Anticancer Original Research Paper

The Glasgow prognostic score as a prognostic factor in patients with advanced non-small cell lung cancer treated with cisplatin-based first-line chemotherapy Ai-Gui Jiang, Hui-Yu Lu Department of Respiratory Diseases, Taizhou People’s Hospital, Taizhou, Jiangsu, P.R. China Objectives: The aim of this study was to assess the predictive value of survival in patients with advanced non-small cell lung cancer (NSCLC) treated with cisplatin-based first-line chemotherapy. Methods: In this study, 138 consecutive patients with advanced NSCLC were included in this study. Glasgow prognostic score (GPS) was calculated before the onset of treatment. The outcome indicators were progression free survival (PFS) and overall survival (OS). Results: Univariate log-rank test showed that GPS was significantly associated with both PFS (P 5 0.01) and OS (P 5 0.02). Multivariate Cox model revealed that the hazard ratios (HRs) for PFS were 0.8(0.5–0.9) for GPS 1 versus GPS 0 and 0.5(0.3–0.8) for GPS 2 versus GPS 0, respectively. The HRs for OS were 0.8(0.4–0.9) for GPS 1 versus GPS 0 and 0.5(0.2–0.8) for GPS 2 versus GPS 0, respectively. Conclusions: The GPS can be used as an independent predictor for survival in patients with advanced NSCLC. Keywords: Advanced non-small cell lung cancer, Cisplatin-based chemotherapy, Glasgow prognostic score, Prognosis

Introduction Lung cancer is one of the most common cancers in the world. A total of 228 190 new lung cancer cases and 159 480 lung cancer deaths were projected to occur in the United States in 2013.1 Non-small cell lung cancer (NSCLC) is the most common type, which accounts for 85% of all lung cancers diagnosed.2 Many patients with NSCLC had already been on the advanced stage IIIB or IV of the disease when diagnosed. Cisplatin-based chemotherapy has been considered as the standard first-line treatment for most patients with advanced NSCLC. However, the patients’ prognosis with cisplatin-based chemotherapy is still below expectation. The median survival time was reported only 10.3 months and the median progression free survival (PFS) time was 4.5 months.3 It is important to find out the factors predicting the prognosis of advanced NSCLC. Some studies have revealed that inflammation was an important factor in deciding the prognosis for NSCLC.4 The inflammation-based Glasgow prognostic score (GPS) is used to predict the prognosis for NSCLC by two indicators: elevated C-reactive protein (CRP) serum levels and hypoalbuminemia.5 An elevated CRP serum level reflects a state of systemic inflammation, Correspondence to: Ai-Gui Jiang, Department of Respiratory Diseases, Taizhou People’s Hospital, 210 Yingchun Road, Taizhou, Jiangsu 225300, P.R. China. Email: [email protected]

ß 2015 Edizioni Scientifiche per l’Informazione su Farmaci e Terapia DOI 10.1179/1973947814Y.0000000188

which indicates the initiation and progression of a variety of cancers.6 Hypoalbuminemia is proven to be related to weight loss, increased morbidity, and adverse outcomes in patients with malignant diseases, and is commonly seen in cancer patients.7 Some recent studies5,8–12 reported that GPS was elevated in patients with breast, colorectal, hepatocellular, gastric, pancreatic, and cervical cancer. The elevated GPS was also found as a factor predicting survival rate, which was independent of age, sex, and deprivation. The aim of the present study was to examine the relationship between an inflammation-based GPS and survival rate in patients with advanced NSCLC treated for cisplatin-based first-line chemotherapy.

Patients and Methods Patients This study was approved by the Ethics Committee of our hospital. A total of 138 consecutive patients with stage IIIB or IV NSCLC were prospectively included into the study cohort between January 2008 and January 2011. Patients’ clinical stages were based on initial evaluation including clinical assessment, chest X-ray, computed tomography of the chest and abdomen, computed tomography or magnetic resonance imaging of the brain, and bone scintigraphy. Demographic characters, including age, gender, histological type of the cancer, clinical stage of the cancer, smoking

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status, and Eastern Cooperative Oncology Group Performance Status (ECOG’s PS) were recorded.

