Christian Baiao | FAPESP Agency – When studying a group of patients with metastatic lung cancer, researchers from Brazil and the United States concluded that performance on simple physical tests – such as sitting, standing and walking – could be a criterion capable of helping the doctor in assessing the diagnosis and in diagnosing the disease. Determine treatment.
search, Released node European Journal of Clinical InvestigationIt also identified two substances in the blood plasma of volunteers – serine and M22G – with the potential to become biomarkers capable of indicating which patients are most likely to respond to chemotherapy.
The work received support (projects 16/20187-6 and 19/17009-7) of FAPESP and involved researchers from the University of São Paulo Medical School (FM-USP) and Harvard Medical School (USP).
As the first author of the article explains. Willian das Neves SilvaAnorexic cachexia syndrome is common among patients with advanced cancer and is characterized by extensive consumption of muscle and adipose tissue, with consequent involuntary weight loss, and is usually associated with decreased appetite, fatigue, and decreased muscle strength.
In the case of lung cancer, and more specifically non-small cell tumors, which are the most common, research results show that when assessing a patient's survival, it is not enough to measure the amount of muscle. It is also necessary to take into account muscle function.
“We saw that this function was more important. It's not just about having muscles, it's about what the patient can do with them. The study shows that physical fitness is more important than muscle mass. Most of the patients were weak and had cachexia.” [perda acentuada de peso e massa muscular] to some extent. “A patient with better physical performance lives longer, and this has nothing to do with his general condition,” explains Silva, who conducted the study during his doctorate, under the guidance of professors. Gilberto de Castro Jrfrom FM-USP, Patricia Shakur Promfrom the University of the South Pacific's School of Physical Education and Sport, and Katherine J. Swoboda, of Massachusetts General Hospital, which is affiliated with Harvard University.
According to the authors, the information collected in the research could help the oncologist better direct chemotherapy and refer anyone who may need help from a complementary or palliative care team.
“We showed that patients with decreased performance on simple physical tests also had a loss in terms of oxygen consumption, while patients with good performance did not. We believe that the tumor-associated inflammatory process leads to the circulating of a range of metabolites in the plasma with potential Causing a negative impact on the metabolism of muscle cells. In some way, toxic damage occurs to these cells, which reduces oxygen consumption, which leads to aggravation of the disease.
According to the National Cancer Institute (IncaLung tumors are the number one killer in men and the second killer in women. Tumors are classified by the type of cell present, and each develops in a different way. The most common is non-small cell carcinoma, which is specifically what was analyzed in this research. It represents more than 80% of all cases.
“It is a very common tumor, but its survival rate is unfortunately short, about ten months,” highlights Castro Junior. Therefore, it is important to emphasize that it is possible to prevent the disease, because in more than 90% of cases lung cancer is associated with smoking.
“We are talking about patients between 60 and 65 years old, but they have been smoking for a long time,” explains the doctor.
methodology
The research was conducted on 55 patients from the Cancer Institute of São Paulo State (Icesp). Most of them were men, and all were smokers. They received treatment between April 2017 and September 2020 and were followed, on average, for approximately three months, throughout their chemotherapy courses in hospital.
Here in Brazil, physical tests were performed and blood tests and CT scans were collected. To assess physical ability before treatment, patients had to get up and walk three meters, then return and sit down again; Sit down and get up ten; Finally, walk for another six minutes. Furthermore, for a smaller group of 23 patients, resistance capacity was measured on a bicycle, using an oxygen mask, with constantly increasing speed.
“Some of these patients had lost about 30 kilograms in the last six months, but we saw that despite their apparent weakness, they were able to withstand exercise. Next, we understood that there was no direct relationship between muscle mass and performance, and that they would also withstand the Chemotherapy: “We realize that physical activity is important, even if it is according to each person's ability, and can contribute positively during treatment,” explains Silva.
At Harvard, metabolic tests were performed using blood plasma collected in Brazil and with samples of muscle cells. In other words, analysis of the intermediate or end products of the metabolism of these cells was performed to try to identify molecules that could be used as markers of disease.
Two substances have been identified that can help analyze which patients are most likely to respond to treatment in the future: serine and M22G.
Serine is a non-essential amino acid that is involved in many metabolic processes. As other studies have already proven, excess intracellular serine is linked to the growth of cancer cells. However, inhibiting or depriving serine can help shrink the tumor, which is why it has been proposed as a potential cancer treatment option.
“What we have shown is that there is a relationship between these substances and the performance of these patients, and perhaps in the future this could serve as an indicator of performance, but we still need to study more,” Silva says.
According to the researcher, in the next stage, the data of all patients participating in the study will be analyzed again with the help of artificial intelligence. The goal is to try to precisely find biomarkers that can help understand the mechanism of the disease.
Another important point is to understand whether physical activity during chemotherapy can also help improve the general condition of those with lung cancer.
Muscle quality
Results of the last group published In the magazine JCSM Communications Researchers have shown that in addition to inflammation and food aversions, intramuscular fat index is also an important predictor of survival for people with metastatic lung cancer.
“We included in this new analysis another group of patients who presented Performance status Worse than the previous study and we analyzed it as one group. In this new phase, we have identified that patients who are more inflamed, who refuse food and who have more fat in their muscles, live shorter. “Muscle fat is an indicator of poor muscle quality, which subsequently leads to poor performance,” explains Silva.
The long-term idea, the researchers say, is to understand whether physical exercise can act as a kind of “medicine” to complement treatment.
“We know that those who have worse muscle function have a worse chance of survival. Is it possible that if we could somehow improve muscle function through exercise, could we reverse the process and make that cell more resistant to inflammation? Breaking the vicious cycle From cachexia and muscle loss, does it have a better antitumor effect for treating cancer? “That's what we want to know now,” Castro Jr. says.
“These studies are a continuation of the thematic project.”Cancer and the heart: new diagnostic and therapeutic paradigms”, led by FM-USP Professor Carlos Eduardo Negrão.
The article Physical performance and plasma metabolic profile as potential prognostic factors in patients with metastatic lung cancer It can be read on: https://onlinelibrary.wiley.com/doi/10.1111/eci.14288.
the study Food aversion, systemic inflammation, and muscle adipose tissue are predictors of mortality in advanced lung cancer patients Available in: https://onlinelibrary.wiley.com/doi/10.1002/rco2.106.
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