Iodinated Contrast Material Shortage: Perspectives from the Cancer Imaging Community

Introduction

CT with intravenous iodinated contrast material remains the primary imaging modality used for detection, treatment planning, and posttreatment surveillance of most cancers. As members of the cancer imaging community know, the world currently faces a global shortage of iodinated contrast material. The shortage arose from yet another consequence of COVID-19 on cancer research and clinical care. An outbreak of COVID-19 and resultant citywide lockdown in Shanghai, China, stopped production at a major facility used by GE Healthcare to produce iohexol for distribution throughout the world (1). GE Healthcare announced the interruption April 19, 2022, with rationing of iodinated contrast material products. Facing reduced supplies of iodinated contrast material through at least the end of June, many institutions had to rapidly implement measures to prioritize use of limited reserves of contrast material while trying to maintain the best clinical care possible. This threat to diagnostic imaging in cancer and interventional oncology follows multiple other disruptions to cancer imaging caused by COVID-19, including losses of data from prospective clinical trials and long-term consequences of persons not completing cancer screening studies.

To better understand the impact of the contrast material shortage on translational research and clinical care, we conducted a nonscientific survey of faculty members and trainees at institutions in the United States and Canada. Respondents provided answers to questions summarized below and could offer additional comments reflecting their local circumstances. Given the time-sensitive nature of the problem of contrast material shortage, I wanted to gather and convey information as quickly as possible. Achieving this goal comes with limitations our readers should note: Perspectives are solely from radiologists at large academic institutions in North America. I welcome follow-up comments and perspectives from persons in other countries, smaller practices, and private practices. I recognize the impact of the contrast material shortage extends beyond cancer to other areas, including cardiothoracic imaging, cardiology, and trauma. Some of the challenges in other areas of imaging, such as CT for pulmonary embolism, clearly encompass patients with cancer but will not be addressed specifically here. Disruptions to the global supply chain also have ramifications outside of health care, as evidenced by shortages in items ranging from microchips to baby formula. I hope this editorial informs our readers of current and potential future effects of the contrast material shortage on cancer imaging. More importantly, as disruptions to the global supply chain become increasingly common and painful, I encourage readers to learn from our past and current shortages. Learning from the past will better prepare us for challenges of the next shortage.

How Has Your Institution Been Affected by the Shortage of Contrast Media?

Like almost all effects of COVID-19, impact of the contrast material shortage varies widely among institutions in different geographic locations and even among institutions in the same city. Institutions using iodinated contrast material from other manufacturers have experienced little or no change in protocols for intravenous contrast-enhanced CT scans, frequencies of enhanced versus nonenhanced studies, and overall utilization of CT for clinical trials or patient care. One center reported that contrast agents in short supply affected only use of oral contrast material for CT scans. Centers not reliant on contrast material from GE Healthcare have asked emergency department providers to limit use of contrast-enhanced CT when possible, and radiologists have become more attentive to judiciously using noncontrast CT when possible. Among seven institutions in one city in Canada, only one has experienced any problems with backorders restricted solely to large bottles of iodinated contrast material. This institution continues to complete examinations with smaller bottles of contrast material available in the local inventory.

Centers predominantly or exclusively reliant on iodinated contrast material from GE Healthcare have faced greater challenges, although none of the respondents described the situation as dire. By necessity, physicians, staff, and administrators at these institutions have led changes in imaging practices for oncology and other areas of medicine and established messaging programs for health care providers and patients. For at least one institution, GE Healthcare notifies the site about the weekly expected (but not guaranteed) delivery time and amount of contrast material, approximately 20% of the preshortage order.

If There Have Been Effects, How Has Your Institution Changed Practices/Reallocated Use of Available Contrast Material?

The biggest changes in allocation of iodinated contrast material focus on CT, which comprises more than 90% of contrast material usage in most practices. Many institutions established command centers with representatives from many different specialties, including diagnostic imaging, emergency medicine, cardiology, and others. Command centers monitor iodinated contrast material inventories versus daily or weekly usage to ensure availability of contrast material for highest priority indications and patients (2). Some respondents noted that institutions have established defined tiers of imaging studies with rank order or priority for iodinated contrast material, like policies enacted for medical procedures, imaging, and clinical trials during early lockdown periods of COVID-19. Institutions commonly have reduced volumes of iodinated contrast material used for CT studies. Rather than administering up to 150 mL for an adult CT scan, practices have decreased amounts to 125 or even 100 mL with no noted loss of image quality. Institutional pharmacies have repackaged contrast material from large volumes in a single container to multiple containers to minimize waste. An institution that tracked and reported weekly contrast material usage documented a 44% reduction in contrast material administration relative to the preshortage benchmark. For CT studies affected by a shortage of iodinated oral contrast material, radiologists are encouraged to forego oral contrast or contrast negative contrast agents, such as sorbitol-mannitol-xanthan gum (Brezza; Beekley Medical).

Has There Been Any Impact on Availability/Frequency of Imaging Studies for Cancer?

Institutions have prioritized iodinated contrast material studies for imaging studies in oncology, particularly diagnosis, preoperative staging, and follow-up studies for suspected recurrence or disease progression. At facilities most affected by the shortage, there are ongoing efforts to use nonenhanced CT scans for persons expected to have stable disease. Respondents from such facilities noted other approaches to reduce use of contrast material, including reallocating contrast material from radiation oncology planning scans, deferring contrast-enhanced studies until July when possible, and performing PET/CT studies without contrast material. When possible, diagnostic radiologists are working with referring physicians to combine multiple contrast-enhanced studies into one CT examination. Efforts to shift studies from CT to MRI confront limited capacity in MRI schedules and availability of qualified technologists as described more fully in the next section.

