Combining robotic-assisted bronchoscopy with rapid on-site evaluation by cytopathologists enables cancer evaluation and diagnosis in one procedure
New technologies are making it possible to both collect a tissue biopsy and diagnose lung cancer during the same procedure. Cytopathologist are essential in this unique approach, which has the potential to greatly shorten the time required to diagnose lung cancer.
At USA Health Mitchell Cancer Institute in Alabama, a team consisting of pulmonology, pathology, surgical, and medical oncology specialists can diagnose lung cancer significantly faster thanks to the combining of a robotic-assisted bronchoscopy (RAB) system with rapid on-site evaluation of biopsies (ROSE) by a cytopathologist during the same procedure.
The RAB platform was created by Auris Health in Redwood City, Calif. According to a USA Health new release, the Auris Health Monarch “enables physicians to see inside the lung and biopsy hard-to-reach nodules using a flexible endoscope. When combined with rapid on-site evaluation (ROSE) it allows for diagnosis at the time of bronchoscopy.”
USA Health says it is the only academic health system in Alabama to combine the Auris Health Monarch (Monarch) with ROSE to diagnose lung cancer in a single procedure.
“Nine-nine percent of the time we make a diagnosis—negative or positive (at time of bronchoscopy). We don’t have to do repeat procedures,” said Elba Turbat-Herrera, MD, Director of Pathological Services at USA Health’s Mitchell Cancer Institute (MCI) and Professor, MCI Interdisciplinary Clinical Oncology, in an exclusive interview with Dark Daily.
The American Society for Cytopathology defines ROSE as “a clinical service provided for patients where a pathologist, or in certain settings, an experienced and appropriately qualified cytotechnologist provides immediate real‐time evaluation of a fine needle aspiration (FNA) biopsy or touch imprints of a core biopsy.”
As a cytopathologist, Turbat-Herrera performs ROSE during procedures at USA Health. “I think we have improved diagnostics very much. With the Monarch equipment, one can see where the needle is traveling in the bronchial tube. It is more precise,” Turbat-Herrera explained.
Patients Benefit from Robotic-assisted Bronchoscopy
Traditionally, anatomic pathologists receive core (tissue sampling) biopsies and fine-needle aspiration biopsies from doctors looking to determine if a lung nodule may be cancerous. But the procedures to secure the biopsies are invasive and stressful for patients waiting for results from clinical laboratories. And some nodules are difficult for surgeons to reach, which can delay care to patients.
“The Monarch and ROSE technologies represent a huge step forward in lung bronchoscopy. Being able to see directly inside the lung and evaluate samples immediately provides the most advanced care for patients,” said Brian Persing, MD (above), Medical Oncologist, Mitchell Cancer Institute, and Assistant Professor of Interdisciplinary Clinical Oncology at the University of South Alabama College of Medicine, in the news release. (Photo copyright: University of South Alabama.)
Currently, more than 112 US healthcare providers use the Monarch robotic-assisted bronchoscopy (RAB) platform, which garnered US Food and Drug Administration (FDA) clearance in 2018, the USA Health news release noted.
The Monarch platform, according to USA Health, “integrates robotics, micro-instrumentation, endoscope design, and data science into one platform to empower physicians.”
Monarch’s “controller-like interface” (seen above) enables physicians to operate the endoscope and access small and “hard-to-reach” lung nodules. “The Monarch platform,” Duluth News Tribune explained, “is an endoscope guided by a handheld controller very similar to an Xbox controller. As the Monarch Platform drives through the lungs, the camera and other diagrams on a screen help the physician locate the nodule, then collect the biopsy with better accuracy and precision.” (Photo copyright: Jed Carlson/Superior Telegram/Duluth News Tribune.)
Eric Swanson, a pulmonologist at Essentia Health-St. Mary’s Medical Center in Duluth, MD, calls Monarch a game changer. “It’s a big, big upgrade from what we had before,” Swanson told the Duluth News Tribune. “(Before), you’d just pass a small catheter through a regular bronchoscope, and you turn it and hope you land in the right spot.”
The Monarch platform has enabled USA Health to step-up diagnosis of lung cancer, as compared to FNA (fine needle aspiration) biopsy on its own, according to Turbat-Herrera.
