Randomized phase 2 trial of tremelimumab and durvalumab in combination versus sequentially in recurrent platinum-resistant ovarian cancer.

BACKGROUND: Single-agent immune checkpoint inhibitors (ICIs) have demonstrated limited responses in recurrent ovarian cancer; however, 30%-40% of patients achieve stable disease. The primary objective was to estimate progression-free survival (PFS) after sequential versus combination cytotoxic T-lymphocyte antigen 4 and programmed death ligand 1 ICIs in patients with platinum-resistant high-grade serous ovarian cancer (HGSOC). METHODS: Patients were randomized to a sequential arm (tremelimumab followed by durvalumab on progression) or a combination arm (tremelimumab plus durvalumab, followed by durvalumab) via a Bayesian adaptive design that made it more likely for patients to be randomized to the more effective arm. The primary end point was immune-related PFS (irPFS). RESULTS: Sixty-one subjects were randomized to sequential (n = 38) or combination therapy (n = 23). Thirteen patients (34.2%) in the sequential arm received durvalumab. There was no difference in PFS in the sequential arm (1.84 months; 95% CI, 1.77-2.17 months) compared with the combination arm (1.87 months; 95% CI, 1.77-2.43 months) (p = .402). In the sequential arm, no responses were observed, although 12 patients (31.6%) demonstrated stable disease. In the combination arm, two patients (8.7%) had partial response, whereas one patient (4.4%) had stable disease. Adverse events were consistent with those previously reported for ICIs. Patient-reported outcomes were similar in both arms. CONCLUSIONS: There was no difference in irPFS for combination tremelimumab plus durvalumab compared to tremelimumab alone (administered as part of a sequential treatment strategy) in a heavily pretreated population of patients with platinum-resistant HGSOC. Response rates were comparable to prior reports, although the combination regimen did not add significant benefit, as has been previously described.

Rectal Adenocarcinoma Presenting as a Cervical Mass: A Case Report.

BACKGROUND Invasive cervical tumors are often seen in clinical practice. However, there are multiple structures within the pelvis, and invasion of the cervix from another site must be included in the differential diagnosis. In such cases, a multidisciplinary approach is needed to define the organ of tumor origin. Ensuring proper staging and histologic analysis are critical for optimal management. CASE REPORT We present a case of a 68-year-old woman who presented to her gynecologist with painless post-menopausal vaginal bleeding. She was diagnosed with a locally aggressive cervical adenocarcinoma, which was histologically confirmed by an in-office biopsy. She was referred to the gynecologic oncology service at a tertiary care hospital for definitive management, where a thorough clinical workup was performed. Physical exam revealed that the mass had invaded the anterior rectal wall. Through a multidisciplinary approach and a repeat biopsy, she was correctly diagnosed with an invasive rectal adenocarcinoma. She was treated with neoadjuvant chemoradiotherapy and underwent curative surgery. Had she been incorrectly treated as having a primary cervical adenocarcinoma, there would have been no role for surgery. The change in the organ of primary drastically altered the patient's management and outcome. She is currently undergoing surveillance with cross-sectional imaging. CONCLUSIONS Cervical masses originating from non-gynecologic organs can be difficult to differentiate on physical exam and histologic analysis. When a mass involves the rectum, an invasive primary rectal adenocarcinoma must be included in the differential. This will have a significant impact on patient management and ultimately on patient survival.

MRI and PSMA PET/CT of Biochemical Recurrence of Prostate Cancer.

