Abstract
Background
Noninvasively differentiating therapy-induced pseudoprogression from recurrent disease in patients with glioblastoma is prospectively difficult due to the current lack of a ...biologically specific imaging metric. Ferumoxytol iron oxide nanoparticle MRI contrast characterizes innate immunity mediated neuroinflammation; therefore, we hypothesized that combined ferumoxytol and gadolinium enhanced MRI could serve as a biomarker of glioblastoma pseudoprogression.
Methods
In this institutional review board-approved, retrospective study, we analyzed ferumoxytol and gadolinium contrast enhanced T1-weighted 3T MRI in 45 patients with glioblastoma over multiple clinical timepoints. Isocitrate dehydrogenase 1 (IDH-1) mutational status was characterized by exome sequencing. Sum of products diameter measurements were calculated according to Response Assessment in Neuro-Oncology criteria from both gadolinium and ferumoxytol enhanced sequences. Enhancement mismatch was calculated as the natural log of the ferumoxytol to gadolinium sum of products diameter ratio. Analysis of variance and Student’s t-test assessed differences in mismatch ratios. P-value <0.05 indicated statistical significance.
Results
With the development of pseudoprogression we observed a significantly elevated mismatch ratio compared with disease recurrence (P < 0.01) within IDH-1 wild type patients. Patients with IDH-1 mutation demonstrated significantly reduced mismatch ratio with the development of pseudoprogression compared with disease recurrence (P < 0.01). Receiver operator curve analysis demonstrated 100% sensitivity and specificity for the use of mismatch ratios as a diagnostic biomarker of pseudoprogression.
Conclusion
Our study suggests that ferumoxytol to gadolinium contrast mismatch ratios are an MRI biomarker for the diagnosis of pseudoprogression in patients with glioblastoma. This may be due to the unique characterization of therapy-induced neuroinflammation.
To evaluate demographics, treatment patterns, radiotherapy utilization and patient outcomes in meningeal melanocytomas.
The National Cancer Database was queried for meningeal melanocytomas diagnosed ...in 2002-2016. The effects of demographic, clinical and treatment variables were determined via Kaplan-Meier log-rank and Cox regression analyses.
The median and 5-year overall survival were 57.46 months and 48%, respectively. Patients earning ≥$48K showed improved survival (p = 0.0319). Radiotherapy and chemotherapy were utilized in 37.7 and 9% of patients, respectively.
Income significantly affected survival. Surgery remains the mainstay approach. Radiotherapy was delivered in more than one-third of patients but did not impact survival. However, further analyses were limited by poor treatment modality information in the database.
•Maximally safe resection remains prevalent in myxopapillary ependymomas.•Race, age, and tumor size significantly affect the likelihood of radiotherapy use.•The effect of radiotherapy on ...progression-free-survival requires further analysis.
Myxopapillary ependymomas (MPE) are WHO Grade I ependymomas that annually occur in 0.05–0.08 per 100,000 people. Surgical resection is the recommended first line therapy. Due to the rarity of the disease, there is a relatively poor understanding of the use of radiotherapy (RT) in managing this disease. The National Cancer Database (NCDB) was analyzed for patterns of care foradult MPE diagnosed between 2002 and 2016. Of 753 qualifying cases, the majority of patients underwent resection (n = 617, 81.9%). A relatively small portion received RT (n = 103, 13.3%) with most receiving RT post-operatively (n = 98, 95.1%). The likelihood of patients to undergo resection and RT was associated with patient age at diagnosis (p = 0.002), tumor size (p < 0.001), and race (p = 0.017). Chemotherapy was not widely utilized (0.27% of patients). One limitation of our analysis is that there was no data on progression free survival (PFS), an important outcome given the high survival rate in this disease. Surgery remains the primary means to manage adult MPE. For spinal MPE, it is understood that gross total resection (GTR) should be attempted whenever possible as GTR has been associated with improved PFS in several studies. The impact of RT on overall survival (OS) is indeterminate given the 1.6% death rate in the cohort. Analyses of the impact of RT on PFS in a larger database would be beneficial for determining an algorithm for post-operative and definitive RT in this disease entity.
The Hirsch index (h-index) has been shown to correlate with radiation oncology residents' having a first job in academics versus private practice, but it is limited by its inability to distinguish ...between the differing significance of coauthor roles in articles.
