Prognostic role of pre-chemotherapy platelet counts in patients with non-small cell lung cancer treated with first-line chemotherapy at IRD SMS medical college Jaipur

Kalim Khan; Bhaskara Kurup Latha Parvathi; Gulab Singh Yadav; Suresh Koolwal

doi:10.4103/AIHB.AIHB_36_20

ORIGINAL ARTICLE

Year : 2020 | Volume : 10 | Issue : 3 | Page : 115-119

Prognostic role of pre-chemotherapy platelet counts in patients with non-small cell lung cancer treated with first-line chemotherapy at IRD SMS medical college Jaipur

Kalim Khan, Bhaskara Kurup Latha Parvathi, Gulab Singh Yadav, Suresh Koolwal
Department of Respiratory Medicine, SMS Medical College, Jaipur, Rajasthan, India

Date of Submission	05-May-2020
Date of Acceptance	10-Aug-2020
Date of Web Publication	22-Sep-2020

Correspondence Address:
Suresh Koolwal
Department of Respiratory Medicine, SMS Medical College, Jaipur, Rajasthan
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/AIHB.AIHB_36_20

Abstract

Introduction: Lung cancer remains the most common cause of cancer death worldwide. The difference in outcome among patients with same clinical stage of disease suggests that advanced non-small cell lung carcinoma (NSCLC) is heterogeneous disease. The patient's heterogeneity is leading to need for identification of prognostic factors for survival. The analysis of these factors will be helpful in advising individuals, choosing treatment, understanding disease and optimising results of chemotherapy. Aim: To study the relationship between pre-chemotherapy platelet count and tumour response in NSCLC patients. Methodology: This was a hospital-based descriptive study. All patients are cytological and/or histological confirmed NSCLC. We divided patients in two group, patients with normal platelet count and patients with thrombocytosis. Platinum-based chemotherapy was started to patients after pre-chemotherapeutic evaluation. After 3^rd and 6^th cycles of chemotherapy, patients were evaluated for radiological response as per RECIST criteria. Results: Total 70 patients were enrolled in the study. Those patients who showed progressive disease after 3^rd cycle and 6^th cycle had higher mean platelet count (4.33 ± 1.21 lakh and 4.14 ± 0.30 lakh, respectively) compared to those patients who showed complete response and partial response. In this study, 78.57% patients with thromboytosis died, while 35.71% patients with normal platelet count died after 6 months of follow-up. Conclusions: The study suggests that pre-chemotherapy thrombocytosis can be considered as a potential negative independent factor for survival and tumour response in patients of NSCLC. Awareness of association between prognostic factor including pre-chemotherapy platelet count and NSCLC may benefit disease outcome.

Keywords: Lung cancer, pre-chemotherapy thrombocytosis, RECIST criteria

How to cite this article:
Khan K, Latha Parvathi BK, Yadav GS, Koolwal S. Prognostic role of pre-chemotherapy platelet counts in patients with non-small cell lung cancer treated with first-line chemotherapy at IRD SMS medical college Jaipur. Adv Hum Biol 2020;10:115-9

How to cite this URL:
Khan K, Latha Parvathi BK, Yadav GS, Koolwal S. Prognostic role of pre-chemotherapy platelet counts in patients with non-small cell lung cancer treated with first-line chemotherapy at IRD SMS medical college Jaipur. Adv Hum Biol [serial online] 2020 [cited 2021 Jan 15];10:115-9. Available from: https://www.aihbonline.com/text.asp?2020/10/3/115/295829

Introduction

Lung cancer remains the most common cause of cancer death worldwide for both men and women.^[1] Lung cancer is the main cause of mortality in cancer patients with a worldwide incidence of approximately 2.09 million/year.^[2] In India, lung cancer constitutes 6.9% of all new cancer cases and 9.3% of all cancer related deaths in both sexes. Out of 28 registries (population-based cancer registries in India), 11 registries encountered lung cancer as the leading malignancy.^[3] There are two main subtypes of lung cancer, small-cell lung carcinoma and non-small cell lung carcinoma (NSCLC), accounting for 15% and 85% of all lung cancer, respectively.^[4]

The mortality rate of lung cancer patients is high even after much research, aggressive treatment and great improvement in treatment. The difference in outcome among patients with the same clinical stage of the disease suggests that advanced NSCLC is a heterogeneous disease.^[5] The patient's heterogeneity is leading to the need for the identification of prognostic factors for survival. The analysis of these factors may define a subgroup of NSCLC patients with similar survival potential. They will be helpful advising individuals, choosing treatment, understanding the disease and optimising the results of chemotherapy.^[6]

Over the past decades, various studies have attempted to identify molecular biomarkers to predict the metastasis or recurrence of NSCLC.^[7],[8] Numerous promising biomarkers have been evaluated as potential prognosis predictors; however, none of these have been demonstrated to be sufficiently effective for clinical use. The majority of these markers are somewhat controversial and inconclusive. More recently, in various studies, a significant association has been found between malignancies and coagulation. A hypercoagulability state is one of the signs of more aggressive disease, while a thromboembolism is one of the major causes of mortality in cancer patients.^[9]

Thrombocytosis has been found to be a marker of poor prognosis in several cancers^[10] including gastrointestinal (Ikeda et al., 2002; Voutsadakis, 2014),^[11] ovarian (Allensworth et al.,2013; Stone et al., 2012),^[12] endometrial (Gücer et al.,1998; Njolstad et al., 2013),^[13] bladder^[14] and renal^[15] cancers. A prognostic significance between the platelet count and lung cancer has been identified.^{[16],[17],[18],[19],[20],[21]} However, the majority of these studies included small cell lung cancer and the samples were relatively small, hence we planned this study.

