = 0.5873, respectively). This initial data provide further insights into ablation-induced biological changes of relevance in informing trial design of immunotherapies combined with ablation.

Treatment for recurrent intracranial neoplasms is often difficult and less standardized. Since its approval by the Food & Drug Administration (FDA), GammaTileTM (GT, GT Medical Technologies, Tempe, AZ), a novel collagen tile cesium brachytherapy, has been investigated for use in this population. This study presents the initial experience with the use of GT for patients with recurrent intracranial neoplasms at a tertiary referral center. A retrospective analysis of all patients with GT implantation from November 2019 to July 2021 was performed. Information regarding demographics, clinical history, imaging data, prior tumor treatment, dosing, surgical complications, and outcomes was collected. Twelve patients were included in this study. Pathologies included gliomas (five patients), meningiomas (five patients), and metastatic tumors (two patients). The median tumor volume treated was 24 cc (IQR: 21.2 - 31.3 cc), and patients had a median of 7.5 tiles implanted (IQR: 5.4 - 10.3). One patient had a delayed epidural hematoma requiring reoperation, which was unrelated to GT implantation. Median follow-up was seven months (IQR: 3 -10), with the longest follow-up time of 20 months. Two patients have had local disease recurrence and three patients have had systemic progression of their disease. Three patients are deceased with survivals of 2.9, 4.8, and 5.8 months. Collagen tile brachytherapy is a safe and viable option for patients with recurrent intracranial tumors. Our data are consistent with early results seen at other institutions. Long-term data with larger patient populations are required to assess efficacy, safety, and indications for the use of this novel technology.

BackgroundReirradiation using brachytherapy (BT) and external beam radiation therapy (EBRT) are salvage strategies with locally radiorecurrent prostate cancer. This systematic review describes the oncologic and toxicity outcomes for salvage BT and EBRT [including Stereotactic Body Radiation Therapy (SBRT)].MethodsAn International Prospective Register of Systematic Reviews (PROSPERO) registered (#211875) study was conducted using Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. EMBASE and MEDLINE databases were searched from inception to December 2020. For BT, both low dose rate (LDR) and high dose rate (HDR) BT techniques were included. Two authors independently assessed study quality using the 18-item Modified Delphi technique.ResultsA total of 39 eligible studies comprising 1967 patients were included (28 BT and 11 SBRT). In 35 studies (90%), the design was single centre and/or retrospective and no randomised prospective studies were found. Twelve BT studies used LDR only, 11 HDR only, 4 LDR or HDR and 1 pulsed-dose rate only. All EBRT studies used SBRT exclusively, four with Cyberknife alone and 7 using both Cyberknife and conventional linear accelerator treatments. Median (range) modified Delphi quality score was 15 (6-18). Median (range) follow-up was 47.5 months (13-108) (BT) and 25.4 months (21-44) (SBRT). For the LDR-BT studies, the median (range) 2-year and 5-year bRFS rates were 71% (48-89.5) and 52.5% (20-79). For the HDR-BT studies, the median (range) 2-year and 5-year bRFS rates were 74% (63-89) and 51% (45-65). For the SBRT studies, the median (range) 2-year bRFS for the SBRT group was 54.9% (40-80). Mean (range) acute and late grade≥3 GU toxicity rates for LDR-BT/HDR-BT/SBRT were 7.4%(0-14)/2%(0-14)/2.7%(0-8.7) and 13.6%(0-30)/7.9%(0-21.3%)/2.7%(0-8%). Mean (range) acute and late grade≥3 GI toxicity rates for LDR-BT/HDR-BT/SBRT were 6.5%(0-19)/0%/0.5%(0-4%) and 6.4%(0-20)/0.1%(0-0.9)/0.2%(0-1.5). One third of studies included Patient Reported Outcome Measures (PROMs).ConclusionsSalvage reirradiation of radiorecurrent prostate cancer using HDR-BT or SBRT provides similar biochemical control and acceptable late toxicity. Salvage LDR-BT is associated with higher late GU/GI toxicity. Challenges exist in comparing BT and SBRT from inconsistencies in reporting with missing data, and prospective randomised trials are needed.

Objectives: Cone beam computed tomography (CBCT) is used for image guidance of stereotactic ablative radiotherapy (SABR), but it is susceptible to bowel motion artefacts. This trial evaluated the impact of hyoscine butylbromide (buscopan) on CBCT image quality and its feasibility within a radiotherapy workflow. Methods: A single-centre feasibility trial (ISRCTN24362767) was performed in patients treated with SABR for abdominal/pelvic oligorecurrence. Buscopan was administered to separate cohorts by intramuscular (IM) or intravenous (i.v.) injection on alternate fractions, providing within-patient control data. 4-point Likert scales were used to assess overall image quality (ranging from excellent to impossible to use) and bowel motion artefact (ranging from none to severe). Feasibility was determined by patient/radiographer questionnaires and toxicity assessment. Descriptive statistics are presented. Results: 16 patients were treated (8 by IM and 8 by i.v. buscopan). The percentage of images of excellent quality with/without buscopan was 47 vs 29% for IM buscopan and 65 vs 40% for i.v. buscopan. The percentage of images with no bowel motion artefact with/without buscopan was 24.6 vs 8.9% for IM buscopan and 25.8 vs 7% for i.v. buscopan. Four patients (25%) reported dry mouth. 14 patients (93%) would accept buscopan as routine. 11 radiographers (92%) reported no delay in treatments. Conclusions: A trend towards improved image quality/reduced bowel motion artefact was observed with IM/i.v. buscopan. Buscopan was well tolerated with limited impact on workflow. Advances in knowledge: This is the first trial of buscopan within a radiotherapy workflow. It demonstrated a trend to improved image quality and feasibility of use.

