Mina S. Makary, MD

Virtual biopsy may provide a robust, non-invasive alternative in the surveillance and management of several types of cancer. This new imaging-based technique can extract encoded data from routine medical imaging scans and formulate likelihoods to help characterize tissue for the purposes of screening for cancer, diagnosing and grading cancer, planning oncologic treatment, and predicting prognosis of disease--all without any surgical or invasive intervention.

Although its use has been primarily studied in the oncologic setting, it can potentially be used for any disease process that requires analysis of its pathogenesis. Here, we discuss the technique of virtual biopsy, the variety of ways physicians can utilize it, and its impact on the outcomes of patients and healthcare.

Virtual biopsy is a non-invasive technique to characterize tissue found in imaging studies. A great wealth of information can be interpreted by radiologists on imaging scans. However, additional encrypted data regarding the tissue’s intrinsic features, gene expression patterns, gene mutations, and molecular pathophysiology are still invisible to the human eye.

Access to this additional information can be granted through the use of radiomics. Radiomics is the applied field of radiogenomics which focuses on extracting objective, quantitative data found in images

. Generally, the workflow includes obtaining the image, processing the image, creating a volume of interest, and then extracting mathematical data in that volume

. This can be possible through several imaging modalities, such as CT, MRI, PET, radiographs, and ultrasound imaging

. Examples of data collected include volume, shape, density, and location in addition to complex mathematical metrics assessing textures and dimensional analysis

Through radiogenomics, these phenotypic data can then be correlated with previous genetic data and can reveal and provide insight to the molecular pathophysiology of disease by mapping out the gene expression of the tissue with the assistance of artificial intelligence and characterization algorithms

Virtual biopsy offers an alternative to traditional surgical biopsies which are used to obtain histological data for the same purpose of diagnosis and treatment planning. Compared to traditional biopsy, the benefits are numerous. With virtual biopsy being a non-invasive procedure, there is a lesser risk of complications to the patient

. Additionally, there is a lower cost associated with the service compared to traditional biopsies due to eliminating the operating room

. Further, the patient would benefit from a quicker report on their tumor pathology, affecting their treatment timetable

. Lastly, virtual biopsies can assist in making surgical biopsies even more conclusive, as discussed next.

One area where virtual biopsy can enhance clinical outcomes is in accurate, early cancer detection. When patients undergo low-specificity screening, it generates increased risk for patients in the form of unnecessary further imaging studies and invasive biopsies of suspected lesions which could be benign. This further workup creates increased radiation and surgical risk exposure, in addition to the increased costs of these services

One example of this narrative is in the setting of lung nodules identified on low-dose CT screening. In a study conducted by Ma. et al., researchers obtained 127 indeterminate pulmonary nodules that posed the question of malignancy

. They were able to identify 583 texture-based features, such as nodule intensity and tumor heterogeneity. After formulating a model, the researchers were able to predict malignancy of the nodules correctly 82.7 percent of the time

Even more remarkable, in another study conducted by Yang et al., virtual biopsy was able to correctly identify malignancies in the setting of complex ground-glass opacities, as well. Their work found that the volume and diameter of ground glass opacity tumors showed correlation with the EGFR status of the tumors, also shedding light on the potential treatment options for the patient

Another area where virtual biopsy can improve cancer screening is in the setting of pancreatic neoplasms. Although there is no routine screening for pancreatic cancer, certain patient populations that are high-risk may undergo routine ultrasound or MR imaging screening

. High-risk patients typically have a family history, symptomatic pancreatitis, new-onset diabetes, or asymptomatic mucinous cystic lesions found incidentally

. These patients can be subject to risky surgical intervention if their pancreatic lesion seems suspicious based on qualitative features on imaging.

However, in one study conducted by Permuth et al., researchers were able to identify 14 radiomic features (11 textural and three non-textural) that differentiated malignant pancreatic neoplasms from benign intraductal papillary mucinous neoplasms. The prediction model that incorporated the 14 radiomic features collectively proved to be fairly accurate in their diagnosis (AUC=0.77 and P<0.05). In fact, the study also reported that three of the cases that had worrisome features on pre-operative scanning were correctly identified as true negatives by radiomic analysis, displaying higher accuracy than conventional feature analysis

. This, in turn, could save patients from particularly invasive biopsies in the future if further studies can reproduce and validate the models used in this study.

Use of Virtual Biopsy in Diagnosing Tumors

There are several applications where virtual biopsies can help diagnose malignant processes in the body. One example of this is in the setting of head and neck squamous cell carcinoma. In a study conducted by Ren et al., using MR imaging, researchers were able to formulate a predictive model that stratified whether the head and neck cancer was high-grade or low-grade in pathology.

