Liver Imaging in Gastroenteropancreatic Neuroendocrine Neoplasms.

ABSTRACT: The incidence of neuroendocrine neoplasms (NENs) has gradually increased over the past few decades with the majority of patients presenting with metastases on initial presentation. The liver is the most common site of initial metastatic disease, and the presence of liver metastasis is an independent prognostic factor associated with a negative outcome. Because NENs are heterogenous neoplasms with variable differentiation, grading, and risk of grade transformation over time, accurate diagnosis and management of neuroendocrine liver lesions are both important and challenging. This is particularly so with the multiple liver-directed treatment options available. In this review article, we discuss the diagnosis, treatment, and response evaluation of NEN liver metastases.

Fully automated deep learning based auto-contouring of liver segments and spleen on contrast-enhanced CT images.

Manual delineation of liver segments on computed tomography (CT) images for primary/secondary liver cancer (LC) patients is time-intensive and prone to inter/intra-observer variability. Therefore, we developed a deep-learning-based model to auto-contour liver segments and spleen on contrast-enhanced CT (CECT) images. We trained two models using 3d patch-based attention U-Net ([Formula: see text] and 3d full resolution of nnU-Net ([Formula: see text] to determine the best architecture ([Formula: see text]. BA was used with vessels ([Formula: see text] and spleen ([Formula: see text] to assess the impact on segment contouring. Models were trained, validated, and tested on 160 ([Formula: see text]), 40 ([Formula: see text]), 33 ([Formula: see text]), 25 (CCH) and 20 (CPVE) CECT of LC patients. [Formula: see text] outperformed [Formula: see text] across all segments with median differences in Dice similarity coefficients (DSC) ranging 0.03-0.05 (p < 0.05). [Formula: see text], and [Formula: see text] were not statistically different (p > 0.05), however, both were slightly better than [Formula: see text] by DSC up to 0.02. The final model, [Formula: see text], showed a mean DSC of 0.89, 0.82, 0.88, 0.87, 0.96, and 0.95 for segments 1, 2, 3, 4, 5-8, and spleen, respectively on entire test sets. Qualitatively, more than 85% of cases showed a Likert score [Formula: see text] 3 on test sets. Our final model provides clinically acceptable contours of liver segments and spleen which are usable in treatment planning.

Multi-disciplinary management of recurrent gastrointestinal stromal tumor harboring KIT exon 11 mutation with the switch-control kinase inhibitor ripretinib and surgery.

Ripretinib is a tyrosine kinase inhibitor that was approved by the United States FDA in 2020 for treatment of advanced gastrointestinal stromal tumor (GIST) in patients who received prior treatment with three or more tyrosine kinase inhibitors. In this case report, we show the durable clinical benefit achieved in a patient with GIST by using ripretinib and repeated timely surgical resection of limited disease progression. The total time on ripretinib was 43 months which is longer than the current reported data from ripretinib clinical trials. Such approach for using multi-disciplinary disease management can improve the durability of response to tyrosine kinase inhibitors, including ripretinib, and associated clinical outcomes.

Blastic plasmacytoid dendritic cell neoplasm: a comprehensive review in pediatrics, adolescents, and young adults (AYA) and an update of novel therapies.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that can involve the bone marrow, peripheral blood, skin, lymph nodes, and the central nervous system. Though more common in older adults, BPDCN has been reported across all age groups, including infants and children. The incidence of pediatric BPDCN is extremely low and little is known about the disease. Pediatric BPDCN is believed to be clinically less aggressive but often with more dissemination at presentation than adult cases. Unlike adults who almost always proceed to a hematopoietic stem cell transplantation in first complete remission if transplant-eligible, the majority of children can be cured with a high-risk acute lymphoblastic leukemia-like regimen. Hematopoietic stem cell transplantation is recommended for children with high-risk disease, the definition of which continues to evolve, or those in relapse and refractory settings where outcomes continue to be dismal. Novel agents used in other hematologic malignancies and CD123 targeted agents, including chimeric antigen receptor T-cells and monoclonal/bispecific antibodies, are being brought into research and practice. Our goal is to provide a comprehensive review of presentation, diagnosis, and treatment by review of pediatric cases reported for the last 20 years, and a review of novel targeted therapies and therapies under investigation for adult and pediatric patients.