PURPOSE: Radical cystectomy currently remains the standard of care for muscle-invasive bladder cancer (MIBC). However, surgery can be associated with considerable morbidity and mortality, including the removal of the bladder. An alternative strategy is to preserve the bladder through concurrent chemo-radiation following a maximal trans-urethral resection of the tumor. National protocols using a bladder preservation approach have demonstrated disease-specific outcomes comparable to radical cystectomy in selected patients, but these results have not been replicated in previously reported population-based series. Here, we describe an outcomes analysis of patients with MIBC treated with either radical surgery or bladder-preserving chemo-radiation (BPCRT) for those patients meeting BPCRT criterion using the National Cancer Database (NCDB). METHODS AND MATERIALS: Using the NCDB, patients with AJCC clinical T2-3, N0, M0 urothelial carcinoma diagnosed between 2004–2013 were included for analysis. Only patients treated with definitive intent with either radical cystectomy or concurrent chemotherapy and radiation after a maximal transurethral tumor resection were included. Propensity-score matching was employed. RESULTS: Among 8,454 eligible patients, 7,276 (86%) underwent radical cystectomy, and 1,178 (14%) underwent BPCRT. Patients undergoing BPCRT were significantly older (median age 77 vs 68, p

Biliary complications post liver transplantation are a significant source of morbidity and mortality and early recognition is paramount to the long-term success of the liver graft. Part II of this series will focus on liver transplant biliary anatomy, including the blood supply to the biliary system and potential problems if it is interrupted. The imaging rationale for investigating suspected biliary complications, potential pitfalls, and treatment options will be discussed. The various biliary complications will be illustrated using a collection of cases.

Purpose Radiosurgery and fractionated intensity modulated radiation therapy (IMRT) are effective treatment modalities for meningiomas and schwannomas. Although fractionated IMRT yields favorable tumor control, daily treatments for 5 to 6 weeks can be burdensome for patients and health care systems. Thus, hypofractionated radiation may be a reasonable alternative. The purpose of this study was to review the results of patients with benign meningiomas or schwannomas treated at our institution with moderately hypofractionated IMRT. Methods and Materials After institutional review board approval, patients treated at a single academic institution between 2008 and 2018 with a primary diagnosis of either meningioma or schwannoma and who received 30 Gy at 3 Gy per fraction were identified. Patient and tumor characteristics, as well as follow-up documentation, were reviewed. Tumor progression was determined by reviewing patient imaging and provider notations. Results From 2008 to 2018, 70 patients with either meningioma or schwannoma were treated to 30 Gy. The median patient age was 73 years (range, 43-92 years). At the median follow up of 3.2 years, the local control was 92.9%. Two patients (2.9%) had disease progression, which occurred at 9.6 and 6.6 years after treatment. One patient developed asymptomatic radiographic changes consistent with radiation necrosis, which resolved without intervention. All patients completed the prescribed course without interruption. The mean tumor volume was 18.9 cm3, median volume was 36.6 cm3 (range, 3.4-245.5 cm3), and tumor volume was not associated with recurrence risk. Both tumors with progression were schwannomas. Conclusions Hypofractionated radiation with 30 Gy at 3 Gy per fraction is an effective, convenient, and well-tolerated alternative for patients with benign meningiomas or schwannomas. Modest hypofractionation provided durable control for a wide range of tumor volumes and should be considered for patients with a limited life expectancy or those unable to receive a more extended fractionated radiation therapy course.

AIM To determine whether machine learning-based radiomic feature analysis of baseline integrated 2-[18F]-fluoro-2-deoxy- d- glucose (FDG) positron-emission tomography (PET) computed tomography (CT) predicts disease progression in patients with locally advanced larynx and hypopharynx squamous cell carcinoma (SCC) receiving (chemo)radiotherapy. MATERIALS AND METHODS Patients with larynx and hypopharynx SCC treated with definitive (chemo)radiotherapy at a specialist cancer centre undergoing pre-treatment PET-CT between 2008 and 2017 were included. Tumour segmentation and radiomic analysis was performed using LIFEx software (University of Paris-Saclay, France). Data were assigned into training (80%) and validation (20%) cohorts adhering to TRIPOD guidelines. A random forest classifier was created for four predictive models using features determined by recursive feature elimination: (A) PET, (B) CT, (C) clinical, and (D) combined PET-CT parameters. Model performance was assessed using area under the curve (AUC) receiver operating characteristic (ROC) analysis. RESULTS Seventy-two patients (40 hypopharynx 32 larynx tumours) were included, mean age 61 (range 41–77) years, 50 (69%) were men. Forty-five (62.5%) had chemoradiotherapy, 27 (37.5%) had radiotherapy alone. Median follow-up 26 months (range 12–105 months). Twenty-seven (37.5%) patients progressed within 12 months. ROC AUC for models A, B, C, and D were 0.91, 0.94, 0.88, and 0.93 in training and 0.82, 0.72, 0.70, and 0.94 in validation cohorts. Parameters in model D were metabolic tumour volume (MTV), maximum CT value, minimum standardized uptake value (SUVmin), grey-level zone length matrix (GLZLM) small-zone low grey-level emphasis (SZLGE) and histogram kurtosis. CONCLUSION FDG PET-CT derived radiomic features are potential predictors of early disease progression in patients with locally advanced larynx and hypopharynx SCC.

There is no consensus regarding optimal interpretative criteria (IC) for Fluorine-18 fluorodeoxyglucose (FDG) Positron Emission Tomography – Computed Tomography (PET-CT) response assessment following (chemo)radiotherapy (CRT) for head and neck squamous cell carcinoma (HNSCC). The aim was to compare accuracy of IC (NI-RADS, Porceddu, Hopkins, Deauville) for predicting loco-regional control and progression free survival (PFS). All patients with histologically confirmed HNSCC treated at a specialist cancer centre with curative-intent non-surgical treatment who underwent baseline and response assessment FDG PET-CT between August 2008 and May 2017 were included. Metabolic response was assessed using 4 different IC harmonised into 4-point scales (complete response, indeterminate, partial response, progressive disease). IC performance metrics (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy) were compared. Kaplan-Meier and Cox proportional hazards regression analyses were performed for survival analysis. 562 patients were included (397 oropharynx, 53 hypopharynx, 48 larynx, 64 other/unknown primary). 420 patients (75%) received CRT and 142 (25%) had radiotherapy alone. Median follow-up was 26 months (range 3–148). 156 patients (28%) progressed during follow-up. All IC were accurate for prediction of primary tumour (mean NPV 85.0% (84.6–85.3), PPV 85.0% (82.5–92.3), accuracy 84.9% (84.2–86.0)) and nodal outcome (mean NPV 85.6% (84.1–86.6), PPV 94.7% (93.8–95.1), accuracy 86.8% (85.6–88.0)). Number of indeterminate scores for NI-RADS, Porceddu, Deauville and Hopkins were 91, 25, 20, 13 and 55, 70, 18 and 3 for primary tumour and nodes respectively. PPV was significantly reduced for indeterminate uptake across all IC (mean PPV primary tumour 36%, nodes 48%). Survival analyses showed significant differences in PFS between response categories classified by each of the four IC (p

