14 minute read
DI Europe Summer 23
Alan Barclay
CEM: the Experience of a Large, Progressive Spanish Hospital Group
The recent approval by the EU and the US of the iodine-based contrast enhanced mammography (CEM) highlights the steady progression of this relatively new breast imaging modality. We thought that this would be a good occasion to take stock of the current status, future potential and likely role of CEM in breast imaging, so we talked to Dr. Julia Camps Herrero, breast radiologist, Corporate Head of Breast Health and responsible for the co-ordination of five breast units in the Ribera Salud group of hospitals in Spain.
◾ Before we get into the details of your experience with CEM, could you please give us a brief overview of the breast imaging services provided by your hospital?
First of all let me explain the structure of the Ribera Salud group in Spain as a whole. Our group, which is devoted to the development of public-private partnership initiatives in the healthcare field, has hospitals in the Valencian community (Hospital del Vinalopó, Hospital de Denia), in the Madrid area (Hospital de Torrejón), and in the Galician community (Hospital Povisa and Hospital Polusa). All these hospitals carry out breast imaging, with three of them (Hospital del Vinalpo, Hospital Torrejon and Hospital Povisa) also equipped with CEM systems.
Against that background, let’s now go more into breast imaging, starting with screening. In Spain, the recommended regimens for population-based breast screening vary by geographical area. In some areas, the recommendation is for screening mammography every two years in women aged 45 to 69, whereas in other areas it is every two years in women aged 50 to 69 years of age. The overall average percentage take-up in the Spanish breast screening programs is approximately 75 percent of all eligible women, but this varies from region to region.
We are the referral clinics for the population-based screening programs in the areas where we have hospitals, so the cases we see are all diagnostic.
To give you an idea of the number of breast imaging procedures we carry out annually, the three medium-sized hospitals which also have CEM carry out a total of almost 9,000 breast exams per year. The majority of these are mammography or tomosynthesis. In addition to this, two of the hospitals also routinely carry out 2,000 CEM examinations per annum, with the third hospital now implementing CEM since February 2023.
Of course it’s not just mammography / tomosynthesis and CEM. We also have a complete armory of other breast imaging modalities from a variety of vendors.
For example:
• Hospital del Vinalopó in Elche, in the Valencian community: Philips Ultrasound machines, Hologic tomosynthesis and CEM, and Philips 1.5T Elition MRI equipped with coil for MR-guided biopsies.
• Hospital de Denia also in the Valencian community: Siemens Ultrasound machines, GE Pristina tomosynthesis, and Siemens 1.5T MRI.
• Hospital de Torrejón in Madrid: Philips and Samsung Ultrasound machines, Hologic tomosynthesis and CEM, and Philips 1.5T Achieva Intera equipped with coil for MR-guided biopsies.
• Hospital de Povisa in Vigo, Galicia: Philips Ultrasound machines, GE Pristina tomosynthesis with contrast-enhanced biopsy, and Philips 1.5T Achieva Intera equipped with coil for MR-guided biopsies.
• Hospital de Polusa in Lugo, Galicia: Canon Ultrasound machines, GE Pristina tomosynthesis, and Siemens 1.5T MRI.
You can see that throughout the group we have a wide selection of equipment from most of the major vendors, so we are well placed to evaluate the relative pros and cons of each manufacturer’s products.
The majority of breast imaging is carried out by mammography / tomoynthesis. CEM has been shown to be more sensitive than mammography or ultrasound for the detection of malignancy, with its sensitivity reported to be approximately the same as that of MRI, which is generally considered as the most sensitive modality for breast imaging.
◾ OK, given that, let’s dwell a bit on breast MRI. Later in our conversation, we will no doubt get on to the subject of comparing the performance characteristics of breast MRI with those of CEM. But for the moment can you describe the principal indications for breast MRI ? There are many such indications:
• In all our centers, we use breast MRI for pre-operative staging. In cases of any contraindications for MRI, we perform CEM in all those centers which are equipped with CEM systems.
• In the evaluation of response to neoadjuvant treatment
• For high-risk patients (those with an estimated breast cancer risk of 20 to 25 percent)
• For patients with high-risk B3 lesions before and after vacuum-assisted biopsy, as well as for the follow-up of those with a higher cancer risk (lobular neoplasia and atypical ductal hyperplasia)
• For patients with equivocal findings in conventional imaging such as mammography
• For patients with a breast cancer of unknown primary origin (CUP)
• Selected patients with a history of breast cancer at higher risk of relapse (triple negative or HER2+ breast cancer patients).
