Assessment of Clinical Response Following Atezolizumab and Bevacizumab Treatment in Patients With Neuroendocrine Tumors: A Nonrandomized Clinical Trial.

Importance: Therapies for patients with advanced well-differentiated neuroendocrine tumors (NETs) have expanded but remain inadequate, with patients dying of disease despite recent advances in NET therapy. While patients with other cancers have seen long-term disease control and tumor regression with the application of immunotherapies, initial prospective studies of single-agent programmed cell death 1 inhibitors in NET have been disappointing. Objective: To evaluate the response rate following treatment with the combination of the vascular endothelial growth factor inhibitor bevacizumab with the programmed cell death 1 ligand 1 inhibitor atezolizumab in patients with advanced NETs. Design, Setting, and Participants: This single-arm, open-label nonrandomized clinical study in patients with rare cancers included 40 patients with advanced, progressive grade 1 to 2 NETs (20 with pancreatic NETs [pNETs] and 20 with extrapancreatic NETs [epNETs]) treated at a tertiary care referral cancer center between March 31, 2017, and February 19, 2019. Data were analyzed from June to September 2021. Interventions: Patients received intravenous bevacizumab and atezolizumab at standard doses every 3 weeks until progression, death, or withdrawal. Main Outcomes and Measures: The primary end point was objective radiographic response using Response Evaluation Criteria in Solid Tumors, version 1.1, with progression-free survival (PFS) as a key secondary end point. Results: Following treatment of the 40 study patients with bevacizumab and atezolizumab, objective response was observed in 4 patients with pNETs (20%; 95% CI, 5.7%-43.7%) and 3 patients with epNETs (15%; 95% CI, 3.2%-37.9%). The PFS was 14.9 (95% CI, 4.4-32.0) months and 14.2 (95% CI, 10.2-19.6) months in these cohorts, respectively. Conclusions and Relevance: In this nonrandomized clinical trial, findings suggest that clinical responses in patients with NET may follow treatment with the combination of bevacizumab and atezolizumab, with a PFS consistent with effective therapies. Trial Registration: ClinicalTrials.gov Identifier: NCT03074513.

Metabolic Imaging Using Hyperpolarization for Assessment of Premalignancy.

There is an unmet need for noninvasive surrogate markers that can help identify premalignant lesions across different tumor types. Here we describe the methodology and technical details of protocols employed for in vivo 13C pyruvate metabolic imaging experiments. The goal of the method described is to identify and understand metabolic changes, to enable detection of pancreatic premalignant lesions, as a proof of concept of the high sensitivity of this imaging modality.

Liver Fibrosis Assessment.

Early diagnosis of hepatic fibrosis (HF) is pivotal for management to cease progression to cirrhosis and hepatocellular carcinoma. HF is the telltale sign of chronic liver disease, and confirmed by liver biopsy, which is an invasive technique and inclined to sampling errors. The morphologic parameters of cirrhosis are assessed on conventional imaging such as on ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI). Newer imaging modalities such as magnetic resonance elastography and US elastography are reliable and accurate. More research studies on novel imaging modalities such as MRI with diffusion weighted imaging, enhancement by hepatobiliary contrast agents, and CT using perfusion are essential for earlier diagnosis, surveillance and accurate management. The purpose of this article is to discuss non-invasive CT, MRI, and US imaging modalities for diagnosis and stratify HF.

Correlation of surgeon radiology assessment with laparoscopic disease site scoring in patients with advanced ovarian cancer.