Clinical outcomes of immune checkpoint inhibitor diabetes mellitus at a comprehensive cancer center.

Introduction: Immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) is a rare adverse event. In this study, we characterize clinical outcomes of patients with ICI-DM and evaluate survival impact of this complication on melanoma patients. Research design & methods: We conducted a retrospective review of 76 patients diagnosed with ICI-DM from April 2014 to December 2020. Results: 68% of patients presented in diabetic ketoacidosis, 16% had readmissions for hyperglycemia, and hypoglycemia occurred in 70% of patients after diagnosis. Development of ICI-DM did not impact overall survival or progression-free survival in melanoma patients. Conclusion: Development of ICI-DM is associated with long-term insulin dependence and pancreatic atrophy; the use of diabetes technology in this patient population can help improve glycemic control.

Cancer treatment with immune checkpoint inhibitors can cause irreversible side effects. In this study, we describe the clinical presentations of 76 patients who developed immune checkpoint inhibitor diabetes mellitus, a rare complication of checkpoint inhibitor therapy that requires lifelong treatment with insulin therapy. Most patients presented with a life-threatening hyperglycemic emergency and had experienced weight loss and hyperglycemia several weeks prior to diagnosis. After diagnosis, these patients are at risk for high and low blood sugars, but the use of glucose monitoring devices and insulin pumps can help improve blood sugar control. In our study, the development of this complication did not affect survival for melanoma patients. We need to improve awareness of this rare complication to ensure timely treatment for patients.

Imaging of pediatric adrenal tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Adrenal tumors other than neuroblastoma are uncommon in children. The most frequently encountered are adrenocortical carcinoma and pheochromocytoma. This paper offers consensus recommendations for imaging of pediatric patients with a known or suspected primary adrenal malignancy other than neuroblastoma at diagnosis and during follow-up.

Malignant Gastrointestinal Neuroectodermal Tumor: A New Kid on the Block?

ABSTRACT: Also referred to as "osteoclast-rich, clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLGT)," malignant gastrointestinal neuroectodermal tumor is a newly described, rare, aggressive sarcoma that commonly arises in the small bowel, stomach, and colon. Histogenesis is likely from an autonomous nervous system-related primitive cell of neural crest origin. The hallmark genetic finding of EWS-CREB1 or EWS-ATF1 fusion transcripts clinches the diagnosis. Annular constrictive lesions tend to be smaller, show homogenous contrast enhancement on computed tomography, and may present with bowel obstruction. Larger, expansile masses tend to be exophytic and show heterogeneous contrast enhancement. Surgical resection is the mainstay of treatment. Frequent recurrences, metastases, and death from disease in 75% of patients portend a poor prognosis. Targeted chemotherapy based on specific tumor pathways is being developed.

Emergence of mTOR mutation as an acquired resistance mechanism to AKT inhibition, and subsequent response to mTORC1/2 inhibition.

Acquired resistance to molecular targeted therapy is a significant challenge of the precision medicine era. The ability to understand these mechanisms of resistance may improve patient selection and allow for the development of rationally designed next-line or combination treatment strategies and improved patient outcomes. AKT is a critical effector of the phosphoinositide 3-kinase signaling cascade, one of the most commonly activated pathways in human cancer. Deregulation of signaling pathways, such as RAF/MEK/ERK are previously described mechanisms of resistance to AKT/PI3K inhibitors. Mutations in the mTOR gene, however, are exceedingly rare. We present a case of acquired mTOR resistance, following targeted AKT inhibition, and subsequent response to mTOR1/2 inhibitor in a patient with metastatic endometrial cancer, the first documented response to ATP-competitive mTOR inhibition in this setting. This case supports mTOR mutation as a mechanism of resistance, and underscores the importance of tumor molecular profiling, exemplifying precision medicine in action.

Imaging of Neuroendocrine Prostatic Carcinoma.

Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer that typically has a high metastatic potential and poor prognosis in comparison to the adenocarcinoma subtype. Although it can arise de novo, NEPC much more commonly occurs as a mechanism of treatment resistance during therapy for conventional prostatic adenocarcinoma, the latter is also termed as castration-resistant prostate cancer (CRPC). The incidence of NEPC increases after hormonal therapy and they represent a challenge, both in the radiological and pathological diagnosis, as well as in the clinical management. This article provides a comprehensive imaging review of prostatic neuroendocrine tumors.