The limited positive predictive value of an incomplete response on PET-CT following (chemo)radiotherapy for head and neck squamous cell carcinoma (HNSCC) means that the optimal management strategy remains uncertain. The aim of the study is to assess the utility of a ‘second-look’ interval PET-CT. Patients with HNSCC who were treated with (chemo)radiotherapy between 2008 and 2017 and underwent (i) baseline and (ii) response assessment PET-CT and (iii) second-look PET-CT following incomplete (positive or equivocal scan) response were included. Endpoints were conversion rate to complete response (CR) and test characteristics of the second-look PET-CT. Five hundred sixty-two patients with HNSCC underwent response assessment PET-CT at a median of 17 weeks post-radiotherapy. Following an incomplete response on PET-CT, 40 patients underwent a second-look PET-CT at a median of 13 weeks (range 6–25) from the first response PET-CT. Thirty-four out of 40 (85%) patients had oropharyngeal carcinoma. Twenty-four out of 40 (60%) second-look PET-CT scans converted to a complete locoregional response. The primary tumour conversion rate was 15/27 (56%) and the lymph node conversion rate was 14/19 (74%). The sensitivity, specificity, positive predictive value and negative predictive value (NPV) of the second-look PET-CT were 75%, 75%, 25% and 96% for the primary tumour and 100%, 92%, 40% and 100% for lymph nodes. There were no cases of progression following conversion to CR in the primary site or lymph nodes. The majority of patients who undergo a second-look PET-CT convert to a CR. The NPV of a second-look PET-CT is high, suggesting the potential to avoid surgical intervention. • PET-CT is a useful tool for response assessment following (chemo)radiotherapy for head and neck squamous cell carcinoma. • An incomplete response on PET-CT has a limited positive predictive value and optimal management is uncertain. • These data show that with a ‘second-look’ interval PET-CT, the majority of patients convert to a complete metabolic response. When there is doubt about clinical and radiological response, a ‘second-look’ PET-CT can be used to spare patients unnecessary surgical intervention.

Objectives The patterns of care for salivary gland adenoid cystic carcinomas (ACC) are unknown. We sought to assess predictors of receiving postoperative radiation and/or chemotherapy for patients with nonmetastatic, definitively resected ACC, as well as report unexpected nodal disease. Methods The National Cancer Data Base was queried for definitively resected nonmetastatic ACC from 2004 to 2014. Logistic regression, Kaplan-Meier, and Cox proportional-hazard models were utilized. Propensity-score matched analysis was employed to reduce confounding variables. Results A total of 3,136 patients met entry criteria: 2,252 (71.8%) received postoperative radiation, with 223 (7.4%) also receiving concurrent chemotherapy. Median follow-up was 4.87 years. In clinically lymph node negative (cN0) patients, 7.4% had pathologically positive lymph nodes (pN) + after elective neck dissection. Patients who lived closer to their treatment facility and had positive margins were more likely to receive postoperative radiation. Black patients and uninsured patients were less likely to receive radiation. Older age, male sex, advancing stage, and positive surgical margins were associated with worse overall survival (OS). With limited follow-up, receipt of radiation or chemotherapy was not associated with OS. Conclusion Postoperative radiation was frequently given for resected ACC, with a minority receiving chemotherapy. Black patients and uninsured patients were less likely to receive radiation. Postoperative radiation and/or chemotherapy had no association with OS but were given in greater frequency in more advanced disease, and our series is limited by short follow-up. The disparity findings for this rare disease need to be addressed in future studies. Level of evidence 2c Laryngoscope, 129:377-386, 2019.

BACKGROUND Treatment for advanced lung adenocarcinoma (AC) has become increasingly personalized based on molecular results. However, for patients with AC brain metastases (BMs), intracranial outcomes based on molecular subtype and the frequency of molecular aberrations are less well defined. This study sought to report targeted next-generation sequencing results and investigate molecularly based outcomes for patients with AC-BMs treated with radiotherapy. METHODS The records of 132 patients with AC-BMs treated at Emory University from September 2008 to August 2016 with successful next-generation sequencing were reviewed. Rates of local disease recurrence, distant brain failure (DBF), and salvage whole-brain radiotherapy (WBRT) were estimated using cumulative incidence with competing risk analysis. Univariate and multivariate analyses were performed. RESULTS The most common aberrations included tumor protein 53 (TP53) (60%), KRAS (29%), epidermal growth factor receptor (EGFR) (20.5%), phosphatase and tensin homolog (PTEN) loss (15.5%), and MET amplification (13%). The majority of patients (62%) were treated with stereotactic radiosurgery alone. In these patients, KRAS mutation, anaplastic lymphoma kinase (ALK) rearrangement, and having ≥ 6 BMs were associated with an increased risk of salvage WBRT (P

Purpose Efforts to define the neurovascular bundle (NVB) for prostate radiation have varied. In this series, we sought to determine the reproducibility and reliability of contouring the classical posterolateral NVB on dedicated pelvic magnetic resonance imaging (MRI) scans. Methods and materials A total of 120 NVB structures were defined on 10 3-Tesla pelvic MRI scans in patients with prostate cancer but without extraprostatic extension. One pelvic radiologist served as the expert in contouring the right and left NVB for each case. Five radiation oncologists, with varying levels of experience, contoured the right and left NVBs on these same cases. The intraclass correlation coefficient across each rater and the expert, Pearson correlation coefficient between each rater and the expert, and the Dice similarity coefficient (DSC) between each rater and the expert were calculated to evaluate contour agreement and overlap. Results The overall intraclass correlation coefficient was 0.89 (95% confidence interval [CI], 0.81-0.95). The Pearson correlation coefficient was 0.95 (95% CI, 0.86-0.98) for rater 1, 0.98 (95% CI, 0.95-0.99) for rater 2, 0.94 (95% CI, 0.86-0.98) for rater 3, 0.98 (95% CI, 0.95-0.99) for rater 4, and 0.84 (95% CI, 0.63-0.93) for rater 5. The mean DSC was 0.72 (standard deviation [SD], 0.07) for rater 1, 0.72 (SD, 0.06) for rater 2, 0.73 (SD, 0.09) for rater 3, 0.74 (SD, 0.09) for rater 4, and 0.68 (SD, 0.13) for rater 5. Overall, across all raters, the average DSC was 0.72 (SD, 0.09). Conclusions The classic posterolateral NVB can be accurately and reliably contoured on 3-Tesla pelvic MRI scans by radiation oncologists.