BACKGROUND: Radiographic triage measures in patients with new advanced ovarian cancer have yielded inconsistent results. OBJECTIVE: To determine the correlation between surgeon radiology assessment and laparoscopic scoring by disease sites in patients with newly diagnosed advanced stage ovarian cancer. METHODS: Fourteen gynecologic oncology surgeons from a single institution performed a blinded review of pre-operative contrast-enhanced CT imaging from patients with advanced stage ovarian cancer. Each of the patients had also undergone laparoscopic scoring assessment, between April 2013 and December 2017, to determine primary resectability using the validated Fagotti scoring method, and assigned a predictive index value score. Surgeons were asked to provide expected predictive index value scores based on their blinded review of the antecedent CT imaging. Linear mixed models were conducted to calculate the correlation between radiologic and laparoscopic score for surgeons individually, and as a group. Once the model was fit, the inter-class correlation and 95% CI were calculated. RESULTS: Radiology review was performed on 20 patients with advanced stage ovarian cancer who underwent laparoscopic scoring assessment. Surgeon faculty rank included assistant professor (n=5), associate professor (p=4), and professor (n=5). The kappa inter-rater agreement was -0.017 (95% CI -0.023 to -0.005), indicating low inter-rater agreement between radiology review and actual laparoscopic score. The inter-class correlation in this model was 0.06 (0.02-0.21), indicating that surgeons do not score the same across all the images. When using a clinical cut-off point for the predictive index value of 8, the probability of agreement between radiology and actual laparoscopic score was 0.56 (95% CI 0.49 to 0.73). Examination of disease site sub-scales showed that the probability of agreement was as follows: peritoneum 0.57 (95% CI 0.51 to 0.62), diaphragm 0.54 (95% CI 0.48 to 0.60), mesentery 0.51 (95% CI 0.45 to 0.57), omentum 0.61 (95% CI 0.55 to 0.67), bowel 0.54 (95% CI 0.44 to 0.64), stomach 0.71 (95% CI 0.65 to 0.76), and liver 0.36 (95% CI 0.31 to 0.42). The number of laparoscopic scoring cases, tumor reductive surgery cases, or faculty rank was not significantly associated with overall or sub-scale agreement. CONCLUSIONS: Surgeon radiology review did not correlate highly with actual laparoscopic scoring assessment findings in patients with advanced stage ovarian cancer. Our study highlights the limited accuracy of surgeon radiographic assessment to determine resectability.

Therapeutic response assessment in pancreatic ductal adenocarcinoma: society of abdominal radiology review paper on the role of morphological and functional imaging techniques.

Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer-related death in the United States and is projected to be the second by 2030. Systemic combination chemotherapy is considered an essential first-line treatment for the majority of patients with PDA, in both the neoadjuvant and palliative settings. In addition, a number of novel therapies are being tested in clinical trials for patients with advanced PDA. In all cases, accurate and timely assessment of treatment response is critical to guide therapy, reduce drug toxicities and cost from a failing therapy, and aid adaptive clinical trials. Conventional morphological imaging has significant limitations, especially in the context of determining primary tumor response and resectability following neoadjuvant therapies. In this article, we provide an overview of current therapy options for PDA, highlight several morphological imaging findings that may be helpful to reduce over-staging following neoadjuvant therapy, and discuss a number of emerging imaging, and non-imaging, tools that have shown promise in providing a more precise quantification of disease burden and treatment response in PDA.

Radiology Education Amid COVID-19 Pandemic and Possible Solutions.

Along with the rest of the world, the United States is inundated by the COVID-19 pandemic. The medical services in the country have been severely affected. The pandemic poses extraordinary challenges to academic institutions including radiology residency and fellowship programs. Herein, we delineate major difficulties faced by our radiology training program and mitigating countermeasures. The primary objective is to discuss the changes in our radiology training programs due to COVID-19 to allow for continued radiology education.

Assessment of the Effectiveness of the Vaginal Contrast Media in Magnetic Resonance Imaging for Detection of Pelvic Pathologies: A Meta-analysis.

