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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 11  |  Issue : 2  |  Page : 106-111

Role of LENT score in prognosis of malignant pleural effusions


Department of Pulmonary Medicine, Government Hospital of Chest and Communicable Diseases, Andhra Medical College, Visakhapatnam, Andhra Pradesh, India

Date of Submission09-Sep-2021
Date of Decision27-Nov-2021
Date of Acceptance06-Dec-2021
Date of Web Publication08-Apr-2022

Correspondence Address:
Dr. Preethi Koyyana
Flat No 223, MK Gold Coast, Yendada, Visakhapatnam - 530 045, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijrc.ijrc_119_21

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  Abstract 


Background: Detection of exfoliated malignant cells in the pleura, i.e., malignant pleural effusion (MPE), is an advanced form of the disease with poor outcome and limited survival in both primary lung and nonlung primary carcinomas. LENT score, the first validated prognostic score, was developed to predict such survival in MPE. The aim of the study is to assess the role of LENT score to predict the survival in MPE along with Eastern Cooperative Oncology Group Performance Status (ECOG PS) score. Materials and Methods: A prospective observational study was conducted on 30 patients who presented with MPE. LENT score along with ECOG PS was calculated, and survival prediction at 1, 3, and 6 months was done using receiver operating characteristic (ROC) analysis. Results: Out of 30 patients, 22 had primary lung and 8 had nonlung primary malignancy. Fourteen patients were in the high-risk group (LENT score 5–7), 15 in the moderate-risk group (LENT score 2–4), and 1 in the low-risk group (LENT score 0–1). Overall median survival was 45 days. Analysis of the area under the ROC curve for LENT and ECOG PS score at predicting survival at 1 month (0.763 vs. 0.855), 3 months (0.889 vs. 0.938), and 6 months (0.920 vs. 0.976) showed no significant difference though ECOG PS was slightly better as a prognostic variable. Kaplan–Meier survival analysis with log-rank test showed that there is a significant difference in survival between the risk groups based on LENT score (Chi-square 20.5469, P ≤ 0.0001). Conclusion: Both LENT and ECOG PS scores are equally good at predicting survival rates in MPE; however, the LENT score is potent, easy to compute, clinically applicable up to the point and helps in guiding treatment selection.

Keywords: Eastern Cooperative Oncology Group Performance Status, LENT score, malignant pleural effusions, pleural fluid lactate dehydrogenase, serum neutrophil-to-lymphocyte ratio


How to cite this article:
Devi YG, Koyyana P, Nookaraju V, Padmaja B, Mounika P, Alekya P. Role of LENT score in prognosis of malignant pleural effusions. Indian J Respir Care 2022;11:106-11

How to cite this URL:
Devi YG, Koyyana P, Nookaraju V, Padmaja B, Mounika P, Alekya P. Role of LENT score in prognosis of malignant pleural effusions. Indian J Respir Care [serial online] 2022 [cited 2022 May 25];11:106-11. Available from: http://www.ijrc.in/text.asp?2022/11/2/106/342769




  Introduction Top


Up to half of patients with various metastatic malignancies develop para-malignant or malignant pleural effusion (MPE)[1],[2] and therefore is a common clinical challenge.[3] MPE is most common in lung cancer, followed by breast cancer, lymphoma, gynecological cancers, and malignant mesothelioma.[4] Primary tumor cannot be identified in 5%–10% of malignant effusions.[5] The present guidelines report that the median survival of MPE is between 3 and 12 months.[6] Data from the study by Dresler et al. and two large randomized controlled trials, time 1 and 2 on evaluating treatment strategies in MPE, suggest that the clinician's prediction on survival of patients with MPE was not accurate. Therefore, estimating patient survival based on clinical judgment alone is not sufficient.[7],[8]

Accurate prediction of prognosis at clinical presentation helps to choose personalized treatment pathways because a wide diversity of novel and advanced treatment options both for pleural effusions and primary tumors are available.[6],[9] Survival in patients with MPEs can be predicted based on numerous factors such as composition of the effusion type of tumor, the extent of disease, and two comorbidities.[10],[11],[12],[13] Inflammation-based markers such as pleural fluid (PF) lactate dehydrogenase (LDH) levels and neutrophil-lymphocyte ratio (NLR) in the serum have been associated with poor prognosis in several various malignancies, including mesothelioma.[14],[15],[16],[17] Previous studies showed that poor Eastern Cooperative Oncological Society Performance Status (ECOG PS) is significantly associated with mortality. However, after the effusions are treated, the ECOG PS may change, and therefore, solely depending on this, the mortality predictions may be suboptimal. The LENT score was the earliest validated risk scoring method; LENT scoring system in MPE consisting of LDH, ECOG-PS, NLR, and tumor type is slightly superior to ECOG PS in predicting survival. The score is clinically relevant, prognosis being easily calculated, thus aiding in explaining the prognosis to patients and also in guiding the selection of appropriate treatment strategies.[18] Moreover, the LENT scoring system is more objective than ECOG PS alone. The present study was undertaken to evaluate the role of the LENT score in predicting survival in MPE.