Intravenous contrast-enhanced CT is a central component of many clinical trials in oncology. Determining eligibility to enroll in a specific clinical trial and quantifying response to therapy are aspects of clinical research most affected by the current shortage of iodinated contrast material. Recognizing challenges to the clinical research community, the United States National Cancer Institute (NCI) issued a memorandum on May 24, 2022, to investigators in the Cancer Therapy Evaluation Program (CTEP) and NCI Community Oncology Research Program (NCORP) (3). The memorandum contained several guiding principles for conducting ongoing clinical trials. Clinical trials define expected time points for follow-up imaging studies but typically allow local institutions to determine the appropriate imaging modality even if contrast-enhanced CT is preferred. For such trials, investigators should follow guidelines at their local institution for clinical management of patients with cancer outside of the clinical trial setting. For studies that do not explicitly require CT with intravenous iodinated contrast material, investigators may use other imaging modalities deemed as clinically appropriate at the local institution. These changes to the imaging protocol would not constitute a protocol deviation. For trials that explicitly require CT with intravenous iodinated contrast material, investigators still should follow local practice guidelines for prioritization of contrast-enhanced studies, although use of other imaging modalities and/or deferring imaging until after the end of the shortage would represent reportable protocol deviations, hopefully minor. Ongoing consultation and communication with the local institutional review board and NCI is encouraged. Fortunately, respondents indicated that institutions adapted policies to prioritize use of iodinated intravenous contrast material for ongoing clinical trials in oncology.

Have Studies Been Shifted Away from CT to Other Approaches?

Responses to this question highlighted differences in practice patterns and constraints on other imaging modalities. Relative to diagnostic radiologists in the United States, physicians in Canada more commonly rely on US than CT for many clinical questions, particularly for liver imaging. This practice pattern lessens the overall demand for contrast-enhanced CT and pressure on the supply of iodinated contrast material. For institutions in the United States, shifting patients to US or MRI faces challenges of staffing and availability independent of questions of appropriate use. Increasing utilization of US for oncology and other applications of contrast-enhanced CT requires more technologists, US instruments, and time slots for patients. Increasing any of these limited resources is challenging and cannot be accomplished in a time span of weeks. Similarly, many institutions already have a backlog of MRI studies and operate scanners on a nearly 24 hours a day, 7 days a week basis to try to meet existing demand. Ramping up MRI capacity does not represent a viable option to mitigate the shortage of iodinated contrast material for CT scans in oncology patients. Shortening US or MRI studies could open additional imaging appointments for patients, but revising existing protocols will require buy-in from both radiologists and providers.

Approval from insurance companies and third-party payers poses another challenge to shifting cancer imaging studies away from contrast-enhanced CT, particularly when the alternative is MRI. Obtaining precertification to replace contrast-enhanced CT with MRI frequently requires extensive time and administrative effort, delaying care for patients and increasing workloads on support staff at institutions.

How Has the Contrast Material Shortage Been Messaged?

Most messaging regarding the contrast material shortage has been directed at referring physicians rather than patients. Representatives from different key departments in command center teams help disseminate information to referring health care providers and establish a communal sense of equity. In some institutions, residents and fellows contact referring physicians to discuss the need for iodinated contrast-enhanced imaging studies and suggest possible alternatives. Referring physicians generally have been receptive to suggested alternative imaging studies without iodinated contrast material. However, one respondent noted instances in which providers responded with hostility and even aggression when asked about switching to a nonenhanced examination or other imaging modality. On the other end of the spectrum, some providers now repeatedly order noncontrast instead of contrast-enhanced studies, even when contrast-enhanced studies are warranted and approved by local practice guidelines. Radiologists have reached out to these providers to order contrast-enhanced CT studies for these patients.

Since institutions generally have prioritized contrast-enhanced CT examinations for patients with suspected or known cancer, respondents did not note concerns from patients or patient advocacy groups in cancer. Some institutions opened more direct communication channels with patients, such as informational websites and live messaging on digital display boards in patient-waiting areas.

Do You Think the Short-Term Response Changes Will Extend Beyond the Immediate Shortage, or Will Use of Contrast Material and Imaging Modalities Return to Business as Usual?

Regarding indications for contrast-enhanced CT and utilization of CT versus other modalities, respondents generally projected a return to business as usual when the shortage ends. However, some adaptations and lessons from the acute shortage likely will endure. While not formalized through controlled studies, experience at multiple sites suggest that decreasing the volume of intravenous contrast material for a CT examination does not affect image quality or diagnostic accuracy. Bundling contrast-enhanced studies of multiple anatomic regions into one examination reduces overall use of intravenous contrast material and improves patient throughput for CT scanners. The need to consider indications for contrast-enhanced CT in oncology more carefully and shift some studies to nonenhanced scans or other imaging modalities may decrease the small, but real, risks of intravenous iodinated contrast material.

From a broader perspective, the COVID-19 pandemic repeatedly has confronted health care facilities and providers with unexpected shortages and disruptions in supply chains. Maintaining limited inventories of critical materials, such as personal protective equipment or iodinated contrast material, places institutions at risk for rationing or even worse, running out, when production and/or shipping slows down or stops. Clearly, maintaining larger inventories ties up more resources and requires more storage space, which may be more feasible for large networks of health care institutions than smaller facilities with less purchasing power. When possible, institutions will benefit from redundancy in suppliers for contrast agents and other critical resources. Improved cooperation among facilities also may help alleviate effects of scarce resources. Finally, institutions at the start of COVID-19 generally established command centers with representatives from key stakeholders to prioritize allocation of resources and tiers of patient priorities for studies. This framework helped many institutions respond rapidly and effectively to the current contrast material shortage. Maintaining the administrative infrastructure for command centers and the ability to quickly identify oncoming challenges is critical to overcome threats of seemingly inevitable future shortages.