Treatment All of the patients received at least two courses of cisplatin-based chemotherapy. The treatment was stopped till the appearance of progressive disease. The cisplatin-based regimens as a 21-day cycle include vinorelbine (25 mg/m2) on days 1 and 8 plus cisplatin (80 mg/ m2) on day 1, and gemcitabine (1000 mg/m2) on days 1 and 8 plus cisplatin (80 mg/m2) on day 1. Tumour response to treatment was evaluated according to response evaluation criteria in solid tumours (RECIST) criteria.13

Glasgow prognostic score evaluation The GPS comprises measurements of serum CRP and serum albumin. Blood samples were collected on the day before chemotherapy. Patients with both an elevated CRP (.10 mg/l) and hypoalbuminemia (,35 g/l) were allocated a score of 2 (GPS 2). Patients with normal serum CRP and albumin levels were allocated a score of 0 (GPS 0). The remaining patients with only one of the two measurements abnormal were assigned a score of 1 (GPS 1).5

Follow-up All patients received 2–5 years follow-up. The outcomes were demonstrated as PFS and overall survival (OS). Progression free survival was defined as the duration between the onset of chemotherapy and the date of first documented disease progression or death from any causes. Overall survival was defined as the duration between the onset of chemotherapy and the date of death from any cause.

Statistical analysis The chi-square test was used to correlate clinicopathological parameters with the GPS. To evaluate the prognostic significance of the GPS for PFS and OS, univariate analyses by the Kaplan–Meier method and log-rank test were performed. In order to adjust for other prognostic factors, multivariate analyses by Cox proportional hazards model in a forward stepwise manner were used. Results were presented as hazard ratio (HR) with 95% confidence interval (95% CI). P , 0.05 was considered significant. All statistical analyses were performed using IBM SPSS statistics software (version 19.0, IBM, Armonk, NY, USA).

Results Characterization of the study Patients’ median age was 55 years ranging from 37 to 81 years. Of all the patients included in this study, 45.7% (n 5 63) patients were over 60 years of age. One hundred and 17 patients (84.8%) were males. Sixtyseven (48.6%) patients had squamous cell carcinoma and 56 (59.6%) were diagnosed as stage IV. Forty-two (30.4%) patients were smokers and 82 (59.5%) patients had an ECOG performance status of 0 or 1. Seventy-six

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(55.1%) patients used DDP z NVB for chemotherapy, while the other 62 (44.9%) patients used DDP z GEM. A total of 81 (58.7%) patients acquired clinical remission (CR z PR). Clinicopathological characters of the patients are listed in Table 1.

Correlation of GPS with clinicopathological parameters The numbers for patients with stage IIIB were 46, 7, and 2 for GPS groups 0, 1, and 2, respectively. The difference of numbers between patients with stage IIIB and patients with stage IV was statistically significant (P 5 0.009). The results showed that increasing GPS was associated with higher NSCLC stages. However, we found that GPS was not significantly associated with the patients’ age, gender, histological type, smoking status, and ECOG’s PS (P . 0.05). Table 2 depicts the results of the correlation of GPS with clinicopathological parameters.

Glasgow prognostic score was an independent prognostic factor of PFS and OS Survival analyses showed that NCSLC stage, ECOG PS, chemotherapy response, and GPS were factors predicting prognosis for advanced NCSLC. Univariate and multivariate survival analyses are listed in Table 3. For GPS risk factors, the median PFS time was 7.5(4.6–10.4), 5.0(2.5–7.5), and 2.8(2.1–3.4) months in GPS 0, GPS 1, and GPS 2 group, respectively. The median OS time was 15.3(9.5–21.1), 11.2(7.1–15.3), and 7.9(3.5–12.3) months in GPS 0, GPS 1, and GPS 2 Table 1 Patients’ clinicopathological characteristics Characteristics Total Age #60 .60 Gender Male Female Histologic type Squamous cell carcinoma Adenocarcinoma Others Stage IIIB IV Smoking status Nonsmoker Smoker Performance status 0 1 2 3 Chemotherapy regimens DDP z NVB DDP z GEM Chemotherapy response CR z PR SD z PD

n

%

138

100.0

75 63

54.3 45.7

117 21

84.8 15.2

67 48 23

48.6 34.8 16.7

55 83

39.9 60.1

96 42

69.6 30.4

35 47 32 24

25.4 34.1 23.2 17.4

76 62

55.1 44.9

81 57

58.7 41.3

DDP: cisplatin; NVB: vinorelbine; GEM: gemcitabine; CR: complete response; PR: partial response; SD: stable disease; PD: progressive disease.