“With FNA alone, you try to get (sample tissue), and you are not sure. Now, if it is there, you should get it because the (Monarch) equipment helps you get there. Our role in pathology is to help guide the hand of the pulmonologist: ‘you don’t have what we need,’ or ‘keep going in that area of the lung,’” she said, adding that physicians have been able to reach tiny lesions.
High Incidence of Lung Cancer
The American Cancer Society, says lung cancer is the second most common cancer, with an estimated 235,760 new lung cancer cases and 131,880 deaths from the disease in 2021.
It’s hoped that healthcare providers’ investment in new robotic technology—such as Monarch and others—may shorten the time required to diagnose lung cancer and eventually save lives.
Providers such as USA Health go a step further by integrating ROSE with RAB. The robotic technology—coupled with on-site rapid evaluation by a cytopathologist that averts repeat biopsy procedures—immediately secures an assessment of sample adequacy and a cancer diagnosis that may benefit patients as well.
This is yet another example of how a new technology in one field can have a benefit for anatomic pathologists.
MIT’s deep learning artificial intelligence algorithm demonstrates how similar new technologies and smartphones can be combined to give dermatologists and dermatopathologists valuable new ways to diagnose skin cancer from digital images
According to an MIT press release, “The paper describes the development of an SPL [Suspicious Pigmented Lesion] analysis system using DCNNs [Deep Convolutional Neural Networks] to more quickly and efficiently identify skin lesions that require more investigation, screenings that can be done during routine primary care visits, or even by the patients themselves. The system utilized DCNNs to optimize the identification and classification of SPLs in wide-field images.”
The MIT scientists believe their AI analysis system could aid dermatologists, dermatopathologists, and clinical laboratories detect melanoma, a deadly form of skin cancer, in its early stages using smartphones at the point-of-care.
“Our research suggests that systems leveraging computer vision and deep neural networks, quantifying such common signs, can achieve comparable accuracy to expert dermatologists,” said Luis Soenksen, PhD (above), Venture Builder in Artificial Intelligence and Healthcare at MIT and first author of the study in an MIT press release. “We hope our research revitalizes the desire to deliver more efficient dermatological screenings in primary care settings to drive adequate referrals.” The MIT study demonstrates that dermatologists, dermatopathologists, and clinical laboratories can benefit from using common technologies like smartphones in the diagnosis of disease. (Photo copyright: Wyss Institute Harvard University.)
Improving Melanoma Treatment and Patient Outcomes
Melanoma develops when pigment-producing cells called melanocytes start to grow out of control. The cancer has traditionally been diagnosed through visual inspection of SPLs by physicians in medical settings. Early-stage identification of SPLs can drastically improve the prognosis for patients and significantly reduce treatment costs. It is common to biopsy many lesions to ensure that every case of melanoma can be diagnosed as early as possible, thus contributing to better patient outcomes.
“Early detection of SPLs can save lives. However, the current capacity of medical systems to provide comprehensive skin screenings at scale are still lacking,” said Luis Soenksen, PhD, Venture Builder in Artificial Intelligence and Healthcare at MIT and first author of the study in the MIT press release.
The researchers trained their AI system by using 20,388 wide-field images from 133 patients at the Gregorio Marañón General University Hospital in Madrid, as well as publicly available images. The collected photographs were taken with a variety of ordinary smartphone cameras that are easily obtainable by consumers.
They taught the deep learning algorithm to examine various features of skin lesions such as size, circularity, and intensity. Dermatologists working with the researchers also visually classified the lesions for comparison.
When the algorithm is “shown” a wide-field image like that above taken with a smartphone, it uses deep convolutional neural networks to analyze individual pigmented lesions and screen for early-stage melanoma. The algorithm then marks suspicious images as either yellow (meaning further inspection should be considered) or red (indicating that further inspection and/or referral to a dermatologist is required). Using this tool, dermatopathologists may be able to diagnose skin cancer and excise it in-office long before it becomes deadly. (Photo copyright: MIT.)
“Our system achieved more than 90.3% sensitivity (95% confidence interval, 90 to 90.6) and 89.9% specificity (89.6 to 90.2%) in distinguishing SPLs from nonsuspicious lesions, skin, and complex backgrounds, avoiding the need for cumbersome individual lesion imaging,” the MIT researchers noted in their Science Translational Medicine paper.
