Part 2: Imaging findings of uncommon but important immune checkpoint inhibitor-related adverse effects.

Oncology care has significantly changed with the emergence of immunotherapy agents, in particular immune checkpoint inhibitors (ICIs). This has had an immediate effect on imaging, with different radiological tumour responses to treatment compared with conventional chemotherapies, and novel imaging findings due to complications caused by these agents (referred to as immune-related adverse effects, irAEs). Some of the more common irAEs may be familiar, but as the use of ICIs increases to a wider variety of cancers, these complications, and in particular, the less common irAEs, will be encountered more frequently on imaging. It will be increasingly important to be familiar with these uncommon irAEs, particularly since they can be difficult to recognise and distinguish from metastatic disease. The aim of this pictorial essay was to describe and illustrate imaging findings that may be encountered related to uncommon but important irAEs as a result of treatment with immune checkpoint inhibitors.

Rapid growth of primary uveal melanoma following intravitreal bevacizumab injection: a case report and review of the literature.

Uveal melanoma size is a significant predictor of tumor metastasis. Although the relationship between antivascular endothelial growth factors (VEGF) and uveal melanoma growth has been studied, results are paradoxical, and the relationship remains controversial. We report the case of a 65-year-old man who presented with elevated intraocular pressure in his right eye, neovascularization of his iris, and significant corneal edema, which obscured the view of the angle. Given his history of proliferative diabetic retinopathy, he was diagnosed with neovascular glaucoma and subsequently received an intravitreal injection of bevacizumab and underwent Ahmed valve insertion. This was complicated by postoperative hyphema. Two and a half months postoperatively, a mass involving the inferior iris and ciliary body became visible, and fine-needle aspiration biopsy confirmed uveal melanoma. Seven weeks after diagnosis, the tumor's largest basal diameter had increased from 2.51 mm to 18.0 mm, and apical height increased from 6.23 mm to 11.0 mm. His right eye was enucleated. Histopathological analysis showed discontinuous invasion next to the Ahmed valve. Tumor progression after injection raises the possibility that in some untreated uveal melanomas, accelerated growth may occur following exposure to anti-VEGF agents.

Gastroparesis and Severity of Delayed Gastric Emptying: Comparison of Patient Characteristics, Treatments and Medication Adverse Events.

BACKGROUND: Gastroparesis is a heterogeneous disorder. Patient characteristics and treatment responsiveness may differ based on the extent of delay in gastric emptying. AIMS: Characterize gastroparesis patients based on the degree of delay in gastric emptying, and assess the relationship of patient demographics, symptoms and response to therapy based on the extent of delay. METHODS: 1333 solid-phase 4-h scintigraphic gastric emptying scans were reviewed. Delayed emptying was categorized on percent retention at 4 h: mild (10-19%), moderate (20-29%), and severe (≥ 30%). Analyses were performed with regard to demographics, symptoms, esophagogastroduodenoscopy findings, medication use, and emergency department (ED) visits/hospitalizations. RESULTS: 284 patients had delayed gastric emptying: mild (42.6%), moderate (19.3%), and severe (37.3%). 79.5% were women, the mean age was 45 years (± 15), and mean symptom duration was 4.6 years (± 6.5). The main categories of gastroparesis were idiopathic and diabetes mellitus. The most commonly prescribed medications were metoclopramide, domperidone and erythromycin. Opiate use (n = 69) was associated with an increased degree of delayed gastric emptying (p = 0.03) with 50% of opiate users having very delayed gastric emptying. One-way analysis revealed that severely delayed gastric emptying correlated with both increased hospitalizations and ED visits. CONCLUSIONS: Severe delay in gastric emptying is a risk factor for increased hospitalizations and ED visits. Opiate use correlates with increased severity of gastric emptying. Identifying at-risk patients, stopping opioids, and instituting a programmatic care plan for patients with severely delayed gastric emptying may reduce ED visits, hospitalizations, and healthcare costs.

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.

Anti-PD-1-Related Exacerbation of Interstitial Lung Disease in a Patient with Non-Small Cell Lung Cancer: A Case Presentation and Review of the Literature.

Immunotherapy is standard first-line therapy for advanced non-small cell lung cancer (NSCLC) either alone or in combination with chemotherapy. Despite significant benefits, immune checkpoint inhibitors (ICI) can cause toxicities within any organ, termed immune related adverse events. Pneumonitis is a potentially life-threatening complication of ICIs. Currently, there are no established guidelines for use of ICIs in patients with underlying autoimmune or interstitial lung disease (ILD) and few studies have been published. We present a case of first-line ICI-chemotherapy in a patient with metastatic NSCLC and ILD who suffered treatment related lung toxicity and acute worsening ILD, which lead to his death.

