In This Article
- More than two-thirds of cancer deaths worldwide are in developing countries
- One of the major challenges in addressing cancer deaths in the developing world is a dearth of diagnostic services
- Researchers at Massachusetts General Hospital and colleagues have reported a novel, fluorescence-based image cytometry analyzer to enable cancer diagnosis in developing countries and other remote locations
- The researchers describe several other possible applications of the technology, including opening the door to greater clinical impact for fine-needle aspiration
More than two-thirds of the nearly 10 million cancer deaths every year occur in low- and middle-income countries, more commonly known as developing countries. A number of factors contribute to the high death rates: not least, delayed diagnoses and missed treatment options due to a lack of diagnostic services.
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Now, in a paper published in August 2020 in Science Translational Medicine, researchers at Massachusetts General Hospital and colleagues have reported a technology for portable cellular analysis that can help address obstacles to rapid cancer diagnosis in developing countries and other resource-limited settings.
First-Generation System Yields Important Lessons
Over a decade ago, Ralph Weissleder, MD, PhD, an interventional radiologist and director of the Center for Systems Biology at Mass General, traveled to Africa in search of deeper understandings of how he and others could help fight cancer in developing countries with then-emerging technologies such as nanomaterials, integrated systems, microfluidics, miniaturization and advanced computation.
Following his return, Dr. Weissleder and colleagues at the Center for Systems Biology, the Mass General Cancer Center and the Harvard School of Public Health, developed a digital holographic method to enable rapid cellular diagnostics in remote settings.
This National Cancer Institute-funded technology worked exceedingly well in lymphoma and cervical cancer trials at Mass General but the researchers had not fully anticipated the challenges of deploying it in Africa. They found the system was too complex to operate and prone to errors in the hands of lay personnel. So, armed with the lessons they had learned on the ground, they returned to the lab to devise a new approach.
Facilitating Diagnosis with Fine-needle Aspiration
The lessons were brought to bear in the system described in the Science Translational Medicine paper: a portable fluorescence-based image cytometry analyzer dubbed CytoPAN. The system enables same-day diagnosis and subtyping of breast cancer, the most prevalent type of cancer in many developing countries, based on analysis of low numbers of cellular specimens obtained with fine-needle aspiration of palpable breast lesions. The technology is fully automated, self-contained and user-friendly, and non-physicians would likely be able to operate it with brief training.
The technology addresses many of the challenges the researchers encountered with their earlier attempt to provide more widely available point-of-care diagnosis in remote locations with little or no access to conventional pathological services. Probably most conspicuous was the need for faster turnaround times.
Especially in developing countries where patients are generally less accustomed to regular appointments with medical professionals or commuting itself involves various sacrifices, they are much more likely to be lost to follow-up if they leave the facility before learning the results. For this reason, same-day diagnosis is critical to any attempt to improve the efficacy of cancer diagnosis in the developing world.
The new technology meets two other prerequisites identified with the earlier, Botswana study. First, sample analysis is based on fine-needle aspirated cells instead of tissue, to enable both fast processing and low morbidity. Also, because the fine-needle aspiration provides fewer cells, the system uses multiplexed assays so it can extract greater amounts of information from each. The researchers chose fluorescence optical imaging as the underlying technology specifically because it served this need, allowing them to assign biomarkers of interest to different fluorescent channels in the system.
In the study described in the paper, the researchers demonstrated successful breast cancer diagnosis and receptor subtyping in only one hour with as few as 100 cancer cells. They reported, in a group of 68 patients who underwent surgery for breast cancer at the Kyungpook National University Chilgok Hospital in Daegu, South Korea, diagnostic accuracy of 100% for cancer detection, with receptor subtyping accuracies of 96% and 93%, respectively, for two key actionable biomarkers of breast cancer: human epidermal growth factor receptor 2 and hormonal receptors (ER/PR). Thus, the system is both faster and less invasive than core biopsy and histopathology, the current, labor-intensive standard for cancer diagnosis.
Additional Applications in Established Health Care Systems
Dr. Weissleder describes several potential applications of the new technology. CytoPAN is being tested for cancer applications at Mass General as well as in Botswana and elsewhere. These trials include longitudinal immune cell profiling in head and neck squamous cell cancer patients undergoing immunotherapy and other primary cancer types. The technology could also play an important role in established health care systems by enhancing the clinical impact of serial fine-needle aspirates, which are much less invasive than large-core needle biopsies. For patients, this means both lower morbidity and higher acceptance. Finally, the researchers are adapting the technology to same-day pathway analysis in interventional drug trials for broader reach.
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