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Table 2 Relationship between clinicopathologic characteristics and GPS in patients with advanced NCSLC Characteristics Age #60 .60 Gender Male Female Histologic type Squamous cell carcinoma Adenocarcinoma Others Stage IIIB IV Smoking status Nonsmoker Smoker Performance status 0 1 2 3 Chemotherapy regimens DDP z NVB DDP z GEM Chemotherapy response CR z PR SD z PD

GPS 0 (n 5 95)

GPS 1 (n 5 32)

GPS 2 (n 5 11)

51 44

20 12

4 7

80 15

28 4

9 2

45 38 12

15 7 10

7 3 1

46 49

7 25

2 9

66 29

23 9

7 4

25 34 21 15

9 11 8 4

1 2 3 5

51 44

18 14

7 4

55 40

20 12

6 5

Chi2

P

2.308

0.315

0.282

0.868

1.693

0.792

9.379

0.009*

0.264

0.876

7.911

0.245

0.418

0.811

0.294

0.863

DDP: cisplatin; NVB: vinorelbine; GEM: gemcitabine; CR: complete response; PR: partial response; SD: stable disease; PD: progressive disease. * P , 0.05.

group, respectively. Univariate log-rank test showed that GPS was significantly associated with both PFS (P 5 0.01) and OS (P 5 0.02). Figure 1(A) and (B) show the PFS and OS curves which were calculated with Kaplan–Meier method according to GPS. Multivariate Cox proportional hazards model revealed that the GPS was an independent factor predicting poor PFS (P 5 0.02) and OS (P 5 0.02) in patients with advanced NSCLC. The HRs for PFS were 0.8(0.5–0.9) for GPS 1 versus GPS 0 and 0.5(0.3– 0.8) for GPS 2 versus GPS 0, respectively. The HRs for OS were 0.8(0.4–0.9) for GPS 1 versus GPS 0 and 0.5(0.2–0.8) for GPS 2 versus GPS 0, respectively.

Discussion The results of the present study indicate that the GPS can be used as an independent predictor for PFS and OS in patients with advanced NSCLC. Leung et al.14 conducted a study by using 5-year cancer-specific mortality as an end point and reported that the pretreatment GPS was an important predictor of cancer-specific survival in patients with inoperable NSCLC, with the area under the receiver operator curve 0.735 (95% CI, 0.566–0.903; P 5 0.024). Their conclusion is consistent with our findings. The GPS is a simple scoring method measuring only serum CRP and albumin levels.5 Numerous studies have reported that the elevated CRP is an indicator of a poor prognosis in a variety of cancers. For example, Kersten reported that the increase of CRP concentrations correlates with poor disease-specific survival in

each stage of colon cancer;15 Shimura found that serum CRP level before chemotherapy was a potential prognostic factor for metastatic gastric cancer;16 Hefler also reported serum CRP can be seen as a novel, widely available independent prognostic variable of ovarian cancer.17 C-reactive protein serum level was also found related to the prognosis of advanced NSCLC.18,19 Hypoalbuminemia can be observed in most advanced cancer patients, and is usually regarded as an index for malnutrition and cachexia. Hypoalbuminemia was proven as an independent prognostic factor for cancer.20 Arrieta et al. reported that malnutrition and hypoalbuminemia were associated with chemotherapyinduced toxicity in NSCLC patients treated with paclitaxel and cisplatin.21 The GPS, based on measuring both serum CRP and albumin levels, might facilitate the evaluation of systemic inflammation and malnutrition in patients with advanced cancer. The findings of the present study may translate to potential improvements in the therapy of advanced NSCLC. A GPS of 2 was associated with very poor survival in the present study. So, for patients with a GPS of 2, more aggressive adjuvant chemotherapy might be recommended. On the other hand, patients with a higher GPS indicated inflammatory response and malnutrition, which indicates that anti-inflammatory therapy and nutritional support are important for better prognosis in these patients. In summary, the results of the present study indicate that GPS, as an inflammation-based scoring