Methodology

This was a yearlong cross-sectional study conducted at Institute of Respiratory Diseases, SMS Medical College, Jaipur (India), in 2018–2019. The study protocol was approved by the Ethical Committee and the Research and Review Board of SMS Medical College, Jaipur.

Inclusion criteria of the study were patients between 18 and 76 years of age, newly diagnosed and pathologically confirmed cases of NSCLC with no prior history of chemotherapy or radiotherapy with normal renal and hepatic function tests. Exclusion criteria of the study werepatients who had any coexisting or previous cancer other than NSCLC, patients with diseases suspected to change the serum platelet concentration, including severe hypertension, splenic diseases and blood coagulation disorders, patients who had acetylsalicylic acid drugs 1 month prior to treatment.

In this study, 70 patients of NSCLC were evaluated. The entire study participants were evaluated in detail with history taking, physical and radiological examinations and routine investigations. Patients were divided in two groups, patients with normal platelet count and patients with elevated platelet count. We considered platelet count <4 lakh as normal count and 4 lakh or more as elevated platelet count. Platinum-based chemotherapy (paclitaxel and carboplatin) was started to all patients after pre chemotherapeutic evaluation. Chemotherapy was repeated at every 21 day for 6 cycles.

After 3^rd cycles and 6^th cycle of chemotherapy, computed tomography (CT) scan was repeated and patients were evaluated for radiological response as per RECIST criteria^[22] (complete response/partial response/stable disease/progressive disease). All patients were followed up to 6 months for survival.

Results

In total 70 patients, 59 (84.29%) were male and 11 (15.71%) were female with the sex ratio of 5.4:1. The mean age of male cancer patients was higher (59.84 ± 9.34 years) as compared to female patients (59.09 ± 9.93 years). In this study, 81.42% of patients were smokers and 18.17% patients were non-smokers. The overall smoker to non-smoker ratio was 4.4:1. Our all 89.83% males and 36.36% females were smokers. In this study, squamous cell carcinoma accounted for 72.85% of NSCLC, while only 24.28% were adenocarcinoma. Thrombocytosis was detected in 28 patients (40.00%) out of 70 patients. Thrombocytosis was seen in 63.63% of female and 35.59% of male patients. Mean pre-chemotherapy platelet count for study population was 3.56 ± 1.33. Moreover, the mean pre-chemotherapy platelet count for male and female patients were 3.81 ± 1.06 and 3.52 ± 1.38, respectively. Patients' demographic characteristics are shown in [Table 1].

Table 1: Patients' demographic characteristics

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In normal platelet count group after applying RECIST criteria after 3^rd cycle chemotherapy, 21 (58.33%) patients showed partial response, 8 (22.22%) patients showed stable disease and 7 (19.44%) patients showed progressive disease while in thrombocytosis group, 9 (50%) patients showed progressive disease, 8 (44.44%) patients showed stable disease and only 1 (5.55%) patient showed partial response. In this study, mean level of platelet count was 4.33 ± 1.21, 3.64 ± 1.04 and 2.47 ± 0.93 in patients who had progressive disease, stable disease and partial response, respectively, after 3^rd cycle of chemotherapy.

In normal platelet count group after 6^th cycle chemotherapy, 15 (57.17%) patients showed complete response, 12 (42.85%) patients showed partial response and 1 (3.57%) patient showed progressive disease while in thrombocytosis group, 1 (10.00%) patients showed complete response, 5 (50.00%) patients showed stable disease and 4 (40.00%) patients showed progressive disease. Mean level of platelet count was 2.34 ± 0.99, 2.76 ± 0.44, 4.57 ± 0.73 and 4.14 ± 0.30 in patients who had complete response, partial response, stable disease and progressive disease respectively after 6^th cycle of chemotherapy [Table 2].

Table 2: Association of platelet count with parameter of patients

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In our study of 70 patients 42 patients had normal platelet count and 28 patients had thromboytosis. Those who had a normal count survived 64.28%, while those who had thrombocytosis survived 21.42% after 6^th month follow-up. The mean platelet count of expired patients was higher than patient who survived after 6^th month. The mean pre-chemotherapy platelet count of expired patients was 4.22 ± 1.16 while mean prechemotherapy platelet count of survived patients was 2.82 ± 1.10.