The LAP07 randomized trial calls into question the role of radiation therapy (RT) in the modern treatment of locally advanced pancreatic cancer (LAPC). However, advances in chemotherapy and RT limit application of the LAP07 results to current clinical practice. Here we utilize the National Cancer Database (NCDB) to evaluate the effects of RT in patients receiving chemotherapy for LAPC. Using the NCDB, patients with American Joint Committee on Cancer (AJCC) clinical stage T2–4, N0–1, M0 adenocarcinoma of the pancreas from 2004 to 2014 were analyzed. Patients were stratified into chemotherapy only (CT) and chemoradiation (CRT) cohorts. Patients undergoing definitive RT, defined as at least 20 fractions or ≥ 5 Gy per fraction [i.e., stereotactic body radiation therapy (SBRT)] were included in the CRT cohort. Propensity-score matching (PSM) and landmark analysis were used to address selection bias and lead-time bias, respectively. 13,004 patients met inclusion criteria, of whom 7034 (54%) received CT and 5970 (46%) received CRT. After PSM, 5215 patients remained in each cohort. The CRT cohort demonstrated better overall survival (OS) compared with CT alone, with median and 1-year OS of 12 versus 10 months, and 50% and 41%, respectively (p

Radiation (RT) dose to the central nervous system (CNS) has been implicated as a contributor to treatment-related fatigue in head and neck cancer (HNC) patients undergoing radiation therapy (RT). This study evaluates the association of RT dose to CNS structures with patient-reported (PRO) fatigue scores in a population of HNC patients.At pre-RT (baseline), 6th week of RT, and 1-month post-RT time points, Multidimensional Fatigue Inventory (MFI-20) scores were prospectively obtained from 124 patients undergoing definitive treatment for HNC. Medulla, pons, midbrain, total brainstem, cerebellum, posterior fossa, and pituitary dosimetry were evaluated using summary statistics and dose-volume histograms, and associations with MFI-20 scores were analyzed.Maximum dose (Dmax) to the brainstem and medulla was significantly associated with MFI-20 scores at 6th week of RT and 1-month post-RT time points, after controlling for baseline scores (p0.05). Each 1Gy increase in medulla Dmax resulted in an increase in total MFI-20 score over baseline of 0.30 (p=0.026), and 0.25 (p=0.037), at the 6th week of RT and 1-month post-RT, respectively. Each 1Gy increase in brainstem Dmax resulted in an increase in total MFI-20 score over baseline of 0.30 (p=0.027), and 0.25 (p=0.037) at the 6th week of RT, 1-month post-RT, respectively. Statistically significant associations were not found between dosimetry for the other CNS structures and MFI-20 scores.In this analysis of PRO fatigue scores from a population of patients undergoing definitive RT for HNC, maximum dose to the brainstem and medulla was associated with a significantly increased risk of acute patient fatigue.

Carotid artery pseudoaneurysm is a rare but serious complication of a retropharyngeal abscess in children. We report the first case of treating an unruptured mycotic pseudoaneurysm of the extracranial internal carotid artery (ICA) in a pediatric patient with vascular plugs. A 3-year-old patient presented with airway compromise and signs of neck sepsis. Successful embolization of the pseudoaneurysm was achieved with 2 Amplatzer vascular plugs to close the front and back door. The patient did not have any neurological deficit. Repeat imaging with ultrasound and computed tomography confirmed no recurrence of the pseudoaneurysm.

Purpose/Objective(s) Hypofractionated radiosurgery is often used for large brain metastases (BM) not amenable to single fraction radiosurgery, though the ideal dose-fractionation schedule has not been defined. This phase 1 dose escalation study was designed to define the maximum tolerated dose (MTD) of 5 fraction radiosurgery for intact BM or resection cavities ≥ 3cm and Materials/Methods Dose was escalated according to Escalation with Overdose Control (EWOC) method with a planned total enrollment of 24 patients in 8 patient cohorts of 3 patients per cohort and the target highest acceptable dose limiting toxicity (DLT) rate was set at 25%. Enrollment was closed for 4 months in between each cohort. DLT was defined as any acute or late central nervous system CTCAE toxicity grade ≥ 3 considered possibly related to treatment. DLTs assessment extended through 2 years after treatment or was censored at the time of removal from the study or re-irradiation to the treatment site. Results Twenty-four patients with 25 target lesions (5 intact BM, 20 resection cavities) were enrolled from October 2012 – February 2021 at the following dose levels with escalation and de-escalation according to EWOC rules: 6 Gy x 5 (level 0, n = 3), 6.5 Gy x 5 (level 1, n = 12), and 7 Gy x 5 (level 2, n = 9). Primary tumor histologies included non-small cell lung cancer (n = 11), esophageal cancer (n = 4), breast cancer (n = 3), melanoma (n = 3), and others (n = 3). The median tumor/cavity size was 18.5cc (range 9.1 - 57.2cc). The median overall follow-up time is 15.6 months (range 0.5 - 81.6) and median DLT assessment follow-up time is 11.5 months (range 0.5 - 27.3). Four DLTs including intracranial hemorrhage (1) and seizure (3) were observe after a median time of 11 months (range 1-14) in 3/9 patients at dose level 2 and 1/12 patients at dose level 1. Two deaths without clear cause in patients with known DLT were considered possibly related to treatment. Symptomatic RN occurred in 4/9 patients at dose level 2, and 2/12 patients at dose level 1. One patient experienced local tumor failure at 36 months. Conclusion The 6.5 Gy x 5 fractions is the maximum tolerated dose and recommended phase 2 dose of 5 fraction radiosurgery for large intact or resected brain metastases. This dose level is well tolerated and local control appears promising, though larger studies are required to further assess treatment efficacy at this dose level.

