A Review of the Mechanisms and Clinical Implications of Precision Cancer Therapy-Related Toxicity: A Primer for the Radiologist.

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.

Imaging of Metastatic Germ Cell Tumors in Male Patients From Initial Diagnosis to Treatment-Related Toxicities: A Primer for Radiologists.

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.

Assessment of Radiology Training During Radiation Oncology Residency.

A strong foundation in diagnostic imaging is essential to the practice of radiation oncology. This study evaluated radiology training in radiation oncology residency. An online survey was distributed to current radiation oncology residents in the USA by e-mail in 2017. Responses were summarized using frequency and percentages and compared with chi-square test and Spearman's rank correlation when appropriate. One hundred five residents completed the survey. Although most residents felt that a strong knowledge base in diagnostic radiology was moderately or extremely important (87%, n = 90/104), the majority were only somewhat confident in their radiology skills (61%, n = 63/104) and were only somewhat, minimally, or not at all satisfied with their training (79%, n = 81/103). Although there was an association between increasing post-graduate training and confidence level (p = 0.01062, ρ = 0.24959), the majority of graduating residents feel only somewhat confident in radiology skills (63%, n = 12/19). Residents were most commonly exposed to radiology via multidisciplinary conferences (96%, n = 100/104), though only 15% (n = 16/104) of residents ranked these as the most beneficial component of their radiology training and 13% (n = 13/101) of residents felt these were the least beneficial. Most residents (60%, n = 63/105) believe there is a need for dedicated radiology training during residency, preferring monthly formal didactics (68%, n = 71/105) co-taught by a radiologist and radiation oncologist (58%, n = 61/105). Radiation oncology residents feel their radiology training is suboptimal, suggesting a need for more guidance and standardization of radiology curriculum. A preferred option may be monthly didactics co-taught by radiologists and radiation oncologists; however, future studies should assess the effectiveness of this model.

A New Look at Toxicity in the Era of Precision Oncology: Imaging Findings, Their Relationship With Tumor Response, and Effect on Metastasectomy.

OBJECTIVE: As cancer care becomes increasingly personalized and patients with metastatic disease live longer, oncologists' approach to drug toxicity is also evolving. CONCLUSION: This article aims to broaden the radiologist's understanding of imaging-evident toxicity by describing how oncologists grade toxicity, exploring toxicity as a biomarker of treatment response, discussing the effect of toxicity in patients who are candidates for metastasectomy, and illustrating how combining drugs of varying classes amplifies toxicity.

Current Concepts in the Molecular Genetics and Management of Thyroid Cancer: An Update for Radiologists.

Substantial improvement in the understanding of the oncogenic pathways in thyroid cancer has led to identification of specific molecular alterations, including mutations of BRAF and RET in papillary thyroid cancer, mutation of RAS and rearrangement of PPARG in follicular thyroid cancer, mutation of RET in medullary thyroid cancer, and mutations of TP53 and in the phosphatidylinositol 3'-kinase (PI3K)/AKT1 pathway in anaplastic thyroid cancer. Ultrasonography (US) and US-guided biopsy remain cornerstones in the initial workup of thyroid cancer. Surgery is the mainstay of treatment, with radioactive iodine (RAI) therapy reserved for differentiated subtypes. Posttreatment surveillance of thyroid cancer is done with US of the thyroid bed as well as monitoring of tumor markers such as serum thyroglobulin and serum calcitonin. Computed tomography (CT), magnetic resonance imaging, and fluorine 18 fluorodeoxyglucose positron emission tomography/CT are used in the follow-up of patients with negative iodine 131 imaging and elevated tumor markers. Certain mutations, such as mutations of BRAF in papillary thyroid carcinoma and mutations in RET codons 883, 918, and 928, are associated with an aggressive course in medullary thyroid carcinoma, and affected patients need close surveillance. Treatment options for metastatic RAI-refractory thyroid cancer are limited. Currently, Food and Drug Administration-approved molecularly targeted therapies for metastatic RAI-refractory thyroid cancer, including sorafenib, lenvatinib, vandetanib, and cabozantinib, target the vascular endothelial growth factor receptor and RET kinases. Imaging plays an important role in assessment of response to these therapies, which can be atypical owing to antiangiogenic effects. A wide spectrum of toxic effects is associated with the molecularly targeted therapies used in thyroid cancer and can be detected at restaging scans. (©)RSNA, 2016.