OBJECTIVE: Magnetic resonance imaging (MRI) is an excellent modality for pelvic imaging. The anatomy of uterine cavity and vagina is optimally evaluated when the walls, which may spontaneously be collapsed, are distended. Distension of these cavities during pelvic MRI for evaluation of gynecologic diseases has been conducted with vagina, filled with ultrasound gel or saline solution. In this meta-analysis, we aim to assess the effectiveness of vaginal contrast media in MRI for improving the detection of pelvic pathologies. METHODS: The PubMed, MEDLINE, EMBASE, Web of Science, Google Scholar, Science Citation Index, and Cochrane Library databases were systematically searched through March 2019 for studies of the accuracy of MRI using vaginal contrast media in the diagnosis and staging of pelvic pathologies. Four eligible studies of a total of 120 patients were included in the meta-analysis. The sensitivity rates and relative risk for MRI, before and after vaginal contrast medium administration, were pooled, and their 95% confidence intervals (CIs) were determined. RESULTS: The pooled sensitivity rate for MRI before administering intravaginal contrast medium in detecting pelvic pathologies was 63% (95% CI, 54%-72%), and that after was 89% (95% CI, 83%-93%). The interstudy heterogeneity rate (assessed using the I statistic) was relatively low: 13% (P = 0.33) and 0% (P = 0.45) before and after vaginal contrast medium use, respectively. The average relative risk was 1.54 (SD, 0.22; 95% CI, 1.18-1.89; median, 1.50; range, 1.34-1.80). This demonstrated that, on average, the sensitivity rate for MRI in detecting pelvic disorders increased by 54% after the use of a vaginal contrast medium. CONCLUSIONS: Use of vaginal contrast media improved the diagnostic ability of MRI in identifying pelvic pathologies.

Volumetric assessment of apparent diffusion coefficient predicts outcome following chemoradiation for cervical cancer.

OBJECTIVE: To determine the utility of volumetric diffusion weighted imaging (DWI) compared to other clinical factors for predicting recurrence and survival in cervical cancer patients treated with definitive chemoradiation. METHODS AND MATERIALS: We retrospectively studied cervical cancer patients treated with definitive chemoradiation between 2009-2013 at a single institution with a baseline MRI with DWI and 18F-FDG positron emission tomography/computed tomography (FDG-PET) scan. To identify clinical and imaging metrics correlated with survival and recurrence endpoints, variable importance values were calculated from random forest models. To provide clinically relevant threshold values, recursive partitioning analysis dichotomized patients into potential risk groups based on selected metrics. Cox's proportional hazard models assessed the effect of clinical and imaging factors on survival endpoints. RESULTS: Ninety-three patients were included in the analysis (median age 50 years). At a median follow-up of 35.6 months, 32 patients (34%) had disease recurrence. In the best multivariate model including clinical and imaging parameters, 90th percentile ADC < 1.917 was the only significantly associated factor with worse progression free survival (PFS). Overall survival, PFS, and distant metastasis free survival (DMFS) were significantly different between patient groups divided on 90th percentile ADC with threshold of 1.917 × 10-3 mm2/s and MRI volume with threshold of 18.9 cc (P = 0.037, P = 0.0002, P = 0.001). High MRI volume and low ADC were associated with worse clinical outcomes. CONCLUSIONS: Volumetric 90th percentile ADC value of the primary tumor on pretreatment MRI was a significant predictor of PFS and DMFS in cervical cancer patients, independent of established clinical factors and SUV on FDG-PET.

[18F]-2-Fluoro-2-Deoxy-D-glucose-PET Assessment of Cervical Cancer.

This article provides an overview of PET in cervical cancer, primarily with regard to the use of 18F-2-fluoro-2-deoxy-d-glucose-PET/computed tomography. A brief discussion of upcoming technologies, such as PET/MR imaging, is presented.

FDG-PET Assessment of Other Gynecologic Cancers.

PET and PET/computed tomography play a role in the staging, monitoring of response to therapy, and surveillance for cervical and ovarian cancers. Currently, it is also an integral part of the assessment of patients with endometrial cancer and other gynecologic malignancies, such as vaginal and vulvar cancers and uterine sarcomas. In this article, we discuss in detail and highlight the potential role of PET and PET/computed tomography in evaluating these gynecologic malignancies using illustrative cases with relevant imaging findings.

Evaluation of Magnetic Resonance (MR) Biomarkers for Assessment of Response With Response Evaluation Criteria in Solid Tumors: Comparison of the Measurements of Neuroendocrine Tumor Liver Metastases (NETLM) With Various MR Sequences and at Multiple Phases of Contrast Administration.