Prostate cancer may recur several years after definitive treatment, such as prostatectomy or radiation therapy. A rise in serum prostate-specific antigen (PSA) level is the first sign of disease recurrence, and this is termed biochemical recurrence. Patients with biochemical recurrence have worse survival outcomes. Radiologic localization of recurrent disease helps in directing patient management, which may vary from active surveillance to salvage radiation therapy, androgen-deprivation therapy, or other forms of systemic and local therapy. The likelihood of detecting the site of recurrence increases with higher serum PSA level. MRI provides optimal diagnostic performance for evaluation of the prostatectomy bed. Prostate-specific membrane antigen (PSMA) PET radiotracers currently approved by the U.S. Food and Drug Administration demonstrate physiologic urinary excretion, which can obscure recurrence at the vesicourethral junction. However, MRI and PSMA PET/CT have comparable diagnostic performance for evaluation of local recurrence after external-beam radiation therapy or brachytherapy. PSMA PET/CT outperforms MRI in identifying recurrence involving the lymph nodes and bones. Caveats for use of both PSMA PET/CT and MRI do exist and may cause false-positive or false-negative results. Hence, these techniques have complementary roles and should be interpreted in conjunction with each other, taking the patient history and results of any additional prior imaging studies into account. Novel PSMA agents at various stages of investigation are being developed, and preliminary data show promising results; these agents may revolutionize the landscape of prostate cancer recurrence imaging in the future. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center. See the invited commentary by Turkbey in this issue. The slide presentation from the RSNA Annual Meeting is available for this article.

Phase I study of sapanisertib with carboplatin and paclitaxel in mTOR pathway altered solid malignancies.

Pre-clinically, the mTORC1/2 inhibitor sapanisertib restored sensitivity to platinums and enhanced paclitaxel-induced cancer cell killing. NCT03430882 enrolled patients with mTOR pathway aberrant tumors to receive sapanisertib, carboplatin and paclitaxel. Primary objective was safety and secondary objectives were clinical response and survival. One patient had a dose-limiting toxicity at dose level 4. There were no unanticipated toxicities. Grade 3-4 treatment-related adverse events included anemia (21%), neutropenia (21%), thrombocytopenia (10.5%), and transaminitis (5%). Of 17 patients evaluable for response, 2 and 11 patients achieved partial response and stable disease, respectively. Responders included a patient with unclassified renal cell carcinoma harboring EWSR1-POU5F1 fusion and a patient with castrate resistant prostate cancer harboring PTEN loss. Median progression free survival was 3.84 months. Sapanisertib in combination with carboplatin plus paclitaxel demonstrated a manageable safety profile, with preliminary antitumor activity observed in advanced malignancies harboring mTOR pathway alterations.

Magnetic Resonance Imaging Directed Surgical Decision Making for Lateral Pelvic Lymph Node Dissection in Rectal Cancer After Total Neoadjuvant Therapy (TNT).

OBJECTIVE: Lateral pelvic lymph node (LPLN) metastases are an important cause of preventable local failure in rectal cancer. The aim of this study was to evaluate clinical and oncological outcomes following magnetic resonance imaging (MRI)-directed surgical selection for lateral pelvic lymph node dissection (LPLND) after total neoadjuvant therapy (TNT). METHODS: A retrospective consecutive cohort analysis was performed of rectal cancer patients with enlarged LPLN on pretreatment MRI. Patients were categorized as LPLND or non-LPLND. The main outcomes were lateral local recurrence rate, perioperative and oncological outcomes and factors associated with decision making for LPLND. RESULTS: A total of 158 patients with enlarged pretreatment LPLN and treated with TNT were identified. Median follow-up was 20 months (interquartile range 10-32). After multidisciplinary review, 88 patients (56.0%) underwent LPLND. Mean age was 53 (SD±12) years, and 54 (34.2%) were female. Total operative time (509 vs 429 minutes; P =0.003) was greater in the LPLND group, but median blood loss ( P =0.70) or rates of major morbidity (19.3% vs 17.0%) did not differ. LPLNs were pathologically positive in 34.1%. The 3-year lateral local recurrence rates (3.4% vs 4.6%; P =0.85) did not differ between groups. Patients with LPLNs demonstrating pretreatment heterogeneity and irregular margin (odds ratio, 3.82; 95% confidence interval: 1.65-8.82) or with short-axis ≥5 mm post-TNT (odds ratio 2.69; 95% confidence interval: 1.19-6.08) were more likely to undergo LPLND. CONCLUSIONS: For rectal cancer patients with evidence of LPLN metastasis, the appropriate selection of patients for LPLND can be facilitated by a multidisciplinary MRI-directed approach with no significant difference in perioperative or oncologic outcomes.

Role of Abdominal and Pelvic CT Scans in Diagnosis of Patients with Immunotherapy-Induced Colitis.

