A New Insight into Chemotherapy for Mesothelioma: How Histology Affects Treatment Outcomes

A New Insight into Chemotherapy for Mesothelioma: How Histology Affects Treatment Outcomes

Malignant pleural mesothelioma (MPM) is a rare and aggressive type of cancer that affects the lining of the lungs and chest cavity. MPM is mainly caused by exposure to asbestos, a mineral fiber that was widely used in construction and industry until its ban in many countries. MPM has a poor prognosis, with a median survival of less than one year after diagnosis.

MPM is difficult to treat, as it has no specific symptoms and is resistant to most conventional therapies, such as surgery, chemotherapy and radiation. Therefore, there is an urgent need for new and effective treatments that can improve the survival and quality of life of patients with MPM.

This article is a summary of a new insight into chemotherapy for MPM that examines how histology affects treatment outcomes ¹. Histology is the study of the microscopic structure and function of tissues and cells. Histology can be used to classify MPM into different subtypes (histotypes), such as epithelioid (the most common and favorable), sarcomatoid (the least common and unfavorable) or biphasic (a mixture of both).

The insight is based on a real-world cohort study that evaluated the efficacy of chemotherapy for MPM according to histology. A real-world cohort study is a type of observational study that follows a group of patients who receive a certain treatment in routine clinical practice and compares their outcomes with another group of patients who receive a different treatment or no treatment. The study also assessed the safety and tolerability of chemotherapy for MPM.

The article was published in the journal Scientific Reports in 2021 by a team of researchers from Italy.

What is chemotherapy?

Chemotherapy is a treatment that uses drugs that kill or stop the growth of cancer cells. Chemotherapy can be given intravenously (by injection into a vein) or orally (by mouth). Chemotherapy can cause side effects, such as nausea, vomiting, hair loss, infection or low blood cell counts.

Chemotherapy is the standard treatment for MPM, as it can improve survival and quality of life compared to supportive care alone. The most commonly used chemotherapy regimen for MPM is pemetrexed plus cisplatin (PC), which combines two drugs that work by different mechanisms: pemetrexed inhibits enzymes that are involved in DNA synthesis and repair, while cisplatin damages DNA directly. PC can improve median survival by about three months compared to cisplatin alone.

However, not all patients with MPM respond equally to chemotherapy, as some may have better or worse outcomes depending on various factors, such as age, sex, performance status (a measure of physical functioning), stage (a measure of tumor extent) or histology.

What was the study design?

The study was a real-world cohort study that evaluated the efficacy of chemotherapy for MPM according to histology. The study included 282 patients who were diagnosed with MPM between 2009 and 2019 at two hospitals in Italy. The study divided the patients into two groups based on their histology: epithelioid (n=199) or non-epithelioid (n=83), which included sarcomatoid and biphasic subtypes.

The study followed the patients until death or last follow-up. The study measured various outcomes, such as:

Primary outcome: The primary outcome was overall survival (OS), which is the time from diagnosis to death from any cause.
Secondary outcomes: The secondary outcomes were progression-free survival (PFS), which is the time from diagnosis to disease progression or death from any cause; objective response rate (ORR), which is the proportion of patients who had a complete or partial reduction in tumor size; disease control rate (DCR), which is the proportion of patients who had a complete or partial reduction or stabilization in tumor size; and safety and tolerability, which are the assessment of adverse events (unwanted or harmful effects) and serious adverse events (life-threatening or requiring hospitalization).

The study also performed a subgroup analysis, which is a type of analysis that compares the outcomes of different subgroups of patients based on certain characteristics, such as age, sex, performance status, stage or chemotherapy regimen.

What were the main results of the study?

The main results of the study were:

Epithelioid histology was associated with better overall survival than non-epithelioid histology: Epithelioid histology was associated with better overall survival than non-epithelioid histology in patients with MPM. The median overall survival was 14.8 months in the epithelioid group and 7.3 months in the non-epithelioid group. The hazard ratio (HR) for death was 0.53 in favor of epithelioid histology, meaning that epithelioid histology reduced the risk of death by 47% compared to non-epithelioid histology. The difference was statistically significant (p lt 0.001), meaning that it was very unlikely to be due to chance.
Epithelioid histology was associated with better progression-free survival than non-epithelioid histology: Epithelioid histology was associated with better progression-free survival than non-epithelioid histology in patients with MPM. The median progression-free survival was 7.1 months in the epithelioid group and 4.1 months in the non-epithelioid group. The hazard ratio for disease progression or death was 0.58 in favor of epithelioid histology, meaning that epithelioid histology reduced the risk of disease progression or death by 42% compared to non-epithelioid histology. The difference was statistically significant (p lt 0.001), meaning that it was very unlikely to be due to chance.
Epithelioid histology was associated with better objective response rate and disease control rate than non-epithelioid histology: Epithelioid histology was associated with better objective response rate and disease control rate than non-epithelioid histology in patients with MPM. The objective response rate was 29% in the epithelioid group and 10% in the non-epithelioid group. The disease control rate was 75% in the epithelioid group and 49% in the non-epithelioid group. The differences were statistically significant (p lt 0.001 and p=0.002, respectively), meaning that they were very unlikely to be due to chance.
Chemotherapy was safe and tolerable for both histologies: Chemotherapy was safe and tolerable for both histologies in patients with MPM. Adverse events were reported by 86% of patients in the epithelioid group and 87% of patients in the non-epithelioid group. Serious adverse events were reported by 18% of patients in the epithelioid group and 20% of patients in the non-epithelioid group. The most common adverse events in both groups were hematological (affecting blood cells), gastrointestinal (affecting digestion) and renal (affecting kidneys). The most common serious adverse events in both groups were hematological, infectious and respiratory.

What are the implications of the study?

The study provides a new insight into chemotherapy for MPM that examines how histology affects treatment outcomes. Histology is the study of the microscopic structure and function of tissues and cells. Histology can be used to classify MPM into different subtypes (histotypes), such as epithelioid (the most common and favorable), sarcomatoid (the least common and unfavorable) or biphasic (a mixture of both).

The study suggests that histology is an important prognostic factor for MPM, as it can influence survival, response and quality of life. The study also suggests that chemotherapy is an effective treatment option for MPM, as it can improve survival, response and quality of life for both histologies, although epithelioid histology has a better outcome than non-epithelioid histology.

The study was conducted by a team of researchers from Italy. The study was published in the journal Scientific Reports in 2021. The title and authors of the original article are:

Cedres, S., Assaf, JD., Iranzo, P. et al. Efficacy of chemotherapy for malignant pleural mesothelioma according to histology in a real-world cohort. Sci Rep 11, 21357 (2021). https://doi.org/10.1038/s41598-021-00831-4,