An example of timely palliative care: Survival results of pleural mesothelioma cases followed in our palliative care clinic

Authors

Abstract

Aim Malignant pleural mesothelioma (MPM) is a rare and deadly cancer with a poor prognosis. This study aimed to assess the effect of timely palliative care on survival and symptom management in MPM patients. We hypothesized that early palliative intervention could alleviate symptom burden and enhance survival outcomes.
Materials and Methods A retrospective analysis was conducted on 66 MPM patients referred to the Palliative Care Service between 2016 and 2023. Patients were categorized as inpatients or outpatients. Data on demographics, cancer history, disease stage, treatment, and survival were collected. Kaplan-Meier survival analysis, chi-square tests, and t-tests were used to compare outcomes.
Results The average survival duration was 20.9 ± 20.4 months, with a 5-year survival rate of 25.8%, exceeding previous reports. Inpatients, despite experiencing a higher symptom burden, lived more than six months longer than outpatients. Weight loss emerged as the strongest predictor of mortality, while age, gender, and BMI had no significant effect on survival.
Discussion Timely palliative care significantly improves survival outcomes in MPM patients by effectively managing symptoms and providing holistic care. Further randomized controlled trials are needed to confirm these findings and optimize strategies, especially in nutrition and symptom management. Early integration of palliative care is essential for better clinical outcomes in mesothelioma patients.

Keywords

Introduction

Palliative care is internationally recognized as a comprehensive approach that seeks to improve the quality of life of patients facing life-threatening illnesses and their families, through appropriate assessment and management of pain, as well as addressing physical, psychosocial, and spiritual needs [1]. Whether there is a need for palliative care has not been established, but there is literature indicating that this stage of policy has been poorly defined, and even overlooked in some cases, with care being only administered at a late stage in the disease process. Thus, it went some levels down; if any were achieved at all, the level of improvement of patients’ quality of life later on in the disease.
According to the theory, palliative care was only appropriate during the last stage of the disease. However, this began to change when it became clear, as in the 2010 study performed by Temel et al, that providing palliative care management early on patients suffering from non-small lung cancer improves their well-being, alleviates depressive symptoms, reduces the availability of aggressive care close to death, and potentially increases life expectancy [1]. These conclusions were next confirmed by statistical analyses of various kinds, indicating similar responses in other oncological and socially important chronic processes [2, 3, 4]. Regardless of these points, early palliative care cannot be implemented on an extensive basis due to some obstacles, such as a lack of funding, wrong ideas regarding palliative care as something that is required at the very end of life only, and wariness among patients and health care providers as well.
In particular, to overcome some of those barriers, Hui et al. [5] suggested a new term ‘timely’ instead of ‘early’ palliative care and clarified when a referral ought to be instituted because the patient may require it, e.g., symptoms may worsen or the patient might deteriorate. Similar principles are effective at places on offer, our hospital runs, where a patient is referred to an onco-palliative care specialist and services are provided as per the requirement of the patients where each time a timely service is provided.
Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer primarily associated with asbestos exposure, ionizing radiation, and genetic factors [6]. Despite advances in multimodal therapies — surgery, radiation, and systemic treatments — median survival remains approximately 12 months, with a 5-year survival rate of only 10% [7]. Given the poor prognosis, palliative care plays a critical role, particularly in managing pain and improving the quality of life for patients with advanced-stage disease [8]. However, most studies on mesothelioma focus primarily on the quality of life of patients and caregivers, with limited data on the demographic characteristics of patients receiving palliative care, and the effects of different palliative care approaches on survival [9, 10]. Additionally, there is a growing body of evidence to indicate that genetic factors, specifically BRCA1-associated protein-1 (BAP1) mutations, can dramatically influence the outcome for mesothelioma patients. Some others have suggested that BAP1-mutated tumors might have a better prognosis, and some have long overall survival similar to those with no family history of the disease [11]. This finding underscores the need to clinically evaluate for these mutations in patients, as their identification could help direct both therapeutic and palliative care. Despite this, genetics is rarely incorporated into palliative care plans, and there might be opportunities to enable more bio-individualized and higher-impact choices.
Another key aspect of effective palliative care in MPM is the integration of a multidisciplinary approach. Studies emphasize the importance of a multidisciplinary team (MDT) in managing mesothelioma, as this approach allows for comprehensive care that addresses the complex needs of patients [12]. MDTs typically include oncologists, thoracic surgeons, palliative care specialists, nurses, nutritionists, and social workers, all collaborating to create individualized care plans that manage both the physical and psychosocial aspects of the disease [13]. This collaborative approach ensures that patients receive not only optimal medical treatments but also emotional, psychological, and social support, which is crucial for improving quality of life in terminal illnesses. In our hospital, MDT meetings are regularly conducted to assess the changing needs of MPM patients, ensuring that care is tailored and adapted as the disease progresses.
The aim of this study is to examine the effects of timely palliative care on survival rates in patients with malignant pleural mesothelioma (MPM). MPM is an aggressive cancer type with a generally poor prognosis, and palliative care plays a critical role in improving the quality of life and managing symptoms in patients. This study seeks to evaluate how early or timely implementation of palliative care influences survival rates and the quality of life of patients. Our hypothesis is that timely and multidisciplinary palliative care will significantly extend the survival time of MPM patients and reduce symptom burden. In this context, the study aims to highlight the potential benefits of palliative care and determine the optimal timing for its application.

