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A system designed for resource-limited settings provides rapid cancer profiling and requires “scant” cellular specimens, according to researchers.
The automated image cytometry system is called CytoPAN. In preclinical experiments, CytoPAN provided accurate cancer detection in 1 hour using as few as 50 cells.
In a prospective study of 68 breast cancer patients, CytoPAN detected cancer with 100% accuracy. The receptor subtyping accuracy was 96% for HER2 and 93% for estrogen and progesterone receptors.
Jouha Min, PhD, of Massachusetts General Hospital, Boston, and colleagues reported these findings in Science Translational Medicine.
The authors explained that the CytoPAN system is designed to address one of the biggest cancer challenges in low- and middle-income countries (LMICs), where more than two-thirds of cancer deaths occur: providing rapid, affordable diagnostics that enable patients to obtain locally available treatments.
Unfortunately, because of bottlenecks in specimen acquisition, complex handling logistics, a lack of pathologists, and limited laboratory infrastructure, diagnosis in many LMICs frequently takes months. Cancers typically are not diagnosed until advanced symptoms such as palpable mass lesions, weight loss, and malaise have become manifest.
Lesion assessment guides management
For women with suspicion of breast cancer, the authors noted, preoperative assessment of focal lesions for receptor status, presence of invasion, histologic type, and tumor grade are crucial for planning therapeutic management. For physicians to provide, for example, tamoxifen, which is commonly available at low cost in LMICs, they must know a patients’ hormone receptor status.
While core and open surgical biopsies yield abundant tissue for embedding, sectioning, and staining for subsequent histopathological analysis, they entail lengthy work flow and call for expensive instrumentation and a trained workforce, the authors noted.
Fine needle aspirations (FNAs) can be performed by nonphysicians after minimal training with very low complication rates. The much smaller–gauge needles (20-25 gauge) used in FNAs are generally well tolerated, the authors added.
This is why CytoPAN was designed for use with specimens obtained via FNA of palpable mass lesions.
Self-contained design
The CytoPAN system was engineered as a self-contained, integrated cytometry platform enabling same-day diagnosis and treatment of breast lesions.
The system was designed to comply with the World Health Organization’s “ASSURED” criteria (affordable, sensitive, specific, user friendly, rapid and robust, equipment free, and deliverable to end users), and to be potentially operable by nonphysicians after brief training.
CytoPAN operators collect cells through minimally invasive FNAs and use lyophilized immunostaining kits with relevant antibodies (not requiring refrigeration). Operators perform imaging using the CytoPAN device, which is then subjected to an automated analysis algorithm with results displayed on a user interface.
CytoPAN classifies detected malignant cells according to four subtypes reflecting estrogen receptor (ER), progesterone receptor (PR), and HER2 status – luminal HER2-negative, luminal HER2-positive, HER2-positive, and triple-negative breast cancer. This is intended to facilitate informed treatment choices (e.g., a selective ER modulator, antiestrogen or aromatase inhibitor for ER/PR-positive patients; an anti-HER2 agent for HER2-positive patients).
The final diagnostic report from a given patient sample includes cancer cell population and molecular subtype distribution. The entire diagnostic procedure takes less than an hour. A repeat biopsy, should the sample be nondiagnostic, can be taken within an hour.
Murine, then human testing
A test of CytoPAN on FNA samples from mouse xenografts representing the spectrum of human breast cancer subtypes showed correct and reproducible molecular subtyping that matched well with flow cytometry reports derived from the same tumors.
To determine the clinical utility of CytoPAN, investigators enrolled 68 treatment-naive breast cancer patients who were referred for primary surgery at the Kyungpook National University Chilgok Hospital in Daegu, South Korea. FNA samples were obtained after visualization of breast masses by ultrasound or CT.
Surgical specimens and/or core biopsies were processed by routine pathology for “gold-standard” comparison. FNA samples had sufficient numbers of cells in 63 (93%) patients, with a mean number of cells among them of 1,308 (range, 93-11,985).
CytoPAN analysis correctly identified malignant breast cancer in 55 patients and benign lesions in 5 patients. Three cases were inconclusive because of low numbers of Quad-positive cells for further analysis. The authors pointed out that roughly 20% of biopsy samples in developed countries are deemed “nondiagnostic” because of insufficient cellular contents.