Beyond the vascular endothelial growth factor axis: update on role of imaging in nonantiangiogenic molecular targeted therapies in oncology.

OBJECTIVE: This article provides a comprehensive review of molecular targeted therapies that do not act directly through vascular endothelial growth factor pathways, highlighting the role of imaging in assessment of treatment response and drug toxicities. CONCLUSION: A substantial number of molecular targeted therapies act on nonantiangiogenic pathways. Familiarity with these drugs, their personalized tumor response criteria, and class- and drug-specific toxicities will help radiologists to be an integral part of the multi-disciplinary oncology team.

Hormonal therapy in oncology: a primer for the radiologist.

OBJECTIVE: The purpose of this article is to provide a comprehensive imaging review of the common hormonal therapies used in oncology and the side effects associated with them. CONCLUSION: Commonly used hormones in oncology include corticosteroids, somatostatin analogues, progestins, gonadotropin-releasing hormone agonists and antagonists, antiandrogens, aromatase inhibitors, and selective estrogen receptor modulators. Familiarity with these hormones and their side effects can help radiologists to be vigilant for the side effects and complications of these agents.

Myxoid soft-tissue neoplasms: comprehensive update of the taxonomy and MRI features.

OBJECTIVE. The purpose of this article is to review the classification, clinical presentation, and histopathologic and MRI features of myxoid soft-tissue neoplasms. CONCLUSION. MRI is the modality of choice for characterization of myxoid soft-tissue tumors. A combination of imaging features (including certain characteristic signs), clinical features, and patient demographics can help the radiologist in coming to a specific diagnosis or in narrowing down the differential diagnoses.

Anti-VEGF molecular targeted therapies in common solid malignancies: comprehensive update for radiologists.

Angiogenesis is an essential component of the growth and dissemination of solid malignancies and is mediated by several proangiogenic factors. The most widely studied proangiogenic factor is vascular endothelial growth factor (VEGF). A major class of molecular targeted therapies (MTTs) inhibit the VEGF axis and are referred to as antiangiogenic MTTs. There are two main types of anti-VEGF MTTs: drugs targeting circulating VEGF and drugs interfering with the activity of the VEGF receptors. The cancers against which antiangiogenic MTTs have had the greatest effect are gliomas, non-small cell lung cancer, colorectal cancer, hepatocellular carcinoma, renal cell carcinoma, and gastrointestinal stromal tumor. These cancers respond to antiangiogenic MTTs in a different way than they respond to conventional chemotherapy. Instead of the traditional Response Evaluation Criteria in Solid Tumors (RECIST), each of these cancers therefore requires its own individualized treatment response criteria (TRC). Examples of individualized TRC include the Response Assessment in Neuro-oncology (RANO) criteria for gliomas, modified RECIST for hepatocellular carcinoma, and Morphology, Attenuation, Size, and Structure (MASS) criteria for renal cell carcinoma. Furthermore, antiangiogenic MTTs have a unique spectrum of class-specific and drug-specific toxic effects, some of which can be detected at imaging. Increasing use of antiangiogenic MTTs in clinical practice necessitates that radiologists be aware of these drugs, their response patterns, and TRC as well as their toxic effect profiles.

Approach to risk stratification in testicular germ cell tumors: a primer for radiologists.

Oncologists increasingly exploit differences in testicular germ cell tumors to deliver more personalized treatment. Imaging is essential in this process, aiding in the selection of risk-stratified management strategies. Consideration of relevant prognostic factors strengthens image interpretation, allowing for a more nuanced radiographic evaluation. This paper uses a clinically focused, stage-by-stage approach to delineate the risk factors for relapse and metastasis that radiologists should consider during staging, response assessment, and surveillance.

Relationship Between the Pathologic Subtype/Initial Stage and Microliths in Testicular Germ Cell Tumors.