Using a total of 970 radiomic features extracted from T2-weighted and contrast enhanced T1-weighted MR images, the study was able to discriminate WHO class grade I-II tumors from grades III-IV head and neck squamous carcinoma within the images

. The final testing cohort yielded an AUC of 0.853 and 0.849 for high grade and low grade respectively, proving it to be fairly accurate

Similarly, MR imaging can also be used for grading neurological tumors. Another study conducted by Bai et al., utilized radiomic data, such as the water molecular diffusion heterogeneity index (WMDHI) and the mean kurtosis values for predicting the grade of gliomas. The study concluded that both of these metrics were higher in high-grade gliomas when compared to low-grade gliomas (P<.05). With the same metrics, the researchers determined specific cut-off values for differentiating high-grade gliomas from low-grade gliomas. After cross-referencing with subsequent surgical biopsies, the sensitivity of 

 the metrics was 92.9 percent, with specificity being 100 percent, demonstrating itself as a precise model

Another paradigm where virtual biopsy can aid in the diagnosis of malignancy is in the setting of invasive ductal carcinoma. In a study conducted by Guo et al., researchers were able to identify 25 computerized texture analysis features (such as neighborhood gray-tone difference matrix-based features and their wavelet decomposition) when describing echogenicity patterns of breast lesions.

The texture analysis of these features yielded a “busyness” score, where the average value for estrogen receptor positive (ER+), progesterone receptor positive (PR+) and human epidermal growth factor receptor 2 (HER2-) tumors was 1.402 and in ER- PR- and HER2- tumors was 1.912 (P<0.001). This study shows there is potential for a reliable model to accurately identify the molecular subtype of breast cancer, not only aiding in diagnosis but also influencing treatment options

Use of Virtual Biopsy in Treatment Planning

Virtual biopsy can not only aid in diagnosis of tumors, but it can also use radiogenomic data to go a step further to help plan the treatments, as well. For example, one study examined its application in treatment planning for patients with glioblastoma. Previous research established that the isocitrate dehydrogenase mutation in glioblastoma is associated with a slower progression rate.

Patients affected with glioblastoma tumors that carry this mutation have completely different treatment options in terms of urgency of surgical intervention and adjuvant therapy. In a study conducted by Arnout et al., through MR imaging and radiogenomics, his team was able to correctly identify IDH status in three different cohorts at an 87 percent-to-89 percent accuracy when confirmed by subsequent brain biopsies

Virtual biopsies can further provide insight on how to perform accurate surgical biopsies for treatment planning. Tumors that are “high grade” tend to exhibit the highest amount of tumor heterogeneity, which alludes to the differential genetic expression across the same tumor mass. This becomes important clinically because the sample obtained during biopsy may or may not paint the whole picture regarding the genetic makeup of the tumor--ultimately impacting how effective the treatment of choice will be.

However, with virtual biopsy, three-dimensional images of the patient’s tumor can be obtained via CT scanning. Using radiomics combined with radiogenomic data, this will allow the physician to map out the areas with the most genetic heterogeneity of the tumor, revealing the most ideal location to biopsy the mass and allowing for a conclusive and accurate biopsy

Virtual biopsy further proves to deliver comprehensive cancer care for patients by providing data on the prognosis for patients, as studied in several of the following tumor settings. One context where virtual biopsies provide prognostic data is bladder cancer. A study conducted by Lin et al., looked to find a predictive model for the prognosis of transitional cell carcinoma of the bladder. The study was able to identify seven radiomic features (wavelets and gradient orientations), which were then used to build a radiomics predictive model. Using the model, the researchers were able to stratify the patients into high-risk or low-risk groups in regard to progression-free tumor survival

Further work conducted by Iwatate et al., looked at the prevalence of p53 gene mutations in the setting of pancreatic ductal adenocarcinoma. The study iterated that the expression of the p53 gene mutation in the pancreatic malignancy was a significant factor for a poorer prognosis. With this, the researchers set out to develop a model that was able to predict if the pancreatic lesion exhibited the p53 mutation based on quantitative imaging features and radiogenomics

Lastly, a study conducted by Tokuda et al., sought to find a predictive model for the prognosis of breast cancer patients regarding recurrence of their disease. This study utilized a previously validated risk-stratifying tool to characterize the breast tumors as high-risk or low-risk for tumor recurrence based on their genetic mutations. Then, using MR imaging and radiomics, researchers concluded that factors, such as medium kinetic volume ratio and delayed phase kurtosis were associated with higher tumor recurrence. This allowed for the stratification of patients into high and low risk of reoccurrence groups

Virtual biopsy has shown to be effective in a variety of manners, including increasing the accuracy of cancer screening, helping diagnose and grade various tumors, and providing input in the treatment and prognosis of patients afflicted by oncologic disease. By virtue of being a non-invasive technique, elimination of unnecessary surgical risk and associated complications will contribute to decreased morbidity and mortality. Additionally, through its increased precision in cancer screening, patients will benefit from earlier diagnosis, directly improving their prognosis in some cases.

Further, patients will also receive tailored treatments consistent with their cancer’s mutational status and prognosis. Lastly, the healthcare system can expect to see a decreased need for invasive procedures, such as costly surgical biopsies, in turn reducing the economic burden cancer creates.

