Utilization of functional MRI in the diagnosis and management of cervical cancer.

Introduction: Imaging is integral part of cervical cancer management. Currently, MRI is used for staging, follow up and image guided adaptive brachytherapy. The ongoing IQ-EMBRACE sub-study is evaluating the use of MRI for functional imaging to aid in the assessment of hypoxia, metabolism, hemodynamics and tissue structure. This study reviews the current and potential future utilization of functional MRI imaging in diagnosis and management of cervical cancer. Methods: We searched PubMed for articles characterizing the uses of functional MRI (fMRI) for cervical cancer. The current literature regarding these techniques in diagnosis and outcomes for cervical cancer were then reviewed. Results: The most used fMRI techniques identified for use in cervical cancer include diffusion weighted imaging (DWI) and dynamic contrast enhancement (DCE). DCE-MRI indirectly reflects tumor perfusion and hypoxia. This has been utilized to either characterize a functional risk volume of tumor with low perfusion or to characterize at-risk tumor voxels by analyzing signal intensity both pre-treatment and during treatment. DCE imaging in these situations has been associated with local control and disease-free survival and may have predictive/prognostic significance, however this has not yet been clinically validated. DWI allows for creation of ADC maps, that assists with diagnosis of local malignancy or nodal disease with high sensitivity and specificity. DWI findings have also been correlated with local control and overall survival in patients with an incomplete response after definitive chemoradiotherapy and thus may assist with post-treatment follow up. Other imaging techniques used in some instances are MR-spectroscopy and perfusion weighted imaging. T2-weighted imaging remains the standard technique used for diagnosis and radiation treatment planning. In many instances, it is unclear what additional information functional-MRI techniques provide compared to standard MRI imaging. Conclusions: Functional MRI provides potential for improved diagnosis, prediction of treatment response and prognostication in cervical cancer. Specific sequences such as DCE, DWI and ADC need to be validated in a large prospective setting prior to widespread use. The ongoing IQ-EMBRACE study will provide important clinical information regarding these imaging modalities.

Trends in the use of radiation for meningioma across the United States.

PURPOSE: Meningiomas are tumors originating from arachnoid cap cells on the surface of the brain or spinal cord. Treatment differs by grade but can consist of observation, surgery, radiation therapy or both. We utilized the National Cancer Database (NCDB) to compare trends in the use stereotactic radiosurgery (SRS) and external beam radiation therapy (EBRT) in the management of meningioma. MATERIALS AND METHODS: We queried the NCDB from 2004-2015 for meningioma patients (grade 1-3) treated with radiation therapy, either SRS or EBRT. Multivariable logistic regression was used to identify predictors of each treatment and to generate a propensity score. Propensity adjusted Kaplan-Meier survival curve analysis and multivariable Cox hazards ratios were used to identify predictors of survival. RESULTS: We identified 5,406 patients with meningioma meeting above criteria with 45%, 44%, and 11% having World Health Organization (WHO) grade 1, 2, and 3 disease, respectively. Median follow up was 43 months. Predictors for SRS were grade 1 disease, distance from treatment facility, and histology. The only predictor of EBRT was grade 3 disease. Treatment year, histology, race and female sex were associated with improved survival. Five- and 10-year survival rates were 89.2% versus 72.6% (p < 0.0001) and 80.3% versus 61.4% (p = 0.29) for SRS and EBRT respectively. After propensity matching 226 pairs were generated. For SRS, 5-year survival was not significantly improved at 88.2% compared with EBRT (p = 0.056). CONCLUSION: In the present analysis, predictors of SRS utilization in management of meningioma include WHO grade 1 disease, distance from treatment facility and histology whereas conventional EBRT utilization was associated with grade 2 and 3 disease. Future studies need to be performed in order to optimize management of atypical and malignant meningioma.

Prognostic and predictive biomarkers for response to neoadjuvant chemoradiation in esophageal adenocarcinoma.