OBJECTIVES: To investigate the relationship between microliths and germ cell tumor histologic subtypes and determine whether microliths correlate with tumor stage at diagnosis. METHODS: A total of 1249 patients with testicular cancer seen between 1999 and 2013 were evaluated; 346 of 1249 patients (28%) with primary testicular tumors and sonographic imaging of unaffected testicular tissue formed the analytic cohort. Age, ethnicity, tumor histologic subtype, and stage at diagnosis were extracted from the medical record. Two examiners concurrently recorded the highest number of microliths per image of unaffected testicular tissue. RESULTS: A total of 175 of 346 patients (51%) had 1 or more microliths; 69 of 346 (20%) had more than 5 microliths per image. The histologic percentage of seminomas positively correlated with the microlith count (rs = 0.12; P = .036); the histologic percentage of embryonal components negatively correlated with the microlith count (rs = -0.15; P = .007). A higher microlith count was associated with a lower stage at diagnosis (P = .0243). Subgroup analysis of pure seminomas suggested a trend toward a higher microlith count in patients with lower-stage disease at diagnosis (P= .07). No association was found between the tumor stage at diagnosis and microlith count in patients with greater than 50% embryonal components of tumors (P= .55). No association was found between microliths and age, tumor size, and presence of lymphovascular/rete testis invasion (P = .120, .500, .629, and .155, respectively). CONCLUSIONS: Patients with testicular cancer who have microliths may be more likely to have a higher percentage of seminomas and a lower percentage of embryonal components in their primary tumors. Microliths also showed an association with earlier stages of disease at diagnosis.

Multimodality Imaging of Tumour Thrombus.

Vascular thrombosis occurs commonly in cancer patients. Once the diagnosis of thrombosis is established, it is important to characterize the nature of thrombus, tumoural versus bland, as each have a different prognosis, clinical significance, and management. This review paper discusses the imaging spectrum of tumour thrombus and its clinical significance emphasizing the role of imaging in differentiating tumour from bland thrombus.

Craniocaudal retroperitoneal node length as a risk factor for relapse from clinical stage I testicular germ cell tumor.

OBJECTIVE: The purpose of this study was to investigate whether retroperitoneal craniocaudal nodal length or nodal volume predicts relapse risk in stage I testicular cancer. MATERIALS AND METHODS: We retrospectively reviewed 826 testicular cancer patients. Of these 826 patients, 118 had stage I disease and either less than 2 years of surveillance or retroperitoneal lymph node dissection with no adjuvant chemotherapy. These patients formed our analytic cohort, and 3D nodal volumes and craniocaudal nodal length were measured. Association between relapse risk and craniocaudal nodal length and nodal volume was evaluated using univariable or multivariable logistic regression models adjusted for known prognostic factors. RESULTS: Sixty-six (56%) of 118 patients had nonseminomatous germ cell tumor and 52 (44%) had seminomatous germ cell tumor. Craniocaudal nodal length proved to be an independent risk factor in nonseminomatous germ cell tumors using a multivariable logistic regression model adjusting for other potential known risk factors of embryonal predominance and lymphovascular invasion. For every 3-mm increase in craniocaudal nodal length, the risk of relapse increased by 52% (odds ratio [OR], 1.52; 95% CI, 1.03-2.25). For patients with seminomas, only primary tumor size was an independent risk factor for relapse (1.34, 1.02-1.75). CONCLUSION: In nonseminomatous germ cell tumors, craniocaudal nodal length was shown to be associated with increased risk of relapse independently of other known risk factors. If validated in an independent cohort, craniocaudal nodal length could provide important additional information to inform management decisions in these patients.

Update on the role of imaging in management of metastatic colorectal cancer.

