Supplementary Figure from Systemic Chemotherapies Retain Antitumor Activity in Desmoid Tumors Independent of Specific Mutations in CTNNB1 or APC: A Multi-institutional Retrospective Study

An 18-year-old White woman was evaluated in the emergency department because of recurrent episodes of abdominal pain associated with nausea, vomiting, and abdominal bloating. Previous examinations, comprising an abdominal ultrasound, a barium swallow test, and an esophagogastroduodenoscopy, were normal. Physical examination revealed diffuse abdominal tenderness. Laboratory investigations were normal. A pelvic magnetic resonance imaging demonstrated a pelvic mass measuring approximately 131 × 92 × 40 mm located within the pouch of Douglas (Figures A and B). The patient was admitted to the pediatric surgery service and underwent exploratory laparotomy with complete removal of the mass. Histologic examination showed splenic parenchyma characterized by diffuse ischemic necrosis and thromboses of venous vessels (Figures C and D). Thus, a diagnosis of wandering spleen was made. After surgical resection, the abdominal pain resolved completely and no recurrences were reported in the following months. Wandering spleen is a rare condition characterized by abnormal migration of the spleen from its normal fixed location in the left upper abdomen. During these movements, the spleen may twist around the splenic vascular pedicle, leading to recurrent episodes of hypoperfusion, abdominal pain, and ultimately infarction and necrosis. Imaging studies are pivotal to help reach a diagnosis and surgical intervention is the only definitive treatment.

Supplementary Figure from Systemic Chemotherapies Retain Antitumor Activity in Desmoid Tumors Independent of Specific Mutations in <i>CTNNB1</i> or <i>APC</i>: A Multi-institutional Retrospective Study

Cancer therapy has evolved from being broadly directed towards tumor types, to highly specific treatment protocols that target individual molecular subtypes of tumors. With the ever-increasing data on imaging characteristics of tumor subtypes and advancements in imaging techniques, it is now often possible for radiologists to differentiate tumor subtypes on imaging. Armed with this knowledge, radiologists may be able to provide specific information that can obviate the need for invasive methods to identify tumor subtypes. Different tumor subtypes also differ in their patterns of metastatic spread. Awareness of these differences can direct radiologists to relevant anatomical sites to screen for early metastases that may otherwise be difficult to detect during cursory inspection. Likewise, this knowledge will help radiologists to interpret indeterminate findings in a more specific manner.

Age, Mean 6 SD 66.4 (12.0) Gender, Male N (%) 5 (35.7) Indication, N (%) Stone Removal/Decompression 13 (92.9) Stricture Diagnosis 1 (7.1) Altered anatomy. N (%) Roux-en-Y Gastric Bypass 10 (71.4) Billroth II 1 (7.1) Duodenal Switch 2 (14.2) Hepaticojejunostomy 1 (7.1) Prior ERCP Attempt, N (%) 3 (21.4) Prior EDGE Attempt, N (%) 1 (7.1) Preprocedural Labs, Mean 6 SD ALT (IU/L) 89.9 6 116.1 ALP (IU/L) 295.4 6 210.6 Total Bilirubin (mg/dL) 1.8 6 1.9 Findings N (%) Multiple Stones 10 (71.4) Single Stone 2 (14.2) Stricture 3 (21.3) No Stone 1 (7.1) Number of Sessions, Median (IQR) 1 (1-2) Therapeutic Device, N (%) EHL 8 (57.1) Balloon 5 (35.7) Basket 2 (14.3) Spybites, N (%) 3 (21.4) Success, N (%) 13 (92.9) Complication, N (%) 0 (0) Follow up Months, Median (IQR) 28.5 (17-36) ERCP: Endoscopic Retrograde Cholangio Pancreatography, EDGE: Endoscopic ultrasound Directed transGastric ERCP, ALT: Alanine aminotransferase, ALP: Alkaline Phosphatase.

Treatment response assessment by imaging plays a vital role in evaluating changes in solid tumors during oncology therapeutic clinical trials. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 is the reference standard imaging response criteria and provides details regarding image acquisition, image interpretation and categorical response classification. While RECIST 1.1 is applied for the majority of clinical trials in solid tumors, other criteria and modifications have been introduced when RECIST 1.1 outcomes may be incomplete. Available criteria beyond RECIST 1.1 can be explored in an algorithmic fashion dependent on imaging modality, tumor type and method of treatment. Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) is available for use with PET/CT. Modifications to RECIST 1.1 can be tumor specific, including mRECIST for hepatocellular carcinoma and mesothelioma. Choi criteria for gastrointestinal stromal tumors incorporate tumor density with alterations to categorical response thresholds. Prostate Cancer Working Group 3 (PCWG3) imaging criteria combine RECIST 1.1 findings with those of bone scans. In addition, multiple response criteria have been created to address atypical imaging responses in immunotherapy.