Purpose: To prospectively evaluate the incidence of post-ablation syndrome (fever and flu-like symptoms) and impact on the quality of life in the first 10 days following percutaneous image-guided cryoablation for renal cell carcinoma (RCC). Materials and Methods: A prospective study of all cryoablation procedures with biopsy proven RCC was conducted with institutional review board approval between 08/2012 and 04/2016. Sixty-four patients (43 males and 21 females) underwent cryoablation. Mean age was 68 (range 24–86). A telephone questionnaire survey was conducted on days 1, 3, 5, 7 and 10 following cryoablation, and complications were recorded. Data collected included temperature, degree of flu-like symptoms, severity of pain, percentage of pain relief with analgesics, interference with general activity and with work (graded on a 0–10 Numeric Intensity Scale). Results: Following cryoablation, six patients (9%) out of 64 developed post-ablation syndrome. Thirty-three patients (52%) developed flu-like symptoms only, which completely resolved by day 10 in 25 patients (39%). One patient had pyrexia only, which was self- limiting by day 10. Twenty-four patients (38%) were asymptomatic. Pain (mean score = 2.1) and interference on general activities (mean score = 1.8) and work (mean score = 2) following cryoablation peaked on day 3 and improved subsequently. Forty-six patients (72%) had 90–100% pain relief by day 10. No major complications were observed. Conclusion: The full spectrum of post-ablation syndrome following cryoablation occurs in approximately 9% of patients; however, 61% of patients experience flu-like symptoms in the first 10 days, which are self-limiting.

Although historical trials have established the role of surgical resection followed by whole brain irradiation (WBRT) for brain metastases, WBRT has recently been shown to cause significant neurocognitive decline. Many practitioners have employed postoperative stereotactic radiosurgery (SRS) to tumor resection cavities to increase local control without causing significant neurocognitive sequelae. However, studies analyzing outcomes of large brain metastases treated with resection and postoperative SRS are lacking. Here we compare outcomes in patients with large brain metastases4 cm to those with smaller metastases ≤4 cm treated with surgical resection followed by SRS to the resection cavity.Consecutive patients with brain metastases treated at our institution with surgical resection and postoperative SRS were retrospectively reviewed. Patients were stratified into ≤4 cm and4 cm cohorts based on preoperative maximal tumor dimension. Cumulative incidence of local failure, radiation necrosis, and death were analyzed for the 2 cohorts using a competing-risk model, defined as the time from SRS treatment date to the measured event, death, or last follow-up.A total of 117 consecutive cases were identified. Of these patients, 90 (77%) had preoperative tumors ≤4 cm, and 27 (23%)4 cm in greatest dimension. The only significant baseline difference between the 2 groups was a higher proportion of patients who underwent gross total resection in the ≤4 cm compared with the4 cm cohort, 76% versus 48%, respectively (P.01). The 1-year rates of local failure, radiation necrosis, and overall survival for the ≤4 cm and4 cm cohorts were 12.3% and 16.0%, 26.9% and 28.4%, and 80.6% and 67.6%, respectively (all P.05). The rates of local failure and radiation necrosis were not statistically different on multivariable analysis based on tumor size.Brain metastases4 cm in largest dimension managed by resection and radiosurgery to the tumor cavity have promising local control rates without a significant increase in radiation necrosis on our retrospective review.

BACKGROUND Previous studies examining the time to initiate chemoradiation (CRT) after surgical resection of glioblastoma have been conflicting. To better define the effect that the timing of adjuvant treatment may have on outcomes, the authors examined patients within the National Cancer Database (NCDB) stratified by a validated prognostic classification system. METHODS Patients with glioblastoma in the NCDB who underwent surgery and CRT from 2004 through 2013 were analyzed. Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class (III, IV, V) was extrapolated for the cohort. Time intervals were grouped weekly, with weeks 4 to 5 serving as the reference category for analyses. Kaplan-Meier analysis, log-rank testing, and multivariate (MVA) Cox proportional hazards regression were performed. RESULTS In total, 30,414 patients were included. RPA classes III, IV, and V contained 5250, 20,855, and 4309 patients, respectively. On MVA, no time point after week 5 was associated with a change in overall survival for the entire cohort or for any RPA class subgroup. The periods of weeks 0 to 1 (hazard ratio [HR], 1.18; 95% CI, 1.02-1.36), >1 to 2 (HR, 1.23; 95% CI, 1.16-1.31), and >2 to 3 (HR, 1.11; 95% CI, 1.07-1.15) demonstrated slightly worse overall survival (all P

Target delineation for radiation therapy treatment planning often benefits from magnetic resonance imaging (MRI) in addition to x-ray computed tomography (CT) due to MRI's superior soft tissue contrast. MRI-based treatment planning could reduce systematic MR-CT co-registration errors, medical cost, radiation exposure, and simplify clinical workflow. However, MRI-only based treatment planning is not widely used to date because treatment-planning systems rely on the electron density information provided by CTs to calculate dose. Additionally, air and bone regions are difficult to separategiven their similar intensities in MR imaging. The purpose of this work is to develop a learning-based method to generate patient-specific synthetic CT (sCT) from a routine anatomical MRI for use in MRI-only radiotherapy treatment planning. An auto-context model with patch-based anatomical features was integrated into a classification random forest to generate and improve semantic information. The semantic information along with anatomical features was then used to train a series of regression random forests based on the auto-context model. After training, the sCT of a new MRI can be generated by feeding anatomical features extracted from the MRI into the well-trained classification and regression random forests. The proposed algorithm was evaluated using 14 patient datasets withT1-weighted MR and corresponding CT images of the brain. The mean absolute error (MAE), peak signal-to-noise ratio (PSNR), and normalized cross correlation (NCC) were 57.45 ± 8.45 HU, 28.33 ± 1.68 dB, and 0.97 ± 0.01. We also compared the difference between dose maps calculated on the sCT and those on the original CT, using the same plan parameters. The average DVH differences among all patients are less than 0.2 Gy for PTVs, and less than 0.02 Gy for OARs. The sCT generation by the proposed method allows for dose calculation based MR imaging alone, and may be a useful tool for MRI-based radiation treatment planning.