Introduction: Colitis is one of the most common immune-related adverse events in patients receiving immune checkpoint inhibitors. Although radiographic changes on computed tomography (CT), such as mild diffuse bowel thickening, mesenteric fat stranding, and mucosal enhancement, have been reported, the utility of CT in diagnosis of patients with suspected immune-related colitis is not well documented. The aim of this retrospective study was to determine the value of CT scans in diagnosis of immunotherapy-induced colitis. Methods: CT scans of the abdomen and pelvis of 34 patients receiving immunotherapy who had a clinical diagnosis of immunotherapy-induced colitis and 19 patients receiving immunotherapy without clinical symptoms of colitis (controls) were evaluated. Segments of the colon (rectum, sigmoid, descending, transverse, ascending, and cecum) were assessed independently by two abdominal imaging specialists, blinded to the clinical diagnosis. Each segment was assessed for radiographic signs such as mucosal enhancement, wall thickening, distension, and periserosal fat stranding. The presence of any of the signs was considered radiographic evidence of colitis. Results: CT findings suggestive of colitis was seen in 20 of 34 patients with symptoms of colitis and in 5 of 19 patients without symptoms of colitis. The sensitivity, specificity, positive predictive value, and negative predictive value for colitis on CT were 58.8%, 73.7%, 80%, and 50%, respectively. Conclusions: We found that CT had a low sensitivity, specificity, and negative predictive value for the diagnosis of immunotherapy-induced colitis. We therefore conclude that CT has a limited role in the diagnosis of patients with suspected uncomplicated immune-related colitis.

Radiologic Diagnosis and Staging of Bladder Cancer: An Update.

Although cystoscopic biopsy is the standard of care for initial diagnosis and local staging of bladder cancer, radiologic imaging plays a major role in identifying local invasion, nodal status, distant metastasis, and posttreatment surveillance. Recent development of the Vesical Imaging-Reporting and Data System for interpretation of multiparametric magnetic resonance imaging of the bladder has expanded the role diagnostic imaging in the management of bladder cancer. This article reviews multimodality imaging appearances, staging, and differential diagnosis of bladder cancer.

MR characteristics of mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney: comparison with clear cell and papillary subtypes of renal cell carcinoma.

PURPOSE: To describe MR features of mucinous tubular spindle cell carcinoma (MTSCC) of the kidney that may help differentiate from clear cell renal cell carcinoma (ccRCC) and papillary RCC (pRCC). METHODS: 15 MTSCCs were retrospectively evaluated by MR with T2-weighted image without fat suppression (n = 15) and dynamic contrast-enhanced (DCE), fat-suppressed T1-weighted GRE (n = 11). Size-matched ccRCC (n = 30) and pRCC (n = 30) were evaluated as control. T2 ratio was calculated as the signal intensity (SI) ratio of the lesion to the renal cortex on T2W images. Enhancement ratio (ER) was calculated as (SIpost - SIpre)/(SIpre), where SIpre (SIpost) is the SI of the entire lesion on each phase of DCE images. Early nodular enhancement was subjectively evaluated in MTSCC. T2 ratio and ER were compared using the Mann-Whitney U test with Bonferroni correction. RESULTS: The mean value of T2 ratio was highest in ccRCC (1.24), followed by MTSCC (1.02), and pRCC (0.84). Difference of T2 ratio was significant between ccRCC and pRCC (p < 0.001), but not between MTSCC and ccRCC (p = 0.4) or between MTSCC and pRCC (p = 0.2). The mean ER of MTSCC, ccRCC and pRCC were 1.33, 1.53 and 0.38 in corticomedullary phase (CMP), 1.60, 1.61 and 0.69 in nephrographic phase (NGP) and 1.79, 1.35 and 0.77 in excretory phase (EP), respectively. ERs were significantly different between MTSCC and pRCC in CMP (p = 0.01), NGP (p = 0.003), and EP (p = 0.002). Early nodular enhancement was observed in 4/11 MTSCC (36%), 17/30 ccRCC (57%), and 2/30 pRCC (7%). CONCLUSIONS: MTSCC has distinct MR features that can help differentiate from ccRCC and pRCC. MTSCC enhances more avidly compared to pRCC and shows gradual progressive enhancement.