However, being a newer technology, there are some limitations, as well. Due to large amounts of data, there are increased computing power and storage requirements that not all institutions have the capacity to accommodate

. Next, the statistical approaches involved to analyze the data need to be fine-tuned: validating these models across several imaging platforms and patient populations with varying genetic makeups is a barrier

. Lastly, the lack of standardization of acquisition parameters used to derive predictive models and inconsistent radiomic methods further hinder the reproducibility of virtual biopsy

This being said, the potential is vast for virtual biopsies, radiomics, and radiogenomics. Medicine is moving in the direction of non-invasive procedures and virtual biopsy fits the trend. Patients can benefit from procedures that can be performed in the outpatient setting, while still benefiting from robust data about their disease that will help their physician treat them with arguably similar accuracy compared to their surgical counterparts.

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 Radiomics in radiation oncology—basics, methods, and limitations. 

Articles

The potential opportunities are numerous for virtual biopsies, radiomics, and radiogenomics.

Virtual Biopsy: A Safer Future for Cancer Management 

Due to advancements in catheter-based therapies in interventional radiology, conditions that once required large open surgeries, months of recovery, and had many associated complications, are now being treated with minimally invasive procedures by radiologists. One such intervention is uterine fibroid embolization (UFE). Although UFE has been performed for almost 25 years, the procedure continues to evolve.

Uterine fibroids are the most common benign tumor of reproductive age women, and they can cause debilitating symptoms. In many instances, conservative medical management fails or is associated with an unfavorable side effect profile. In these cases, the gold standard has been either myomectomy or hysterectomy. However, both are major invasive surgeries, associated with significant costs, long hospitalizations/recovery, and significant morbidity. Given recent concerns regarding long-term effects on cardiovascular and hormonal health, uterine sparing therapies have grown in popularity.

UFE has emerged as a minimally invasive alternative after first being performed in the mid 1990s. The techniques have been borrowed from transcatheter embolization of the uterine arteries in pelvic trauma/bleeding. In this instance, the temporary occlusion of the uterine arteries supplying the uterus results in infarction of uterine fibroids. UFE has been shown to have numerous benefits, including shorter hospital stays, earlier return to normal activities, and the ability to use conscious sedation rather than general anesthesia

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Despite the fact that UFE has been shown to be a safe and effective treatment, the procedure remains under-utilized. A reported 65 times more hysterectomies are performed per year in the United States compared to UFE interventions

. This is partly due to patient awareness. A recent Society of Interventional Radiology report shows that only 62 percent of women have even heard of UFE treatment. Of the women who have heard of UFE, approximately three-fourths of those patients had not heard about it from their gynecologist

. Interventional radiologists need to play a larger role in the multidisciplinary team when discussing treatment options for symptomatic fibroids. There also needs to be a greater emphasis on patient awareness and marketing moving for UFE forward.

Treatment options for patients who wish to preserve their uterus and future fertility include myomectomy and UFE. In 2020, the FEMME trial (A Randomized Trial of Treating Fibroids with Either Embolization or Myomectomy to Measure the Effect on Quality of Life Among Women Wishing to Avoid Hysterectomy) was published in the 

 directly comparing the two therapies. This study served as the first robust multicenter, randomized label trial evaluating the topic

. The study demonstrated a four-point difference in the quality-of-life questionnaire score in favor of myomectomy at two years (84.6 vs 80.0), which was statistically significant but likely not a clinically meaningful difference. Furthermore, UFE patients had shorter hospital stay, quicker return to work, fewer bleeding adverse events, and similar pregnancy rates to myomectomy patients. Lastly, they also both had similar results in regard to willingness of women to have their particular procedure again

One of the main barriers to widespread adoption of UFE is post-procedural pain. Initial post-embolization pain can last up to 24 hours and can be severe in nature. Most commonly, it is managed with controlled analgesia or epidural anesthesia, requiring hospital admission. Secondary pain can last days after the initial procedure, and is commonly managed with narcotics. Recently, Superior Hypogastric Nerve Block (SHNB) interventions have been performed in conjunction with UFE and have been shown to be effective post-procedural pain suppressants. This enhanced procedure reduces overall pain scores, need for opioids, and allows for same day discharge

. The widespread use of SHNB may alleviate patient fears regarding the procedure and allow for further adoption of UFE as a first line therapy for symptomatic fibroids.

In summary, UFE has proven to be a safe and highly effective treatment for symptomatic uterine fibroids. Recent studies have proven that it compares favorably with myomectomy. Post-embolization pain has been a barrier to widespread adoption. However, the recent use of combined pain interventions, such as Superior Hypogastric Nerve Blocks in conjunction with UFE, have been shown as highly effective in reducing pain, ultimately allowing for same day outpatient procedures. These advancements, along with continued public exposure, and patient education, point towards the widespread adoption of UFE as a first line therapy for symptomatic uterine fibroids.