Pre-operative stereotactic radiosurgery (pre-SRS) has been shown as a viable treatment option for resectable brain metastases (BM). The aim of this study is to compare oncologic outcomes and toxicities for pre-SRS and post-operative WBRT (post-WBRT) for resectable BM. We reviewed records of consecutive patients who underwent resection of BM and either pre-SRS or post-WBRT between 2005 and 2013 at two institutions. Overall survival (OS) was calculated using the Kaplan-Meier method. Cumulative incidence was used for intracranial outcomes. Multivariate analysis (MVA) was performed using the Cox and Fine and Gray models, respectively. Overall, 102 patients underwent surgical resection of BM; 66 patients with 71 lesions received pre-SRS while 36 patients with 42 cavities received post-WBRT. Baseline characteristics were similar except for the pre-SRS cohort having more single lesions (65.2% vs. 38.9%, p = 0.001) and smaller median lesion volume (8.3 cc vs. 15.3 cc, p = 0.006). 1-year OS was similar between cohorts (58% vs. 56%, respectively) (p = 0.43). Intracranial outcomes were also similar (2-year outcomes, pre-SRS vs. post-WBRT): local recurrence: 24.5% vs. 25% (p = 0.81), distant brain failure (DBF): 53.2% vs. 45% (p = 0.66), and leptomeningeal disease (LMD) recurrence: 3.5% vs. 9.0% (p = 0.66). On MVA, radiation cohort was not independently associated with OS or any intracranial outcome. Crude rates of symptomatic radiation necrosis were 5.6 and 0%, respectively. OS and intracranial outcomes were similar for patients treated with pre-SRS or post-WBRT for resected BM. Pre-SRS is a viable alternative to post-WBRT for resected BM. Further confirmatory studies with neuro-cognitive outcomes comparing these two treatment paradigms are needed.

BACKGROUND Postoperative management of prostate cancer with lymph node involvement (LNI) is controversial. Retrospective evidence supports the selective use of radiotherapy (RT) after extended pelvic lymph node dissection. It is unclear whether this is generalizable to practice in the United States, where extended dissection is uncommon. The authors identified patients with LNI who potentially could derive a survival benefit with adjuvant RT plus androgen-deprivation therapy (ADT). METHODS Patients with N1M0 prostate adenocarcinoma who underwent radical prostatectomy (RP) and subsequently received ADT from 2003 through 2011 were identified from the National Cancer Database. Kaplan-Meier analyses, log-rank tests, and multivariable Cox proportional hazards regression were performed using overall survival (OS) as the primary outcome. RESULTS In total, 906 of 2569 eligible patients (35.3%) received RT, and RT was more frequently received by patients who were diagnosed in later years, had fewer positive lymph nodes, had involved surgical margins, and were aged

BACKGROUND Stage II and III rectal cancers have been effectively treated with neoadjuvant chemoradiotherapy (NCRT) followed by definitive resection. Advancements in surgical technique and systemic therapy have prompted investigation of neoadjuvant multiagent chemotherapy (NMAC) regimens with the elimination of radiation (RT). The objective of the current study was to investigate factors that predict for the use of NCRT versus NMAC and compare outcomes using the National Cancer Data Base (NCDB) for select stage II and III rectal cancers. METHODS In the NCDB, 21,707 patients from 2004 through 2012 with clinical T2N1 (cT2N1), cT3N0, or cT3N1 rectal cancers were identified who had received NCRT or NMAC followed by low anterior resection. Kaplan-Meier analyses, log-rank tests, and Cox-proportional hazards regression analyses were conducted along with propensity score matching analysis to reduce treatment selection bias. RESULTS The 5-year actuarial overall survival (OS) rate was 75% for patients who received NCRT versus 67.2% for those who received NMAC (P

BACKGROUND Stereotactic radiosurgery (SRS) is an increasingly common modality used with surgery for resectable brain metastases (BM). OBJECTIVE To present a multi-institutional retrospective comparison of outcomes and toxicities of preoperative SRS (Pre-SRS) and postoperative SRS (Post-SRS). METHODS We reviewed the records of patients who underwent resection of BM and either Pre-SRS or Post-SRS alone between 2005 and 2013 at 2 institutions. Pre-SRS used a dose-reduction strategy based on tumor size, with planned resection within 48 hours. Cumulative incidence with competing risks was used to determine estimated rates. RESULTS A total of 180 patients underwent surgical resection for 189 BM: 66 (36.7%) underwent Pre-SRS and 114 (63.3%) underwent Post-SRS. Baseline patient characteristics were balanced except for higher rates of performance status 0 (62.1% vs 28.9%, P < .001) and primary breast cancer (27.2% vs 10.5%, P = .010) for Pre-SRS. Pre-SRS had lower median planning target volume margin (0 mm vs 2 mm) and peripheral dose (14.5 Gy vs 18 Gy), but similar gross tumor volume (8.3 mL vs 9.2 mL, P = .85). The median imaging follow-up period was 24.6 months for alive patients. Multivariable analyses revealed no difference between groups for overall survival (P = .1), local recurrence (P = .24), and distant brain recurrence (P = .75). Post-SRS was associated with significantly higher rates of leptomeningeal disease (2 years: 16.6% vs 3.2%, P = .010) and symptomatic radiation necrosis (2 years: 16.4% vs 4.9%, P = .010). CONCLUSION Pre-SRS and Post-SRS for resected BM provide similarly favorable rates of local recurrence, distant brain recurrence, and overall survival, but with significantly lower rates of symptomatic radiation necrosis and leptomeningeal disease in the Pre-SRS cohort. A prospective clinical trial comparing these treatment approaches is warranted. ABBREVIATIONS BM, brain metastasesCI, confidence intervalCTV, clinical target volumeDBR, distant brain recurrenceGTV, gross tumor volumeLC, local controlLMD, leptomeningeal diseaseLR, local recurrenceMVA, multivariable analysisOS, overall survivalPost-SRS, postoperative stereotactic radiosurgeryPre-SRS, preoperative stereotactic radiosurgeryPTV, planning target volumeRN, radiation necrosisSRN, symptomatic radiation necrosisSRS, stereotactic radiosurgeryWBRT, whole-brain radiation therapy.

A 44-year-old male initially presented with a right thalamic brain tumor that was confirmed with stereotactic biopsy to be glioblastoma (GBM). The patient was treated with radiotherapy and temozolomide for 6 weeks. At 1 month after completing chemoradiation therapy, the patient underwent follow-up imaging that revealed the primary lesion had mildly responded to chemoradiation, but a secondary lesion had developed along the biopsy needle tract. This secondary lesion was outside of the field of radiation therapy for the primary tumor and concluded to be intracranial spread of GBM along the biopsy tract. The patient’s final imaging 4 months after initial diagnosis revealed the primary and secondary lesions had enlarged. Subsequently, the patient clinically deteriorated and died 7 months after initial diagnosis.