Materials and Methods

Our study is a retrospective examination of 66 pathologically confirmed MPM (Malignant Pleural Mesothelioma) patients who were referred to the Palliative Care Service by the medical oncology clinic, either as outpatients or inpatients, between 2016 and 2023 at a university hospital in Istanbul, Turkey. The palliative care services were organized using a multidisciplinary approach, involving a team of oncologists, thoracic surgeons, palliative care specialists, nurses, nutritionists, and social workers. This multidisciplinary team met regularly to assess and adjust treatment plans based on the evolving needs of the patients. Each team member played a specific role in ensuring comprehensive care: oncologists focused on systemic treatments, thoracic surgeons handled surgical interventions, while the palliative care team managed symptom relief, psychological support, and end-of-life care. Nurses monitored daily patient progress, nutritionists addressed malnutrition and weight loss, and social workers provided family support and counseling.
Ethical approval for this study was obtained from the university’s ethics committee, ensuring that all research was conducted in accordance with ethical standards. Patient records were analyzed in terms of gender, age, cancer history, environmental exposure, weight loss, tumor cell type, disease stage, treatment modalities, metastasis sites, supportive treatments used, and survival data. Environmental exposure data were determined based on the Turkish National Mesothelioma Surveillance and Environmental Asbestos Exposure Control Program study, examining where the patients were born and/or lived [14].
Patients were classified according to the TNM staging system established by the International Mesothelioma Interest Group (IMIG), with staging determined through a combination of pathological and clinical data, including imaging results [8].
Statistical Analyses
Data analysis was conducted using SPSS 22.0 software for Windows. Descriptive statistics, including the mean, standard deviation, minimum and maximum values, medians, and percentage distributions, were calculated. The Kolmogorov- Smirnov test was employed to assess whether the data conformed to a normal distribution. For categorical variables, comparisons between groups were made using chi-square or Fisher’s exact tests. In cases where parametric assumptions were met, Student’s t-test was used to evaluate differences between group means. Kaplan-Meier survival analysis was utilized to estimate survival times. A p-value of less than 0.05 was considered statistically significant.
Ethical Approval
This study was approved by the Ethics Committee of Süreyyapaşa Chest Diseases and Chest Surgery Training and Research Hospital (Date: 2023-10-19, No: 116.2017.R-332).