Machine Learning and Deep Learning in Oncologic Imaging: Potential Hurdles, Opportunities for Improvement, and Solutions-Abdominal Imagers' Perspective.

ABSTRACT: The applications of machine learning in clinical radiology practice and in particular oncologic imaging practice are steadily evolving. However, there are several potential hurdles for widespread implementation of machine learning in oncologic imaging, including the lack of availability of a large number of annotated data sets and lack of use of consistent methodology and terminology for reporting the findings observed on the staging and follow-up imaging studies that apply to a wide spectrum of solid tumors. This short review discusses some potential hurdles to the implementation of machine learning in oncologic imaging, opportunities for improvement, and potential solutions that can facilitate robust machine learning from the vast number of radiology reports and annotations generated by the dictating radiologists.

Temporal evolution of metastatic disease: part I-an in-depth review of the evolution of metastatic disease across diverse spectrum of non-neural solid tumors on serial oncologic imaging studies and relevant practical applications.

With improved survival rates of patients with metastatic disease due to continuously evolving multimodality treatment options, radiologists are increasingly interpreting imaging studies from patients with protracted metastatic disease. It is thus crucial for radiologists to have an in-depth understanding of the temporal evolution of metastatic spread and the accompanying findings on imaging studies, to provide accurate interpretation that supports optimal management. A general overview of the evolution of cancer spread on serial imaging studies and common pathways of tumor spread across multiple tumor types and tumor locations is not readily available in radiology literature. The key common pathways of tumor spread across diverse spectrum of tumors relevant to radiologists are summarized in a logical schematic approach which focusses on aiding radiologists to understand the pathways of spread resulting in current sites of metastatic disease involvement and then to potentially predict future sites of metastatic involvement. This article also summarizes the practical applications of this knowledge to the routine oncologic imaging interpretation.

Temporal evolution of metastatic disease: part II-a novel proposal for subcategorization of metastatic disease from non-neural solid tumors with diverse histologies and locations.

Tumor spread is a continuous process and metastases can further disseminate. Currently, metastatic disease from most primary tumors is subcategorized as M0 if absent and M1 if present. However, metastatic disease in different locations may have different prognostic implications, even if it is from the same primary tumor. The current staging systems for metastatic disease have not evolved to match our understanding of the disease's evolution or the evolving treatment paradigms. Primary tumor-specific subcategorization of metastatic disease is currently available for a few tumors, but not all of them imply further remote spread of tumor, similar to tumor (T) and N (node) subcategorizations of the TNM staging, nor are they applicable to wide spectrum of other tumors. In this era of precision medicine, tumor-type agnostic therapies based on common biomarkers rather than primary tumor sites are emerging, but a subcategorization system applicable to metastatic disease from diverse primary tumor locations and with diverse histologies is not available. In this article, we discuss the need to further classify the metastatic disease and present a subcategorization applicable to metastatic disease from non-neural solid tumors from different primary tumor sites and with different histologies, which is based on the temporal spread of metastatic disease. Our proposed subcategorization scheme for metastatic disease into M0, M1, M2 and M3, is universally applicable to a diverse spectrum of non-neural solid tumors, and increasing M subcategorization represents further remote spread of tumor.

Second Malignancies after Radiation Therapy: Update on Pathogenesis and Cross-sectional Imaging Findings.

