Massachusetts General Hospital Researchers Develop Tool for Detecting Lung Cancer from the Metabolites in a Drop of Blood

Potential is for a clinical laboratory test that can help pathologists identify early-stage lung cancer in people long before symptoms appear

In a proof-of-concept study, researchers from Harvard-affiliated Massachusetts General Hospital (MGH) have created a metabolomic screening model that can uncover early-stage lung cancer in asymptomatic patients from a single drop of the patient’s blood.

The NIH’s National Center for Biotechnology Information defines metabolomics as the “comprehensive analysis of metabolites in a biological specimen” and states that the emerging technology “holds promise in the practice of precision medicine.”

The technology is similar to the concept of a liquid biopsy, which uses blood specimens to identify cancer by capturing tumor cells circulating in the blood.

According to the American Cancer Society, lung cancer is responsible for approximately 25% of cancer deaths in the US and is the leading cause of cancer deaths in both men and women. The ACS estimates there will be about 236,740 new cases of lung cancer diagnosed in the US this year, and about 130,180 deaths due to the disease.

Early-stage lung cancer is typically asymptomatic which leads to later stage diagnoses and lowers survival rates, largely due to a lack of early disease detection tools. The current method used to detect early lung cancer lesions is low-dose spiral CT imaging, which is costly and can be risky due to the radiation hazards of repeated screenings, the news release noted.

MGH’s newly developed diagnostic tool detects lung cancer from alterations in blood metabolites and may lead to clinical laboratory tests that could dramatically improve survival rates of the deadly disease, the MGH scientist noted in a news release.

Leo Cheng, PhD

“Our study demonstrates the potential for developing a sensitive screening tool for the early detection of lung cancer,” said Leo Cheng, PhD (above), in the news release. Cheng is Associate Professor of Radiology at Harvard Medical School and Associate Biophysicist in Radiology at Massachusetts General Hospital. “The predictive model we constructed can identify which people may be harboring lung cancer. Individuals with suspicious findings would then be referred for further evaluation by imaging tests, such as low-dose CT, for a definitive diagnosis,” he added. Oncologists may soon have a clinical laboratory test for screening patients with early-stage lung cancer. (Photo copyright: OCSMRM.)

The researchers published their findings in Proceedings of the National Academy of Sciences, titled, “Screening Human Lung Cancer with Predictive Models of Serum Magnetic Resonance Spectroscopy Metabolomics.”  

Detecting Lung Cancer in Blood Metabolomic Profiles

The MGH scientists created their lung-cancer predictive model based on magnetic resonance spectroscopy which can detect the presence of lung cancer from alterations in blood metabolites.

The researchers screened tens of thousands of stored blood specimens and found 25 patients who had been diagnosed with non-small-cell lung carcinoma (NSCLC), and who had blood specimens collected both at the time of their diagnosis and at least six months prior to the diagnosis. They then matched these individuals with 25 healthy controls.

The scientists first trained their statistical model to recognize lung cancer by measuring metabolomic profiles in the blood samples obtained from the patients when they were first diagnosed with lung cancer. They then compared those samples to those of the healthy controls and validated their model by comparing the samples that had been obtained from the same patients prior to the lung cancer diagnosis.

The predictive model yielded values between the healthy controls and the patients at the time of their diagnoses.

“This was very encouraging, because screening for early disease should detect changes in blood metabolomic profiles that are intermediate between healthy and disease states,” Cheng noted.

The MGH scientists then tested their model with a different group of 54 patients who had been diagnosed with NSCLC using blood samples collected before their diagnosis. The second test confirmed the accuracy of their model.

Predicting Five-Year Survival Rates for Lung Cancer Patients

Values derived from the MGH predictive model measured from blood samples obtained prior to a lung cancer diagnosis also could enable oncologists to predict five-year survival rates for patients. This discovery could prove to be useful in determining clinical strategies and personalized treatment decisions.

The MGH study was co-led by Cheng and David Christiani, MD, Professor of Environmental Health at Harvard T.H. Chan School of Public Health, and was funded by the National Cancer Institute.

The researchers plan to analyze the metabolomic profiles of the clinical characteristics of lung cancer to understand the entire metabolic spectrum of the disease. They hope to create similar models for other illnesses and have already created a model that can distinguish aggressive prostate cancer by measuring the metabolomics profiles of more than 400 patients with that disease.