One other occasional use we make of MRI is in the estimation of breast density, although we usually determine breast density by visual examinations of mammography images.
◾ To start with, since when have you been using CEM? In what clinical situations do you use the modality and what is your opinion of its value in these situations?
Our experience with CEM is already quite extensive and increasing steadily. Precise details of experience vary from hospital to hospital:
• In the Hospital del Vinalopó (Valencia) we have been using Hologic tomosynthesis and CEM system since February 2020. Since then we have carried out more than 3,100 CEM examinations, the majority for monitoring cancer patients.
• In the Hospital de Torrejón (Madrid) our experience dates a little further back: we have been using Hologic tomosynthesis and CEM since September 2019. From then till January 2023 we have performed 2,600 CEM procedures, again mostly for the monitoring of breast cancer patients
• In the Povisa hospital in Galicia we have a Pristina tomosynthesis system from GE which also has the possibility of taking contrast-enhanced biopsies.
◾ So how does the performance of CEM compare to that of MRI?
As mentioned above, it should be remembered that CEM has been shown to be more sensitive than mammography or ultrasound for the detection of malignancy, so the most meaningful comparison of CEM with other modalities is indeed with MRI.
In most of the published metaanalyses of comparative performance parameters, CEM has been shown to have sensitivities and specificities that are broadly similar to those of MRI.
However, I find that in general MRI performs better than CEM in terms of detection and characterization of lesions because through ultrafast and dynamic sequences it yields superior kinetic information, as well as providing diffusion data, which is helpful for lesion characterization and thus for differentiation between malignant and benign lesions. In addition, MRI can yield multiplanar and 3D reconstructions and also provides more extensive anatomical coverage such as of the axillary tail, posterior regions of the breast, and internal mammary lymph nodes, all of which can be difficult, if not impossible, to image in CEM. Signal-to-noise ratio is also better in MRI and the pooled diagnostic odds ratio indicates a higher overall diagnostic performance of MRI compared to CEM.
However, in non-mass lesions adjacent to breast cancers, CEM seems to perform better (higher specificity) than MRI although we have not analyzed this finding in-depth. In the future this might enable us to reduce biopsies. In patients with up-front BI-RADS four lesions, CEM also gives us the possibility of avoiding unnecessary biopsies, especially in architectural distortions and asymmetric densities, as well as pseudonodules. CEM is especially helpful in patients referred from the populational screening setting, avoiding follow-up exams and unnecesary biopsies.
The above comments are made on the basis of the comparison of performance characteristics, but clearly there are other factors such as length of time of the exam, accessibility to the imaging system and its cost, which also must be considered. Those mentioned all favor CEM. For us, it is always easier to schedule a CEM examination than an MRI (on average, we perform 16 CEM procedures per week in each of the two hospitals where the technique has been established for some time now). In our clinics, the waiting times for CEM examinations are virtually non-existent.
The time needed for the whole CEM procedure, including the intravenous access, to be carried out is around 15 minutes, so shorter than that needed for MRI. Currently we don’t have a programmable contrast medium injector. Such an accessory could render the whole procedure more efficient and could be helpful in calculating the exact contrast dose for each patient.
However, despite the advantages of CEM, the cornerstone technique for breast cancer staging remains MRI. It’s not a question of either CEM or MRI — the techniques complement each other and are synergistic.
◾ What are the clinical applications where CEM is most useful?
• Clearly it is of use in breast cancer patients for whom MRI would normally be used but is, for one reason or another, contraindicated. In addition, CEM also has the advantage that it can depict additional lesions and helps us to stage the patient. This use of CEM also applies to patients who are undergoing neoadjuvant treament but cannot have MRI.
• We also find CEM to be helpful in ruling out malignancies in patients with equivocal lesions, for example in distortions or asymmetries. It should be noted however that CEM is less helpful in microcalcifications.
• In addition, the comparatively easy access to and availability of CEM systems compared to MRI as mentioned above opens up the promise of a “blanket” use of the modality in all patients with a history of breast cancer. To examine the feasibility of such an approach, we are currently analyzing our data using a cohort of 2,000 patients, 70 percent of whom have had more than two CEM exams.1
◾ What about biopsies?