Discussion

Identifying prognostic factors in non-small cell lung cancer has been the focus of many investigators. They are helpful in advising individuals, choosing treatment, understanding the disease and optimising the results of chemotherapy. Because of the heterogeneity of the disease and the variation in the chemotherapy regimens as well as the patient's characteristics, these prognostic factors vary from one study to another.

In this study, we examined 70 consecutive patients with inoperable NSCLC and found 28 patients (40%) who had thrombocytosis at the time of their first evaluation in our hospital. In previously published studies, the prevalence of thrombocytosis in patients with lung cancer varies widely between different series, ranging from 13% to 60%. In normal platelet count group, 6 patients were expired before 3^rd cycle chemotherapy and 8 were expired between 3 and 6^th cycle chemotherapy and 1 patient expired between 6^th cycle chemotherapy and 6^th month. In thrombocytosis group, 10 patients were expired before 3^rd cycle chemotherapy and 8 were expired between 3^rd and 6^th cycle chemotherapy and 4 patients expired between 6^th cycle chemotherapy and 6^th month.

Recent studies on the epidemiology of lung cancer in India have shown that the disease continues to be diagnosed more in male than female. In this study, squamous cell carcinoma accounted for 72.85% of NSCLC, while only 24.28% were adenocarcinoma, which is similar to study done by Davidov^[23] who reported squamous cell carcinoma in 74.2% and adenocarcinoma in 18.1%. In our study, majority of patients were classified in stage IVA (35.71%), followed by Stage IIIA (24.29%) and Stage IIIB (18.57%). Stage IIIC and IVB were 14.29% and 7.14%, respectively. This was in contrast to the study done by Forrest et al.^[24] where 47% patients were in Stage III and 52% were in Stage IV. This difference may be due to the fact that CT abdomen/CT brain/bone scan was not done for all patients and PET scan was also not done which may cause missing of occult distant metastasis.

In our study, 40.48% of patients with normal platelet count had performance status 0 and same 40.48% had performance status 1. Overall, 67.86% patients with thrombocytosis had performance status 2 which is similar to study done by Aoe et al.^[18] who reported that thrombocytosis was more common those with a worse performance status. Thrombocytosis is usually recognised as a complication occurring at a late or terminal stage of disease, especially in lung cancer. After 3^rd cycle chemotherapy, weight loss (≥10%) was more in patients with elevated platelets count (54.54%). Weight loss (<10%) was more in patients with normal platelet count (81.25%).

The prevalence of thrombocytosis did not differ significantly between ages, sex and histology. On the contrary, in the present study, we identified significant association between elevated platelet counts and advanced stage, worse PS and weight loss more than 10% on 3^rd cycle chemotherapy from pre-chemotherapy weight.

In our study, mean level of platelet count was 4.33 ± 1.21, 3.64 ± 1.04 and 2.47 ± 0.93 in patients who had progressive disease, stable disease and partial response, respectively, after 3^rd cycle of chemotherapy (P < 0.05). The mean level of platelet count was 2.34 ± 0.99, 2.76 ± 0.44, 4.57 ± 0.73 and 4.14 ± 0.30 in patients who had complete response, partial response, stable disease and progressive disease, respectively, after 6^th cycle of chemotherapy (P < 0.05).

A study done by Wang et al.^[15] evaluated the possibility of platelet level as a biomarker for response to platinum-based therapy in NSCLC by retrospective analysis of 167 NSCLC patients. In the complete response plus partial response, the pretreatment platelet count was 2.47 ± 0.89, while in stable disease plus progressive disease, pretreatment platelet count was 3.55 ± 1.19. In our study, the mean platelet count was high because patients had more advanced stage of tumour and many patients were smokers.

The precise reason for association between an elevated platelet count and the worse outcome for NSCLC remains unknown. First, the increase in platelet count may promote tumour cells growth and angiogenesis. Platelets release various cytokines, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), during blood clotting. The VEGF and PDGF family of proteins has a significant role in regulating angiogenesis. The invasiveness of the cancer cells may be enhanced by the plasma components in stored platelets.^[25] Moreover, platelets promote the formation of capillary like structures by endothelial cells, via integrins mediating cell-cell adhesion.^[26] Second, platelet enhance tumour metastasis by protecting the tumour cells from the host's immune system. Platelets expressing immunoregulatory proteins, including glucocorticoid induced tumour necrosis factor receptor related protein, may protect the cancer.^[27]

Hence, platelet level is an important inflammatory marker to predict radiological progression and overall survival in advanced non-small cell lung cancer.

Conclusions

The present study suggests that pre-chemotherapy thrombocytosis can be considered as a potential negative independent factor for survival and tumour response in patients of NSCLC treated with first-line chemotherapy. Pre-chemotherapy thrombocytosis should be considered important in the decision regarding indication for adjuvant therapy in patients of NSCLC.

As part of routine pre-chemotherapy, a complete blood count panel and platelet count may represent one of the easiest measuring tools as an independent prognostic marker for survival in NSCLC patients.

Awareness of association between prognostic factor including pre-chemotherapy platelet count and NSCLC in clinical practice may benefit disease outcome.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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