Walter Alexander

In an international survey, most oncologists said they would recommend cytotoxic chemotherapy, immune checkpoint inhibitors, and steroids less often during the COVID-19 pandemic.

While neoadjuvant treatment recommendations were not strongly affected by the pandemic, about half of oncologists reported increased hesitancy over recommending frontline chemotherapy for metastatic disease, and a vast majority said they would recommend second- or third-line chemotherapy less often in the metastatic setting.

Most oncologists said they did not perform routine COVID-19 testing via reverse transcriptase–polymerase chain reaction (RT-PCR) before treating cancer patients. In fact, only 3% said they performed COVID-19 RT-PCR testing routinely.

Yüksel Ürün, MD, of Ankara (Turkey) University, and colleagues reported these findings in JCO Global Oncology.

The goal of the survey was to “understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision-making was influenced by the pandemic,” the authors wrote.

The online survey was conducted among 343 oncologists from 28 countries. Responses were collected anonymously, a majority (71%) from university or academic centers, with 95% received between April 1 and April 29, 2020.

Use of telemedicine was common (80%) among respondents, as was use of surgical masks (90%) and personal protective equipment in general.

Only 33% of respondents described using N95 masks. However, the proportion of oncologists who had access to N95 masks while caring for patients known to have COVID-19, especially while doing invasive procedures such as intubation, bronchoscopy, and any airway-related manipulations, was not captured by the survey.
 

COVID testing and cancer treatment

Most respondents (58%) said they did not perform routine COVID-19 RT-PCR testing prior to administering systemic cancer treatment, with 39% stating they performed RT-PCR tests in selected patients, and 3% saying they performed such testing in all patients.

The survey indicated that hormonal treatments, tyrosine kinase inhibitors, and bone-modifying agents were considered relatively safe, but cytotoxic chemotherapy and immune therapies were not.

Nearly all oncologists said the pandemic would cause them to make no change to their recommendations regarding hormone therapy, and nearly 80% said they would make no changes regarding tyrosine kinase inhibitors or bone-modifying agents.

However, more than 90% of respondents said they would recommend cytotoxic chemotherapy less often, about 70% said they would recommend corticosteroids less often, and around 50% said they would recommend anti–programmed death-1/PD-ligand 1 or anti–cytotoxic T-lymphocyte–associated protein 4 antibodies less often.

The pandemic made most respondents more reluctant to recommend second- or third-line chemotherapy in the metastatic setting. About 80% and 70% of respondents, respectively, would recommend second- or third-line chemotherapy less often.

However, first-line chemotherapy for metastatic disease, as well as adjuvant and neoadjuvant therapy, were less affected. About 30% of respondents said they would recommend neoadjuvant therapy less often, and 50%-55% would recommend adjuvant therapy or frontline chemotherapy for metastatic disease less often.

Most respondents (78%) said they would use granulocyte colony–stimulating factor (G-CSF) more frequently during the pandemic.

The factors most likely to affect oncologists’ treatment decisions were patient age (81%) and concomitant disease (92%). Additionally, 80% of respondents’ treatment decisions were influenced by Eastern Cooperative Oncology Group performance status of 2 or higher, or the presence of chronic obstructive pulmonary disease.

Interpretation and implications

“These results highlight that, even in the early phases of COVID-19 – during which there was considerable uncertainty – basic core principles were guideposts for oncologists,” observed Aly-Khan Lalani, MD, of Juravinski Cancer Centre and McMaster University, Hamilton, Ont., who was not involved in this study.

“For example, [oncologists were] prioritizing strategies for treatments with the largest expected impact and carefully tailoring treatment according to patient comorbidities and performance status,” Dr. Lalani said.

Another oncologist who was not involved in the study expressed concern over reductions in adjuvant therapy supported by half of oncologists surveyed.

“Although benefits may be marginal in some cases, these are curative settings and especially warrant careful individual-level risk/benefit discussions,” said Kartik Sehgal, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston.

His concern extended as well to the small proportion (3%) of oncologists testing for COVID-19 in all patients. “Systematic testing is the need of the hour,” Dr. Sehgal said.

In their discussion of the findings, Dr. Ürün and colleagues noted a lack of consensus on monoclonal antibody and immunotherapy safety among surveyed oncologists. The steroids needed to manage severe immune-mediated toxicity with immune checkpoint inhibitors has led to some prescribing reluctance during the pandemic.