Evolution in the treatment of metastatic colorectal cancer (mCRC) has led to significant improvement in the survival of these patients. Surgery is useful in patients with resectable disease. Liver-directed therapies such as hepatic arterial infusion, transarterial radio- and chemoembolization, and percutaneous ablation are sometimes used by oncologists when the liver is the only site of metastatic disease. Unresectable mCRC is typically treated with systemic chemotherapy. First-line systemic chemotherapeutic regimens for mCRC are FOLFOX (combination of 5-fluorouracil/leucovorin [5-FU/LV] and oxaliplatin) and FOLFIRI (combination of 5-FU/LV and irinotecan) combined with molecular targeted drugs. Molecular targeted therapies that are effective in treating mCRC include antiangiogenic agents such as bevacizumab-an antibody against vascular endothelial growth factor-and antibodies directed against epidermal growth factor receptor (EGFR). EGFR-directed antibodies such as cetuximab and panitumumab have been shown to produce activity only in wild-type KRAS tumors. Imaging modalities such as multidetector computed tomography (CT), magnetic resonance imaging, and positron emission tomography/CT play a major role in the selection of appropriate treatment strategies. Assessment of treatment response in patients who undergo liver-directed and systemic therapy requires imaging at regular intervals. Recent studies have shown that alternative treatment response criteria may be more predictive of pathologic response in mCRC than conventional criteria such as Response Evaluation Criteria in Solid Tumors. Awareness of unusual response patterns, as well as of complications and toxicities, is helpful in guiding patient management.

Update on imaging of vulvar squamous cell carcinoma.

OBJECTIVE: The purpose of this article is to describe the advantages and diagnostic and prognostic implications of imaging in the management of vulvar carcinoma. CONCLUSION: As the treatment of vulvar carcinoma evolves to tailored surgery and chemoradiation therapy to reduce morbidity, the importance of pretreatment assessment of vulvar carcinoma increases. Advances in imaging, such as pelvic MRI and PET, add to the benefits of clinical evaluation in pretreatment planning, assessment of response to chemoradiation therapy, and posttreatment surveillance.

Ipilimumab-associated colitis: CT findings.

OBJECTIVE: The purpose of this article is to describe the CT findings of ipilimumab-associated colitis. MATERIALS AND METHODS: In this retrospective study, 16 patients diagnosed with ipilimumab-associated colitis and available CT scans obtained at the time of symptoms were found by a search through the electronic medical record database. Two radiologists reviewed the CT images in consensus for the presence of bowel wall thickening, bowel mucosal enhancement, bowel distention, pneumatosis, pericolic fat stranding, and mesenteric vessel engorgement. Medical records were reviewed to note clinical features, management, and outcome. RESULTS: The common CT findings of ipilimumab-associated colitis were mesenteric vessel engorgement (13/16 [81.3%]) followed by bowel wall thickening (12/16 [75%]) and fluid-filled colonic distention (4/16 [25%]). None of the patients had pneumatosis or halo or target signs. Two distinct CT patterns of ipilimumab-associated colitis were observed: first, the diffuse colitis pattern (n = 12), which is characterized by mesenteric vessel engorgement with mild diffuse bowel wall thickening or fluid-filled distended colon; and, second, the segmental colitis associated with diverticulosis (SCAD) pattern (n = 4), which is characterized by segmental moderate wall thickening and associated pericolic fat stranding in a segment of preexisting diverticulosis. Clinical features and management also differed according to the CT pattern. Patients with the diffuse colitis pattern presented with watery diarrhea and were treated with steroids, whereas the patients with the SCAD pattern presented with mixed watery and bloody diarrhea and cramping pain and were treated with steroids and antibiotics. CONCLUSION: Two different radiologic and clinical manifestations of ipilimumab-associated colitis were observed: the diffuse colitis pattern and the SCAD pattern.

Pneumatosis intestinalis and bowel perforation associated with molecular targeted therapy: an emerging problem and the role of radiologists in its management.

