Search

Standard of care for lower-grade glioma (LGG) is maximal safe resection and risk-adaptive adjuvant therapy. While patients who benefit the most from adjuvant chemotherapy have been elucidated in prospective randomized studies, comparable insights for adjuvant radiotherapy (RT) are lacking. We sought to identify and validate patterns of gene expression that are associated with differential outcomes among LGG patients treated by RT from two large genomics databases.Patients from The Cancer Genome Atlas (TCGA) with LGG (WHO grade II-III glioma) treated by surgery and adjuvant RT were randomized 1:1 to a discovery cohort or an internal validation cohort. Using the discovery cohort only, associations between tumor RNA-seq expression and progression-free survival (PFS) as well as overall survival (OS) were evaluated with adjustment for clinicopathologic covariates. A Genomic Risk Score (GRS) was then constructed from the expression levels of top genes also screened for involvement in glioma carcinogenesis. The prognostic value of GRS was further assessed in the internal validation cohort of TCGA and a second distinct database, compiled by the Chinese Glioma Genome Association (CGGA).From TCGA, 289 patients with LGG received adjuvant RT alone (38 grade II, 30 grade III) or chemoradiotherapy (CRT) (51 grade II, 170 grade III) between 2009 and 2015. From CGGA, 178 patients with LGG received adjuvant RT alone (40 grade II, 13 grade III) or CRT (41 grade II, 84 grade III) between 2004 and 2016. The genes comprising GRS are involved in MAP kinase activity, T cell chemotaxis, and cell cycle transition: MAP3K15, MAPK10, CCL3, CCL4, and ADAMTS1. High GRS, defined as having a GRS in the top third, was significantly associated with poorer outcomes independent of age, sex, glioma histology, WHO grade, IDH mutation, 1p/19q co-deletion, and chemotherapy status in the discovery cohort (PFS HR 1.61, 95% CI 1.10-2.36, P = 0.014; OS HR 2.74, 95% CI 1.68-4.47, P 0.001). These findings were replicated in the internal validation cohort (PFS HR 1.58, 95% CI 1.05-2.37, P = 0.027; OS HR 1.84, 95% CI 1.13-3.00, P = 0.015) and the CGGA external validation cohort (OS HR 1.72, 95% CI 1.27-2.34, P 0.001). Association between GRS and outcomes was observed only among patients who underwent RT, in both TCGA and CGGA.This study successfully identified an expression signature of five genes that stratified outcomes among LGG patients who received adjuvant RT, with two rounds of validation leveraging independent genomics databases. Expression levels of the highlighted genes were associated with PFS and OS only among patients whose treatment included RT, but not among those with omission of RT, suggesting that expression of these genes may be predictive of radiation treatment response. While additional prospective studies are warranted, interrogation of these genes may be considered in the multidisciplinary management of LGG.

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.

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.

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

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.

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.

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.

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.

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.

Ampullary adenocarcinoma is a rare malignancy associated with a relatively favorable prognosis. Given high survival rates in stage I patients reported in small series with surgery alone, adjuvant chemoradiotherapy (CRT) has traditionally been recommended only for patients with high risk disease. Recent population-based data have demonstrated inferior outcomes to previous series. We examined disease-related outcomes for stage I tumors treated with pancreaticoduodenectomy, with and without CRT.All patients with stage I ampullary adenocarcinoma treated from 1976 to 2011 at Duke University were reviewed. Disease-related endpoints including local control (LC), metastasis-free survival (MFS), disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method.Forty-four patients were included in this study. Thirty-one patients underwent surgery alone, while 13 also received adjuvant CRT. Five-year LC, MFS, DFS and OS for patients treated with surgery only and surgery with CRT were 56% and 83% (P=0.13), 67% and 83% (P=0.31), 56% and 83% (P=0.13), and 53% and 68% (P=0.09), respectively.The prognosis for patients diagnosed with stage I ampullary adenocarcinoma may not be as favorable as previously described. Our data suggests a possible benefit of adjuvant CRT delivery.