In addition, the algorithm agreed with the consensus of experienced dermatologists 88% of the time and concurred with the opinions of individual dermatologists 86% of the time, Medgadget reported.
Modern Imaging Technologies Will Advance Diagnosis of Disease
According to the American Cancer Society, about 106,110 new cases of melanoma will be diagnosed in the United States in 2021. Approximately 7,180 people are expected to die of the disease this year. Melanoma is less common than other types of skin cancer but more dangerous as it’s more likely to spread to other parts of the body if not detected and treated early.
More research is needed to substantiate the effectiveness and accuracy of this new tool before it could be used in clinical settings. However, the early research looks promising and smartphone camera technology is constantly improving. Higher resolutions would further advance development of this type of diagnostic tool.
In addition, MIT’s algorithm enables in situ examination and possible diagnosis of cancer. Therefore, a smartphone so equipped could enable a dermatologist to diagnose and excise cancerous tissue in a single visit, without the need for biopsies to be sent to a dermatopathologist.
Currently, dermatologists refer a lot of skin biopsies to dermapathologists and anatomic pathology laboratories. An accurate diagnostic tool that uses modern smartphones to characterize suspicious skin lesions could become quite popular with dermatologists and affect the flow of referrals to medical laboratories.
Determining how dogs do this may lead to biomarkers for new clinical laboratory diagnostics tests
Development of new diagnostic olfactory tools for prostate and other cancers is expected to result from research now being conducted by a consortium of researchers at different universities and institutes. To identify new biomarkers, these scientists are studying how dogs can detect the presence of prostate cancer by sniffing urine specimens.
Funded by a grant from the Prostate Cancer Foundation, the pilot study demonstrated that dogs could identify prostate samples containing cancer and discern between cancer positive and cancer negative samples.
Canine Olfactory Combined with Artificial Intelligence Analysis Approach
The part of a canine brain that controls smell is 40 million times greater than that of humans. Some dog breeds have 300 to 350 million sensory receptors, compared to about five million in humans. With their keen sense of smell, dogs are proving to be vital resources in the detection of some diseases.
The pilot study examined how dogs could be trained to detect prostate cancer in human urine samples.
Claire Guest, CEO and Chief Scientific Officer of UK-based Medical Detection Dogs and one of the study authors, is shown above with one of her cancer detecting dogs. In a Prostate Cancer Foundation article, she said, “Prostate cancer is not going to turn out to be a single note. What dogs are really good at discovering is a tune. Think of Beethoven’s Fifth Symphony, those first few notes. We suspect the cancer signature is something like that. It’s a pattern; the dogs are really good at recognizing the pattern. Machines that recognize the notes but can’t read the pattern are not reliable biomarkers,” she noted. The researchers believe the best solution for developing a clinical laboratory diagnostic that detects prostate cancer may be a combined approach using canine olfaction and AI neural networks. (Photo copyright: Janine Warwick/NPR.)
To perform the study, the researchers trained two dogs to sniff urine samples from men with high-grade prostate cancer and from men without the cancer. The two dogs used in the study were a four-year-old female Labrador Retriever named Florin, and a seven-year-old female wirehaired Hungarian Vizsla named Midas. The dogs were trained to respond to cancer-related chemicals, known as volatile organic compounds, or VOCs, the researchers added to the urine samples, and to not respond to the samples without the VOCs.
Both dogs performed well in their cancer detection roles, and both successfully identified five of seven urine samples from men with prostate cancer, correlating to a 71.4% accuracy rate. In addition, Florin correctly identified 16 of 21 non-aggressive or no cancer samples for an accuracy rate of 76.2% and Midas did the same with a 66.7% accuracy rate.
“We wondered if having the dogs detect the chemicals, combined with analysis by GC-MS, bacterial profiling, and an artificial intelligence (AI) neural network trained to emulate the canine cancer detection ability, could significantly improve the diagnosis of high-grade prostate cancer,” said Alan Partin, MD, PhD, Professor of Urology, Pathology and Oncology, Johns Hopkins University School of Medicine and one of the authors of the study, told Futurity.
The researchers determined that canine olfaction was able to distinguish between positive and negative prostate cancer in the samples, and the VOC and microbiota profiling analyses showed a qualitative difference between the two groups. The multisystem approach demonstrated a more sensitive and specific way of detecting the presence of prostate cancer than any of the methods used by themselves.