PURPOSE: Our aim was to compare the interobserver and intraobserver variability for the measurement of the size of liver metastases in patients with carcinoid tumors with various magnetic resonance (MR) series. MATERIALS AND METHODS: In this retrospective institutional review board-approved study, 30 patients with liver metastases from a carcinoid primary had a complete MR examination of the abdomen at 1.5 T with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA). The complete MR examination included T1 (in-phase [IP]/out-of-phase [OOP], T2, diffusion-weighted imaging, pre-Gd-EOB-DTPA and post-Gd-EOB-DTPA 3D gradient echo (4 phases plus 20-minute hepatobiliary phase [HBP] Gd]). Four readers reviewed each series independently. The measurement for each lesion was compared to HBP-Gd images. The sensitivity for detection of each lesion was compared to HBP-Gd. Variance component analysis was used to estimate variance due to patient, lesion within patient, and reader by sequence. Linear mixed model was used to compare lesion size between sequences. RESULTS: The HBP-Gd had the smallest interreader variability. There was no significant difference between series with respect to interreader variability. Lesion sizes measured in diffusion-weighted imaging was significantly higher. T2-weighted imaging was the closest to HBP-Gd. Lesion sizes measured with the other sequences were significantly smaller. There was significant difference in sensitivity of lesion detection of some series when compared to HBP-Gd. CONCLUSION: The HBP-Gd series had the smallest interreader variability and is the recommended series to measure lesion size for evaluation of response to treatment.

Feasibility of a reduced field-of-view diffusion-weighted (rFOV) sequence in assessment of myometrial invasion in patients with clinical FIGO stage I endometrial cancer.

PURPOSE: To compare the clinical usefulness of reduced field-of-view diffusion-weighted imaging (rFOV) with other imaging techniques in determining the depth of myometrial invasion (DMI) in endometrial cancer. MATERIALS AND METHODS: In this prospective study we reviewed 3T magnetic resonance images of 51 patients with clinical Stage I endometrial cancer who underwent total abdominal hysterectomy with bilateral salphingoopherectomy within 3 days after imaging. rFOV with apparent diffusion coefficient reconstruction was obtained in three standard planes followed by sagittal T2 -weighted (T2 WI) images and 3D dynamic T1 -weighted and contrast-enhanced imaging (DCE MRI). Two radiologists with expertise in imaging gynecologic cancers evaluated images independently. The DMI was recorded on imaging and correlated with surgical pathology results. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for DMI were calculated (<50% vs. >50%). RESULTS: Compared with sagittal T2 WI + DCE MRI, rFOV imaging yielded greater specificity (82.2% vs. 90.0%, positive predictive value (42.8% vs. 60.0%), and accuracy (84.0% vs. 92%) for DMI determined by reader 1 and greater the sensitivity (83.3% vs. 100%) for DMI determined by reader 2. The error of measurement of DMI as a continuous variable in millimeters did not differ significantly between the rFOV and pathology results (P < 0.21). However, there was a statistically significant difference for the DMI measured on the dynamic sequence. The DMI on DCE was greater than that seen on pathology at P = 0.02. CONCLUSION: rFOV can be used to assess DMI in clinical Stage I endometrial cancer.

Quantitative and Qualitative Comparison of Single-Source Dual-Energy Computed Tomography and 120-kVp Computed Tomography for the Assessment of Pancreatic Ductal Adenocarcinoma.

PURPOSE: The aim of this study was to compare contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) between pancreatic-phase dual-energy computed tomography (DECT) and 120-kVp CT for pancreatic ductal adenocarcinoma (PDA). MATERIALS AND METHODS: Seventy-eight patients underwent multiphasic pancreatic imaging protocols for PDA (40, DECT; 38, 120-kVp CT [control]). Using pancreatic phase, CNR and SNR for PDA were obtained for DECT at monochromatic energies 50 through 80 keV, iodine material density images, and 120-kVp images. Using a 5-point scale (1, excellent; 5, markedly limited), images were qualitatively assessed by 2 radiologists in consensus for PDA detection, extension, vascular involvement, and noise. Wilcoxon signed rank and 2-sample tests were used to compare the qualitative measures, CNR and SNR, for DECT and 120-kVp images. Bonferroni correction was applied. RESULTS: Iodine material density image had significantly higher CNR and SNR for PDA than any monochromatic energy images (P < 0.0001) and the 120-kVp images. Qualitatively, 70-keV images were rated highest in the categories of tumor extension and vascular invasion and were similar to 120-kVp images. CONCLUSIONS: Our results indicate that DECT improves PDA lesion conspicuity compared with routine 120-kVp CT, which may allow for better detection of PDA.