A wide spectrum of second cancers occur as late complications of radiation therapy (RT) used to treat various malignancies. In addition to the type and dose of radiation, lifestyle, environmental, and genetic factors are important to the development of second malignancies in cancer survivors. Typically, RT-induced malignancies (RTIMs) are biologically aggressive cancers with a variable period of 5-10 years for hematologic malignancies and 10-60 years for solid tumors between RT and the development of the second cancer. Although carcinomas and leukemias commonly develop after low-dose RT, sarcomas occur in tissues or organs that receive high-dose RT. Angiosarcomas and unclassified pleomorphic sarcomas are the two most common RT-associated sarcomas; other sarcomas include malignant peripheral nerve sheath tumors, leiomyosarcomas, osteosarcomas, chondrosarcomas, and dedifferentiated or pleomorphic liposarcomas. Select RTIMs show tumor genetic characteristics that allow accurate diagnosis. Nearly all cutaneous angiosarcomas after RT for breast cancer and 90% of RT-associated malignant peripheral nerve sheath tumors are characterized by MYC gene amplifications and loss of H3 K27me3 expression, respectively. Classic papillary thyroid carcinomas that develop after RT frequently harbor RET/PTC rearrangements and have a favorable prognosis, despite their advanced stage at patient presentation. Select RTIMs demonstrate characteristic imaging findings and typically develop in the prior radiation field. Imaging is essential to early diagnosis, characterization, localization, and staging of RTIMs. Familiarity of radiologists with the diverse spectrum of RTIMs is essential for early diagnosis and optimal management. An invited commentary by Shapiro is available online. ©RSNA, 2021.

Distant Metastases From Childhood Differentiated Thyroid Carcinoma: Clinical Course and Mutational Landscape.

CONTEXT: Distant metastases (DM) from childhood differentiated thyroid carcinoma (DTC) are uncommon and published studies are limited. OBJECTIVE: This work aimed to describe the outcomes of patients with DM from childhood DTC and to evaluate the molecular landscape of these tumors. METHODS: A retrospective study was conducted at a tertiary cancer center including patients with pediatric DTC (diagnosed at age ≤ 18 years from 1946 to 2019) and DM. RESULTS: We identified 148 patients; 144 (97%) had papillary thyroid carcinoma (PTC) and 104 (70%) were female. Median age at DTC diagnosis was 13.4 years (interquartile range [IQR], 9.9-15.9 years). Evaluable individuals received a median of 2 (IQR, 1-3) radioactive iodine (RAI) treatments at a median cumulative administered activity of 238.0 mCi (IQR, 147.5-351.0 mCi). The oncogenic driver was determined in 64 of 69 PTC samples: RET fusion (38/64; 59%), NTRK1/3 fusions (18/64; 28%), and the BRAF V600E mutation (8/64; 13%). At last evaluation, 93% had persistent disease. The median overall and disease-specific survival after DTC diagnosis were 50.7 and 52.8 years, respectively. Eight (5%) PTC patients died of disease after a median of 30.7 years (IQR, 20.6-37.6 years). CONCLUSION: Childhood DTC with DM persists in most patients despite multiple courses of RAI, but disease-specific death is uncommon, typically occurring decades after diagnosis. Fusion genes are highly prevalent in PTC, and all identified molecular alterations have appropriate targeted therapies. Future studies should focus on expanding genotype-phenotype correlations, determining how to integrate molecularly targeted therapy into treatment paradigms, and relying less on repeated courses of RAI to achieve cure in patients with DM from childhood DTC.

Atypical pulmonary metastases in children: pictorial review of imaging patterns.

Pulmonary metastases typically present as well-circumscribed solid nodules, often with a basilar and peripheral distribution due to hematogenous spread. When an atypical pattern of metastasis occurs, a lack of recognition may result in understaging or a delay in diagnosis. The purpose of this article is to review the imaging findings of atypical pulmonary metastatic disease in children. Atypical pulmonary metastatic patterns that can be seen in children include cavitary lesions, calcified pulmonary nodules, nodules with peritumoral halos, tree-in-bud or strial pattern secondary to tumor in peripheral pulmonary arterial branches, lymphangitic carcinomatosis, and miliary disease. An awareness of the spectrum of imaging findings of atypical pulmonary metastases along with an understanding of histopathological underpinnings will allow the radiologist to make an accurate diagnosis.

Coincidental Expression of Classic Hodgkin Lymphoma and Neurofibromatosis Type I and Literature Review.

Neurofibromatosis Type 1 (NF1) is a genetic disorder with an incidence of 1 in 2600 to 3000 individuals. It is a clinical diagnosis characterized by café-au-lait macules, neurofibromas, and axillary and/or groin freckling. Because of genetic mutations in the NF1 gene affecting the Ras/mitogen-activated protein kinase pathway, there is also risk of associated soft tissue sarcomas and hematologic malignancies. However, reports of classic Hodgkin lymphoma in patients with NF1 are sparse. We report an adolescent with NF1 who developed classic Hodgkin lymphoma. Although there is an unclear association between mutations in the NF1 gene and classic Hodgkin lymphoma, further studies are warranted.