In their paper, the researchers concluded that “this study demonstrated feasibility and identified the challenges of a multiparametric approach as a first step towards creating a more effective, non-invasive early urine diagnostic method for the highly aggressive histology of prostate cancer.”
Can Man’s Best Friend be Trained to Detect Cancer and Save Lives?
Prostate cancer is the second leading cause of cancer deaths among men in the developed world. And, according to data from the National Cancer Institute, standard clinical laboratory blood tests, such as the prostate-specific antigen (PSA) test for early detection, sometimes miss the presence of cancer.
Establishing an accurate, non-invasive method of sensing the disease could help detect the disease sooner when it is more treatable and save lives.
The American Cancer Society estimates that there will be about 248,530 new cases of prostate cancer diagnosed in 2021 and that there will be approximately 34,130 deaths resulting from the disease during the same year.
Of course, more testing will be needed before Man’s best friend can be put to work detecting cancer in medical environments. But if canines can be trained to detect the disease early, and in a non-invasive way, more timely diagnosis and treatment could result in higher survival rates.
Meanwhile, as researchers identify the elements dogs use to detect cancer and other diseases, this knowledge can result in the creation of new biomarkers than can be used in clinical laboratory tests.
The discovery is yet another factor that must be considered when developing a liquid biopsy test clinical laboratories can use to detect cancer
How often do disruptive elements present in Liquid biopsies result in misdiagnoses and unhelpful drug therapies for cancer? Researchers at the University of Washington School of Medicine (UW Medicine) in Seattle wanted to know. And the results of their study provide another useful insight for pathologists about the elements that circulate in human blood which must be understood so that liquid biopsy tests can be developed that are not affected by that factor.
Based on their case series study of 69 men with advanced prostate cancer, the UW Medicine researchers determined that 10% of men have a clonal hematopoiesis of indeterminate potential (CHIP) that can “interfere” with liquid biopsies and cause incorrect reports and unneeded prostate cancer treatment, according to their paper published in the journal JAMA Oncology.
The UW Medicine researchers advised testing for “variants in the cell-free DNA (cfDNA)” shed in blood plasma to enable appropriate treatment for people with already diagnosed prostate cancer, noted to a UW Medicine news release.
According to pathologist Colin Pritchard, MD, PhD, Associate Professor of Laboratory Medicine and Pathology at the UW Medicine, who led the research team, “clonal hematopoiesis can interfere with liquid biopsies. For example, mutations in the genes BRCA1, BRCA2, and ATM have been closely linked to cancer development.
“The good news is that, by looking at the blood cellular compartment, you can tell with pretty good certainty whether something is cancer, or something is hematopoiesis,” he said in the news release.
What Does CHIP Interference Mean to a Clinical Laboratory Blood Test?
In their published study, the UW Medicine researchers stressed the “urgent need to understand cfDNA testing performance and sources of test interferences” in light of recent US Food and Drug Administration (FDA) clearance of two PARP inhibitors (PARPi) for prostate cancer:
“We found that a strikingly high proportion of DNA repair gene variants in the plasma of patients with advanced prostate cancer are attributable to CHIP,” the researchers wrote. “The CHIP variants were strongly correlated with increased age, and even higher than expected by age group.
“The high rate of CHIP may also be influenced by prior exposure to chemotherapy,” they added. “We are concerned that CHIP interference is causing false-positive cfDNA biomarker assessments that may result in patient harm from inappropriate treatment, and delays in delivering alternative effective treatment options.
“Without performing a whole-blood control, seven of 69 patients (10%) would have been misdiagnosed and incorrectly deemed eligible for PARP-inhibitor therapy based on CHIP interference in plasma. In fact, one patient in this series had a BRCA2 CHIP clone that had been previously reported by a commercial laboratory testing company with the recommendation to use a PARPi. To mitigate these risks, cfDNA results should be compared to results from whole-blood control or tumor tissue,” the researchers concluded.
To find the clinically relevant CHIP interference in prostate cancer cfDNA testing, researchers used the UW-OncoPlex assay (developed and clinically available at UW Medicine). The assay is a multiplexed next-generation sequencing panel aimed at detecting mutations in tumor tissues in more than 350 genes, according to the UW Medicine Laboratory and Pathology website.