  Materials and Methods Top


This was a single-center prospective observational study conducted on 30 patients with MPEs who presented to the department of pulmonary medicine.

Inclusion criteria

All patients aged 18 years and above with proved MPEs were included in the study.

Exclusion criteria

  1. Patients who have HIV-positive serology
  2. Patients with comorbid diseases such as end-stage renal disease, left ventricular failure, and idiopathic pulmonary fibrosis which is likely to influence survival
  3. Patients not willing to participate in the study.


Patients with suspected MPEs were admitted to the hospital for further workup. The patient's demographic data were collected and noted. Detailed present and relevant history was taken. Thorough general physical examination was done.

The diagnosis of pleural effusion was done based on chest X-ray and ultrasound chest. All patients were subjected to routine baseline investigations such as complete blood count and metabolic profile and PF analysis. The PF analysis included total count, differential count, acid-fast staining, adenosine deaminase (ADA) levels, LDH levels, protein, sugar, cytology, and cellblock. Repeat cytology was done after 2 weeks if the initial report was negative for malignant cells. Contrast-enhanced computed tomography (CECT) was done in all cases after draining of the PF. Wherever indicated, histological diagnosis of the mass or nodular lesion found on CECT, ultrasound, computed tomography (CT)-guided fine-needle aspiration cytology (FNAC), or biopsy was done. A pleural biopsy was done in one case. In patients where both PF cytology and cell block were negative for malignancy, diagnosis is made based on the PF characteristics such as the color (hemorrhagic), low ADA, and lymphocyte-predominant effusions with a histologically proven malignancy in other organs. In eight cases, the primary malignancy was other than lungs. LENT score was calculated based on PF LDH, ECOG prognostic scale, peripheral blood NLR, and primary tumor. Based on the LENT score, patients were divided into high, moderate, and low risk and were followed up at 1, 3, 6 months or until death whichever was earlier. Survival is defined as the time from the diagnosis of effusion to death.

Ethical consent

Institutional ethical committee approval was taken, and written informed consent was taken from the study group before enrolling in the study.

Statistics

Statistical analysis was performed using SPSS Version 17 (IBM, Chicago Illinois, USA). Receiver operating characteristic (ROC) analysis comparing survival at 1, 3, 6 months using LENT and ECOG scores was done. Kaplan–Meier survival analysis with log-rank test was done for LENT score.


  Results Top


Thirty cases were taken for further study analysis. The mean age of the patients was 59.5 years (18–75). The majority of the patients were in the age group of 50–70 years (66.66%). The male-to-female ratio was 8:7. Pleural effusions were more common on the right side. The number of right, left, and bilateral effusions was 17, 12, and 1, respectively. In patients with carcinoma lung, the side of the effusion was on the side of the lesion. PF cytology was positive for malignant cells in 21 cases, and pleural biopsy was done in one case. In 8 cases, unexplained pleural effusions with histologically proven malignancies were found in organs other than the lung. Of the 30 patients, carcinoma lung was diagnosed in 22 and 8 had primary outside the lung. Two patients had a history of carcinoma cervix, one patient had a history of carcinoma breast, one case had malignant mesothelioma, one patient had a history of thymoma, one patient had a history of carcinoma thyroid, one patient had a history of carcinoma esophagus, and one case had a history of osteogenic sarcoma [Table 1]. Histopathology of the lung cancer was obtained using either FNAC or biopsy of the lung mass under image guidance of U/S or CT chest scanning. Adenocarcinoma was observed in 12 cases, squamous cell pathology in 7, and undifferentiated malignancy in 3. Seven patients had PF LDH levels >1500 IU, but a majority of the patients had their LDH levels between 500 and 1000 IU. The majority of the patients (24/30–80%) had an ECOG PS score of 2 or more. In patients with ECOG PS 0–2, the survival rates at 1, 3, and 6 months were 93%, 33%, and 26%, respectively, and in patients with ECOG PS 3 and 4, the survival rates at 1, 3, and 6, months were 39%, 6.6%, and 6.6%, respectively [Table 2]. In the present study, 14 patients were in a high-risk group (LENT score of 5–7) of which 7 were male and 7 were female, and 15 in a moderate-risk group (LENT score of 2–4) of which 8 were male and 7 were female, and only one patient in the low-risk group (LENT score of 0 and 1) [Table 3]. The median survival in the LENT high-risk group (n = 14) was 30 days (16–73 days) and the moderate-risk group (n = 15) was 75 days (18–270 days). Overall median survival was 45 days. One-month survival for high-risk category was only 42%. The rest died in <1 month. In the moderate-risk group, the survival rates at 1, 3, and 6 months were 93%, 33%, and 26%, respectively [Table 4].
Table 1: Primary tumor type

