Background: Malignant peritoneal mesothelioma (MPM) is a rare but aggressive cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) was the preferred choice for selected patients. The purpose of this study was to thoroughly examine the impact of the combined treatment and the prognostic variables, particularly the neutrophil-to-lymphocyte ratio (NLR).
Methods: Characteristics of [ malignant peritoneal mesothelioma (MPM) ] patients who underwent CRS combined HIPEC treatment, followed by adjuvant chemotherapy were retrospectively collected. The univariable analysis was performed to identify the decisive influential factor. Using Kaplan-Meier analysis, the cumulative probability of survival was determined. Using Univariate Cox analysis, the prognostic factors—particularly NLR—and its correlation with survival were assessed. In the multivariate Cox proportional hazards model, predictive factors that demonstrated significance in univariate analysis were used. The degree of connection between predictors and survival was evaluated through the use of hazard ratios (HRs) and 95% confidence intervals (95% CIs).
Results: A total of 64 patients were enrolled in this study. The 1, 3, 5 years survival rates were 70.3%, 65.6%, 59.4%, respectively. According to multivariate Cox analysis, [ malignant peritoneal mesothelioma (MPM) ] patients’ survival was found to be substantially associated with post-operative NLR (HR 0.180, 0.067–0.531), Ki-67 (HR 0.184, 0.024–0.817), post-operative neutrophil count (HR 0.228, 0.075–0.696), and bidirectional pathological type (HR, 0.375, 0.146–0.964).
Conclusions: NLR is associated with the [ malignant peritoneal mesothelioma (MPM) ] patients’ prognosis after CRS combined HIPEC treatment.
Malignant peritoneal mesothelioma (MPM) is a rare but aggressive cancer originating from the mesothelial cells that line the peritoneum. Risk factors include exposure to asbestos [1] and non-asbestos mineral fibers [2], a history of radiation therapy for other cancers [3], and germline BAP1 inactivation syndrome or other germline mutations [4]. [ Malignant peritoneal mesothelioma (MPM) ] is usually identified at an advanced stage because to its nonspecific symptoms, which include diminished appetite, weight loss, abdominal pain, swelling, or ascites, and intestinal blockage.
Treatment for [ malignant peritoneal mesothelioma (MPM) ] involves a multimodal approach, including surgery, chemotherapy, targeted therapy, and immunotherapy. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) followed by chemotherapy are considered the preferred options for selected patients [5, 6]. Typically, the Chemotherapy regimens may include pemetrexed, pemetrexed plus cisplatin, or cisplatin plus gemcitabine [7, 8]. Bevacizumab has demonstrated effectiveness in treating malignant pleural mesothelioma when combined with pemetrexed and cisplatin [9]. When compared to chemotherapy alone (median 14.1 months), combination immunotherapy utilizing PD-1 inhibition (nivolumab) and CTLA-4 inhibition (ipilimumab) has dramatically enhanced overall survival in some patients [10]….
Our work offers a conventional therapy for [ malignant peritoneal mesothelioma (MPM) ] with remarkable outcomes. The survival rates at 1, 3, and 5 years were 70.3%, 65.6%, and 59.4%, respectively, indicating a highly encouraging outcome. Numerous variables, such as pathogenic kind, post-operative neutrophil count, and post-operative NLR, can reflect a patient’s prognosis. The NLR was the most valuable of them all. Those with lower post-operative NLRs had higher overall survival rates.
Considering the neutrophil and lymphocyte counts, Kaplan-Meier analysis showed that a high neutrophil count was a risk factor rather than a high lymphocyte count. This suggests that the association between NLR and [ malignant peritoneal mesothelioma (MPM) ] patients’ survival is due to inflammatory cytokines rather than depletion of lymphocytes.
NLR, an inflammatory marker, has been linked to cancer patients’ survival rates, albeit the underlying process is still not fully understood. By preventing immune cells including lymphocytes, activated T cells, and natural killer cells from destroying other immune cells, neutrophilia may be able to suppress the immune system [18, 19]. Furthermore, increased NLR may draw immune-suppressive macrophages into tumors, which may then secrete immune-suppressive cytokines like interferon γ, platelet-derived growth factor, IL-17, IL-1ra, IL-6, IL-7, IL-8, IL-9, and IL-12 [20].
Few studies have examined the effect of NLR in patients undergoing CRS combined with HIPEC, despite the fact that numerous MPM studies have shown the impact of NLR levels on the survival of patients receiving chemotherapy or optimal supportive care [16, 17]. This study shows that MPM patients’ survival can be impacted by post-operative NLR and NLR change. A comparable association was discovered in cases of malignant pleural mesothelioma. NLR was discovered to be coupled with immune cell PD-L1 expression and a high NLR was linked to a poor prognosis [21].
Previous studies reported that hyperthermia might impair the cytolytic activity of cytotoxic T lymphocytes and affect the functions and counts of key immune cells, including NK cells and monocytes [22, 23]. Mild hyperthermia enhanced immune cell recruitment by increasing vascular perfusion and upregulation of vascular adhesion molecules such as ICAM-1, promoting immune cell infiltration [24]. Several preclinical studies showed that mild hyperthermia results in reduced tumor growth and improved animal survival, in parallel with enhanced infiltration and activation of immune cell populations, including natural killer (NK), CD4 + T, and CD8 + T cells [25].
In addition to NLR, pathological type has been identified as another independent risk factor influencing patient survival. This emphasizes how crucial it is to take pathological type into account while formulating treatment plans and carrying out prognosis assessment.
However, there are certain limitations on our study. This study lacks controls and is limited to a retrospective case series analysis. To validate our findings, multicenter studies and larger-scale random controlled trials were required. Furthermore, more thorough investigation is necessary to elucidate the mechanisms through which NLR may impact patients’ survival.
NLR is associated with the [ malignant peritoneal mesothelioma (MPM) ] patients’ prognosis after CRS combined HIPEC treatment.
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