“To improve cfDNA assay performance, we developed an approach that simultaneously analyzes plasma and paired whole-blood control samples. Using this paired testing approach, we sought to determine to what degree CHIP interferes with the results of prostate cancer cfDNA testing,” the researchers wrote in JAMA Oncology.
Men May Receive Unhelpful Prostate Cancer Drug Therapies
The research team studied test results from 69 men with advanced prostate cancer. They analyzed patients’ plasma cfDNA and whole-blood control samples.
Tumor sequencing enabled detection of germline (cells relating to preceding cells) variants from CHIP clones.
The UW Medicine study suggested CHIP variants “accounted for almost half of the somatic (non-germline) DNA repair mutations” detected by liquid biopsy, according to the news release.
> “About half the time when the plasma is thought to contain a mutation that would guide therapy with these drugs, it actually contains CHIP variants, not prostate cancer DNA variants. That means that in about half of those tested, a patient could be told that he should be administered a drug that is not indicated to treat to his cancer,” said Colin Pritchard, MD, PhD, pathologist and Associate Professor of Laboratory Medicine and Pathology at UW Medicine in the new release. (Photo copyright: University of Washington School of Medicine.)
Other detailed findings of the UW Medicine Study:
CHIP variants of 2% or more were detected in cfDNA from 13 of 69 men.
Seven men, or 10%, having advanced prostate cancer “had CHIP variants in DNA repair genes used to determine PARPi candidacy.
CHIP variants rose with age: 0% in those 40 to 50; 12.5% in men 51 to 60; 6.3% in those 61 to 70; 20.8% in men 71 to 80; and 71% in men 81 to 90.
Whole-blood control made it possible to distinguish prostate cancer variants from CHIP interference variants.
“Men with prostate cancer are at high risk of being misdiagnosed as being eligible for PARPi therapy using current cfDNA tests; assays should use a whole-blood control sample to distinguish CHIP variants from prostate cancer,” the researchers wrote in JAMA Oncology.
Liquid Biopsies Are ‘Here to Stay’
Surgical oncologist William Cance, MD, Chief Medical and Scientific Officer, American Cancer Society (ACS) in Atlanta, recognizes the challenge of tumor biology to liquid biopsies.
“Genetic abnormalities are only one piece of the puzzle. We need to look comprehensively at tumors for the best therapy, from their metabolic changes and protein signatures in the blood to the epigenetic modifications that may occur, as cancers take hold,” he told Oncology Times. “It’s not just shed DNA in the blood.”
The UW Medicine study demonstrates the importance of understanding how all elements in liquid biopsies interact to affect clinical laboratory test results.
“I think liquid biopsies are here to stay,” Cance told Oncology Times. “They’re all part of precision medicine, tailored to the individual.”
Wait times blamed on the Irish National Health System’s ‘overstretched’ services and ‘under-resourced’ commitment to cancer genetic testing done by medical laboratories
Histopathologists in the UK and anatomic pathologists in the US understand the important role predictive genetic testing can play in helping patients understand their risk for certain types of breast, bowel, and ovarian cancers. While timely access to cancer testing may be routine in the United States, a report out of Ireland reveals patients in that country’s government-run healthcare system may have to wait up to two years or more for genetic counseling and testing.
UK Patients in Need of Genetic Services Are Switching from Public to Private Healthcare
While early access to genetic testing can provide opportunities for preventative treatments or earlier diagnosis of cancer, many patients in Ireland with a family history of cancer must wait months or years for genetic services. UCC Nursing Professor and Physiologist Josephine Hegarty, PhD, lead author of the ICS report, stated in a news release that “public cancer genetic services are overstretched. Waiting lists exist at every point on the pathway for people who need genetic services.”
She added, “Many patients spoken to seemed to abandon the waiting for overstretched public services in favor of paying for private testing and treatment.”
While the ICS report’s survey sample size was small—154 patients, family members, or members of the public—the data revealed:
One in seven respondents waited 13-24 months and one in 27 waited over 24 months for counseling and testing appointments.
Many people had changed from the public health system to private healthcare to speed up access to genetic testing.
The cumulative waiting time from referral to counseling, testing, receipt of genetic test results, and onwards to screening, surveillance, or prophylactic treatments [aka, preventive healthcare] can be up to four years, which patients see as time lost in terms of cancer prevention and early intervention.