The authors’ summary underscored CytoPAN’s affordable system using cellular rather than tissue specimens, actionable results in an hour, lack of moving parts, multiplexed analysis, and user-friendly interface.
Cancer detection accuracy was 100% (no false negatives or false positives), and receptor subtyping accuracy was 97% for HER2 and 93% for ER/PR.
“Based on these results, we envision prospective clinical trials in remote, decentralized locations,” the authors wrote. The system is being tested further in Botswana.
“I find the data in this paper compelling – particularly for those patients presenting with a palpable mass on clinical exam. ... Certainly in resource-limited settings, this would have significant appeal,” William J. Gradishar, MD, of Northwestern University, Chicago, said in an interview.
Dr. Gradishar explained that, while palpable masses that lead to a diagnosis of noninvasive disease alone are uncommon in the United States because of routine screening mammography, they may still be an issue in other parts of the world.
The authors received funding from the National Institutes of Health, the MGH Scholar Fund, and Robert Wood Johnson Foundation. Some authors disclosed relationships with Akili, Accure Health, ModeRNA, Tarveda, Lumicell, and Noul. Dr. Gradishar reported having no disclosures.
SOURCE: Min J et al. Sci Transl Med. 2020 Aug 5. doi: 10.1126/scitranslmed.aaz9746.
A system designed for resource-limited settings provides rapid cancer profiling and requires “scant” cellular specimens, according to researchers.
The automated image cytometry system is called CytoPAN. In preclinical experiments, CytoPAN provided accurate cancer detection in 1 hour using as few as 50 cells.
In a prospective study of 68 breast cancer patients, CytoPAN detected cancer with 100% accuracy. The receptor subtyping accuracy was 96% for HER2 and 93% for estrogen and progesterone receptors.
Jouha Min, PhD, of Massachusetts General Hospital, Boston, and colleagues reported these findings in Science Translational Medicine.
The authors explained that the CytoPAN system is designed to address one of the biggest cancer challenges in low- and middle-income countries (LMICs), where more than two-thirds of cancer deaths occur: providing rapid, affordable diagnostics that enable patients to obtain locally available treatments.
Unfortunately, because of bottlenecks in specimen acquisition, complex handling logistics, a lack of pathologists, and limited laboratory infrastructure, diagnosis in many LMICs frequently takes months. Cancers typically are not diagnosed until advanced symptoms such as palpable mass lesions, weight loss, and malaise have become manifest.
Lesion assessment guides management
For women with suspicion of breast cancer, the authors noted, preoperative assessment of focal lesions for receptor status, presence of invasion, histologic type, and tumor grade are crucial for planning therapeutic management. For physicians to provide, for example, tamoxifen, which is commonly available at low cost in LMICs, they must know a patients’ hormone receptor status.
While core and open surgical biopsies yield abundant tissue for embedding, sectioning, and staining for subsequent histopathological analysis, they entail lengthy work flow and call for expensive instrumentation and a trained workforce, the authors noted.
Fine needle aspirations (FNAs) can be performed by nonphysicians after minimal training with very low complication rates. The much smaller–gauge needles (20-25 gauge) used in FNAs are generally well tolerated, the authors added.
This is why CytoPAN was designed for use with specimens obtained via FNA of palpable mass lesions.
Self-contained design
The CytoPAN system was engineered as a self-contained, integrated cytometry platform enabling same-day diagnosis and treatment of breast lesions.
The system was designed to comply with the World Health Organization’s “ASSURED” criteria (affordable, sensitive, specific, user friendly, rapid and robust, equipment free, and deliverable to end users), and to be potentially operable by nonphysicians after brief training.
CytoPAN operators collect cells through minimally invasive FNAs and use lyophilized immunostaining kits with relevant antibodies (not requiring refrigeration). Operators perform imaging using the CytoPAN device, which is then subjected to an automated analysis algorithm with results displayed on a user interface.
CytoPAN classifies detected malignant cells according to four subtypes reflecting estrogen receptor (ER), progesterone receptor (PR), and HER2 status – luminal HER2-negative, luminal HER2-positive, HER2-positive, and triple-negative breast cancer. This is intended to facilitate informed treatment choices (e.g., a selective ER modulator, antiestrogen or aromatase inhibitor for ER/PR-positive patients; an anti-HER2 agent for HER2-positive patients).