A list of 2016 radiation oncology resident graduates and their postresidency career choices was compiled. The Scopus bibliometric citation database was then searched to collect h-index data for articles limited to first author only (h
) and first or second-author only (h
) for each resident.
Mean h
was 2.06 for all resident graduates, and mean h
was 2.77. Residents with PhDs had significantly higher h
(3.11 versus 1.76, P < .01) and h
(4.50 versus 2.28, P < .01). There was no statistically significant difference between male and female residents for h
(2.19 versus 1.61, P = .11) or h
(2.91 versus 2.25, P = .15). Residents choosing academia had higher h
(2.72 versus 1.44, P < .01) and h
(3.57 versus 2.01, P < 0.01) than those in private practice. Fewer than 20% of graduates with h
= 0 and only 10% of graduates with h
= 0 secured academic jobs.
The average radiation oncology resident graduate has published a minimum of two first- and/or second-author articles cited at least twice. Graduates with PhDs and/or choosing academic careers were more likely to have higher h
and h
scores; there was no significant score difference by gender. Only 10% of graduates without any first- and/or second-author articles cited at least once secured academic jobs. These findings indicate that stratifying publications by first or second authorship when developing benchmarks for evaluating resident productivity and postresidency career type may be useful.
The impact of hospital volume on cancer patient survival has been demonstrated in the surgical literature, but sparsely for patients receiving radiation therapy (RT). This analysis addresses the ...impact of hospital volume on patients receiving RT for the most common central nervous system tumor: brain metastases.
Analysis was conducted using the National Cancer Database (NCDB) from 2010-2015 for patients with metastatic brain disease from lung cancer, breast cancer, and colorectal cancer requiring RT. Hospital volume was stratified as high-volume (≥ 12 brain RT/year), moderate (5-11 RT/year), and low (< 5 RT/year). The effect of hospital volume on overall survival was assessed using a multivariable Cox regression model.
A total of 18,841 patients 9479 (50.3%) men, 9362 (49.7%) women; median age 64 years met the inclusion criteria. 16.7% were treated at high-volume hospitals, 36.5% at moderate-volume, and the remaining 46.8% at low-volume centers. Multivariable analysis revealed that mortality was significantly improved in high-volume centers (HR: 0.95, p = 0.039) compared with low-volume centers after accounting for multiple demographics including age, sex, race, insurance status, income, facility type, Charlson-Deyo score and receipt of palliative care.
Hospitals performing 12 or more brain RT procedures per year have significantly improved survival in brain metastases patients receiving radiation as compared to lower volume hospitals. This finding, independent of additional demographics, indicates that the increased experience associated with increased volume may improve survival in this patient population.
Solitary fibrous tumors (SFT) are a rare neoplasm of mesenchymal origin. There is limited evidence on the epidemiology, treatment, and outcomes of SFT in the central nervous system (CNS). The ...National Cancer Database (NCDB) was queried for patients diagnosed with an SFT in the CNS as their only tumor diagnosis between 2003 and 2011. The final cohort included 155 patients who received surgery and had adequate information for analysis. Descriptive statistics, logistic regression, and Kaplan-Meier survival analyses were performed. Significance was calculated using a t-test, Fisher's exact test, chi-square, log-rank test, or Cox model. Twenty-three patients (15%) underwent both surgery and adjuvant radiation while 132 (85%) underwent surgery alone. The treatment groups had comparable demographics and tumor size; median age 53 (range 25-80) and 11 females (48%) in the surgery and adjuvant radiation group, compared to 55 (20-89) and 71 (54%) in the surgery alone group, respectively. Radiotherapy methods included conventional and stereotactic dose and fractionations schemes. Information on margin status and re-resection rates was not available. No variables were significantly associated with receipt of adjuvant radiation. In single (p = 0.78) and multivariable (p = 0.86) survival analyses, the addition of adjuvant radiation did not significantly affect overall survival. Five-year overall survival was 88% with surgery alone versus 93% with adjuvant radiation. SFTs are rare neoplasms, especially in the CNS. Our study did not demonstrate an overall survival benefit for adjuvant radiation. The role of adjuvant radiation is still unclear and warrants further investigation.
While most meningiomas are benign, aggressive meningiomas are associated with high levels of recurrence and mortality. A single institution's Gamma Knife radiosurgical experience with atypical and ...malignant meningiomas is presented, stratified by the most recent WHO classification.