In case of an extensive non-mass lesion identified only by CEM, we perform an additional ultrasound examination. Most of the time, there is a good correlation between the ultrasound and CEM findings. In the rare case of a nodule or a small lesion not seen in ultrasound, we will perform an MR-guided vacuum-assisted biopsy (VAB). We ensure radio-pathologic correlation with a 2D mammography post-biopsy. In our Povisa hospital, we now have a CEM-guided biopsy system which we are currently setting up and evaluating. Of course a CEM-guided biopsy system seems logical for lesions identified by CEM.
We usually try to carry out a CEM examination upfront for all BI-RADS 4C or BI-RADS 5 lesions so that we can biopsy on the same day not only the suspicious lesion but any additional suspicious lesions. Thereafter, we always try to perform MRI in order to confirm that all the significant lesions have been biopsied and tagged with clips.
◾ How do the patients react to CEM? And what about the technologists and radiologists?
In general, patients react very well to CEM, mainly because the exam only takes a little bit longer than standard 2D mammography and tomosynthesis, techniques with which they are usually already familiar. Occasionally patients complain of the metallic taste left after the contrast injection, but this is transient. The procedure is well tolerated — the percentage of allergic reactions we have observed is well under one percent and we have had no severe allergic reaction or death in a total of more than 6,000 exams.
Inevitably, there was a learning curve when CEM was first implemented, but for the technicians this didn’t last any more than two or three months. The learning curve for the breast radiologists was perhaps slightly longer, mainly because of the diversity and varied nature of CEM findings — it can take some time to get used to background parenchymal enhancement, the various artifacts, as well as the heterogeneous grades of enhancement in mass and non-mass lesions, etc. Previous experience with breast MRI makes the learning curve easier for the breast radiologists.
◾ And now, looking ahead, how do you see the future role of CEM in general and in your hospitals in particular?
As I hope you have seen from our conversation so far, the role of CEM in our hospitals is very well established and already plays an important role in the indications we have talked about.
As for the future, in addition to its current roles, I can imagine CEM being increasingly used in the following clinical scenarios:
• In patients at a high risk of breast cancer. The risk is usually identified using risk-assessment protocols. By the way, the role of artificial intelligence (AI) in such risk-assessment protocols is likely to become more important in the future — AI has already been shown to improve the accuracy of risk assessment compared to classical risk-assessment methods.
Women with a family history of breast cancer should have a risk assessment carried out — currently this is not done routinely.
• Women with dense breasts. Although studies have shown that breast MRI can be of undoubted benefit in patients with very dense breasts, the reality is that there are simply not enough MRI systems
available to follow-up all such patients. However we might be able – perhaps using advanced AI analysis – to stratify which dense breast patients should undergo MRI and who can benefit from CEM. Such assessment need not necessarily be carried out every 12 months as the DENSE trial showed (every two to four years is cost-effective in patients with very dense breasts) 2 .
In the context of relatively difficult accessibility to MRI, the increased use of abbreviated MRI might help –it would be very interesting to analyze the performance of abbreviated MRI in women with dense breasts and compare it to that of CEM.
• Speaking of AI-derived algorithms, these are currently not generally available for image interpretation in CEM. In the future, however, AI could enable us to avoid unnecessary biopsies and follow-up exams, as well as perhaps build prediction models of the likely response to therapeutic regimens used to treat specific breast cancers. Likewise AI-derived protocols could also be used to evaluate early response to neoadjuvant treatments (hormone therapy as well as chemotherapy) in order to de-escalate any unnecessary further chemotherapy.
In addition to helping us widen the spectrum of patients in whom we can perform high-quality functional imaging, CEM may also be able to avoid unnecessary radiation therapy in patients with unifocal and early breast cancers, as has been shown with MRI in the PROSPECT trial3. Other MR-guided de-escalation trials such as the MiniVAB (NCT04107636) have shown that we may be able to de-escalate unnecesary surgery in patients with unifocal breast cancer. CEM could conceivably play a role here. In summary, all breast cancer treatment procedures could/should be guided by CEM.
REFERENCES
1 Contrast Enhanced Mammography. 2022. A supplement to ACR BI-RADS® Mammography 2013 2022. https://www.mdpi.com/2075-4418/13/6/1011
2 Veenhuizen SGA et al. Supplemental Breast MRI for Women with Extremely Dense Breasts: Results of the Second Screening Round of the DENSE Trial. Radiology. 2021; 299(2): 278. http://dx.doi.org/10.1148/radiol.2021203633
3 Mann et al. Results of ANZ 1002 : Post-operative Radiotherapy Omission in Selected Patients with Early breast Cancer Trial (PROSPECT) following pre-operative breast MRI http://dx.doi.org/10.1016/S0959-8049(22)01476-9