Immunosuppressive properties of immune checkpoint inhibitors also raise concern that they can increase COVID-19 severity. Studies are few, and findings to date are inconsistent with respect to the effect of immune checkpoint inhibitors on COVID-19 clinical course. However, a recently presented study suggested that immune checkpoint inhibitors do not increase the risk of death among cancer patients with COVID-19 (AACR: COVID-19 and Cancer, Abstract S02-01).

Dr. Ürün and colleagues noted that greater COVID-19 severity has been shown in patients with performance status greater than 1, hematologic malignancies, lung cancer, stage IV metastatic disease, chemotherapy within the prior 3 months, cancer treatment in the last 14 days, and the presence of chronic obstructive pulmonary disease. Nonmetastatic cancer has not been shown to affect COVID-19 severity, however.

Dr. Ürün and colleagues also underscored the need for research evidence to balance potential reductions in neutropenic complications with G-CSF (and therefore, reduced hospitalizations) with a theoretical risk of G-CSF–mediated pulmonary injury through its stimulation of an excessive immune response.

Finally, the authors urged oncologists to evaluate each proposed therapy’s risk/benefit ratio on an individual patient basis, and the team tasked the oncology community with gathering comprehensive, rigorous data.

There was no funding source declared for this study. Dr. Ürün and colleagues disclosed various relationships with many pharmaceutical companies, which included receiving research funding. Dr. Sehgal and Dr. Lalani reported no relevant conflicts.
 

SOURCE: Ürün Y et al. JCO Glob Oncol. 2020 Aug;6:1248-57.

In an international survey, most oncologists said they would recommend cytotoxic chemotherapy, immune checkpoint inhibitors, and steroids less often during the COVID-19 pandemic.

While neoadjuvant treatment recommendations were not strongly affected by the pandemic, about half of oncologists reported increased hesitancy over recommending frontline chemotherapy for metastatic disease, and a vast majority said they would recommend second- or third-line chemotherapy less often in the metastatic setting.

Most oncologists said they did not perform routine COVID-19 testing via reverse transcriptase–polymerase chain reaction (RT-PCR) before treating cancer patients. In fact, only 3% said they performed COVID-19 RT-PCR testing routinely.

Yüksel Ürün, MD, of Ankara (Turkey) University, and colleagues reported these findings in JCO Global Oncology.

The goal of the survey was to “understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision-making was influenced by the pandemic,” the authors wrote.

The online survey was conducted among 343 oncologists from 28 countries. Responses were collected anonymously, a majority (71%) from university or academic centers, with 95% received between April 1 and April 29, 2020.

Use of telemedicine was common (80%) among respondents, as was use of surgical masks (90%) and personal protective equipment in general.

Only 33% of respondents described using N95 masks. However, the proportion of oncologists who had access to N95 masks while caring for patients known to have COVID-19, especially while doing invasive procedures such as intubation, bronchoscopy, and any airway-related manipulations, was not captured by the survey.
 

COVID testing and cancer treatment

Most respondents (58%) said they did not perform routine COVID-19 RT-PCR testing prior to administering systemic cancer treatment, with 39% stating they performed RT-PCR tests in selected patients, and 3% saying they performed such testing in all patients.

The survey indicated that hormonal treatments, tyrosine kinase inhibitors, and bone-modifying agents were considered relatively safe, but cytotoxic chemotherapy and immune therapies were not.

Nearly all oncologists said the pandemic would cause them to make no change to their recommendations regarding hormone therapy, and nearly 80% said they would make no changes regarding tyrosine kinase inhibitors or bone-modifying agents.

However, more than 90% of respondents said they would recommend cytotoxic chemotherapy less often, about 70% said they would recommend corticosteroids less often, and around 50% said they would recommend anti–programmed death-1/PD-ligand 1 or anti–cytotoxic T-lymphocyte–associated protein 4 antibodies less often.

The pandemic made most respondents more reluctant to recommend second- or third-line chemotherapy in the metastatic setting. About 80% and 70% of respondents, respectively, would recommend second- or third-line chemotherapy less often.

However, first-line chemotherapy for metastatic disease, as well as adjuvant and neoadjuvant therapy, were less affected. About 30% of respondents said they would recommend neoadjuvant therapy less often, and 50%-55% would recommend adjuvant therapy or frontline chemotherapy for metastatic disease less often.

Most respondents (78%) said they would use granulocyte colony–stimulating factor (G-CSF) more frequently during the pandemic.