A Simplified Preoperative Assessment Predicts Complete Cytoreduction and Outcomes in Patients with Low-Grade Mucinous Adenocarcinoma of the Appendix.

BACKGROUND: Complete cytoreduction with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been shown to improve survival in patients with low-grade mucinous adenocarcinoma (LGMA). However, incomplete cytoreduction exposes patients to significant morbidity without a similar survival benefit. Preoperative assessment of the ability to achieve CRS is therefore a critical step in selecting patients for CRS/HIPEC. OBJECTIVE: The aim of this study was to develop and validate a preoperative scoring system to accurately predict the ability to achieve complete cytoreduction in patients with LGMA of the appendix. METHODS: A simplified preoperative assessment for appendix tumor (SPAAT) score was developed based on computed tomography scan findings thought to predict incomplete cytoreduction. We applied the SPAAT score to patients with LGMA to determine the ability of the score to predict complete cytoreduction. This scoring system was then applied to a separate cohort of patients from a different institution. Sensitivity and specificity were determined for the SPAAT score. Survival was calculated and correlated with the SPAAT score and the completeness of cytoreduction score. RESULTS: A SPAAT score of <3 is a significant predictor of complete cytoreduction in the derivation cohort. In the validation cohort, 40 of 42 patients with a SPAAT score <3 achieved a complete cytoreduction, for a positive predictive value of 95.2 % and a negative predictive value of 100 %. Additionally, the SPAAT score was a significant predictor of disease-free survival. CONCLUSIONS: The SPAAT score is a useful tool in the preoperative assessment of patients with LGMA who are under consideration for cytoreductive surgery. Prospective analysis of this scoring system is warranted to appropriately select patients who will benefit from CRS/HIPEC.

In vivo CT dosimetry during CT colonography.

OBJECTIVE: The purpose of this study was to develop a method of measuring rectal radiation dose in vivo during CT colonography (CTC) and assess the accuracy of size-specific dose estimates (SSDEs) relative to that of in vivo dose measurements. MATERIALS AND METHODS: Thermoluminescent dosimeter capsules were attached to a CTC rectal catheter to obtain four measurements of the CT radiation dose in 10 volunteers (five men and five women; age range, 23-87 years; mean age, 70.4 years). A fixed CT technique (supine and prone, 50 mAs and 120 kVp each) was used for CTC. SSDEs and percentile body habitus measurements were based on CT images and directly compared with in vivo dose measurements. RESULTS: The mean absorbed doses delivered to the rectum ranged from 8.8 to 23.6 mGy in the 10 patients, whose mean body habitus was in the 27th percentile among American adults 18-64 years old (range, 0.5-67th percentile). The mean SSDE error was 7.2% (range, 0.6-31.4%). CONCLUSION: This in vivo radiation dose measurement technique can be applied to patients undergoing CTC. Our measurements indicate that SSDEs are reasonable estimates of the rectal absorbed dose. The data obtained in this pilot study can be used as benchmarks for assessing dose estimates using other indirect methods (e.g., Monte Carlo simulations).

Update on 3D and multiplanar MDCT in the assessment of biliary and pancreatic pathology.

The development of multidetector row computed tomography (MDCT) has led to the acquisition of true isotropic voxels that can be postprocessed to yield images in any plane of the same resolution as the original axially acquired images. This, coupled with rapid MDCT imaging during peak target organ enhancement has led to a variety of means to review imaging information beyond that of the axial perspective. Postprocessing can be utilized to identify variant biliary anatomy to guide preoperative planning of biliary-related surgery, determine the level and cause of biliary obstruction and assist in staging of biliary cancer. Postprocessing can also be used to identify pancreatic ductal variants, visualize diagnostic features of pancreatic cystic lesions, diagnose and stage pancreatic cancer, and differentiate pancreatic from peripancreatic disease.