Hyperprogression and Immunotherapy: Fact, Fiction, or Alternative Fact?

Immunotherapy (IO) has altered the therapeutic landscape for multiple cancers. There are emerging data from retrospective studies on a subset of patients who do not benefit from IO, instead experiencing rapid progression with dramatic acceleration of disease trajectory, termed 'hyperprogressive disease' (HPD). The incidence of HPD ranges from 4% to 29% from the studies reported. Biological basis and mechanisms of HPD are currently being elucidated, with one theory involving the Fc region of antibodies. Another group has shown EGFR and MDM2/MDM4 amplifications in patients with HPD. This phenomenon has polarized oncologists who debate that this could still reflect the natural history of the disease. Thus, prospective studies are urgently needed to confirm the underlying biology, predict patients who are susceptible to HPD, and determine the modality of therapy post progression.

Adrenal cortical carcinoma: pathology, genomics, prognosis, imaging features, and mimics with impact on management.

Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. Most tumors are either metastatic or locally invasive at the time of diagnosis. Differentiation between ACC and other adrenal masses depends on clinical, biochemical, and imaging factors. This review will discuss the genetics, pathological, and imaging feature of ACC.

Potential Application of Dual-Energy CT in Gynecologic Cancer: Initial Experience.

OBJECTIVE: The purpose of this article is to review the use of dual-energy CT (DECT) in the assessment of gynecologic cancer. CONCLUSION: DECT has the potential to improve diagnostic performance, may improve the ability to differentiate between simple cystic lesions and primary ovarian cancer, and may also improve the detection of musculoskeletal and liver metastases. Additional studies will be needed to determine the direction of future developments and the degree to which DECT will affect the imaging and management of gynecologic cancer.

STUMP un"stumped": anti-tumor response to anaplastic lymphoma kinase (ALK) inhibitor based targeted therapy in uterine inflammatory myofibroblastic tumor with myxoid features harboring DCTN1-ALK fusion.

BACKGROUND: Recurrent, metastatic mesenchymal myxoid tumors of the gynecologic tract present a management challenge as there is minimal evidence to guide systemic therapy. Such tumors also present a diagnostic dilemma, as myxoid features are observed in leiomyosarcomas, inflammatory myofibroblastic tumors (IMT), and mesenchymal myxoid tumors. Comprehensive genomic profiling was performed in the course of clinical care on a case of a recurrent, metastatic myxoid uterine malignancy (initially diagnosed as smooth muscle tumor of uncertain malignant potential (STUMP)), to guide identify targeted therapeutic options. To our knowledge, this case represents the first report of clinical response to targeted therapy in a tumor harboring a DCTN1-ALK fusion protein. METHODS: Hybridization capture of 315 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer was applied to >50 ng of DNA extracted from this sample and sequenced to high, uniform coverage. Therapy was given in the context of a phase I clinical trial ClinicalTrials.gov Identifier: ( NCT01548144 ). RESULTS: Immunostains showed diffuse positivity for ALK1 expression and comprehensive genomic profiling identified an in frame DCTN1-ALK gene fusion. The diagnosis of STUMP was revised to that of an IMT with myxoid features. The patient was enrolled in a clinical trial and treated with an anaplastic lymphoma kinase (ALK) inhibitor (crizotinib/Xalkori®) and a multikinase VEGF inhibitor (pazopanib/Votrient®). The patient experienced an ongoing partial response (6+ months) by response evaluation criteria in solid tumors (RECIST) 1.1 criteria. CONCLUSIONS: For myxoid tumors of the gynecologic tract, comprehensive genomic profiling can identify clinical relevant genomic alterations that both direct treatment targeted therapy and help discriminate between similar diagnostic entities.

Diagnostic approach to hereditary renal cell carcinoma.

OBJECTIVE: The purpose of this article is to discuss the histopathologic features, genetics, clinical presentation, and imaging of hereditary renal cancer syndromes. CONCLUSION: Hereditary renal cell carcinoma syndromes can be diagnosed with a pattern-based approach focused on the predominant histologic renal cell carcinoma subtype and associated renal and extrarenal features of each syndrome.

Uncommon pancreatic tumors and pseudotumors.

A heterogeneous group of uncommon neoplastic and non-neoplastic pancreatic pathologies exists that can mimic pancreatic adenocarcinoma. These "imitators" are unique and may demonstrate characteristic clinical and imaging features. Imaging characteristics of some of these diverse lesions are not well described in the literature, and erroneous diagnoses of these entities as pancreatic carcinoma may be responsible for unnecessary surgeries. Knowledge of these selected pancreatic pathologies is essential to facilitate optimal patient management.

Current update on combined hepatocellular-cholangiocarcinoma.

Combined hepatocellular-cholangiocarcinoma is a rare but unique primary hepatic tumor with characteristic histology and tumor biology. Recent development in genetics and molecular biology support the fact that combined hepatocellular-cholangiocarcinoma is closely linked with cholangiocarcinoma, rather than hepatocellular carcinoma. Combined hepatocellular cholangiocarcinoma tends to present with an more aggressive behavior and a poorer prognosis than either hepatocellular carcinoma or cholangiocarcinoma. An accurate preoperative diagnosis and aggressive treatment planning can play crucial roles in appropriate patient management.