In addition, they are working on a similar model to screen for Alzheimer’s disease using blood samples and cerebrospinal fluid.  

More research and clinical studies are needed to validate the utilization of blood metabolomics models as early screening tools in clinical practice. However, this technology might provide pathologists and clinical laboratories with diagnostic tests for the screening of early-stage lung cancer that could save thousands of lives each year.

JP Schlingman

Related Information:

Early-stage Lung Cancer May be Detected from a Drop of Blood

Cancer Clues in a Drop of Blood

Screening Human Lung Cancer with Predictive Models of Serum Magnetic Resonance Spectroscopy Metabolomics

Metabolomics: An Emerging but Powerful Tool for Precision Medicine

Metabolomics Promises to Provide New Diagnostic Biomarkers, Assays for Personalized Medicine and Medical Laboratories


Europe Implements New Anatomic Pathology Guidelines to Reduce Nurse Exposure to Formaldehyde and Other Toxic Histology Chemicals

University of Turin study in Italy shows under-vacuum sealing systems reduce exposure to formaldehyde by 75% among nurses handling tissue biopsy specimens during surgery

Histology technicians and anatomic pathology (AP) laboratories regularly handle dangerous chemicals such as formaldehyde. They understand the risks exposure brings and take precautions to minimize those risks. However, in operating suites worldwide, nurses assisting surgeons also are being exposed to this nasty chemical.

Nurses must place biopsies and other tissues into buckets of formaldehyde to preserve the tissue between the operating room (OR) and histology laboratory. Formaldehyde, along with toluene, and xylene, is used to process and preserve biopsy tissue, displace water, and to create glass slides. It is an important substance that has long been used to maintain the viability of tissue specimens. Thus, exposure to formaldehyde among nurses is well-documented.

According to a National Academy of Sciences report, formalin, a tissue preservative that is a form of formaldehyde, has been linked to:

·       Myeloid leukemia;

·       Nasopharyngeal cancer; and,

·       Sinonasal cancer.

However, as Dark Daily previously reported, “One alternative to storing specimens in buckets with formalin is to vacuum-seal specimens … [so] that both the quality management of the patient specimen and worker safety for handling the specimens are greatly improved.” (See Dark Daily, “Anatomic Pathology Labs Adopt New Ways to Package, Transport, and Store Specimens to Reduce Formalin and Improve Staff Safety in Operating Theaters and Histology Laboratories,” October 13, 2014.)

Now, motivated by increasing formaldehyde regulations in Europe, as well as the need to increase awareness of exposure risks, the University of Turin (Unito), and other hospitals in Italy’s Piedmont region, conducted a cross-sectional study of 94 female nurses who were being potentially exposed to formaldehyde.

Researchers Aim for “Formalin-Free” Hospitals

The Unito study showed that nurses using an under-vacuum sealing (UVS) system in ORs are exposed to levels of formaldehyde 75% lower than those who did not use the system. This study differs from other similar tests because the level of exposure is not just potential, due to environmental contamination, but confirmed with analytic data from specific urine analyses.

The researchers divided the nurses into two groups:

·       One group immersed samples in containers of formaldehyde following standard procedures;

·       The other group worked in operating rooms equipped with a UVS system.

The researchers described a UVS system that called for the tissue removed during surgery to be sealed in a medical grade vacuum bag and refrigerated at four degrees centigrade before being transferred to the lab for fixation.

One example of a UVS system is TissueSAFE plus, developed by Milestone Medical, located in Bergamo, Italy, and Kalamazoo, Mich. According to the company’s website, the system, “Eliminates formalin in the operating theatre and allows a controlled formalin-free transfer of biospecimens to the laboratory.”

The image above is from a research paper by Richard J. Zarbo, MD, Pathology and Laboratory Medicine, Henry Ford Health System. It describes “five validation trials of new vacuum sealing technologies that change the approach to the preanalytic ‘front end’ of specimen transport, handling, and processing, and illustrate their adaptation and integration into existing Lean laboratory operations with reduction in formalin use and personnel exposure to this toxic and potentially carcinogenic fixative.” (Image copyright: Henry Ford Health System/Springer International Publishing.)