OBJECTIVE: The purpose of this article is to study the imaging features, management, and outcome of pneumatosis intestinalis and bowel perforation associated with molecular targeted therapy. MATERIALS AND METHODS: In this retrospective study, 48 patients with cancer who developed pneumatosis or intestinal perforation were found by searching a radiology database. Of these patients, 24 patients (13 women and 11 men; mean age, 61 years; range, 39-83 years) receiving molecular targeted therapy without any confounding factors for pneumatosis or perforation were selected. Initial and follow-up CT scans were evaluated by two radiologists; medical records were reviewed to note clinical features, management, and outcome. RESULTS: Seventeen (70.8%) patients were asymptomatic. Colorectal cancer (n = 10) and renal cell carcinoma (n = 5) were the most common malignancies; bevacizumab (n = 14) and sunitinib (n = 6) were the most common associated drugs. Imaging findings included intestinal perforation (20 sites in 18 patients), pneumatosis (n = 10), ascites (n = 8), pneumoperitoneum (n = 7), fistula formation (n = 7), and fluid collections (six collections in five patients). Fifteen (62.5%) patients were treated conservatively, seven (29.2%) underwent surgery, and two (8.3%) underwent percutaneous drainage. Molecular targeted therapy was discontinued in 22 of 24 patients; findings resolved in 19 patients, remained stable in one, and worsened in one. One patient died after surgery. In both instances where the drug was continued, the abnormality worsened. Findings recurred in three of four patients in whom the drug was restarted after initial resolution. CONCLUSION: Radiologists should be aware of intestinal complications associated with molecular targeted therapy, including pneumatosis, bowel perforation, and fistula formation. Most patients can be treated conservatively after discontinuation of molecular targeted therapy. Continuing or restarting molecular targeted therapy can cause worsening or recurrent pneumatosis or perforation.

Synovial sarcoma: imaging features of common and uncommon primary sites, metastatic patterns, and treatment response.

OBJECTIVE: The purpose of this review is to describe the imaging features, common and uncommon sites, metastatic pattern, and treatment response of synovial sarcoma. CONCLUSION: Synovial sarcoma primarily occurs in young adults, most commonly in the lower extremities; presents as a large, noninfiltrative, well-circumscribed mass adjacent to joints, often with punctuate calcifications; and may exhibit a triple signal pattern on T2-weighted images. Small synovial sarcomas can mimic benign lesions. This tumor has a propensity for late local recurrence and metastasis, most commonly to lung.

Customized Residency Leadership Tracks: A Review of What Works, What We're Doing and Ideas for the Future.

Effective leaders are essential to ensure the future of radiology. Radiologists often find themselves in leadership positions despite a lack of formal leadership training. The fourth year of residency is the ideal time to expose young physicians to leadership and extraclinical specialization, as such leadership development prior to fellowship may still impact academic career choice. In this manuscript, we discuss prior successes of leadership tracks within medicine and review the evidence supporting the saying that "leaders are made, not born". Finally, we describe the evolution of our institution's residency leadership tracks highlighting key components, challenges, early successes and future endeavors.

Quantifying Decreased Radiation Exposure From Modern CT Scan Technology and Surveillance Programs of Germ Cell Tumors.

INTRODUCTION: Upgrading computerized tomography (CT) scanners to iterative reconstruction techniques (IRT) decreases radiation dose. This reduction, combined with changes in surveillance protocols in clinical stage I testicular cancer (CS1TC) measurably decrease the lifetime attributable risk (LAR) of dying of radiation-associated cancer. MATERIALS AND METHODS: This IRB-approved study enrolled 24 CS1TC patients who had CT scans on the same Toshiba Aquilion 64 CT before and after IRT software installation. Dose-length product and CT dose index volume were recorded. A physicist calculated effective doses. Radiation doses were compared using the Wilcoxon signed rank test. Median effective dose per scan was multiplied by scan number based on 16 versus 7 scans in 5-year AS protocols to calculate estimated cumulative dose (ECD). LAR of dying of radiation-associated solid tumor was estimated using ECD for a single exposure at age 35 with the excess absolute risk transport model from the BEIR VII analysis of long-term atomic bomb survivors. RESULTS: Median preupgrade and postupgrade effective doses were 12.5 and 7.7 mSv, respectively (P<0.0001). A linear regression model with a constrained zero intercept fit to the data found that IRT dose was estimated as 61% of filtered back projection dose (95% confidence interval, 0.56-0.66). The IRT upgrade reduced the LAR of the 16-scan protocol 35%. Combination of IRT upgrade and 7-scan protocol reduced surveillance LAR 72%. CONCLUSIONS: Modern CT technology combined with reduced scanning strategies can markedly decrease lifetime radiation exposure, further lowering the already small potential mortality of imaging-associated cancers.