Factors related to the adverse events of antiepileptic drugs.

OBJECTIVE: The aim of the present study was to explore the factors related to the severity of the adverse effects of antiepileptic drugs (AEDs), experienced by patients with epilepsy. MATERIALS AND METHODS: A case study was conducted in adult patients with epilepsy and followed up at the Epilepsy Outpatients of the University Hospital of Ioannina in Northwest Greece. The Adverse Event Profile (AEP) questionnaire for AEDs adverse effects assessment, the Defense style questionnaire (DSQ-88) and the Patient Health Questionnaire (PHQ-9) for depression' severity evaluation were used to estimate the severity of adverse effects, the defense style, and the depressive symptoms, respectively. RESULTS: Sixty-three patients with epilepsy (M/F:28/35), with a mean age of 37.6 ±â€¯13.41, were recruited in the study. The univariate analysis showed that both the Maladaptive style of defense and the PHQ-9 score were significantly associated with the AEP score. After multivariate regression analysis female gender, the load of AEDs, the PHQ-9 score, and the Adaptive defense style remained significant coefficients. CONCLUSION: There are also nonpharmacological factors that may contribute to the severity of the adverse effects of AEDs, experienced by the patients with epilepsy.

Imaging of Novel Oncologic Treatments in Lung Cancer Part 1: Systemic Therapies.

Thoracic tumors are a leading cause of cancer-related morbidity and mortality. In recent years, developments in oncologic treatments for these tumors have ushered in an era of targeted therapy, and, in many cases, these novel treatments have replaced conventional strategies to become standard therapeutic options, particularly in those with lung cancer. Targeted medical therapies for lung cancer now include angiogenesis inhibitors, tyrosine kinase inhibitors, and immunotherapeutic agents. Several novel ablative therapies have also gained widespread acceptance as alternatives to conventional surgical options in appropriately selected patients. Tumors treated with targeted medical therapies can respond to treatment differently when compared with conventional therapies. For example, pseudoprogression is a well-described phenomenon in patients receiving checkpoint inhibitor immunotherapy in which an initial increase in tumor burden is followed by a decrease in tumor burden and sometimes partial or complete response, while the frequent cavitating responses seen when antiangiogenic agents are used can be difficult to quantify using existing response assessment criteria. In some cases, novel response assessment criteria are needed to adequately capture response. In addition, numerous treatment-related side effects have been described, which are important to recognize, both to ensure appropriate treatment and to avoid misclassification as worsening tumor. Imaging plays a vital role in the assessment of patients receiving targeted medical therapy, and it is essential that thoracic radiologists are familiar with the rationale underpinning these treatments and the expected posttherapy findings.

Defect evaluation by infant photographs in a multicenter pharmaceutical clinical trial.

OBJECT: The NT-04 clinical trial of investigational medication NT100 had a limited, though geographically diverse, study population. To enhance potential birth defect identification, photographic dysmorphology exam of infants was performed along with review of prenatal and postnatal medical records. METHODS: Standardized photographic views were developed: full body (prone and supine), face, both profiles, dorsal and ventral hands and feet, genitalia, and birthmarks/skin lesions. Professional photographers were identified and trained. Photos were taken in the first month of life at the subject's home and uploaded to a secure electronic online photo viewer. The evaluating geneticist accessed the photos electronically and submitted an evaluation. RESULTS: Forty subjects had 39 evaluable outcomes (55 babies). Twelve photographers were recruited, 10 of whom worked with multiple subjects. Photographic dysmorphology evaluation was done on 38 pregnancy outcomes. Only one baby had missing photos due to an apparent protocol error. Four babies were photographed with diaper on. CONCLUSIONS: The standardized photographs worked well. Advantages include: a single clinician evaluating all infants, the photographs could be reviewed repeatedly as needed, and minor malformations were more uniformly identified. Difficulties were: identifying local photographers and supplying training and training materials. There was no protocol for retaking or obtaining new photos and the study consent form did not include permission to publish the photographs. This was a successful pilot study of infant photographic assessment to detect congenital anomalies in a clinical trial.

Left ventricle segmental function in childhood cancer survivors using speckle-tracking echocardiography.