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6. Caridi TM, Spies JB, Kohi MP. Myomectomy versus Uterine Artery Embolization: More Alike than Different. 

. 2020;31(11):1838-1839. doi:10.1016/j.jvir.2020.08.023

7. Yoon J, Valenti D, Muchantef K, et al. Superior Hypogastric Nerve Block as Post-Uterine Artery Embolization Analgesia: A Randomized and Double-Blind Clinical Trial. 

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The need for a growing role for interventional radiologists.

Uterine Fibroid Embolization: Past, Present, and Future

Lung cancer remains the leading cause of cancer death in the United States, with more than half of all cases (57 percent) being diagnosed at a late stage with an average five-year survival rate of 22.6 percent

 However, there are signs of progress, with the rate of new cases going down 9 percent nationally and an increase in the five-year survival rate by 13.1 percent over the past five years

. This is likely due to reduced smoking rates, increased radon testing, more stringent air pollution regulations, and improvements in treatment

. However, the implementation of lung cancer screening to detect the deadly disease at an earlier stage has undoubtedly played a role in these gains, as well.

In 2011, the National Lung Screening Trial reported a 20-percent relative reduction in lung cancer amongst adults who smoked heavily and received low-dose CT (LDCT) annual screening compared to those who received annual chest radiographs

. Based on this evidence, the United States Preventive Services Task Force recommended annual lung cancer screening (LCS) with LDCT for high-risk adults (defined as 55-to-80-year-old persons who have a 30-plus pack year smoking history and quit less than 15 years ago).

Insurance companies and Medicare/Medicaid began to cover LCS in 2014-2015. Despite these guidelines and financial reimbursement, patient and physician uptake to the guideline has been slow. Less than 4 percent of eligible adults received screenings in 2015, and that figure had a marginal increase to 5.7 percent in 2020

. However even with the lagging adoption, early diagnosis rates have increased 33 percent over the past five years

. Of all cases, 23 percent are caught at an early stage, which has a much higher five-year survival rate at 59 percent

Why have the rates for LCS with LDCT remained low? There are many potential factors at play, such as healthcare providers not collecting a sufficiently detailed smoking history to identify eligible patients, smokers being a demographic with a predisposition to have less contact with primary care providers (PCP), PCPs not recommending screening due to lack of time and other priorities, lack of insurance incentivization, high rate of false positives on LDCT, perhaps even the perception that smoking is a lifestyle choice and that resources should not be spent on this population.

Cancer Screening Challenges in the Face of COVID-19

As for the argument of the unacceptable number of false positives, there is, indeed, a 20-percent rate of over-diagnosis of lung cancer, which is consistent with the rate of over-diagnosis in breast cancer

. However, it also prevents one death for every 250 screens, which far exceeds the number needed to treat (NNT) of 2,000 for screening mammography

. According to one meta-analysis of annual LCS with LDCT, all-cause mortality was not reduced in a significant manner, which is reassuring that the increased amount of screening and over-diagnosis of lung cancer did not increase other causes of mortality

What can we do to increase adherence to this useful screening tool? Many possible obstacles can be targeted, such as using clinical navigators to assist patients in following up appropriately, implementing algorithms to better identify eligible patients by using existing electronic health care data. There are two reports that attempted to increase it in two different manners, one more clinically, one involving more of the community.

In the first scenario, within the Kaiser Northern California system, they implemented a reporting system in 2015 that standardized radiology reports of pulmonary findings with tags. Tags that were indicative of lung cancer were automatically forwarded to a coordinator who sent a list of cases to a triage physician. The physician, then, either sent the case to a multidisciplinary committee or the patient's primary care physician (PCP) with management recommendations.

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The committee was composed of a care coordinator, pulmonologist, thoracic surgeon, and often a radiologist and oncologist, and the group met weekly to discuss cases. They would, then, either manage the case or send recommendations to the PCP. From the data that was collected pre- and post-implementation from nearly 100,000 patients, they found that lung cancer was detected at the early stage 26 percent of the time pre-intervention, and 30 percent of the time post-intervention. 

The intervention was associated with a 24-percent increase in odds of early-stage lung cancer diagnosis within 120 days, with a quicker time to surgical intervention (46 days vs 41 days) without biopsies. It appears that standardization of the radiologic reporting coupled with the multi-disciplinary committee increased the rate of detection of early-stage cancer which ultimately leads to improved long-term outcomes

The other instance is the state Kentucky which has one of the highest LCS rates in the country. Kentucky has expanded the Medicaid program, which removes the need for preauthorization for LCS. The government supports the cause with the governor publicly committing to reduce lung cancer mortality. In 2013, the Kentucky Lung Cancer Education Awareness Detection Survivorship Collaborative was created and implemented two LCS projects.