BACKGROUND: Esophageal adenocarcinoma is a lethal disease. For locally advanced patients, neoadjuvant chemoradiotherapy followed by surgery is the standard of care. Risk stratification relies heavily on clinicopathologic features, particularly pathologic response, which is inadequate, therefore establishing the need for new and reliable biomarkers for risk stratification. METHODS: Thirty four patients with locally advanced esophageal adenocarcinoma were analyzed, of which 21 received a CROSS regimen with carboplatin, paclitaxel, and radiation. Capture-based targeted sequencing was performed on the paired baseline and post-treatment samples. Differentially mutated gene analysis between responders and non-responders of treatment was performed to determine predictors of response. A univariate Cox proportional hazard regression was used to examine associations between gene mutation status and overall survival. RESULTS: A 3-gene signature, based on mutations in EPHA5, BCL6, and ERBB2, was identified that robustly predicts response to the CROSS regimen. For this model, sensitivity was 84.6% and specificity was 100%. Independently, a 9 gene signature was created using APC, MAP3K6, ETS1, CSF3R, PDGFRB, GATA2, ARID1A, PML, and FGF6, which significantly stratifies patients into risk categories, prognosticating for improved relapse-free (p = 4.73E-03) and overall survival (p = 3.325E-06). The sensitivity for this model was 73.33% and the specificity was 94.74%. CONCLUSION: We have identified a 3-gene signature (EPHA5, BCL6, and ERBB2) that is predictive of response to neoadjuvant chemoradiotherapy and a separate prognostic 9-gene classifier that predicts survival outcomes. These panels provide significant potential for personalized management of locally advanced esophageal cancer.

Trends in Radiation Fractionation for Bone Metastases: A Contemporary Nationwide Analysis.

PURPOSE: Radiation therapy remains an important palliative tool for patients with bone metastases. The guidelines from the American Society for Therapeutic Radiation Oncology recommend the use of fewer fractions based on randomized data. We used the National Cancer Database to examine trends in radiation fractionation for patients with bone metastases. METHODS AND MATERIALS: We queried breast, prostate, and non-small cell lung cancer in the National Cancer Database from 2010 to 2015 for patients with bone metastases at the time of diagnosis who received bone-directed radiation therapy of 8 Gy in 1 fraction, 20 Gy to 24 Gy in 5 to 6 fractions, 30 Gy in 10 fractions, or >30 Gy in 10 fractions. We tabulated the baseline characteristics, and a multivariable logistic regression analysis was used to identify predictors of single-fraction treatment. RESULTS: We identified 17,859 patients who met the study criteria. The median patient age was 67 years, and the majority of patients (67%) had primary prostate cancer. Most patients (62%) received spine treatment. Single-fraction treatment increased over time from 3% in 2010 to 7% by 2015. Use of more protracted courses (>30 Gy in 10 fractions) decreased from 34% to 15% over the same interval. The most commonly used regimen (50%-60% of cases) remained 30 Gy in 10 fractions. Predictors of single-fraction treatment included increased age, no systemic therapy, increasing distance from facility, treatment at an academic center, nonspine/nonskull metastasis, and more recent treatment year. CONCLUSIONS: Use of single-fraction radiation for bone metastases has increased steadily but still accounts for <10% of palliative courses. The use of more protracted regimens has decreased significantly, although 30 Gy in 10 fractions remains the most widely used regiment.

Improving Time to Antibiotic Administration for Bone Marrow Transplant Patients With First Fever.

BACKGROUND AND OBJECTIVE: Timely antibiotic administration in immunocompromised patients is associated with improved outcomes. The aim of our study was to decrease the mean time to administration of antibiotics in hospitalized bone marrow transplant patients with fever from 75 to <60 minutes. METHODS: By using the Model of Improvement, we performed plan-do-study-act cycles to design, test, and implement high-reliability interventions to decrease time to antibiotics. Nursing, physician, and pharmacy interventions were successfully applied to improve timely antibiotic administration. RESULTS: The study period was from April 2014 through March of 2017. Through heightened awareness, dedicated roles and responsibilities, a standardized order set specifically used for first fever patients, notification to the pharmacy about newly febrile first fever patients through a dedicated order, the creation of a dedicated sticker ("STAT first dose antibiotic, give directly to nurse") to be printed when antibiotics were entered via the order set in the pharmacy, and prioritization of antibiotic delivery on arrival on the floor, we saw an increase in the percentage of patients receiving antibiotics within 60 minutes of documented fever from a mean of 40% to over 90%. Our mean time for antibiotic administration decreased from 75 to 45 minutes. CONCLUSIONS: Implementation of a standardized process for notifying providers of new fever in patients, prioritization of antibiotic preparation in the central pharmacy, and timely antibiotic order entry resulted in improved times to antibiotic administration in the febrile bone marrow transplant population.