Assessment of Renal Cell Carcinoma by Texture Analysis in Clinical Practice: A Six-Site, Six-Platform Analysis of Reliability.

BACKGROUND. Multiple commercial and open-source software applications are available for texture analysis. Nonstandard techniques can cause undesirable variability that impedes result reproducibility and limits clinical utility. OBJECTIVE. The purpose of this study is to measure agreement of texture metrics extracted by six software packages. METHODS. This retrospective study included 40 renal cell carcinomas with contrast-enhanced CT from The Cancer Genome Atlas and Imaging Archive. Images were analyzed by seven readers at six sites. Each reader used one of six software packages to extract commonly studied texture features. Inter- and intrareader agreement for segmentation was assessed with intraclass correlation coefficients (ICCs). First-order (available in six packages) and second-order (available in three packages) texture features were compared between software pairs using Pearson correlation. RESULTS. Inter- and intrareader agreement was excellent (ICC, 0.93-1). First-order feature correlations were strong (r ≥ 0.8, p < .001) between 75% (21/28) of software pairs for mean intensity and SD, 48% (10/21) for entropy, 29% (8/28) for skewness, and 25% (7/28) for kurtosis. Of 15 second-order features, only cooccurrence matrix correlation, gray-level nonuniformity, and run-length nonuniformity showed strong correlation between software packages (r = 0.90-1, p < .001). CONCLUSION. Variability in first- and second-order texture features was common across software configurations and produced inconsistent results. Standardized algorithms and reporting methods are needed before texture data can be reliably used for clinical applications. CLINICAL IMPACT. It is important to be aware of variability related to texture software processing and configuration when reporting and comparing outputs.

Lexicon for renal mass terms at CT and MRI: a consensus of the society of abdominal radiology disease-focused panel on renal cell carcinoma.

PURPOSE: There is substantial variation in the radiologic terms used to characterize renal masses, leading to ambiguity and inconsistency in clinical radiology reports and research studies. The purpose of this study was to develop a standardized lexicon to describe renal masses at CT and MRI. MATERIALS AND METHODS: This multi-institutional, prospective, quality improvement project was exempt from IRB oversight. Thirteen radiologists belonging to the Society of Abdominal Radiology (SAR) disease-focused panel on renal cell carcinoma representing nine academic institutions participated in a modified Delphi process to create a lexicon of terms used to describe imaging features of renal masses at CT and MRI. In the first round, members voted on terms to be included and proposed definitions; subsequent voting rounds and a teleconference established consensus. One non-voting member developed the questionnaire and consolidated responses. Consensus was defined as ≥ 80% agreement. RESULTS: Of 37 proposed terms, 6 had consensus to be excluded. Consensus for inclusion was reached for 30 of 31 terms (13/14 basic imaging terms, 8/8 CT terms, 6/6 MRI terms and 3/3 miscellaneous terms). Despite substantial initial disagreement about definitions of 'renal mass,' 'necrosis,' 'fat,' and 'restricted diffusion' in the first round, consensus for all was eventually reached. Disagreement remained for the definition of 'solid mass.' CONCLUSIONS: A modified Delphi method produced a lexicon of preferred terms and definitions to be used in the description of renal masses at CT and MRI. This lexicon should improve clarity and consistency of radiology reports and research related to renal masses.

Epidemiology, prevention, screening, diagnosis, and evaluation: update of the ICUD-SIU joint consultation on bladder cancer.

PURPOSE: To update current recommendations on prevention, screening, diagnosis, and evaluation of bladder cancer (BC) based on a thorough assessment of the most recent literature on these topics. METHODS: A non-systematic review was performed, including articles until June 2017. A variety of original articles, reviews, and editorials were selected according to their epidemiologic, demographic, and clinical relevance. Assessment of the level of evidence and grade of recommendations was performed according to the International Consultation on Urological Diseases grading system. RESULTS: BC is the ninth most common cancer worldwide with 430,000 new cases in 2012. Currently, approximately 165,000 people die from the disease annually. Absolute incidence and prevalence of BC are expected to rise significantly during the next decades because of population ageing. Tobacco smoking is still the main risk factor, accounting for about 50% of cases. Smoking cessation is, therefore, the most relevant recommendation in terms of prevention, as the risk of developing BC drops almost 40% within 5 years of cessation. BC screening is not recommended for the general population. BC diagnosis remains mainly based on cystoscopy, but development of new endoscopic and imaging technologies may rapidly change the diagnosis algorithm. The same applies for local, regional, and distant staging modalities. CONCLUSIONS: A thorough understanding of epidemiology, risk factors, early detection strategies, diagnosis, and evaluation is essential for correct, evidence-based management of BC patients. Recent developments in endoscopic techniques and imaging raise the hope for providing better risk-adopted approaches and thereby improving clinical outcomes.