Results

A total of 66 people were included in the study, and the mean age of the patients was 61.9 ± 10.1 (min: 38, max: 88) years. Of the participants, 19 (28.8%) were female and 47 (71.2%) were male. While 30 (45%) of the cases were followed up as inpatients in palliative care, 36 (55%) were followed up as outpatients (Table 1). The most common complaints of the patients who were decided to be hospitalized according to general parameters and symptoms, were pain (40%) and shortness of breath (37%). Other than these symptoms, they were hospitalized with complaints of poor general condition (34%), malnutrition (27%), pleurisy (20%), and ascites (17%), and some had more symptoms elsewhere. The rate of non- smokers was 40.9%. Environmental exposure was detected in 35 of the patients (53.3%), and interestingly, half of the patients had a family history of cancer. The most common cancer types in the family were lung in 11 cases, breast in 6 cases, mesothelioma in 3 cases, and other cancer types in 13 cases. More interestingly, 9 cases with a history of cancer in more than one relative were found.
The number of hospitalizations for patients ranged from 1 to 7 times, with an average of 1.9. The length of hospital stays ranged from 1 to 28 days, with an average of 10.69 days. The follow-up periods for patients ranged from 1 to 107 months, with an average of 20 months.
19.7% of the patients received only chemotherapy, 28.7% received both chemotherapy and radiotherapy, 7.8% underwent surgery, 10.6% received both chemotherapy and surgery, 3.3% received palliative care, 30.3% received surgery, chemotherapy, and radiotherapy, and 55% received palliative radiotherapy. It was determined that 19 of 30 patients (63%) died in the palliative care.
As a result of the statistical analysis, it was determined that the mean BMI of those who died during palliative care was statistically significantly lower than that of those who survived (p = 0.004).
It was determined that the symptoms of pain and shortness of breath, and therefore the rates of painkiller and morphine use in palliative patients, were statistically significantly higher than in those who were not hospitalized (p < 0.005).
No statistically significant difference was detected between the groups in terms of other characteristics. While the survival of those who were not hospitalized in palliative care was 17.7 months, the survival of those who were hospitalized was calculated as 23.7 months. Although there was a 6-month longer survival between the groups, no statistically significant difference was found.
As a result of the statistical analysis, the weight loss of the patients who died was statistically significantly higher than the weight loss of survivors (p = 0.043).
Also, as a result of the analysis, it was determined that the mean weight loss of the patients who died was statistically significantly slightly higher than the weight loss rate of survivors (p = 0.046) (Table 2).
As a result of the statistical analysis, no statistically significant difference was found between exitus and survivors in terms of environmental exposure, family history of cancer, paracentesis, and pleurodesis.
Fifty-two (78.8%) of the cases died. The mean duration of survival was 20.9 ± 20.4 (min: 1, max: 100) months (Figure 1). As a result of the statistical analysis, the mean duration of survival of those who received trimodal therapy was statistically significantly longer than the mean survival of those who received monotherapy or dual therapy (p=0.006).
The mean survival was 30.4 ± 29.1 months in Stage I patients, 21.3±17.9 months in Stage II patients, 17.7±11.7 months in Stage III patients, and 11.9 ± 8.7 months in Stage IV patients. As a result of the statistical analysis, it was observed that the duration of survival decreased as the cancer stage increased, but no statistically significant difference was found between the groups (p=0.07). In the double comparison, a statistically significant difference was detected between Stage I and Stage IV in terms of mean duration of survival (p=0.03).
Among the participants in the study, the rate of survival at the end of 1 year was 71.2%, after 2 years was 39.4%, after 3 years was 30.3%, and after 5 years was 25.8%.