In attempt to improve long-term disease control outcomes for high-risk prostate cancer, numerous clinical trials have tested the addition of chemotherapy (CTX)-either adjuvant or neoadjuvant-to definitive local therapy, either radical prostatectomy (RP) or radiation therapy (RT). Neoadjuvant trials generally confirm safety, feasibility, and pre-RP PSA reduction, but rates of pathologic complete response are rare, and no indications for neoadjuvant CTX have been firmly established. Adjuvant regimens have included CTX alone or in combination with androgen deprivation therapy (ADT). Here we provide a review of the relevant literature, and also quantify utilization of CTX in the definitive management of localized high-risk prostate cancer by querying the National Cancer Data Base. Between 2004 and 2013, 177 patients (of 29,659 total) treated with definitive RT, and 995 (of 367,570 total) treated with RP had CTX incorporated into their treatment regimens. Low numbers of RT + CTX patients precluded further analysis of this population, but we investigated the impact of CTX on overall survival (OS) for patients treated with RP +/- CTX. Disease-free survival or biochemical-recurrence-free survival are not available through the National Cancer Data Base. Propensity-score matching was conducted as patients treated with CTX were a higher-risk group. For nonmatched groups, OS at 5-years was 89.6% for the CTX group vs. 95.6%, for the no-CTX group (P0.01). The difference in OS between CTX and no-CTX groups did not persist after propensity-score matching, with 5-year OS 89.6% vs. 90.9%, respectively (Hazard ratio 0.99; P = 0.88). In summary, CTX was not shown to improve OS in this retrospective study. Multimodal regimens-such as RP followed by ADT, RT, and CTX; or RT in conjunction with ADT followed by CTX-have shown promise, but long-term follow-up of randomized data is required.

Preclinical evidence suggests angiotensin blockade therapy (ABT) decreases late radiation toxicities. This study aims to investigate the association between ABT and symptomatic radiation necrosis (SRN) following stereotactic radiosurgery (SRS). Resected brain metastases (rBM) and arteriovenous malformation (AVM) patients treated with SRS from 2002 to 2015 were identified. Patients in the ABT cohort were on therapy during SRS and at 1-month follow up. Kaplan Meier method and cumulative incidence model were used to analyze overall survival (OS) and intracranial outcomes. 228 consecutive patients were treated with SRS: 111 with rBM and 117 with AVM. Overall, 51 (22.4%) patients were in the ABT group: 32 (28.8%) in the rBM and 19 (16.2%) in AVM cohorts. Baseline characteristics were similar, except for higher Graded Prognostic Analysis (3–4) in the rBM (ABT: 25.0% vs. non-ABT: 49.0%, p = 0.033) and median age in the AVM (ABT: 51.4 vs. non-ABT: 35.4, p

Due to glioblastoma's infiltrative nature, an optimal radiation therapy (RT) plan requires targeting infiltration not identified by anatomical magnetic resonance imaging (MRI). Here, high-resolution, whole-brain spectroscopic MRI (sMRI) is used to describe tumor infiltration alongside anatomical MRI and simulate the degree to which it modifies RT target planning. In 11 patients with glioblastoma, data from preRT sMRI scans were processed to give high-resolution, whole-brain metabolite maps normalized by contralateral white matter. Maps depicting choline to N-Acetylaspartate (Cho/NAA) ratios were registered to contrast-enhanced T1-weighted RT planning MRI for each patient. Volumes depicting metabolic abnormalities (1.5-, 1.75-, and 2.0-fold increases in Cho/NAA ratios) were compared with conventional target volumes and contrast-enhancing tumor at recurrence. sMRI-modified RT plans were generated to evaluate target volume coverage and organ-at-risk dose constraints. Conventional clinical target volumes and Cho/NAA abnormalities identified significantly different regions of microscopic infiltration with substantial Cho/NAA abnormalities falling outside of the conventional 60 Gy isodose line (41.1, 22.2, and 12.7 cm3, respectively). Clinical target volumes using Cho/NAA thresholds exhibited significantly higher coverage of contrast enhancement at recurrence on average (92.4%, 90.5%, and 88.6%, respectively) than conventional plans (82.5%). sMRI-based plans targeting tumor infiltration met planning objectives in all cases with no significant change in target coverage. In 2 cases, the sMRI-modified plan exhibited better coverage of contrast-enhancing tumor at recurrence than the original plan. Integration of the high-resolution, whole-brain sMRI into RT planning is feasible, resulting in RT target volumes that can effectively target tumor infiltration while adhering to conventional constraints.

Background: Intra-luminal thrombosis is a key factor in Abdominal Aortic Aneurysms (AAA) growth. Patients with AAA form dense clots that are resistant to fibrinolysis. Thrombin-activatable fibrinolysis inhibitor (TAFI) has been shown to influence AAA development in murine models. Objective: The aim of this study is to characterise the role of TAFI in human AAA. Methods: Plasma levels of TAFI, TAFI activation peptide (TAFI-AP), activated/inactivated TAFI (TAFIa/ai) and plasmin-α2-antiplasmin complex were measured by ELISAs in patients with AAA (n=202) and controls (n=188). Results: TAFIa/ai and TAFI-AP levels were higher in patients than controls (median (IQR): 20.3 (14.6-32.8) vs. 14.2 (11.2-19.3) and 355.0 (232.4-528.1) vs. 248.6 (197.1-328.1) ng/ml). TAFIa/ai was positively correlated with TAFI-AP (r=0.164). Intact TAFI levels were not different between patients and controls (13.4 (11.2-16.1) vs. 12.8 (10.6-15.4) μg/ml). Plasmin-α2-antiplasmin was higher in AAA patients than controls (690.0 (489.1-924.3) vs. 480.7 (392.6-555.3) ng/ml). Conclusions: The increase in TAFIa/ai and TAFI-AP suggest an increased TAFI activation in patients with AAA. Prospective studies are required to further elucidate the role of TAFI and fibrinolysis in AAA pathogenesis.