Unravelling Adrenal Oncocytic Neoplasm.

Oncocytic neoplasms are rare tumors arising in the adrenal glands and usually considered as nonfunctional and benign. We report 4 cases of adrenal oncocytic neoplasm. The paucity of literature describing this entity increases the chance for misdiagnosis. Confirmatory diagnosis is by tissue sampling with adrenalectomy as the mainstay of treatment.

Current Update on Desmoid Fibromatosis.

OBJECTIVE: The purpose of this article is to review the etiopathogenesis, molecular cytogenetics, histopathology, clinical features, and multimodality imaging features of desmoid fibromatosis. Recent advances in the management of desmoid fibromatosis will also be discussed. CONCLUSIONS: Desmoid fibromatosis is a rare soft tissue neoplasm with a high incidence of local recurrence. Imaging plays an important role in the diagnosis and management of this disease.

Accuracy of High-Frequency Endoluminal Ultrasonography for Clinical Staging of Upper Tract Urothelial Carcinoma.

INTRODUCTION: Staging of upper tract urothelial carcinoma (UTUC) remains a dilemma due to imaging and biopsy limitations leading to understaging. We seek to determine the accuracy of endoluminal ultrasound (ELUS) for clinical staging of UTUC. MATERIALS AND METHODS: Patients evaluated for UTUC underwent retrograde pyelography, ureteroscopy, and ELUS. ELUS was performed using mechanical radial scanning at 20 MHz in B-mode with a 5F probe. Cine clips were evaluated by 2 radiologists blinded to ureteroscopic and pathology findings. Results were compared to pathology from nephroureterectomy. Inclusion criteria were patients who underwent nephroureterectomy without pretreatment or managed endoscopically for cTa-1 disease and were without recurrence for >1 year. RESULTS: From 2008 to 2013, 53 patients underwent ELUS without complication. Twenty-seven patients met inclusion criteria with conclusive ELUS imaging. ELUS accurately identified 16 of 21 patients with non-muscle invasive (MI) disease (18 pTa, 2 pT1, 1 CIS) and 1 of 6 patients with at least MI disease (2 pT2, 4 pT3). For MI disease, the positive predictive value (PPV), negative predictive value, and accuracy was 76.2%, 16.7%, and 63%, respectively, while for non-organ confined (OC) disease results were 0%, 81.8%, and 66.7%, respectively. CONCLUSIONS: With current technique and instrumentation, ELUS may prove useful in select cases to confirm findings of non-MI and OC disease. However, it has insufficient PPV for stage pT2-3 disease. Further studies and better instrumentation are needed before incorporation into clinical practice.

Carcinoma of the urethra.

Primary carcinomas of the urethra are rare and poorly understood lesions; hence, their clinical and pathologic spectrum is not completely defined. We analyzed a series of 130 primary urethral tumors and classified 106 of them as primary urethral carcinomas. The age at diagnosis of patients with primary urethral carcinomas ranged from 42 to 97 years (mean, 69.4 years; median, 70 years). There were 73 male and 33 female patients with a ratio of 2.2:1. In male patients, the tumors most frequently developed in the bulbous-membranous segment of the urethra. In female patients, the entire length of the urethra was typically involved. Microscopically, they were poorly differentiated carcinomas with hybrid squamous and urothelial features and developed from precursor intraepithelial conditions such as dysplasia and carcinoma in situ, which were frequently present in the adjacent urethral mucosa. High-risk human papilloma virus infection could be documented in 31.6% of these tumors. Follow-up information was available for 95 patients. Twenty-three patients died of the disease with a mean and median survival of 39 and 21 months, respectively. Urethral carcinomas are aggressive tumors with a high propensity for regional and distant metastases with mean and median survival of 39 and 21 months, respectively. Our observations have important implications for the management of patients with primary carcinoma of the urethra by defining them as a unique entity linked to human papilloma virus infection.