Discussion

In our study, we found that the mean survival was approximately 2 times higher than the literature. We think that the most important reason for this is that patients in need of palliative care are directed by medical oncology to palliative care in a coordinated manner, and maximum supportive treatments are provided for complications of the disease without wasting time as outpatient or inpatient treatment, depending on the patient’s condition. We have also determined that when the symptoms are controlled, the patients are referred back to oncology and the planned treatments can be applied immediately, thus the patients receive long-term follow-up and treatment, and therefore their survival is prolonged. As a result, the effectiveness of timely palliative care was demonstrated for the first time in a study.
In the systematic review by Breen et al., it was reported that patients and caregivers wanted improvements in diagnosis and access to palliative care, and that patients also wanted emotional support, patient-centered treatment, more information about disease progression and death, and meeting other people with mesothelioma [15]. In the literature, studies on palliative care are often related to quality of life and caregiver burdens [9, 10, 15]. However, very few patients are referred to palliative care and worldwide access to palliative care is approximately 14%. As an example, it has been detected in England, where hospice and palliative care are quite developed, that only 40% of patients seeking support for planning end-of-life care received this support [16].
Worldwide, the mean annual mesothelioma risk, with or without asbestos exposure, has been reported as 1.3/100,000 person- years for men and 0.2/100,000 person-years for women [8]. In our country, the annual mean incidence rate is calculated as 2.33/100,000 person/year. The higher incidence in men is due to occupational relationships. In our study, gender ratios and mean age were found to be consistent with the literature [8]. Interestingly, in our study, a family history of cancer was found in half of the patients. Genetic factors may also play a role in MPM. There are rare families with mutations in the BRCA1- related protein-1 (BAP1) gene, and survival is prolonged in patients with BAP1 mutations [8, 11]. In our study, genetic factors were not examined, but it is noteworthy that there is a 50% rate of cancer history in the family.
Histological identification is crucial in guiding treatment decisions because patients with different subtypes often have varying prognoses [7]. In our study, the distribution of mesothelioma subtypes aligns with the literature, with epithelioid mesothelioma being the most commonly observed, detected in 84.85% of cases (n = 56). Sarcomatoid mesothelioma was identified in 9.09% of cases (n = 6), while the mixed type (biphasic mesothelioma) was present in 6.06% of cases (n = 4). The predominance of the epithelioid subtype in our cohort is consistent with its association with better outcomes compared to sarcomatoid or biphasic types, further highlighting the importance of accurate histological classification in optimizing treatment strategies [17, 18].
The most frequently reported symptoms among pleural mesothelioma patients include shortness of breath (39%), fatigue (36%), generalized pain (34%), anxiety (29%), chest pain (25%), cough (22%), sweating (22%), and constipation (22%) [19, 20]. Similarly, in our study, the primary reasons for hospitalization were pain (40%) and shortness of breath (37%), based on the patients’ overall condition and presenting symptoms. In addition to these, other significant complaints leading to hospitalization included poor general condition (34%), malnutrition (27%), pleurisy (20%), and ascites (17%), with several patients exhibiting multiple symptoms simultaneously. As a result of statistical analyses performed on inpatients, it was found that the rates of pain, shortness of breath, painkiller use, and morphine use were statistically significantly higher than those who were not hospitalized. Therefore, the presence of inpatient palliative care services in hospitals is very important for patients with high symptom burden. It was found that 19 of 30 patients (63%) died while in palliative care. This result shows that the palliative service is a cost-effective process for the end of life and reduces unnecessary intensive care admissions, in line with studies in the literature.
National Comprehensive Cancer Network Guidelines recommend that patients with MPM should be managed by a multidisciplinary team experienced in MPM [7]. In patients with medically operable MPM, the use of chemotherapy, surgery, and hemithoracic RT is called trimodality therapy. In studies conducted with trimodality, it has been found that the prognosis is much improved. Median survival of up to 20 to 29 months has been reported for patients who complete trimodality therapy [7, 21, 22, 23, 24, 25]. In our study, consistent with the literature, the mean survival was 16.6 ± 15.9 months in those receiving monotherapy, 14.3 ± 10.1months in those receiving dual therapy, and 34.7 ± 28 months in those receiving trimodal therapy. These data were statistically significant, and it was determined that higher survival rates were obtained according to the literature data.
Surgery in the treatment of MPM should be performed in medically operable cases in combined modality treatment in patients with Stage I-III A [8, 17]. It is known that palliative radiotherapy provides effective pain control in more than half of mesothelioma patients [8]. Palliative radiotherapy was applied to 36 (55%) of our cases for pain.
When the final condition was evaluated, it was found that 21% (n = 14) of the cases survived and 79% (n = 52) died. Follow-up periods ranged between 1-107.1 months, and the mean was calculated as 20.18 months. In large case series, survival is given as between 6 and 17 months, with a mean of around or below 12 months. On the other hand, new treatment options provide relatively long life expectancy [18]. In our study, the mean survival was calculated as 20.9 ± 20.4 (min: 1, max: 100) months. In the literature, 5-year survival was found to be 10% [8, 14], while in another study, 1-year survival was found to be 38% and 3-year survival was 7% (RCP, 2018). In our study, the survival rate of patients at the end of 1 year was 71.2%, after 2 years was 39.4%, after 3 years was 30.3% and after 5 years was 25.8%. These rates were found to be considerably higher than those in the literature, almost twice as high, thus proving once again the effectiveness of timely palliative care.
Many factors that determine prognosis have been identified in the literature. Early tumor stage is among the most important factors affecting survival in MPM. Twenty-five of our cases were determined as stage I, 5 as stage II, 19 as stage III, and 17 as stage IV. We think that the reason why we have a high number of Stage I cases is that it is a specialized hospital where chest diseases, thoracic surgery, and oncology are combined, and there is no time wasted in diagnosis and treatment. The mean survival was 30.4 ± 29.1 months in Stage I patients, 21.3 ± 17.9 months in Stage II patients, 17.7 ± 11.7 months in Stage III patients, and 11.9 ± 8.7 months in Stage IV patients. In Rusch et al. study, the mean survival time was 22.9 months in stage 1 and 10.1 months in stage 4. In our study, we also found that survival was higher, especially in the early stages, compared to the literatüre [19]. As a result of the statistical analysis, it was seen that the survival decreased as the cancer stage increased, but no statistically significant difference was detected between the groups (p = 0.07). In the double comparison, a statistically significant difference was detected between Stage I and Stage IV in terms of mean survival (p = 0.03).
According to the literature, factors associated with a more favorable prognosis include younger age, undergoing surgery, receiving radiotherapy, having the epithelial histological subtype, as well as receiving a combination of chemotherapy and radiotherapy, or undergoing trimodal therapy [20, 21, 22, 23]. However, in our study, no statistically significant differences were observed in terms of age, gender, or BMI in relation to mortality outcomes.
Malnutrition is an important cause of morbidity and mortality in all diseases. In aggressive tumors such as mesothelioma, weight loss is inevitable, especially in the terminal period, resulting in malnutrition and sarcopenia [24, 25]. In our study, malnutrition was common in patients. Among the patients who survived or died, both weight loss and weight loss rate were found to be statistically significantly high, so it is very important to monitor malnutrition and make the necessary interventions in a timely manner.