Novel anticancer agents have replaced conventional chemotherapy as first line agents for many cancers, with continued new and expanding indications. Small molecule inhibitors act on cell surface or intracellular targets and prevent the downstream signaling that would otherwise permit tumor growth and spread. Anticancer antibodies can be directed against growth factors or may be immunotherapeutic agents. The latter act by inhibiting mechanisms that cancer cells use to evade the immune system. Hormonal agents act by decreasing levels of hormones that are necessary for the growth of certain cancer cells. Cancer therapy protocols often include novel anticancer agents and conventional chemotherapy used successively or in combination, in order to maximize survival and minimize morbidity. A working knowledge of anti-cancer drug classification will aid the radiologist in assessing response on imaging.

The role of imaging in cancer diagnosis and treatment has evolved at the same rapid pace as cancer management. Over the last twenty years, with the advancement of technology, oncology has become a multidisciplinary field that allows for researchers and clinicians not only to create individualized treatment options for cancer patients, but also to evaluate patients’ response to therapy with increasing precision. Familiarity with these concepts is a requisite for current and future radiologists, as cancer imaging studies represent a significant and growing component of any radiology practice, from tertiary cancer centers to community hospitals.In this review we provide the framework to teach cancer imaging in the era of genomic oncology. After reading this article, readers should be able to illustrate the basics cancer genomics, modern cancer genomics, to summarize the types of systemic oncologic therapies available, their patterns of response and their adverse events, to discuss the role of imaging in oncologic clinical trials and the role of tumor response criteria and to display the future directions of oncologic imaging.

AbstractPurpose:Determine whether specific CTNNB1 or APC mutations in patients with desmoid tumor were associated with differences in clinical responses to systemic treatments.Experimental Design:We established a multi-institutional dataset of previously treated patients with desmoid tumor across four U.S. sarcoma centers, including demographic and clinicopathologic characteristics, treatment regimens, and clinical and radiographic responses. CTNNB1 or APC mutation status was determined from prior pathology records, or archival tissue was requested and analyzed by Sanger sequencing and/or next-generation sequencing. Evaluable patients with mutation results were analyzed to determine clinical progression-free survival (cPFS), RECIST 1.1 PFS (rPFS), time to next treatment (TTNT), and overall survival (OS). Kaplan–Meier analysis and Cox proportional hazards regression were performed to identify differences in cPFS, rPFS, TTNT, and OS by mutation subtype, desmoid tumor location, and treatment regimen.Results:A total of 259 evaluable patients were analyzed for at least one of the survival outcomes, with 177 patients having mutation data. First- and second-line cPFS, rPFS, and TTNT were not significantly affected by mutation subtype; however, APC-mutant desmoid tumors demonstrated nonstatistically significant inferior outcomes. Extremity/trunk desmoid tumor location and treatment with doxorubicin-based, methotrexate/vinca alkaloids and sorafenib regimens were associated with better clinical outcomes compared with surgery or “other” therapies, including estrogen-receptor blockade and imatinib. OS was significantly worse with APC or CTNNB1 negative/other mutations.Conclusions:Mutation subtype did not affect responses to specific systemic therapies. APC mutations and nonextremity desmoid tumor locations remain prognostic for worse outcomes, and earlier initiation of systemic therapy for these higher-risk desmoid tumors should be prospectively evaluated.See related commentary by Greene and Van Tine, p. 3911

1. The local dilative effect of the calcium entry blocker nifedipine on forearm arteries and dorsal hand veins has been studied in 27 healthy male volunteers. 2. Nifedipine induced an increase of blood flow by 1190% (P less than 0.001) in the forearm. 3. The construction of the hand veins induced by stimulation of either postsynaptic alpha 1- or alpha 2-adrenoceptors was reduced (P less than 0.001) by nifedipine. 4. The calcium entry blocker nifedipine is a potent dilator of human forearm arteries as well as of dorsal hand veins.

The past decade has witnessed a change in landscape of cancer management with the advent of precision oncology. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and have played an important role in improving patient survival. While the patients are living longer, treatment with ICIs are sometimes associated with adverse effects, some of which could be fatal. Radiologists can play a crucial role by early identification of some of these adverse effects during restaging scans. Our paper focuses on the imaging features of commonly occurring ICI toxicities based on organ system.

Objective: Spectral detector CT (SDCT) has many applications in advanced liver imaging. If appropriately utilized, this technology has the potential to improve image quality, provide new diagnostic information, and allow for decreased radiation dose. The purpose of this review is to familiarize radiologists with the uses of SDCT in liver imaging. Conclusion: SDCT has a variety of post-processing techniques, which can be used in advanced liver imaging and can significantly add value in clinical practice.