The factors most likely to affect oncologists’ treatment decisions were patient age (81%) and concomitant disease (92%). Additionally, 80% of respondents’ treatment decisions were influenced by Eastern Cooperative Oncology Group performance status of 2 or higher, or the presence of chronic obstructive pulmonary disease.

Interpretation and implications

“These results highlight that, even in the early phases of COVID-19 – during which there was considerable uncertainty – basic core principles were guideposts for oncologists,” observed Aly-Khan Lalani, MD, of Juravinski Cancer Centre and McMaster University, Hamilton, Ont., who was not involved in this study.

“For example, [oncologists were] prioritizing strategies for treatments with the largest expected impact and carefully tailoring treatment according to patient comorbidities and performance status,” Dr. Lalani said.

Another oncologist who was not involved in the study expressed concern over reductions in adjuvant therapy supported by half of oncologists surveyed.

“Although benefits may be marginal in some cases, these are curative settings and especially warrant careful individual-level risk/benefit discussions,” said Kartik Sehgal, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston.

His concern extended as well to the small proportion (3%) of oncologists testing for COVID-19 in all patients. “Systematic testing is the need of the hour,” Dr. Sehgal said.

In their discussion of the findings, Dr. Ürün and colleagues noted a lack of consensus on monoclonal antibody and immunotherapy safety among surveyed oncologists. The steroids needed to manage severe immune-mediated toxicity with immune checkpoint inhibitors has led to some prescribing reluctance during the pandemic.

Immunosuppressive properties of immune checkpoint inhibitors also raise concern that they can increase COVID-19 severity. Studies are few, and findings to date are inconsistent with respect to the effect of immune checkpoint inhibitors on COVID-19 clinical course. However, a recently presented study suggested that immune checkpoint inhibitors do not increase the risk of death among cancer patients with COVID-19 (AACR: COVID-19 and Cancer, Abstract S02-01).

Dr. Ürün and colleagues noted that greater COVID-19 severity has been shown in patients with performance status greater than 1, hematologic malignancies, lung cancer, stage IV metastatic disease, chemotherapy within the prior 3 months, cancer treatment in the last 14 days, and the presence of chronic obstructive pulmonary disease. Nonmetastatic cancer has not been shown to affect COVID-19 severity, however.

Dr. Ürün and colleagues also underscored the need for research evidence to balance potential reductions in neutropenic complications with G-CSF (and therefore, reduced hospitalizations) with a theoretical risk of G-CSF–mediated pulmonary injury through its stimulation of an excessive immune response.

Finally, the authors urged oncologists to evaluate each proposed therapy’s risk/benefit ratio on an individual patient basis, and the team tasked the oncology community with gathering comprehensive, rigorous data.

There was no funding source declared for this study. Dr. Ürün and colleagues disclosed various relationships with many pharmaceutical companies, which included receiving research funding. Dr. Sehgal and Dr. Lalani reported no relevant conflicts.
 

SOURCE: Ürün Y et al. JCO Glob Oncol. 2020 Aug;6:1248-57.

In an international survey, most oncologists said they would recommend cytotoxic chemotherapy, immune checkpoint inhibitors, and steroids less often during the COVID-19 pandemic.

While neoadjuvant treatment recommendations were not strongly affected by the pandemic, about half of oncologists reported increased hesitancy over recommending frontline chemotherapy for metastatic disease, and a vast majority said they would recommend second- or third-line chemotherapy less often in the metastatic setting.

Most oncologists said they did not perform routine COVID-19 testing via reverse transcriptase–polymerase chain reaction (RT-PCR) before treating cancer patients. In fact, only 3% said they performed COVID-19 RT-PCR testing routinely.

Yüksel Ürün, MD, of Ankara (Turkey) University, and colleagues reported these findings in JCO Global Oncology.

The goal of the survey was to “understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision-making was influenced by the pandemic,” the authors wrote.

The online survey was conducted among 343 oncologists from 28 countries. Responses were collected anonymously, a majority (71%) from university or academic centers, with 95% received between April 1 and April 29, 2020.

Use of telemedicine was common (80%) among respondents, as was use of surgical masks (90%) and personal protective equipment in general.

Only 33% of respondents described using N95 masks. However, the proportion of oncologists who had access to N95 masks while caring for patients known to have COVID-19, especially while doing invasive procedures such as intubation, bronchoscopy, and any airway-related manipulations, was not captured by the survey.
 