AIM: Anthracycline-associated cardiotoxicity in childhood cancer survivors may relate to global or segmental left ventricular abnormalities from associated thromboembolic events and myocardial microinfarcts. We characterized left ventricular segmental changes by two-dimensional speckle-tracking echocardiography in anthracycline-treated asymptomatic childhood cancer survivors. METHODS AND RESULTS: Childhood cancer survivors' echocardiograms with normal left ventricular fractional shortening >1 year after anthracycline chemotherapy were studied. Cancer-free control children had normal echocardiograms. Apical two-, three-, and four-chamber peak systolic left ventricular longitudinal and global longitudinal strain, and peak systolic left ventricular radial and circumferential strain at papillary muscle levels were analyzed. The mean (standard deviation) age was 12.7 (3.8) years in 41 childhood cancer survivors. The median (interquartile range) follow-up after anthracycline chemotherapy was 4.73 (2.15-8) years. The median (range) cumulative anthracycline dose was 160.2 (60-396.9) mg/m2. In childhood cancer survivors, the mean (standard deviation) left ventricular longitudinal strain was lower in two- (-18.6 [3.2] versus -21.3 [2.5], p < 0.001), three- (-16.3 [6.0] versus -21.7 [3.0], p < 0.001), and four- (-17.6 [2.7] versus -20.8 [2.0], p < 0.001) chamber views compared to controls. The left ventricular global longitudinal strain (-17.6 [2.7] versus -21.3 [2.0]) and circumferential strain (-20.8 [4.3] versus -23.5 [2.6], p < 0.001) were lower in childhood cancer survivors. Among childhood cancer survivors, 12 out of 16 left ventricular segments had significantly lower longitudinal strain than controls. CONCLUSIONS: Asymptomatic anthracycline-treated childhood cancer survivors with normal left ventricular fractional shortening had lower global longitudinal and circumferential strain. The left ventricular longitudinal strain was lower in majority of the segments, suggesting that anthracycline cardiotoxicity is more global than regional.

Acute Toxic Leukoencephalopathy: Etiologies, Imaging Findings, and Outcomes in 101 Patients.

BACKGROUND AND PURPOSE: Prior studies regarding acute toxic leukoencephalopathy (ATL) are either small, or preliminary. Our aim was to evaluate etiologies of and differences in imaging severity and outcomes among various etiologies of ATL. MATERIALS AND METHODS: MRIs of patients with suspected ATL over 15 years were retrospectively reviewed; inclusion criteria were: MRI <3 weeks of presentation with both DWI and FLAIR. These were jointly graded by two neuroradiologists via a previously described score of severity. Clinical outcome was evaluated via both modified Rankin (mRS) and ATL outcome (ATLOS) scores, each being correlated with the DWI and FLAIR scores. Etiologic subgroups of n > 6 patients were statistically compared. RESULTS: Of 101 included patients, the 4 subgroups of n > 6 were the following: chemotherapy (n = 35), opiates (n = 19), acute hepatic encephalopathy (n = 14), and immunosuppressants (n = 11). Other causes (n = 22 total) notably included carbon monoxide (n = 3) metronidazole (n = 2), and uremia (n = 1). The mean DWI/FLAIR severity scores were 2.6/2.3, 3.3/3.3, 2.1/2.1 and 2.0/2.5 for chemotherapeutics, opiates, AHE and immunosuppressants, respectively, with significant differences in both imaging severity and outcome (P = .003-.032) among subgroups, particularly immunosuppressant versus chemotherapy-related ATL and immunosuppressants versus opiates (P = .004-.032) related ATL. DWI and FLAIR severity weakly correlated with outcome (ρ = 0.289-.349, P < .005) but correlated stronger in the chemotherapy (ρ = 0.460-.586, P < .010) and opiate (ρ =.472-.608, P < .05) subgroups, which had the worst outcomes. ATL clinically resolved in 36%, with severe outcomes in 23% (coma or death, 9/16 deaths from fludarabine). Notable laboratory results were elevated CSF myelin basic protein levels in 8/9 patients and serum blood urea nitrogen levels in 24/91. CONCLUSIONS: Clinical outcomes of ATL vary on the basis of etiology, being worse in chemotherapeutic- and opiate-related ATL. Uremia may be a predisposing or exacerbating factor.

Adverse effects and radiological manifestations of new immunotherapy agents.