The first one educated hundreds of PCPs on lung cancer prevention, early detection, treatment, and survivorship. The second project gave feedback to LCS programs on how to best deliver screening and engage healthcare providers. Due to this combined effort from the community with government support, Kentucky has the third highest screening rate in the nation, leading to more lung cancer survivors. They have provided a framework for other states with high lung cancer burdens to follow

As evidence continues to grow that LDCT is an effective tool at increasing lung cancer survivorship – and awareness increases amongst the public – LCS rates will likely increase in the following years. However, there is still much work to be done to achieve the rates that would benefit the most vulnerable populations. 

As demonstrated by these two cases, there are issues that can be improved at every level of the system – educating patients about the benefits of annual LDCT, promoting the value of LCS to PCPs, standardization of lung cancer findings and templates within an electronic medical record, improved coordination of care, and further research into how to refine screening populations and screening modalities. With widespread adoption by healthcare providers, this intervention will surely improve both the longevity and quality-of-life for increased numbers of at-risk individuals who receive the diagnosis of lung cancer.

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State of Lung Cancer 2020 Report (Rep.). (2020, November 17). Retrieved https://www.lung.org/getmedia/381ca407-a4e9-4069-b24b-195811f29a00/solc-2020-report-final.pdf

Stacey A Fedewa, PhD, Ella A Kazerooni, MD, MS, Jamie L Studts, PhD, Robert A Smith, PhD, Priti Bandi, PhD, Ann Goding Sauer, MSPH, Megan Cotter, MPH, Helmneh M Sineshaw, MD, MPH, Ahmedin Jemal, DVM, PhD, Gerard A Silvestri, MD, MS, State Variation in Low-Dose Computed Tomography Scanning for Lung Cancer Screening in the United States, JNCI: Journal of the National Cancer Institute, 2020;, djaa170, https://doi.org/10.1093/jnci/djaa170

Urbania, T. H., Dusendang, J. R., Herrinton, L. J., Alexeeff, S., Corley, D. A., Ely, S., . . . Sakoda, L. C. (2020). Standardized reporting and management of suspicious findings on chest ct imaging is associated with improved lung cancer diagnosis in an observational study. Chest, 158(5), 2211-2220. doi:10.1016/j.chest.2020.05.595

Gøtzsche, P. C., & Nielsen, M. (2006). Screening for breast cancer with mammography. The Cochrane database of systematic reviews, (4), CD001877. https://doi.org/10.1002/14651858.CD001877.pub2

Ebell, M. H., Bentivegna, M., &amp; Hulme, C. (2020). Cancer-Specific mortality, all-cause mortality, and overdiagnosis in lung cancer Screening Trials: A meta-analysis. The Annals of Family Medicine, 18(6), 545-552. doi:10.1370/afm.2582

Two interventions to increase lung cancer screening rates from the clinical and community perspectives. 

Lung Cancer Screening: Challenges and Opportunities

The COVID-19 pandemic is proving to be a long-lasting issue, posing the question of whether the benefits of preventive screening are worth the risks of infection exposure. Many difficult decisions had to be made quickly early in 2020 when the world was beginning to see the deadly impact of the novel coronavirus. In particular, imaging preventive screenings for breast and lung cancer took an abrupt nose-dive, and the consequences of the delayed and decreased utilization of care, as well as how it has affected radiology, will likely have a long-term effects.

According to a study that analyzed health insurance claims across the United States, there was a regression-adjusted rate per 10,000 persons change of -149.1 percent and -342.1 percent from March and April of 2018 compared to March and April of 2020 for mammograms, respectively

. Many factors contributed to this significant decrease, such as patient fear of infectious exposure, decreased ability to pay for medical care, a shortage of personal protective equipment (PPE), inconsistent guidelines from the Centers for Disease Control & Prevention (CDC), the World Health Organization (WHO), and various state policies that led to loose interpretations of what procedures to postpone or cancel.

From a study that rated different professions’ risk of COVID-19, radiology technologists and sonographers were two of the highest scorers (84 and 80 out of 100, respectively). In order to mitigate risk to both patients and personnel, the American College of Radiology (ACR) released jointly with American Society of Breast Surgeons recommending to “postpone all breast screening exams (to include screening mammography, ultrasound, and MRI),” as well as discontinuing routine and non-urgent breast health appointments in March 2020.

From these recommendations, there was a subsequent large decline in breast screening. From a survey conducted by ACR and the Radiology Business Management Association, 97.4 percent of 228 radiology practices decreased in imaging volume in March and April of 2020. Elective procedures dropped by more than 90 percent with urgent procedures dropping around 60 percent. Breast imaging was especially hard hit and has been the slowest at recovering. Screening mammography was reduced by as much as 99 percent in calendar weeks 15 and 16. The largest healthcare system in New York reported that mammography decreased 94 percent, MR imaging 74 percent, and ultrasound by 64 percent

Radiology practices adapted to these limitations by restructuring reading rooms, setting up home PACS, and increasing usage of telehealth. However, even with these changes, the significant decrease in reading volumes have had devastating financial impacts on radiologists. One survey found that 50 percent of radiology practices had marked reductions in income, research, hours, personal and academic protected time, financial incentives, and retirement allocations. In addition to these tangible effects, there has also been a toll on the mental health of radiologists, with 60 percent rating their anxiety as a 7/10 during the pandemic

At this point, it is unclear exactly what mortality cost the pandemic has had due to the lack of breast cancer screening. One model that assumed a 6-month disruption of service estimated the potential excess deaths from breast and colorectal cancer would be an excess of more than 10,000 deaths in the next decade

.There is also the question of how this pandemic will shape the future of teleradiology and how this will continue to change the radiologists' workflow.