Increased Scrutiny Leads to New Pathology Guidelines

In a paper published in Toxicology Research, a journal of The Royal Society of Chemistry, the researchers noted a marked difference related to the adoption of the under-vacuum sealing procedure, as an alternative to formaldehyde for preserving tissues. “Nurses, operating in surgical theatres, are traditionally exposed to formaldehyde because of the common and traditional practice of immersing surgical samples, of a size ranging between two and 30 centimeters, in this preservative liquid (three to five liters at a time) to be later transferred to a [histopathology] lab,” the authors wrote. “We evaluated the conditions favoring the risk of exposure to this toxic reagent and the effect of measures to prevent it.”

Throughout Europe, increased scrutiny has forced medical pathology associations to write new guidelines that accept alternative methods to formaldehyde-based tissue preservation methods.

“In Europe, and in Italy in particular, the level of attention to formaldehyde exposure in the public health hospital system has become very high, forcing pathology associations to rewrite guidelines,” Marco Bellini, General Manager of the Medical Division at Milestone Medical, told Dark Daily. “What makes this study unique from many other similar tests is that the level of exposure has been confirmed with data from specific urine analyses,” he added.

The Italian Society of Pathological Anatomy and Diagnostic Cytology (SIAPEC), a division of the International Academy of Pathology, wrote general guidelines for AP labs that have been accepted and officially published by the Italian Ministry of Health.

The main topic of these guidelines is the preanalytical aspects of specimen collection, transportation, and preservation, where the vacuum method has been indicated as a valid alternative to improve the standardization of these crucial steps in pathology. By moving the starting point for specimen fixation from the OR to the histology labs, parameters can be controlled and documented, with the main advantage of reducing formaldehyde exposure by operators at the collection point.

These guidelines will be presented at the European Society of Pathology (ESP) with the intent to extending them throughout Europe.

Toluene’s and Xylene’s Effects Studied 

Formaldehyde is not the only potentially harmful substance in the clinical laboratory. As previously noted, common solvents toluene and xylene also are potentially hazardous.

In fact, a study of pathologists, lab technicians, and scientists who work with toluene and xylene published in the Journal of Rheumatology found that the chance of acquiring Raynaud Syndrome (a vascular condition) doubled for those workers. (See Dark Daily, “Health of Pathology Laboratory Technicians at Risk from Common Solvents like Xylene and Toluene,” July 5, 2011.)

Medical laboratory leaders are reminded to initiate processes that ensure safe specimen handling, transport, and processing, as well as workflow changes that eliminate chemical odors in the lab. Studies, such as those cited above, may provide information necessary to affect change.

—Donna Marie Pocius

Related Information:

Formaldehyde Fact Sheet

Towards a Formalin-Free Hospital: Levels of 15-F2t-isoprostane and malondialdehyde to Monitor Exposure to Formaldehyde in Nurses from Operating Theatres

Histologic Validation of Vacuum Sealed, Formalin-Free Tissue Preservation, and Transport System

Notes Regarding the Use of Formalin, Reclassified as “Carcinogenic”

Formaldehyde Substitute Fixatives:  Analysis of Macroscopy, Morpholologic Analysis, and Immunohistochemical Analysis

Anatomic Pathology Labs Adopt New Ways to Package, Transport, and Store Specimens to Reduce Formalin and Improve Staff Safety in Operating Theaters and Histology Laboratories

Health of Pathology and Laboratory Technicians at Risk from Common Solvents Like Xylene and Toluene

National Academy of Sciences Confirms that Formaldehyde Can Cause Cancer in a Finding that has Implications for Anatomic Pathology and Histology Laboratories

National Academy of Sciences Confirms That Formaldehyde Can Cause Cancer in a Finding That Has Implications for Anatomic Pathology and Histology Laboratories

Confirmation of the risks of exposure to formaldehyde and formalin may encourage safety officers in pathology labs to use tissue processing methods that don’t use this chemical

Pathologists, histotechnologists, and other medical laboratory professionals who regularly work with formalin and other chemicals used in histology laboratories, know they are dangerous to the health of those who work with them daily. These other chemicals include xylene and toluene.

Last summer, the National Academy of Sciences (Academy) issued a statement declaring that the Academy concurs with the 2011 Report of Carcinogens (RoC) listing formaldehyde as a known cause of cancer in humans. It was in August when the Academy issued its statement on this issue.

Exposure to Formaldehyde Linked to Three Types of Cancer

The Report of Carcinogens concluded that there is positive correlation between exposure to formaldehyde and three types of cancer: (more…)