Immunotherapy has had increasing use in Medical Oncology for a diverse range of primary malignancies. There are various types of immunotherapy which are grouped based on mechanism of action. In recent decades, the immune checkpoint inhibitors (ICI) immunotherapies have been at the forefront of Medical Oncology, sparked by very encouraging results. Some patients with metastatic cancer who were previously deemed palliative were seeing durable response rates and significant increased survival with ICIs. The mechanism of action of ICIs vary wildly compared to the conventional, cytotoxic chemotherapy, upon which traditional radiology response criteria were based and validated upon. Novel responses such as pseudo progression, disease response in the context of new metastases and prolonged stable disease were observed and correlated with improved patient survival with ICI. New radiology response criteria were proposed to better capture disease response to ICI; however, the criteria have been applied heterogeneously and there is continued work in this sector. In addition to the novel responses, ICIs have been linked to numerous, diverse immune-related adverse events (irAE) affecting multiple systems. A large majority of these are mild, but some irAEs are life threatening. Only some of the irAEs have radiological manifestations. It is important that the reporting radiologist recognises potential irAE so clinical teams can be alerted, ICI treatment paused or cessated and steroid treatment initiated. This review will discuss the evolution of the radiology response criteria in ICI and the varied radiological appearances of irAE.

Whole-body Imaging of Cell Death Provides a Systemic, Minimally Invasive, Dynamic, and Near-real Time Indicator for Chemotherapeutic Drug Toxicity.

PURPOSE: Response to toxicity in chemotherapies varies considerably from tissue to tissue and from patient to patient. An ability to monitor the tissue damage done by chemotherapy may have a profound impact on treatment and prognosis allowing for a proactive management in understanding and mitigating such events. For the first time, we investigated the feasibility of using whole-body imaging to map chemotherapeutic drug-induced toxicity on an individual basis. EXPERIMENTAL DESIGN: In a preclinical proof-of-concept, rats were treated with a single clinical dose of cyclophosphamide, methotrexate, or cisplatin. In vivo whole-body imaging data were acquired using 99mTc-duramycin, which identifies dead and dying cells as an unambiguous marker for tissue injury in susceptible organs. Imaging results were cross-validated using quantitative ex vivo measurements and histopathology and compared with standard blood and serum panels for toxicology. RESULTS: The in vivo whole-body imaging data detected widespread changes, where spatially heterogeneous toxic effects were identified across different tissues, within substructures of organs, as well as among different individuals. The signal changes were consistent with established toxicity profiles of these chemotherapeutic drugs. Apart from generating a map of susceptible tissues, this in vivo imaging approach was more sensitive compared with conventional blood and serum markers used in toxicology. Also, repeated imaging during the acute period after drug treatment captured different kinetics of tissue injury among susceptible organs in males and females. CONCLUSIONS: This novel and highly translational imaging approach shows promise in optimizing therapeutic decisions by detecting and managing drug toxicity on a personalized basis.Toxicity to normal tissues is a significant limitation in chemotherapies. This work demonstrated an in vivo imaging-based approach for characterizing toxicity-induced tissue injury in a systemic, dynamic, and near-real time fashion. This novel approach shows promise in optimizing therapeutic decisions by monitoring drug toxicity on a personalized basis.

A Qualitative Analysis of the Impact of Carboplatin AUC 10 on Physical, Work Functioning and Bone Marrow Toxicity Among Seminoma Patients - A Single-centre Experience.

BACKGROUND: Single-agent carboplatin at area under the curve 10 (AUC10) is an effective treatment for metastatic seminoma. As far as we are aware of, there have been no studies reporting its effects on short-term quality of life. The objective was to study the efficacy, safety and tolerability, using health-related quality of life, of carboplatin AUC10 chemotherapy in patients with metastatic seminoma. PATIENTS AND METHODS: Forty-four patients with metastatic seminoma treated at Mount Vernon Cancer Centre with carboplatin AUC10 were included in this study. Response to treatment was determined by radiological imaging (Response Evaluation Criteria in Solid Tumors v 1.1) and serum tumour markers. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events Version 4.0. Quality of life treatment-related toxicities were assessed during treatment at pre-chemotherapy assessments. After treatment, toxicity was assessed using a defined telephone questionnaire consisting of four questions relating to hair loss, hearing impairment, days absent from work, and neuropathy. RESULTS: At a median follow-up of 27.5 (range=4-84) months, no patient had experienced relapse. Grade 3/4 neutropenia was seen in 15 (35%) patients, nine (21%) required prophylactic granulocyte colony-stimulating factor, 13 (30%) patients had grade 3/4 thrombocytopenia. Commonest non-haematological toxicities were fatigue in 28 (65%) and nausea 14 (33%) patients. They were grade 1 in 82% and 92% of cases, respectively. Six out of 44 (14%) had residual tinnitus. One patient had residual grade 1 peripheral neuropathy. Ten patients continued to work throughout treatment and two patients were retired. Of the remaining patients, 16 (37%), took fewer than 5 days off work. CONCLUSION: Carboplatin AUC10 is a safe and effective treatment for stage II/III seminoma with better health-related quality of life than experienced with combination cisplatin-based chemotherapy.

