Abdominal CT manifestations of adverse events to immunotherapy: a primer for radiologists
Authors: Ali Pourvaziri1 · Anushri Parakh1 · Pierpaolo Biondetti1 · Dushyant Sahani2 · Avinash Kambadakone1
Journal: Abdominal Radiology (2020) 45:2624–2636
Dr Rajiv B. Karia (Consultant GI/HPB and Interventional Radiologist. Chesterfield Royal Hospital & Nottingham University Hospitals, UK)
Cancer treatment with chemotherapy has been expanded from conventional chemotherapy agents which cause death of rapidly dividing cells to also involve new therapies which target specific molecules or pathways and also more recently immunotherapeutic agents which rely on the patient’s immune system to act on the neoplastic cells. As more and more immunotherapies have become approved over last few years these are becoming a mainstream option for variety of advanced malignancies [1]. The adverse effects of these therapies are unique and diverse. This paper reviewed the radiological findings of the adverse effects and concentrated on the gastrointestinal tract.
Immunotherapeutic agents are either passive or active. Passive immunotherapy target cancer cells with specific antibodies (prepared outside the body), and do not stimulate the immune system, but cause destruction of the cells by complement mediated response or elicit antibody dependent cellular cytotoxicity (ADCC). Active immunotherapy however, utilises the immune system (humoral and cellular immunity) to fight the tumour. Recombined interleukins (IL), cytokines, vaccines (e.g. for prostate cancer), and check point inhibitors (CPI) are all examples of these agents. In addition autologous T-cells can be genetically modified to express T-cell receptors (TCR) that recognise tumour antigen or chimeric antigen receptors (CARs).
Immune related adverse events (irAE) are wide spectrum of side effects that arise from immunotherapeutic agents. Check point inhibitors prevent immune system inhibition mechanisms, and hence favour development of autoimmune manifestations. Side effects of conventional cytotoxic agents are generally more predictable, and usually directed to specific organs. Adverse effects discussed in this paper were outlined generally and specific to type of agents used. It is suggested that irAE appear to be dose dependent with anti-CTLA-4 inhibitors but not with anti-PD/PD-1 inhibitors [2, 3].
The paper illustrates the various presentations of colitis with the use of immunotherapy. Colitis is the most common irAE that often necessitates discontinuation of therapy [4]. There is a mortality rate of approximately 1% and generally occurs 5 to 10 weeks after initiation therapy. Knowing this helps focuses reporting radiologist’s interpretation and direct the report to the most likely aetiology. The paper described the different types and distribution of colitis with good examples together with pointers on how to differentiate with other causes. Interestingly it was described by the authors that CAR T-cell therapy has been implicated in colonic perforations.
Within the hepatobiliary system, two general patterns have been described; hepatocellular and cholestatic [5, 6]. Immune related hepatitis occur between 6 and 14 weeks after initiation of therapy. Ultrasound demonstrates periportal oedema and gall bladder wall oedema. CT demonstrates hepatomegaly, diffuse parenchymal hypo-attenuation and patchy enhancement together with periportal lymphadenopathy. It was suggested by the authors that MRI maybe needed to differentiate parenchymal changes from metastatic disease. Following discontinuation of therapy and administration of steroids there is regression of the imaging findings [7-9]. The paper also illustrated these findings using dual energy CT.
Pancreatitis related to the immunotherapy can manifest similar to “classic” autoimmune pancreatitis with diffuse enlargement of the gland, stranding in the peripancreatic fat and heterogeneous enhancement pattern. Authors gave pointers to help differentiate this from autoimmune pancreatitis. Imaging illustrations in the paper demonstrate patients on nivolumab and ipilimumab, showing diffuse enlargement with loss of pancreatic lobulations, but with later images following treatment with steroids showing an atrophic pancreas.
The paper also illustrated renal injuries secondary to different immunotherapy together with illustrations of rheumatological and musculoskeletal adverse effects. Interestingly manifestation of sarcoid like reaction was described in great detail and there was focus on illustrations of how to help differentiate this from progressive disease. These changes have been reported with the use of CPI’s, and involve the abdomen, lungs, skin and lymph nodes. Biopsy may demonstrate non-caseating granulomas [10]. With these changes care must be taken not to over diagnose this benign finding as progressive disease.
This review paper has clearly outlined the mechanisms of action of these new agents in a systematic and illustrative format, helping the reader to understand the irAR and their radiological findings. The paper points out that the abdomen is a common site for both disease recurrence and manifestation of irAR.Imagining findings can only be interpreted based on appropriate clinical history and within a clinical context; this paper has shown the importance of this in the context of cancer therapies. It is hence imperative that clinicians who request imaging, communicate accurately which agents the patient is on.
Abdominal imaging review papers focusing on oncological methodologies, their actions, together with their imaging findings are not very common and hence this is a refresher for all GI radiologist; a worthy read.
References
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Dr Rajiv Karia is a radiologist from Chesterfield Royal Hospital (Chesterfield, UK), specialising in GI/HPB and interventional radiology. Graduated from University of Nottingham and completed radiology training in Nottingham, having previously worked in surgery. Active ESGAR member since 2012, regularly attending annual meetings and has also completed the ESGAR/ESOR Exchange Programme for Abdominal Radiology Fellowship. Rajiv has a keen interest in technology and advances in medical applications, and is an associate member of the institution of Engineering and Technology (IET).
Comments may be sent to rajiv.karia@doctors.org.uk