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Table 2: Survival at 1,3,6 months based on eastern co-operative oncology group performance status

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Table 3: LENT score risk groups

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Table 4: Survival rates at 1,3,6 months based on LENT scoring (n=30)

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Receiver operative curve curves for survival at 1, 3, and 6 months using Eastern Cooperative Oncology Group Performance Status

ROC for survival at 1 month using ECOG PS: Area under curve (AUC) is 0.855, associated criterion is ECOG PS >2, sensitivity is 90%, specificity is 75%, and P = 0.0001; ROC for survival at 3 months: AUC 0.938, associated criterion ECOG PS >1, sensitivity 91.6%, specificity 83.3%, and P = 0.0001; ROC for survival at 6 months: AUC 0.976, associated criterion ECOG PS >1, sensitivity 92%, specificity 100%, and P = 0.0001 [Figure 1].
Figure 1: Receiver operating characteristic curves for survival at 1, 3, and 6 months using Eastern Cooperative Oncology Group Performance Status

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Receiver operative curve for survival at 1, 3, 6 months by using LENT score

ROC for survival at 1 month: AUC is 0.763, associated criterion is LENT score >4, P = 0.0044, sensitivity 80%, specificity 70%.[6] ROC for survival at 3 months: AUC is 0.889, associated criterion is LENT >4, sensitivity 58.33% specificity 100%, P ≤ 0.0001. ROC for survival at 6 months: AUC is 0.920, associated criterion is LENT >4, sensitivity 58.33%, specificity 100%, P ≤ 0.0001 [Figure 2].
Figure 2: Receiver operative curve for survival at 1, 3, and 6 months using LENT score

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Receiver operative curve for survival at 1, 3, and 6 months by using the LENT score and Eastern Cooperative Oncology Group Performance Status

ROC for survival at 1 month using LENT score and ECOG PS: AUC for LENT and ECOG is 0.760 and 0.855, respectively, and P = 0.1252. ROC for survival at 3 months: AUC for LENT and ECOG PS is 0.889 and 0.938, respectively (P = 0.2424). ROC for survival at 6 months: AUC for LENT and ECOG PS is 0.920 and 0.976, respectively (P = 0.2645) [Figure 3].
Figure 3: Receiver operating characteristic for survival at 1, 3, and 6 months using LENT score and Eastern Cooperative Oncology Group Performance Status

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Kaplan–Mier Survival Analysis

[Table 5] shows Mean and median survival with 95% confidence interval (CI) based on LENT score (high, moderate, and low).The hazard ratio (HR) for high and moderate risk was 6.2728 (95% CI 1.4062–27.9808) and 1.6995 (95% CI 0.4580–6.3056), respectively. The Kaplan–Meier analysis showed a significant change in survival among different risk categories of LENT score Chi-squared 20.546, P ≤ 0.0001) [Figure 4].
Table 5: Kaplan Meier analysis: Mean, median survival in days with 95% confidence interval

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Figure 4: Kaplan–Meier survival analysis

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  Discussion Top


Malignant cells in PF and/or parietal pleura signifies disseminated or advanced disease and a reduced life expectancy in patients with cancer.[19] Recently to predict the survival of patients with MPE, several efforts have been made.[18],[20],[21],[22]

Formation of risk categorization using LENT score and early validation based on international cohorts of MPE patients was the most important among them.[18] This LENT scoring system divides patients into low-, moderate-, and high-risk groups based on PF LDH, COG performance status, serum NLR, and tumor type. Low-, moderate-, and high-risk groups are based on PF LDH, ECOG PS, serum NLR, and tumor type. The above scoring system also has the benefit of providing information on prognosis for both patients and doctors. The score has better interpretation than ECOG PS. As the LENT scoring system has more clinical relevance, it helps in deciding the treatment options tailoring to individual's predicted survival.[23]