The final diagnostic report from a given patient sample includes cancer cell population and molecular subtype distribution. The entire diagnostic procedure takes less than an hour. A repeat biopsy, should the sample be nondiagnostic, can be taken within an hour.
Murine, then human testing
A test of CytoPAN on FNA samples from mouse xenografts representing the spectrum of human breast cancer subtypes showed correct and reproducible molecular subtyping that matched well with flow cytometry reports derived from the same tumors.
To determine the clinical utility of CytoPAN, investigators enrolled 68 treatment-naive breast cancer patients who were referred for primary surgery at the Kyungpook National University Chilgok Hospital in Daegu, South Korea. FNA samples were obtained after visualization of breast masses by ultrasound or CT.
Surgical specimens and/or core biopsies were processed by routine pathology for “gold-standard” comparison. FNA samples had sufficient numbers of cells in 63 (93%) patients, with a mean number of cells among them of 1,308 (range, 93-11,985).
CytoPAN analysis correctly identified malignant breast cancer in 55 patients and benign lesions in 5 patients. Three cases were inconclusive because of low numbers of Quad-positive cells for further analysis. The authors pointed out that roughly 20% of biopsy samples in developed countries are deemed “nondiagnostic” because of insufficient cellular contents.
The authors’ summary underscored CytoPAN’s affordable system using cellular rather than tissue specimens, actionable results in an hour, lack of moving parts, multiplexed analysis, and user-friendly interface.
Cancer detection accuracy was 100% (no false negatives or false positives), and receptor subtyping accuracy was 97% for HER2 and 93% for ER/PR.
“Based on these results, we envision prospective clinical trials in remote, decentralized locations,” the authors wrote. The system is being tested further in Botswana.
“I find the data in this paper compelling – particularly for those patients presenting with a palpable mass on clinical exam. ... Certainly in resource-limited settings, this would have significant appeal,” William J. Gradishar, MD, of Northwestern University, Chicago, said in an interview.
Dr. Gradishar explained that, while palpable masses that lead to a diagnosis of noninvasive disease alone are uncommon in the United States because of routine screening mammography, they may still be an issue in other parts of the world.
The authors received funding from the National Institutes of Health, the MGH Scholar Fund, and Robert Wood Johnson Foundation. Some authors disclosed relationships with Akili, Accure Health, ModeRNA, Tarveda, Lumicell, and Noul. Dr. Gradishar reported having no disclosures.
SOURCE: Min J et al. Sci Transl Med. 2020 Aug 5. doi: 10.1126/scitranslmed.aaz9746.
A system designed for resource-limited settings provides rapid cancer profiling and requires “scant” cellular specimens, according to researchers.
The automated image cytometry system is called CytoPAN. In preclinical experiments, CytoPAN provided accurate cancer detection in 1 hour using as few as 50 cells.
In a prospective study of 68 breast cancer patients, CytoPAN detected cancer with 100% accuracy. The receptor subtyping accuracy was 96% for HER2 and 93% for estrogen and progesterone receptors.
Jouha Min, PhD, of Massachusetts General Hospital, Boston, and colleagues reported these findings in Science Translational Medicine.
The authors explained that the CytoPAN system is designed to address one of the biggest cancer challenges in low- and middle-income countries (LMICs), where more than two-thirds of cancer deaths occur: providing rapid, affordable diagnostics that enable patients to obtain locally available treatments.
Unfortunately, because of bottlenecks in specimen acquisition, complex handling logistics, a lack of pathologists, and limited laboratory infrastructure, diagnosis in many LMICs frequently takes months. Cancers typically are not diagnosed until advanced symptoms such as palpable mass lesions, weight loss, and malaise have become manifest.
Lesion assessment guides management
For women with suspicion of breast cancer, the authors noted, preoperative assessment of focal lesions for receptor status, presence of invasion, histologic type, and tumor grade are crucial for planning therapeutic management. For physicians to provide, for example, tamoxifen, which is commonly available at low cost in LMICs, they must know a patients’ hormone receptor status.