Limitations

The main limitations of our study are that it is a retrospective study, a larger number of patients is needed to perform subgroup analyses, and genetic examinations of the patients were not performed. Despite the lack of comparison between cases that received palliative care support and those that did not receive palliative care support in our hospital, as a shortcoming of the study, it is also obvious that such symptomatic patients are in great need of palliative care from an ethical perspective.

Conclusion

In conclusion, our study demonstrated that the survival duration and 5-year survival rates of mesothelioma patients receiving palliative care were significantly higher than those reported in the existing literature. We attribute this improvement primarily to the timely initiation of palliative care, which likely helped address the symptom burden more effectively and provided crucial support during critical stages of the disease. Notably, although inpatients exhibited a higher symptom burden, their survival was extended by more than six months compared to outpatients, with a considerable number of inpatients passing away in palliative care. Additionally, our findings highlighted the importance of weight loss as a predictor of mortality in mesothelioma patients, emphasizing the need for nutritional interventions as part of comprehensive care.
Despite these promising findings, our study was observational, and randomized controlled trials are necessary to further validate the impact of timely palliative care on mesothelioma outcomes. Future research should also explore targeted strategies for symptom management and nutritional support to optimize quality of life and extend survival in this patient population. Overall, our results underscore the critical role of palliative care in improving the prognosis of mesothelioma patients and call for its timely and integrated implementation into treatment protocols.

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