There is more concrete evidence about how the decrease in lung cancer screening has affected cancer diagnoses. Mortality from lung cancer has declined significantly in the past decade due to the introduction of annual low-dose CT (LDCT) for high-risk patients. Due to the pandemic – and likely multifactorial reasons discussed previously – cancer diagnoses were decreased across six common malignancies in the United States, and in the Netherlands, it was a 30 percent decrease in all primary cancer diagnoses

. Early in the pandemic, the American College of Chest Physicians recommended delaying screening of new patients and delaying annual LDCT for established patients

In a study of one institution's LDCT database, from January 2012 to July 2020, there were 2,153 unique patients, with a mean number of 54 pack years. Of patients, 4.7 percent were diagnosed with lung cancer. Lung cancer screening was cancelled from March 13, 2020, with phased re-opening from May 5, 2020, and full re-opening on June 1, 2020. Overall, 818 LDCTs were cancelled during this time, and both new (56 down to 14) and routine (146 down to 39) screenings were significantly decreased, with an increase in no-shows (15 percent up to 40 percent). Especially concerning was that once screening resumed, the percentage of patients with lung nodules suspicious for malignancy increased from 8 percent to 29 percent, with a concurrent increase in referrals for intervention by surgery or pulmonology (21.2 percent up to 44 percent)

Similar to breast cancer, lung cancer societies, such as the Thoracic Surgery Outcomes Research Network released updated guidelines later during the pandemic which recommended deferring operations for three months in hospitals with resources limited by COVID-19. For hospitals with only a few cases, they recommended limited operations for node positive lung cancer, tumors greater than or equal to 2 cm, or for those who only received neoadjuvant therapy. A study from the United Kingdom estimated that there was a 4.8 percent to 5.3 percent increase in lung cancer mortality due to diagnostic delays

From these cases, there is growing evidence that the cancellations and backlog of preventive screening created by the pandemic are demonstrating the expected effect of delayed malignancy diagnoses in later stages. As we are adapting to the multiple surges and ebbs of the coronavirus, it is apparent that we must develop ways to mitigate the risk of COVID-19 exposure, as well as continue screening with safe methods.

Multiple cancer-related societies are lobbying to change guidelines to be more lenient to resume operations

. In addition to that, we must make sure that patients feel safe coming back to their appointments. They must be educated that in most cases having a pre-cancer diagnosis does not make them more susceptible to the virus, and that it is safe for them to come with appropriate masking and social distancing. The factors that they have listed as most important to them in resuming elective imaging are how much their clinician encourages them, use of masks by staff, social distancing, short waiting times, and symptom screening on arrival, minimizing trips outside of their house, and most importantly, staff friendliness

. With the continuing roll-out of vaccines and these measures being implemented, hopefully, we can soon stabilize toward a new normal for cancer screening in radiology.

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The impacts of the pandemic have been long-lasting – what has the effect been, and what prompts patients to return.

Imagine a motorcycle rider crashes his bike on his way to work. He hits his head on the road. He is taken to the hospital, but the CT scanner is broken. The patient feels fine and leaves the hospital. Later he becomes obtunded and passes away. If access to a CT scanner was available, the epidural bleed would have been seen. And, his life would have been saved.

The World Health Organization (WHO) estimates that two-thirds of the world’s population, such as this patient, lacks access to basic radiology care. Interventional radiology is even more inaccessible, and the influence this field can have on patient care is just as remarkable. Interventional radiology is challenging to implement in resource-limited settings because of difficulty maintaining and acquiring radiographic equipment, as well as a dearth of trained practitioners. Fortunately, these are not insurmountable challenges. Through adaptation and education, interventional radiologists can bring their services to populations throughout the world.

The first challenge is physical capital. Interventional radiology relies on equipment that is expensive to purchase and expensive to maintain. A CT scanner can cost up to $2.5 million, and an MRI scanner can cost up to $3 million. The average cost of an angiography system is $1.5 million. The WHO estimates that donations account for 80 percent of the medical equipment in developing countries.