COVID testing and cancer treatment

Most respondents (58%) said they did not perform routine COVID-19 RT-PCR testing prior to administering systemic cancer treatment, with 39% stating they performed RT-PCR tests in selected patients, and 3% saying they performed such testing in all patients.

The survey indicated that hormonal treatments, tyrosine kinase inhibitors, and bone-modifying agents were considered relatively safe, but cytotoxic chemotherapy and immune therapies were not.

Nearly all oncologists said the pandemic would cause them to make no change to their recommendations regarding hormone therapy, and nearly 80% said they would make no changes regarding tyrosine kinase inhibitors or bone-modifying agents.

However, more than 90% of respondents said they would recommend cytotoxic chemotherapy less often, about 70% said they would recommend corticosteroids less often, and around 50% said they would recommend anti–programmed death-1/PD-ligand 1 or anti–cytotoxic T-lymphocyte–associated protein 4 antibodies less often.

The pandemic made most respondents more reluctant to recommend second- or third-line chemotherapy in the metastatic setting. About 80% and 70% of respondents, respectively, would recommend second- or third-line chemotherapy less often.

However, first-line chemotherapy for metastatic disease, as well as adjuvant and neoadjuvant therapy, were less affected. About 30% of respondents said they would recommend neoadjuvant therapy less often, and 50%-55% would recommend adjuvant therapy or frontline chemotherapy for metastatic disease less often.

Most respondents (78%) said they would use granulocyte colony–stimulating factor (G-CSF) more frequently during the pandemic.

The factors most likely to affect oncologists’ treatment decisions were patient age (81%) and concomitant disease (92%). Additionally, 80% of respondents’ treatment decisions were influenced by Eastern Cooperative Oncology Group performance status of 2 or higher, or the presence of chronic obstructive pulmonary disease.

Interpretation and implications

“These results highlight that, even in the early phases of COVID-19 – during which there was considerable uncertainty – basic core principles were guideposts for oncologists,” observed Aly-Khan Lalani, MD, of Juravinski Cancer Centre and McMaster University, Hamilton, Ont., who was not involved in this study.

“For example, [oncologists were] prioritizing strategies for treatments with the largest expected impact and carefully tailoring treatment according to patient comorbidities and performance status,” Dr. Lalani said.

Another oncologist who was not involved in the study expressed concern over reductions in adjuvant therapy supported by half of oncologists surveyed.

“Although benefits may be marginal in some cases, these are curative settings and especially warrant careful individual-level risk/benefit discussions,” said Kartik Sehgal, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston.

His concern extended as well to the small proportion (3%) of oncologists testing for COVID-19 in all patients. “Systematic testing is the need of the hour,” Dr. Sehgal said.

In their discussion of the findings, Dr. Ürün and colleagues noted a lack of consensus on monoclonal antibody and immunotherapy safety among surveyed oncologists. The steroids needed to manage severe immune-mediated toxicity with immune checkpoint inhibitors has led to some prescribing reluctance during the pandemic.

Immunosuppressive properties of immune checkpoint inhibitors also raise concern that they can increase COVID-19 severity. Studies are few, and findings to date are inconsistent with respect to the effect of immune checkpoint inhibitors on COVID-19 clinical course. However, a recently presented study suggested that immune checkpoint inhibitors do not increase the risk of death among cancer patients with COVID-19 (AACR: COVID-19 and Cancer, Abstract S02-01).

Dr. Ürün and colleagues noted that greater COVID-19 severity has been shown in patients with performance status greater than 1, hematologic malignancies, lung cancer, stage IV metastatic disease, chemotherapy within the prior 3 months, cancer treatment in the last 14 days, and the presence of chronic obstructive pulmonary disease. Nonmetastatic cancer has not been shown to affect COVID-19 severity, however.

Dr. Ürün and colleagues also underscored the need for research evidence to balance potential reductions in neutropenic complications with G-CSF (and therefore, reduced hospitalizations) with a theoretical risk of G-CSF–mediated pulmonary injury through its stimulation of an excessive immune response.

Finally, the authors urged oncologists to evaluate each proposed therapy’s risk/benefit ratio on an individual patient basis, and the team tasked the oncology community with gathering comprehensive, rigorous data.

There was no funding source declared for this study. Dr. Ürün and colleagues disclosed various relationships with many pharmaceutical companies, which included receiving research funding. Dr. Sehgal and Dr. Lalani reported no relevant conflicts.
 

SOURCE: Ürün Y et al. JCO Glob Oncol. 2020 Aug;6:1248-57.

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.