The current study was a prospective observational study conducted in patients with MPE, to evaluate the role of LENT score. The median age in our study group was 60 years with a majority between 50 and 70 years of age group. Of the 30 subjects, 16 7 were male and 14 were female. These findings were similar to other studies.[14],[17],[20] Lung malignancy was the most common tumor in our study (n = 22) and adenocarcinoma was the most common histological tumor type (n = 12/22), which was in concordance with other studies. Many studies evaluated the primary site of malignancy as a prognostic indicator in MPEs, with bronchogenic carcinoma having poor and breast and gynecological tumors having the best prognosis. The median survival among the lung cancer group in the present study was 37 days and 44 days in a study by O'clive et al.[18] The concentration of LDH in PF was known to be associated with the prognosis of the patients. Higher LDH levels were associated with worsened survival of patients. In the present study, an LDH level of >1500 (which is allowed a score 1) was seen in only seven patients. Moreover, the majority of the patients had levels between 500 and 1000 IU. In a study by Martínez-Moragón et al., LDH concentration of >600 U/L was a significant predictor of poor survival (6 vs. 10 months, P < 0.01).[24] However, in a multivariate study by Amiz Z et al.,[25] high LDH concentration insignificantly corresponded to the 30-day survival of the patients. The present study showed that with PF LDH alone, there was no significant association with survival which was similar to other studies.[17],[25] The mechanisms for poor outcomes of malignancy with high NLR are poorly understood. In a systemic review and meta-analysis on the prognostic role of NLR in solid tumors by Templeton et al., the median cutoff for NLR was 4.[26] The prognostic effect of NLR was highest in mesothelioma, followed by pancreatic cancer, renal cell carcinoma, colorectal carcinoma, gastroesophageal cancer, and nonsmall-cell lung cancer. NLR cutoff in LENT score is 9; in our study, only one patient had an NLR of >9, although 16 patients had neutrophilia, they did not reach the cutoff value. ECOG scale evaluates disease progression and quantifies the extent to which the disease affects the daily living abilities of the patient. Chemotherapy trials of bronchogenic carcinoma had a cutoff of PS of 1 because patients with PS of 2 or more have been shown to have a particularly poor outcome in clinical trials after treatment.[27]

In our study, the AUC in ROC analysis of survival at 1, 3, and 6 months using ECOG PS was 0.855, 0.938, and 0.976 (P ≤ 0.0001). These values suggest that ECOG PS is a good predictor of prognosis in MPE, which was similar to the findings of studies by Zamboni et al. and Anevlavis et al.[17],[20] However, there are some limitations in prognostication by using the ECOG PS system.[28] The median survival periods for high-, moderate-, and low-risk groups by the LENT scoring system and the overall median survival were low in the present study compared to studies by O'Clive and Psallidas.[5],[18] The possible explanation for the low survival was because of small study group and more importantly due to the significant number of lung cancer cases (22/30) which is a high-risk tumor with a poor survival in the present study compared to other studies.

ROC analysis for survival at 1, 3, and 6, months for LENT score showed AUC of 0.760 (0.570–0.896, P = 0.0044), 0.889 (0.720–0. 974, P ≤ 0.0001), and 0.920 (0.761–0.987, P ≤ 0.0001), respectively. This is in agreement with other studies by Amelia et al. and Psallidas et al.[5],[18] Kaplan–Meier survival analysis with log rank test showed that there is a significant difference in survival between the risk groups based on LENT score (Chi-square 20.5469, P ≤ 0.0001). The Kaplan–Meier survival analysis and ROC indicate that the LENT score was a significant prognostic score and can be used for predicting survival and risk stratifying of patients with MPE, in accordance with other studies. The AUC in ROC analysis of survival at 1, 3, and 6 months using LENT was 0.760, 0.889, and 0.920 (P ≤ 0.0001), respectively, and for ECOG PS was 0.855, 0.938, and 0.976 (P ≤ 0.0001). These values suggest that ECOG PS was slightly better than LENT scoring as prognostic variable though it was not a significant difference. Similar results were shown by Kato et al., who evaluated the role of LENT score in patients of nonsmall cell lung cancer and concluded that both LENT and ECOG PS are good prognostic predictors for survival at 1, 3, and 6 months and there is no difference between the two in predicting the survival. These results are in contrary to the study by O'clive et al.


  Conclusion Top


  1. Both the LENT score and ECOG PS are good at predicting the survival rates in MPEs, and there is no statistically significant difference between ECOG PS and LENT scoring system in predicting prognosis
  2. Although the findings from our study suggest that ECOG PS is a statistically significant prognostic factor, its subjective nature and the possibility of improvement in performance after PF drainage/ICT, might alter the prediction. Hence, depending only on ECOG PS may lead to misclassification of the patient risk
  3. The LENT prognostic score is potent, easy to compute clinically relevant score on prognosis, which may aid in explaining the patients about prognosis and thereby guiding in the selection of proper treatment pathways.


Limitations

  1. Small sample size
  2. Less number of extrapulmonary malignancies or low-risk tumors.


Future studies are required which employ larger sample size with both high- and low-risk malignancies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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[PUBMED]  [Full text]  
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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