Decoding Genes: Current Update on Radiogenomics of Select Abdominal Malignancies.

Technologic advances in chromosomal analysis and DNA sequencing have enabled genome-wide analysis of cancer cells, yielding considerable data on the genetic basis of malignancies. Evolving knowledge of tumor genetics and oncologic pathways has led to a better understanding of histopathologic features, tumor classification, tumor biologic characteristics, and imaging findings and discovery of targeted therapeutic agents. Radiogenomics is a rapidly evolving field of imaging research aimed at correlating imaging features with gene mutations and gene expression patterns, and it may provide surrogate imaging biomarkers that may supplant genetic tests and be used to predict treatment response and prognosis and guide personalized treatment options. Multidetector CT, multiparametric MRI, and PET with use of multiple radiotracers are some of the imaging techniques commonly used to assess radiogenomic associations. Select abdominal malignancies demonstrate characteristic imaging features that correspond to gene mutations. Recent advances have enabled us to understand the genetics of steatotic and nonsteatotic hepatocellular adenomas, a plethora of morphologic-molecular subtypes of hepatic malignancies, a variety of clear cell and non-clear cell renal cell carcinomas, a myriad of hereditary and sporadic exocrine and neuroendocrine tumors of the pancreas, and the development of targeted therapeutic agents for gastrointestinal stromal tumors based on characteristic KIT gene mutations. Mutations associated with aggressive phenotypes of these malignancies can sometimes be predicted on the basis of their imaging characteristics. Radiologists should be familiar with the genetics and pathogenesis of common cancers that have associated imaging biomarkers, which can help them be integral members of the cancer management team and guide clinicians and pathologists. Online supplemental material is available for this article. ©RSNA, 2020 See discussion on this article by Luna (pp 1627-1630).

Hereditary and Sporadic Pancreatic Ductal Adenocarcinoma: Current Update on Genetics and Imaging.

Pancreatic ductal adenocarcinoma (PDAC) is a genetically heterogeneous, biologically aggressive malignancy with a uniformly poor prognosis. While most pancreatic cancers arise sporadically, a small subset of PDACs develop in patients with hereditary and familial predisposition. Detailed studies of the rare hereditary syndromes have led to identification of specific genetic abnormalities that contribute to malignancy. For example, germline mutations involving BRCA1, BRCA2, PRSS1, and mismatch repair genes predispose patients to PDAC. While patients with Lynch syndrome develop a rare "medullary" variant of adenocarcinoma, intraductal papillary mucinous tumors are observed in patients with McCune-Albright syndrome. It is now well established that PDACs originate via a multistep progression from microscopic and macroscopic precursors due to cumulative genetic abnormalities. Improved knowledge of tumor genetics and oncologic pathways has contributed to a better understanding of tumor biology with attendant implications on diagnosis, management, and prognosis. In this article, the genetic landscape of PDAC and its precursors will be described, the hereditary syndromes that predispose to PDAC will be reviewed, and the current role of imaging in screening and staging assessment, as well as the potential role of molecular tumor-targeted imaging for evaluation of patients with PDAC and its precursors, will be discussed. Keywords: Abdomen/GI, Genetic Defects, Oncology, Pancreas Supplemental material is available for this article. © RSNA, 2020.

Imaging in pediatric ovarian tumors.

The spectrum of ovarian tumors in the pediatric population differs significantly from that in adults. Germ cell tumors are the predominant class of ovarian tumors in children, whereas epithelial tumors are the most common in adults. Ultrasonography is the modality of choice for the initial evaluation of pediatric ovarian tumors. Determining the diagnosis based on imaging may prove difficult, and combining the imaging findings with the clinical scenario is very helpful in reaching a differential diagnosis during clinical practice. We will discuss the spectrum of ovarian neoplasms in the pediatric population and describe their clinical, pathologic, and imaging characteristics. A few unique entities related to ovarian tumors, such as growing teratoma syndrome, anti-N-methyl-D-aspartate receptor encephalitis, and hereditary ovarian tumor syndromes, are also discussed. In addition, we will review several entities that may mimic ovarian neoplasms as well as their distinct imaging features.