Bone Toolbox: Biomarkers, Imaging Tools, Biomechanics, and Histomorphometry.

Bone is a unique tissue with turnover, metabolic, and cellular activities that vary through development to aging and with a mineralized matrix in which the current state and the history of a bone coexist. Qualitative histopathology often lacks sensitivity to detect changes in bone formation, mineralization and resorption, which often requires chronic dosing to result in structural changes such as variation in bone mass and geometry. A large panel of modalities can be used to fully analyze the health of the skeleton, including biomarker evaluation in serum or urine, imaging techniques ranging from radiology to computed tomography, biomechanical testing, and undecalcified tissue processing with bone histomorphometry. The use of clinically relevant biomarkers provides an important noninvasive, sensitive, rapid, and real-time tool to monitor bone activity at the whole skeleton level when conducting safety assessments in a preclinical setting. Imaging modalities also allow in vivo longitudinal assessments with a powerful, noninvasive and clinically translatable tools to monitor drug effects. Different imaging modalities are used in the preclinical studies to evaluate the bone tissues: standard radiography, dual-energy X-ray absorptiometry, peripheral quantitative computed tomography (pQCT), micro-computed tomography, and high-resolution pQCT. Bone histomorphometry is an important tool that provides sensitive evaluation to detect effects of test articles on bone resorption, formation, mineralization, remodeling rates and growth to address a potential target- or class-related theoretical bone liability. Ultimately, the measurement of bone mechanical properties in pharmaceutical testing is critical to understand the potential effects of that pharmaceutical on bone health and fracture risk. Important considerations are required for including these different techniques in toxicology rodents and nonrodent studies, to actually integrate these into safety assessment.

Unintended Consequences of Systemic and Ablative Oncologic Therapy in the Abdomen and Pelvis.

Human cancers are genetically complex and diverse. Although advances in oncologic therapy aim to define and target unique steps in carcinogenesis, oncologists often rely on less discriminate anticancer therapies that have consequences for normal tissues. Even many of the so-called targeted therapies currently employed can adversely affect normal cells, leading to complications that necessitate dose reductions or cessation of specific therapies. This article explores the unintended consequences of currently employed systemic and ablative anticancer therapies that might manifest at imaging examinations of the abdomen and pelvis, including cytotoxic, molecular targeted, and immunologic agents; ablation; and hematopoietic stem cell transplant. Each of these treatments can have both major and minor unintended effects in the targeted organ(s), in local or adjacent structures, or at distant sites. Timely detection and reporting of adverse consequences of anticancer therapies by the astute imager can result in critical treatment modifications and/or lifesaving interventions; therefore, knowledge of these unintended effects is paramount for radiologists interpreting the results of imaging examinations in cancer patients. ©RSNA, 2018.

Detection of immune-related adverse events by medical imaging in patients treated with anti-programmed cell death 1.

BACKGROUND: Programmed death receptor-1 blocking antibodies (anti-PD1) are a new standard of care in many cancer types. Patients benefit from improved survival but have the risk of immune-related adverse events (irAE). We evaluated if medical imaging procedures, used for anti-tumour response assessment, can detect irAEs. MATERIALS AND METHODS: All consecutive patients treated with anti-PD1 and with a medical imaging acquisition performed within 2 weeks with irAEs ≥2 were retrospectively included. Data were gathered from June 2014 to February 2017, and a central review was performed. The primary and secondary end-points were i) to evaluate the overall detection rate of irAEs by medical imaging and ii) to provide a comprehensive radiological description of irAEs. RESULTS: Fifty-three patients (31 women, 22 men; average age: 61 years) were included. The primary tumour was melanoma (n = 32), lung cancer (n = 18) and other (n = 3). Patients were treated with nivolumab (n = 27) or pembrolizumab (n = 26). Of 74 medical imaging procedures analysed (ratio = 1.4 medical imaging per patient), 55 irAE were detected. The detection rate was overall: 74% (95 confidence interval: 63-84%), positron emission tomography with 18F-fludeoxyglucose integrated with computed tomography (18F-FDG PET/CT): 83% (n = 10/12), magnetic resonance imaging: 83% (n = 5/6), computed tomography scan: 79% (n = 19/24), ultrasonography: 70% (n = 19/27), standard X-rays: 40% (n = 2/5), lung/mediastinum: 100% (n = 7/7), enterocolitis: 100% (n = 8/8), hypophysitis: 100% (n = 3/3), thyroiditis: 75% (n = 15/20), hepatitis: 67% (n = 2/3), arthralgia or arthritis: 40% (n = 2/5) and pancreas: 28% (n = 2/7). CONCLUSION: Medical imaging detected 74% of irAE in patients treated with anti-PD1. Beyond response assessment, medical imaging can detect irAE and guide towards specific management. We described the most frequent sites and patterns of imaging findings.