When equipment is acquired through a donation, it is often misallocated in resource-limited settings

. A clinic in rural Africa may receive a CT scanner. However, if the CT scanner malfunctions, there may be no nearby technician to fix the machine. The CT scanner will quickly become dormant. A reliable power grid and climate-controlled settings are also uncommon, yet essential, for interventional radiology equipment. Fluoroscopy, CT, angiography, MRI, nuclear medicine, and advanced ultrasound equipment are often found in “medical equipment graveyards.” While 1 percent of medical equipment is out-of-service in high-income countries, 40 percent of medical equipment is out-of-service in low and middle-income countries

Human capital is another challenge that faces the practice of interventional radiology in resource-limited settings. For example, there were fewer than five practicing interventional radiologists in Nigeria in 2019. With a population of 200 million people, supply cannot meet demand

. The training paradigm for interventional radiology in the United States incorporates four years of training in diagnostic imaging. A foundation in image interpretation is essential for the safe practice of interventional radiology.

Unfortunately, diagnostic radiologists and imaging educators are also few in number in resource-limited settings. For instance, prior to RAD-AID, a non-profit organization serving imaging needs worldwide, Guyana had no radiology training program. In the 20 francophone countries in Africa, there are 117 radiologists. Some Asian countries have one radiologist per million population

. To increase the number of interventional radiologists, the number of trained diagnostic radiologists also needs to increase. Though the current number of radiologists is inadequate, continued growth is likely and will promote better access to interventional radiology.

Adapting procedures is one mechanism that can be used to overcome the challenges associated with the practice of resource-limited interventional radiology. When certain equipment is not available, many procedures can still be performed effectively and safely through alternative protocols and techniques. For instance, portal vein embolization through a trans-ileocolic approach has been successfully performed with hysterosalpingography catheters

. Percutaneous nephrostomy using only a trocar catheter is a viable alternative to the typical needle/wire/dilator/catheter combination

. Gastrostomy tube placements and vascular malformation corrections have been successfully performed with ultrasound

. Ethanol ablation of hepatocellular carcinoma has been shown to be an alternative to thermal ablation

. Adaptations to “high cost” interventional radiology procedures indicate hope for the practice of interventional radiology throughout the world. With continued innovation, interventional radiology procedures can be practiced in settings outside of the typical modern procedural suite.

Training initiatives can also aid the spread of interventional radiology to resource limited regions. Through offering webinars and open-access training documents, interventional radiologists can teach basic procedures to providers in remote settings. Simple biopsies and drainages, vascular access, and embolization procedures are excellent opportunities for low-cost, minimally invasive, treatments.

Ultrasound and fluoroscopy are relatively inexpensive, ranging $10,000-to-$200,000 and $20,000-to-$80,000, respectively, and can be used for many procedures

. Though the needs of communities in North America are very different compared to places, such as Sub-Saharan Africa, re-evaluation and assessment of local needs can be met through tailored teachings in more advanced procedures

. Volunteer-based efforts led by non-profit organizations, such as RAD-AID, have focused on developing a global interventional radiology curriculum. Collaborations with Ethiopia, Ghana, Guyana, Kenya, Nigeria, and Vietnam have resulted in regular webinars and workshops. Through volunteerism, there is ample opportunity for interventional radiologists to contribute to efforts such as these initiatives.

The practice of interventional radiology faces several hurdles to becoming a global practice. Through the adaptation of procedures and the education of practitioners, the spread of interventional radiology to resource-limited settings is possible. Interventional radiologists will continue to display ingenuity through creative procedural adaptations and teaching modalities. In the future, maybe a rider will, again, fall from his motorcycle. Not only will he be able to receive high-quality and timely imaging, but he will also be able to receive a high-efficacy percutaneous procedure for treatment: a radiology procedure that has yet to be realized!

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What will it take to bring interventional radiology to these areas?

The Feasibility of Global Interventional Radiology: Opportunities in Resource-Limited Settings

COVID-19 dominated healthcare in 2020. The virus simultaneously crushed some radiologists with an overwhelming workload while leaving others parched for scans to interpret. But, it is now a New Year with a brand new horizon. What can you expect out of the next 12 months?

 spoke with Mina S. Makary, M.D., an interventional radiologist with The Ohio State University Wexner Medical Center about what he saw as areas in the specialty and industry that deserve your attention. From the lingering pandemic to technological developments to radiology’s culture, he shared his insights.

This is the biggest issue radiology is dealing with right now. We’re continuing to learn more about its imaging manifestation, including the extra-pulmonary manifestations. It doesn’t only affect the lungs. There are also neurological and cardiac findings. Learning more and more about this disease – having a bigger knowledge base and further characterization of COVID – is going to help us as radiologists as we prepare for future pandemics.

It will also affect our workflow and healthcare systems. The initial wave had a huge impact, and now we’re getting into the second wave that’s even higher than the first. It impacts radiology workflow, department readiness, workforce resilience – all kinds of factors. We will need to focus on how we will utilize our resources most effectively – where do we want to scan our patients, how many can we help in a safe fashion, and with what precautions? How will we deal with staff issues if members of our teams end up exposed and we have to work with less resources? We must determine how to optimize our departments to continue to deal with this epidemic from a clinical, personnel, and business standpoint.

The American College of Radiology and other radiology associations are lobbying Congress because there are new Medicare cuts in 2021. This is coming in the middle of a pandemic when there is less volume and less revenue in healthcare systems, groups, and radiology practices. It’s just going to be another layer that will impact a great deal of everyone’s practice – especially radiologists who are in smaller practices that are trying to make it through.