Thirty-one patients with atypical and 4 patients with malignant meningiomas treated with Gamma Knife radiosurgery between July 2000 and July 2011 were retrospectively reviewed. All patients underwent prior surgical resection. Overall survival was the primary endpoint and rate of disease recurrence in the brain was a secondary endpoint. Patients who had previous radiotherapy or prior surgical resection were included. Kaplan-Meier and Cox proportional hazards models were used to estimate survival and identify factors predictive of recurrence and survival.
Post-Gamma Knife recurrence was identified in 11 patients (31.4%) with a median overall survival of 36 months and progression-free survival of 25.8 months. Nine patients (25.7%) had died. Three-year overall survival (OS) and progression-free survival (PFS) rates were 78.0% and 65.0%, respectively. WHO grade II 3-year OS and PFS were 83.4% and 70.1%, while WHO grade III 3-year OS and PFS were 33.3% and 0%. Recurrence rate was significantly higher in patients with a prior history of benign meningioma, nuclear atypia, high mitotic rate, spontaneous necrosis, and WHO grade III diagnosis on univariate analysis; only WHO grade III diagnosis was significant on multivariate analysis. Overall survival was adversely affected in patients with WHO grade III diagnosis, prior history of benign meningioma, prior fractionated radiotherapy, larger tumor volume, and higher isocenter number on univariate analysis; WHO grade III diagnosis and larger treated tumor volume were significant on multivariate analysis.
Atypical and anaplastic meningiomas remain difficult tumors to treat. WHO grade III diagnosis and treated tumor volume were significantly predictive of recurrence and survival on multivariate analysis in aggressive meningioma patients treated with radiosurgery. Larger tumor size predicts poor survival, while nuclear atypia, necrosis, and increased mitotic rate are risk factors for recurrence. Clinical and pathologic predictors may help identify patients that are at higher risk for recurrence.
Kralik et al. reported a seven percent rate of radiation-induced large vessel cerebral vasculopathy in children treated with proton RT, 80% of whom manifested with acute stroke with demonstrated MRI ...evidence of acute infarcts in clinically expected vascular distributions; all strokes occurred in vessels proximal to targeted tumors and occurred at a median time of 1.5 years following proton RT 1. A prospective randomized study involving 47 patients with subtotally resected benign meningiomas treated with an 80% to 20% proton/photon ratio revealed a greater than 20% stroke rate 2, far higher than that expected from either natural history 3,4, following photon RT 5, or following photon stereotactic radiosurgery 6; stroke developed at a median time of 5.6 years after RT completion 2–6. Most recently, Underwood et al. compared breast cancer patients treated with photon versus proton RT and found that follow-up CT scans revealed evidence of lung fibrosis consistent with a relative biological effectiveness (RBE) exceeding the 1.1 for proton RT generally presumed for clinical practice and recommended by the International Commission on Radiation Units and Measurements; this elevated dose was not prevalent in patients who received photon-based RT 7.
Currently, there are no consensus guidelines about handling incidental radiological findings on radiotherapy planning CT simulation scans. Retrospective studies analyzing incidental findings on CT ...simulations show a small, but not insignificant, rate of both oncologic and non-oncologic findings. These findings may have medico-legal, financial, and clinical implications. Given a lack of guidelines, we obtained a formal survey of multiple academic institutions to evaluate how CT simulations are handled in regard to incidental findings.
A formal survey was developed consisting of 12 questions related to institutional practices regarding CT simulation scans. From 7/18/21 to 8/27/21 and 5/6/22 to 5/24/22, the survey was administered electronically by REDCap to key personnel at Academic Radiation Oncology Programs identified through the American Society for Radiation Oncology (ASTRO) with inclusion criteria including an active ACGME approved Radiation Oncology residency program.
In total, 88 academic radiation oncology programs were surveyed with total of 45 responses (51%). 1 out of 45 departments who responded has formal guidelines regarding workup of incidental findings. There is variability about sending CT simulation scans for official radiology review if an incidental finding is identified.
Based on a measurable rate of incidental findings on radiotherapy planning CT simulations and their possible implications, our survey illustrates a likely need for consensus recommendations for handling such findings to improve patient care and safety.
PDF