Barriers to Genetic Services Affect Treatment Decisions
A separate survey of 52 healthcare professionals highlighted barriers for accessing services with six in 10 respondents saying they are under-resourced and four in 10 concerned about access to follow-up surgery for patients deemed to be at high risk.
In the ICS news release, breast cancer patient Margaret Cuddigan said genetic testing was not available to her at diagnosis.
“In those 13 months waiting for a result, I went through chemotherapy, a lumpectomy, and radiotherapy on my breast, only for a double mastectomy to be required once the BRCA mutation was known. Had I known this earlier, my course of treatment could have been very different,” Cuddigan said.
“I had to postpone a radiation treatment to go up to Dublin from Cork to do the genetic test, as it would have taken up to another 12 months in Cork, and then I waited over four months for the results. Once I received the news of the gene mutation, I had to navigate a path of risk-reducing surgeries,” she noted, adding, “I researched and sought out a surgeon myself.”
Long Waits for Genetic Testing Are Common in Single-Payer Healthcare
The waiting list for genetic cancer testing has long been an issue in Ireland. A 2017 article in the Irish Examiner, titled, “Woman Faces 18-month Wait for Vital Cancer Test,” brought to light the 18-month waiting time for BRCA1 and BRCA2 mutation testing for breast cancer. While the COVID-19 pandemic has further exacerbated the backlog of cancer treatment services, such issues are not new in single-payer healthcare systems.
Across the Irish Sea in Great Britain, some patients have experienced delays of six months before getting cancer test results. In “Shortage of Histopathologists in the United Kingdom Now Contributing to Record-Long Cancer-Treatment Waiting Times in England,” Dark Daily reported how prolonged wait times for cancer test results in the United Kingdom’s National Health Service are one disadvantage of a government-run, single-payer health system. With limited funds, frequently the government health program under invests in certain clinical services. It is not until several years later that the underinvestment reveals itself in the form of lengthy wait times.
Meanwhile, it is cancer patients and their families who pay the price for underinvestment because delays in their cancer test results then delay timely treatment decisions. This is particularly true when an immediate start of therapy for an aggressive form of cancer is imperative.
ICS Executive Director, Advocacy and External Relations, Rachel Morrogh, argues the solution is prioritizing cancer prevention within the Health Service Executive, which runs Ireland’s national healthcare system.
“The reality is the focus must be on urgent care, but we’re missing chances to keep people healthy (through genetic testing),” Morrogh told the Irish Independent. “We can prevent four in 10 cancers, but we have to prioritize prevention. There needs to be a significant investment and the expansion of capacity across all the follow-on services that someone with a genetic risk of cancer may need, focusing on the development of a dedicated and resourced pathway for them.
Irish Cancer Society’s Director of Advocacy and External Affairs Rachel Morrogh (above left with Donal Buggy, Director of Services, Delivery and Innovation at ICS) maintains that “Patients [in the Irish healthcare system] need a dedicated group of multi-disciplinary doctors following them so that they can be offered options and psycho-oncology support when they need it.” She added, “The government must now listen to patients and those working in our hospitals and provide more resourcing and staffing.” (Photo copyright: Irish Examiner.)
The ICS report found that limited access to timely genetically-guided health and oncology services is the result of multiple barriers to care.
“It is apparent from engaging directly with service users that waiting lists exist at every point on the pathway for people who need genetic [cancer testing] services,” the report states. “For those who may have a genetic risk of cancer, the wait times for access to [genetic cancer] testing alone (before counselling treatment, prophylactic surgery, etc.) can be up to two years. Barriers to accessing cancer genetic services include costs of tests, long processing time for referrals to tests, restrictive referral criteria, and difficulty in accessing information on cancer genetic services.”
In the forward she wrote for the ICS report, ICS Chief Executive Officer Averil Power said her organization would continue its push for improved access to genetic testing services. “Government needs to not only expand capacity for testing and counselling, but also ensure that the follow-on services that are needed by people diagnosed with a genetic risk of cancer are in place and can be accessed swiftly.”
The ICS report is another reminder to histopathologists in the UK—as well as anatomic pathologists in the US—that a single-payer healthcare system comes with its own flaws and access-to-care issues.