Pre-operative stereotactic radiosurgery (pre-SRS) has been shown as a viable treatment option for resectable brain metastases (BM). The aim of this study is to compare oncologic outcomes and toxicities for pre-SRS and post-operative WBRT (post-WBRT) for resectable BM. We reviewed records of consecutive patients who underwent resection of BM and either pre-SRS or post-WBRT between 2005 and 2013 at two institutions. Overall survival (OS) was calculated using the Kaplan–Meier method. Cumulative incidence was used for intracranial outcomes. Multivariate analysis (MVA) was performed using the Cox and Fine and Gray models, respectively. Overall, 102 patients underwent surgical resection of BM; 66 patients with 71 lesions received pre-SRS while 36 patients with 42 cavities received post-WBRT. Baseline characteristics were similar except for the pre-SRS cohort having more single lesions (65.2% vs. 38.9%, p = 0.001) and smaller median lesion volume (8.3 cc vs. 15.3 cc, p = 0.006). 1-year OS was similar between cohorts (58% vs. 56%, respectively) (p = 0.43). Intracranial outcomes were also similar (2-year outcomes, pre-SRS vs. post-WBRT): local recurrence: 24.5% vs. 25% (p = 0.81), distant brain failure (DBF): 53.2% vs. 45% (p = 0.66), and leptomeningeal disease (LMD) recurrence: 3.5% vs. 9.0% (p = 0.66). On MVA, radiation cohort was not independently associated with OS or any intracranial outcome. Crude rates of symptomatic radiation necrosis were 5.6 and 0%, respectively. OS and intracranial outcomes were similar for patients treated with pre-SRS or post-WBRT for resected BM. Pre-SRS is a viable alternative to post-WBRT for resected BM. Further confirmatory studies with neuro-cognitive outcomes comparing these two treatment paradigms are needed.

4103 Background: The recently reported LAP07 randomized trial calls into question the role of radiation therapy (RT) in the modern treatment of locally advanced pancreatic cancer (LAPC). However, advances in chemotherapy and RT limit application of the LAP07 results to current clinical practice. Here we utilize the National Cancer Database (NCDB) to evaluate the effects of RT in patients receiving chemotherapy for LAPC. Methods: Using the NCDB, patients with AJCC clinical stage T2-T4, N0-1, M0 adenocarcinoma of the pancreas from 2004-2014 were analyzed. Only those that received chemotherapy and did not undergo surgery were included. Patients were stratified into chemotherapy only (CT) and chemoradiation (CRT) cohorts. Patients undergoing definitive RT, defined as at least 20 fractions (fxs) or ≥ 5 Gy per fraction (i.e. SBRT) were included in the CRT cohort. Propensity-score matching (PSM) and landmark analysis were used to address selection bias and lead-time bias, respectively. The primary endpoint was overall survival (OS). Results: 13,004 patients met inclusion criteria, of which 7,034 (54%) received CT and 5,970 (46%) received CRT. After PSM, 5,215 patients remained in each cohort. Median follow-up was 22.6 months. The CRT group had younger median age (65 vs. 67) and less treatment at academic centers (44 vs. 51%); performance status was similar between groups. The median fractionated RT dose was 50.4 Gy in 28 fxs and SBRT dose was 24 Gy in 3 fxs. The CRT cohort demonstrated better OS compared with CT alone, with median and 1-yr OS of 12 vs. 10 months, and 50% and 41%, respectively (p < 0.001). On multivariable analysis, CRT was associated with superior OS with a hazard ratio (HR) of 0.79 (95% confidence interval (CI): 0.76-0.83, p < 0.001) compared with CT alone. The SBRT subgroup demonstrated the best survival (HR 0.71 [95% CI: 0.64-0.80], p < 0.001). OS was superior for CRT after PSM and for all patient subsets. Conclusions: In unresected LAPC, the addition of definitive radiotherapy to chemotherapy is associated with superior OS when compared with chemotherapy alone. Survival was greatest when SBRT was used. Definitive radiotherapy should remain a standard option for LAPC but optimal selection criteria remain unclear.

366 Background: As systemic therapy has improved for locally advanced pancreatic cancer (LAPC), efforts to improve local control have become critical. While conventionally fractionated radiation therapy (CFRT) has more recently shown a limited role in LAPC, stereotactic body irradiation (SBRT) is an emerging approach that delivers higher doses of radiation therapy, to small volumes, over a much shorter period of time. With no studies to date comparing SBRT to CFRT for LAPC, we utilized the National Cancer Database (NCDB) to evaluate these two modalities. Methods: Using the NCDB, patients with AJCC clinic cT2-4, N0-1, M0 adenocarcinoma of the pancreas diagnosed from 2004-2013 were analyzed. Radiation therapy delivered at 2 Gy per fraction or less was deemed CFRT, and 4 Gy or more per fraction was considered SBRT to allow inclusion of practice variations. Kaplan-Meier, log-rank test, and multivariable Cox proportional hazards regression were performed with overall survival (OS) as the primary outcome. Propensity score matching was employed to reduce treatment selection bias. Results: Among 8,450 patients, 7,819 (92.5%) were treated with CFRT, and 631 (7.5%) underwent SBRT. The median dose per fraction and number of fractions for CFRT and SBRT cohorts were 1.8 Gy per fraction in 28 fractions and 8 Gy per fraction in 5 fractions, respectively. Using propensity score matching, 988 patients were matched, with 494 patients in each cohort. Within the propensity-matched cohorts, the median OS was higher with SBRT (13.9 vs. 10.7 months), and 2-year OS of 21.5% and 15.9% for the SBRT and CFRT groups, respectively ( p = 0.0014). Multivariable analysis confirmed SBRT was a significant predictor for OS (Hazard ratio:0.84; 95% confidence interval: 0.75-0.93, p = 0.001). Additionally, pancreatoduodenectomy, low comorbidity index, chemotherapy use, and node negative disease also positively impacted survival. Conclusions: SBRT appears to be associated with an improved OS compared to CFRT for LAPC. Further prospective studies investigating these hypothesis-generating results are warranted.

28 Background: The postoperative management of prostate cancer with regional lymph nodal involvement (LNI) is controversial. Prospective evidence to guide the role of radiotherapy (RT) in this setting does not exist. Randomized studies demonstrate an improvement in disease-related outcomes with adjuvant RT in high-risk patients without LNI following prostatectomy (RP). Retrospective evidence supports the selective use of RT with LNI following extended pelvic lymph node dissection. It is unclear if this experience is generalizable to practice in the United States where extended dissection is uncommon. We sought to identify patients with LNI who may derive a survival benefit following adjuvant RT. Methods: The National Cancer Data Base was queried for M0 patients with prostate adenocarcinoma who underwent RP with pathologic LNI. Adjvuant RT was defined as delivered within 6 months following RP. Kaplan-Meier, log-rank test, and multivariable Cox proportional hazards regression were performed with overall survival (OS) as the primary outcome. Propensity score matching (PSM) was employed to further reduce treatment selection bias. Results: 7,902 patients diagnosed between 2003-2011 were eligible for analysis; 1,439 (18.2%) received RT. RT was more frequently employed in patients with lower Charlson-Deyo Comorbidity Score, higher T stage