Feasibility of Contrast-Enhanced Intraoperative Ultrasound for Detection and Characterization of Renal Mass Undergoing Open Partial Nephrectomy.

OBJECTIVES: To determine the feasibility of obtaining intraoperative contrast-enhanced ultrasound (CEUS) imaging in patients undergoing open partial nephrectomy for renal cancer. We hypothesize that the study was feasible and the addition of CEUS would improve lesion identification and characterization. METHODS: The study population consisted of 10 patients with known renal mass scheduled for intraoperative ultrasound-guided open partial nephrectomy. After dissection and exposure of the kidney by the surgeon, an intraoperative pre- and post-CEUS was performed by the radiologist. Feasibility was defined as successful imaging in 8 of 10 patients with intraoperative CEUS. Image quality, lesion conspicuity/contrast, lesion vascularity, morphology, and size were assessed and graded with pre- and post-contrast images. RESULTS: Intraoperative ultrasound was successfully acquired in 10 of 11 patients for renal mass detection and characterization. One study was canceled intraoperatively as a result of clinical complications related to a difficult surgery. Tumor size ranged from 1.3 to 4.2 cm. All lesions were solid. No additional lesions were found on CEUS compared with baseline imaging. Image quality post-contrast ranged from acceptable to excellent. There were no adverse events recorded for all 10 patients. CONCLUSIONS: In our feasibility study consisting of 10 patients, CEUS for detection and characterization of renal mass undergoing open partial nephrectomy was feasible and safe. Because intraoperative ultrasound during open partial nephrectomy can affect the extent of surgery, CEUS can be used to help detect and characterize renal mass for surgical planning/resection intraoperatively.

State-of-the-Art Imaging and Staging of Plasma Cell Dyscrasias.

Monoclonal gammopathy of unknown significance (MGUS) is a clinically asymptomatic premalignant clonal plasma cell or lymphoplasmacytic proliferative disorder. Smoldering multiple myeloma, also called asymptomatic multiple myeloma, is an intermediate stage between MGUS and symptomatic multiple myeloma. As the name implies, extraosseous or extramedullary myeloma refers to the presence of myeloma deposits outside the skeletal system. Waldenström macroglobulinemia is a distinct subtype of plasma cell dyscrasia characterized by lymphoplasmacytic lymphoma in the bone marrow with an associated IgM monoclonal gammopathy. Amyloidosis is a condition characterized by extracellular deposition of fibrils composed of a variety of normal serum proteins.

ACR Appropriateness Criteria Renal Cell Carcinoma Staging.

Renal cell carcinoma accounts for 2%-3% of all visceral malignancies. Preoperative imaging can provide important staging and anatomic information to guide treatment decisions. Size of the primary tumor and degree of local invasion, such as involvement of perinephric fat or renal sinus fat, and tumor thrombus in renal veins and inferior vena cava are important detriments to local staging of primary tumor. Both kidneys are assessed for presence of other synchronous lesions. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and application by the panel of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria indeterminate renal mass.

Renal masses are increasingly detected in asymptomatic individuals as incidental findings. An indeterminate renal mass is one that cannot be diagnosed confidently as benign or malignant at the time it is discovered. CT, ultrasonography, and MRI of renal masses with fast-scan techniques and intravenous (IV) contrast are the mainstays of evaluation. Dual-energy CT, contrast-enhanced ultrasonography, PET/CT, and percutaneous biopsy are all technologies that are gaining traction in the characterization of the indeterminate renal mass. In cases in which IV contrast cannot be used, whether because of IV contrast allergy or renal insufficiency, renal mass classification with CT is markedly limited. In the absence of IV contrast, ultrasonography, MRI, and biopsy have some advantages. Owing to the low malignant and metastatic potential of small renal cell carcinomas (≤4 cm in diameter), active surveillance is additionally emerging as a diagnostic strategy for patients who have high surgical risk or limited life expectancy. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and application by the panel of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.