Drug discovery and approval in oncology is mediated by the use of imaging to evaluate drug efficacy in clinical trials. Imaging is performed while patients receive therapy to evaluate their response to treatment. Response criteria, specifically Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), are standardized and can be used at different time points to classify response into the categories of complete response, partial response, stable disease, or disease progression. At the trial level, categorical responses for all patients are summated into image-based trial endpoints. These outcome measures, including objective response rate (ORR) and progression-free survival (PFS), are characteristics that can be derived from imaging and can be used as surrogates for overall survival (OS). Similar to OS, ORR and PFS describe the efficacy of a drug. U.S. Food and Drug Administration (FDA) regulatory approval requires therapies to demonstrate direct evidence of clinical benefit, such as improved OS. However, multiple programs have been created to expedite drug approval for life-threatening illnesses, including advanced cancer. ORR and PFS have been accepted by the FDA as adequate predictors of OS on which to base drug approval decisions, thus substantially shortening the time and cost of drug development (1). Use of imaging surrogate markers for drug approval has become increasingly common, accounting for more than 90% of approvals through the Accelerated Approval Program and allowing for use of many therapies which have altered the course of cancer. Keywords: Oncology, Tumor Response  RSNA, 2021.

OBJECTIVE. The purpose of this article is to review the spectrum of imaging manifestations of epithelioid hemangioendothelioma across different organ systems and briefly describe its current treatment strategies.CONCLUSION. Epithelioid hemangioendothelioma is a rare, locally invasive neoplasm with metastatic potential. Although most commonly occurring in liver, lungs, and bones, it can also present at multiple other sites. Because of its nonspecific clinical and imaging manifestations, it is often misdiagnosed. The possibility of epithelioid hemangioendothelioma must be considered in the presence of a slowly growing mass that invades adjacent structures. Imaging can help plan percutaneous biopsy, detect sites of disease, and identify poor prognostic factors.

OBJECTIVE. The purpose of this review is to elucidate the mechanisms, types, and clinical significance of molecular targeted therapy (MTT) and immune checkpoint inhibitors (ICIs) and their related toxicity, emphasizing the radiologic manifestations. CONCLUSION. The related toxicities of MTT and ICIs can have acute, recurrent, chronic, and delayed presentations. These toxicities may serve as markers of response and survival. By understanding the clinical significance of drug toxicities, radiologists can play an important role in personalized cancer therapy.

OBJECTIVE. This review describes the influence of histology and metastatic sites on prognosis in male patients with metastatic germ cell tumors (GCTs) and explains the role imaging in assessing therapeutic response, residual disease, recurrence, sand treatment-related toxicities. CONCLUSION. Seminomatous and nonseminomatous GCTs differ in imaging appearance, pattern of spread, and prognosis, and an organ-based approach is helpful in prognostication. Multimodality imaging aids in accurate staging, prognostication, characterization of treatment response, and identification of therapy-related toxicity.

Imaging must be utilized judiciously for the management of coronavirus disease 2019, to minimize the inadvertent risk of transmission of the virus.Currently, known imaging manifestations encompass a broad spectrum of nonspecific findings which radiologists must recognize.Chest radiography has a lower sensitivity compared to computed tomography (CT), but can be a quick and inexpensive tool to establish a baseline in patients with moderate to severe disease.CT must be limited to selected patients with other justified indications.The radiology community must continue to share knowledge and direct research to further define the role of imaging in containing this pandemic.

OBJECTIVE. The purpose of this review is to elucidate the mechanisms, types, and clinical significance of molecular targeted therapy (MIT) and immune checkpoint inhibitors (ICIs) and their related toxicity, emphasizing the radiologic manifestations. CONCLUSION. The related toxicities of MTT and ICIs can have acute, recurrent, chronic, and delayed presentations. These toxicities may serve as markers of response and survival. By understanding the clinical significance of drug toxicities, radiologists can play an important role in personalized cancer therapy.

The past decade has witnessed a paradigm shift in cancer therapy owing to the introduction of immune checkpoint inhibitors (ICIs) and it is now commonplace for radiologists to image patients on therapy with these agents. The purpose of this review is to detail the mechanism, radiological manifestations and clinical significance of ICI related toxicities, according to the organ system involved. ICI related toxicities that have known imaging manifestations include colitis, enterocolitis, pancreatitis, hepatitis, endocrine toxicities, pneumonitis, cardiovascular toxicity and musculoskeletal toxicity. These toxicities may be acute, recurrent or chronic in nature. Radiologists must be aware of the imaging features and clinical significance of these toxicities in order to effectively participate in personalized cancer therapy.