While core and open surgical biopsies yield abundant tissue for embedding, sectioning, and staining for subsequent histopathological analysis, they entail lengthy work flow and call for expensive instrumentation and a trained workforce, the authors noted.
Fine needle aspirations (FNAs) can be performed by nonphysicians after minimal training with very low complication rates. The much smaller–gauge needles (20-25 gauge) used in FNAs are generally well tolerated, the authors added.
This is why CytoPAN was designed for use with specimens obtained via FNA of palpable mass lesions.
Self-contained design
The CytoPAN system was engineered as a self-contained, integrated cytometry platform enabling same-day diagnosis and treatment of breast lesions.
The system was designed to comply with the World Health Organization’s “ASSURED” criteria (affordable, sensitive, specific, user friendly, rapid and robust, equipment free, and deliverable to end users), and to be potentially operable by nonphysicians after brief training.
CytoPAN operators collect cells through minimally invasive FNAs and use lyophilized immunostaining kits with relevant antibodies (not requiring refrigeration). Operators perform imaging using the CytoPAN device, which is then subjected to an automated analysis algorithm with results displayed on a user interface.
CytoPAN classifies detected malignant cells according to four subtypes reflecting estrogen receptor (ER), progesterone receptor (PR), and HER2 status – luminal HER2-negative, luminal HER2-positive, HER2-positive, and triple-negative breast cancer. This is intended to facilitate informed treatment choices (e.g., a selective ER modulator, antiestrogen or aromatase inhibitor for ER/PR-positive patients; an anti-HER2 agent for HER2-positive patients).
The final diagnostic report from a given patient sample includes cancer cell population and molecular subtype distribution. The entire diagnostic procedure takes less than an hour. A repeat biopsy, should the sample be nondiagnostic, can be taken within an hour.
Murine, then human testing
A test of CytoPAN on FNA samples from mouse xenografts representing the spectrum of human breast cancer subtypes showed correct and reproducible molecular subtyping that matched well with flow cytometry reports derived from the same tumors.
To determine the clinical utility of CytoPAN, investigators enrolled 68 treatment-naive breast cancer patients who were referred for primary surgery at the Kyungpook National University Chilgok Hospital in Daegu, South Korea. FNA samples were obtained after visualization of breast masses by ultrasound or CT.
Surgical specimens and/or core biopsies were processed by routine pathology for “gold-standard” comparison. FNA samples had sufficient numbers of cells in 63 (93%) patients, with a mean number of cells among them of 1,308 (range, 93-11,985).
CytoPAN analysis correctly identified malignant breast cancer in 55 patients and benign lesions in 5 patients. Three cases were inconclusive because of low numbers of Quad-positive cells for further analysis. The authors pointed out that roughly 20% of biopsy samples in developed countries are deemed “nondiagnostic” because of insufficient cellular contents.
The authors’ summary underscored CytoPAN’s affordable system using cellular rather than tissue specimens, actionable results in an hour, lack of moving parts, multiplexed analysis, and user-friendly interface.
Cancer detection accuracy was 100% (no false negatives or false positives), and receptor subtyping accuracy was 97% for HER2 and 93% for ER/PR.
“Based on these results, we envision prospective clinical trials in remote, decentralized locations,” the authors wrote. The system is being tested further in Botswana.
“I find the data in this paper compelling – particularly for those patients presenting with a palpable mass on clinical exam. ... Certainly in resource-limited settings, this would have significant appeal,” William J. Gradishar, MD, of Northwestern University, Chicago, said in an interview.
Dr. Gradishar explained that, while palpable masses that lead to a diagnosis of noninvasive disease alone are uncommon in the United States because of routine screening mammography, they may still be an issue in other parts of the world.
The authors received funding from the National Institutes of Health, the MGH Scholar Fund, and Robert Wood Johnson Foundation. Some authors disclosed relationships with Akili, Accure Health, ModeRNA, Tarveda, Lumicell, and Noul. Dr. Gradishar reported having no disclosures.
SOURCE: Min J et al. Sci Transl Med. 2020 Aug 5. doi: 10.1126/scitranslmed.aaz9746.
FROM SCIENCE TRANSLATIONAL MEDICINE