Over the last few years, the impact of artificial intelligence and machine learning has been exponential, and it’s only going to keep growing that way. More and more – every day – new applications are coming up to help us improve specific disease diagnosis.

One thing we will continue to work on, as a specialty, is how we can integrate this technology into our clinical workflow. Rather than worrying about artificial intelligence replacing radiologists, everyone is now thinking about how artificial intelligence will augment their performance to become better, quicker, and more accurate. Our goal now is to determine the best role for it. There are a lot of amazing applications coming up with opportunities for improving patient care with the new wave of technology focusing on improving a radiologist’s efficiency.

In the past, we had plain film. Then, we had a huge efficiency impact on our specialty with the introduction of PACS systems that we now use to view images. That took us from looking at individual films that you’d hang up in the dark room to being able to view studies and large number of images in an electronic way. Now, the next big jump is being able to handle thousands and thousands of images, and artificial intelligence is being leveraged to help us take our specialty through the next transformation phase in 2021 and beyond.

This may not necessarily be in 2021, but in the long term, 3D printing will continue to be among the next generation of technologies for radiology. And, it is huge – so much so that RSNA dedicates an entire section to just 3D printing. It’s being used for patient education, to train surgeons and other colleagues with practice surgeries, and for surgical planning. If we need to visualize a complex structure, a 3D printer can create a model we can use to observe, teach, explain the disease better to students and patients.

In addition to these growing innovations in the diagnostic core of radiology, the interventional side is also evolving new ways to implement cutting-edge therapies using imaging guidance. There are many exciting procedures that have been developed that are now gaining more and more applications. For example, geniculate artery embolization where interventional radiologists, through a small incision and vascular access via microcatheters and wires, are able to target the vessels that contribute to knee inflammation in patients with moderate-to-severe osteoarthritis. Patients can feel significantly improvement in pain and quality of life after this same-day outpatient procedure without the need for invasive surgery.

Additional innovative ways embolization is having a huge impact include for men with symptomatic enlarged prostate glands and in women who are suffering with fibroids. For example, instead of a hysterectomy, we can stop the blood flow to the fibroids and shrink them while preserving the uterus, so the patient can go home same-day with quick recovery, no scars, less risk of complications, and in a cost-effective fashion. So, there are a lot of minimally invasive therapies that are developing, and radiologists are at the center of this revolution. Not only we are effective in diagnosing patients, but we are now more than ever also using that knowledge to treat patients and provide great outcomes in minimally invasive ways.

Our country has had a larger national conversation about race, gender, and equality issues over the past few years. As a reflection of this, there is a move in organized radiology for diversity and inclusion across the board. We can see that all levels of organizations, such as the American College of Radiology and the Society of Interventional Radiology, promoting diversity and providing opportunities to all members from a variety of backgrounds. These trends are only going to continue to grow and make us stronger as a specialty. It serves to make us one big family.

It’s a New Year – what should you keep your eyes on and where should you anticipate change?

Six Trends to Watch in 2021

The ongoing COVID-19 pandemic has resulted in significant disruptions to the healthcare system, including imaging care. One study estimated decreases in imaging volumes of 50 percent-to-70 percent for at least three months and encouraged measures like reduced working hours, salary cuts, and even layoffs to help offset the revenue cuts due to the pandemic

. To comply with social distancing measures and protect personnel and patients against the spread of disease, many radiology practices have adopted teleradiology, or remote interpretation of medical images.

This has been a significant change in routine for many practitioners, and it is not entirely clear what work will look like once the pandemic subsides and providers are allowed to physically return to their workplaces. In this piece, we explore the challenges for adopting telemedicine and remote services in the imaging arena, as well as potential benefits that may encourage radiology practices to leverage teleradiology for the long term.

By definition, teleradiology is performed remotely and misses out on the benefits associated with being physically present. Keeping a physical presence can help foster a more collaborative community and bolster teamwork and relationships, whether it is with radiologists, radiology technologists, nurses, or other inter-and multi-disciplinary stakeholders. Referring physicians also appreciate having onsite radiologists for consultation purposes and collaborative conferences, such as tumor boards.

Teleradiology presents both benefits and challenges for post-pandemic imaging.

Mina S. Makary, MD

Articles

Virtual Biopsy: A Safer Future for Cancer Management

Uterine Fibroid Embolization: Past, Present, and Future

Lung Cancer Screening: Challenges and Opportunities

Cancer Screening Challenges in the Face of COVID-19

The Feasibility of Global Interventional Radiology: Opportunities in Resource-Limited Settings

Six Trends to Watch in 2021

Teleradiology in the Age of COVID and Beyond

The Changing Landscape of Interventional Neuroradiology

Patient Perceptions of Imaging Modalities and Ionizing Radiation

Future Trends and Technologies in Interventional Radiology: What to Expect