Diaphragmatic hernia after esophagectomy in 440 patients with long-term follow-up.

BACKGROUND: Postesophagectomy diaphragmatic hernia (PDH) is a recognized but severely under-reported and potentially hazardous event. Information regarding the natural course of this condition and guidelines regarding indications for reoperative intervention are lacking. In this study we aim to describe the frequency, predictors of incidence, and indications for repair. METHODS: Cross-sectional imaging (computed tomography scan) from patients who underwent esophagectomy between January 2001 and December 2007 at a single center were reviewed by two radiologists blinded to previous reports and clinical outcomes. Patients with PDH were compared with a similar cohort who did not have hernia. Patient characteristics, outcomes, and hernia descriptors including longitudinal progression were recorded. Multivariable logistic regression analyses identified predictors of PDH and need for repair. RESULTS: Of a total of 440 patients who underwent esophagectomy, 67 (15%) were radiologically diagnosed with PDH. Of these, only 7 of 67 cases (10%) were prospectively reported by the radiologist. Median time interval from esophagectomy to hernia was 2 years. Type of esophagectomy was an independent predictor for hernia developing (p = 0.027). Patients with high body mass index were less prone to have PDH (p = 0.043). Thus far, 9 patients (2%) have required surgical intervention, all for hernia-related symptoms or progression. Despite mesh repair, 4 of 9 have recurred and 2 were re-repaired. There was 1 PDH-associated death, 8 years after transhiatal resection. CONCLUSIONS: Variables contributing to PDH are both technical and patient dependent. Whereas the majority of patients with PDH have not required repair, a small portion who became symptomatic or had large, progressive hernia required remedial surgery. Postesophagectomy patients require long-term surveillance for PDH.

Solid pseudo-papillary tumors of the pancreas: current update.

Solid pseudo-papillary tumors are rare pancreatic tumors, which occur in females and are typically indolent neoplasms. However, atypical, aggressive variants can occur with locally advanced disease or metastases. They have characteristic imaging features, which vary according to size. This article provides a current update on the molecular biology, histopathology, clinico-radiological features, and management of these tumors.

Complications of oncologic therapy in the abdomen and pelvis: a review.

Cancer therapy has significantly improved in the past few decades with development of various newer classes of cytotoxic chemotherapy as well as novel, molecularly targeted chemotherapy. Similar to chemotherapy, radiotherapy is another important therapeutic option used in the curative and palliative management of various abdominal malignancies. However, both these treatments affect the tumor as well as the normal tissues, leading to significant toxicity. These side effects range from mild to life threatening, and may involve multiple organs. Imaging plays an important role in the early identification of such complications, which may allow more effective patient management. The aim of this article is to discuss and illustrate the wide spectrum of chemotherapy and radiotherapy induced complications in the abdomen and pelvis.

Diaphragmatic hernia after esophagectomy for esophageal malignancy.

PURPOSE: Diaphragmatic hernia (DH) is an uncommon complication after esophagectomy, with <150 cases reported in the literature. The objective of our study was to determine the incidence and clinical presentation of this condition and to describe the prospective recognition of this finding in radiologic reports. MATERIALS AND METHODS: Cross-sectional imaging studies of all patients who underwent an esophagectomy between January 2001 and December 2007 at a single tertiary care center were retrospectively reviewed by 2 radiologists who were blinded to the clinical information and radiologic reports. Patients with DH were identified and their demographics, characteristics of hernia, and patient outcome were recorded. Radiology reports issued at the time of study were reviewed independently by a third reviewer to assess whether the hernia was prospectively reported. RESULTS: A total of 458 patients underwent esophagectomy during the study time period, of whom 440 patients were eligible to be included in the study. Forty-four patients developed postesophagectomy DH. Thirty-six patients with DH were asymptomatic, whereas 8 had hernia-related symptoms. Only 7 cases were prospectively reported by the radiologists. Of the 37 cases not reported by the radiologists, 6 required surgical intervention during the follow-up. CONCLUSIONS: Postesophagectomy DH is difficult to diagnose clinically but is usually apparent on cross-sectional imaging. Some asymptomatic patients may develop hernia-related complications, which significantly increases the mortality rate. Hence, radiologists need to be aware of this rare postoperative complication and should report this finding so that affected patients can be optimally managed by surgeons.

Portal vein embolization: cross-sectional imaging of normal features and complications.

OBJECTIVE: The purpose of this article is to describe the role of cross-sectional imaging before portal vein embolization, the normal imaging findings after the procedure, and the imaging findings of postprocedural complications. CONCLUSION: With the increasing emphasis on aggressive resection of hepatic malignancies, portal vein embolization has evolved into a leading technique. Radiologists need to be familiar with the normal imaging findings after this procedure and with the imaging findings of postprocedural complications.