Application of Imaging Techniques to Cases of Drug-Induced Crystal Nephropathy in Preclinical Studies.

A number of drugs can cause precipitates within renal tubules leading to crystal nephropathy. Crystal nephropathy is usually an exposure-related finding and is not uncommon in preclinical studies, where high doses are tested. An understanding of the nature of precipitates is important for human risk assessment and further development. Our aim was to investigate the ability of various imaging techniques to detect the presence of drugs or metabolites in renal crystals. We applied matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS) imaging, Raman and infrared microspectroscopy, scanning electron microscopy coupled with energy dispersive X-ray (SEM/EDX) spectroscopy and standard histopathology to cases of drug-induced crystal nephropathy, induced in rodents and primates by 4 compounds. MALDI-FTICR MS imaging enabled the identification of the drug-related crystal content in all 4 cases of nephropathy, without reference material and with high accuracy. Crystals were composed of unchanged parent drug and/or metabolites. Similar results were obtained using Raman and infrared microspectroscopy for 2 compounds. In the absence of reference standards of metabolites, Raman and infrared microspectroscopy showed that the crystals consisted of components similar, but not identical, to the administered drug for the other compounds, a limitation for these techniques. SEM/EDX showed which counter ions were colocalized with the identified drug-related material, complementing the MALDI-FTICR MS findings. Therefore, we recommend MALDI-FTICR MS as a first-line methodology to characterize crystal nephropathies. Raman and infrared microspectroscopy may be useful when MALDI-FTICR MS imaging cannot be applied. SEM/EDX could be considered as a complementary technology.

Radiological manifestations of immune-related adverse effects observed in patients with melanoma undergoing immunotherapy.

Immunotherapy drugs work by stimulating the patient's own immune system to recognize and destroy cancer cells. This subclass of drugs is increasingly administered to patients with advanced melanoma. They are also commonly incorporated into other cancer therapies such as non-small cell lung cancer, renal cancer, head and neck cancers and Hodgkin lymphoma. The most commonly administered immunotherapeutic agents in the treatment of melanoma include programmed cell death protein 1 (PD-1) inhibitors, cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors and a subclass of cytokines. During treatment with these antibodies, a unique set of adverse effects may occur which are often called immune-related adverse events (irAEs). It is vital for radiologists to be aware of and document these side effects during routine staging or body imaging during therapy. Some of these include pneumonitis, colitis, hypophysitis, lymphadenopathy or sarcoid-like syndrome and myositis. IrAEs such as sarcoid-like lymphadenopathy can mimic progression of disease. Serious side effects are seen in less than 10% of patients, and typically emerge between 6 and 12 weeks after commencing treatment. The clinical manifestations of these side effects typically vary from mild to severe and so do the radiological findings. Patients with mild side effects are often treated successfully with systemic corticosteroids, while severe cases require cessation of immunotherapy. We provide a pictorial article on the common irAEs and the associated radiological manifestations.

[Immunotherapy is cancer treatment with a novel side-effect profile].

Within the last few years we have treated still more types of cancer with immune checkpoint inhibitors - anti-cytotoxic T-lymphocyte-associated-4 antibodies and anti-program-med cell death 1/anti-programmed cell death ligand 1 antibodies. A unique set of side effects called immune related adverse events irAEs may occur during treatment. Although severe irAEs remain rare they can become life-threatening. Early detection of irAEs and initiation of relevant treatment are therefore crucial to reduce the risk of long-term seque-lae. We provide a detailed overview of irAEs and recommendations for treatment according to established guidelines.