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1 0.7(0.5–2.2) 0.7(0.4–3.8) 1 0.6(0.4–0.9) 1 0.9(0.6–2.1) 1 0.7(0.2–0.9) 1 1.3(0.8–2.9) 1 0.8(0.4–0.9) 1 0.7(0.4–0.9) 0.5(0.2–0.8)

7.1(4.5–9.7) 4.3(2.5–6.1)

5.5(3.4–7.5) 5.0(3.3–6.7)

7.3(4.4–10.1) 4.1(2.3–5.9)

5.1(3.4–6.8) 5.3(3.6–7.0)

7.5(4.5–10.5) 4.2(2.2–6.1)

7.5(4.6–10.4) 5.0(2.5–7.5) 2.8(2.1–3.4)

1 1.6(0.8–2.5)

4.9(3.5–6.3) 5.2(3.8–6.5)

5.3(3.9–6.6) 5.1(3.2–6.9) 5.1(3.0–7.1)

1 0.8(0.6–4.2)

HR(95%CI)

5.3(4.0–6.6) 5.1(3.5–6.6)

Median (95% CI)

0.01*

0.03*

0.26

0.02*

0.58

0.01*

0.36

0.18

0.21

P

1 0.8(0.5–0.9) 0.6(0.2–0.8)

1 0.8(0.6–1.2)

1 1.6(0.7–3.6)

1 0.6(0.3–0.9)

1 0.8(0.4–3.3)

1 0.5(0.4–0.9)

1 0.6(0.4–5.6) 0.6(0.3–6.8)

1 1.8(0.7–3.9)

1 0.7(0.5–4.4)

HR(95%CI)

Multivariate

0.03*

0.13

0.32

0.02*

0.62

0.02*

0.34

0.26

0.35

P

15.3(9.5–21.1) 11.2(7.1–15.3) 7.9(3.5–12.3)

14.3(9.2–19.3) 7.3(5.1–9.4)

10.8(7.5–14.1) 12.0(5.9–18.1)

13.7(9.1–18.2) 7.9(5.3–10.4)

12.7(6.5–18.9) 10.3(6.4–14.1)

14.3(9.8–18.7) 7.5(5.1–9.8)

12.1(8.1–16.1) 10.6(7.5–13.6) 10.6(7.1–14.1)

11.4(7.6–15.2) 12.0(7.9–16.1)

12.8(8.6–16.9) 11.1(8.1–14.1)

Median (95% CI)

1 0.8(0.5–0.9) 0.5(0.3–0.8)

1 0.7(0.5–1.1)

1 1.7(0.6–3.2)

1 0.7(0.2–0.9)

1 0.8(0.4–3.2)

1 0.5(0.4–0.9)

1 0.7(0.5–2.7) 0.6(0.4–6.9)

1 1.4(0.6–3.7)

1 0.8(0.3–4.1)

HR(95%CI)

Univariate

0.02*

0.15

0.34

0.02*

0.21

0.03*

0.42

0.37

0.25

P

OS (months)

1 0.8(0.4–0.9) 0.5(0.2–0.9)

1 0.8(0.6–1.2)

1 1.5(0.4–4.1)

1 0.7(0.2–1.9)

1 0.7(0.3–4.1)

1 0.6(0.3–0.9)

1 0.8(0.4–4.2) 0.7(0.5–6.2)

1 1.6(0.5–4.4)

1 0.8(0.5–5.2)

HR(95%CI)

Multivariate

0.02*

0.18

0.41

0.23

0.35

0.03*

0.62

0.35

0.33

P

OS: overall survival; HR: hazard ratio; ECOG PS: Eastern Cooperative Oncology Group Performance Status Scale; DDP: cisplatin; NVB: vinorelbine; GEM: gemcitabine; CR: complete response; PR: partial response; SD: stable disease; PD: progressive disease. * P , 0.05.

Age #60 .60 Gender Male Female Histologic type Squamous cell carcinoma Adenocarcinoma Others Stage IIIB IV Smoking status Nonsmoker Smoker ECOG PS 0–1 2–3 Chemotherapy regimens DDP z NVB DDP z GEM Chemotherapy response CR z PR SD z PD Glasgow prognostic score 0 1 2

Characteristics

Univariate

Disease-free survival (months)

Table 3 Univariate and multivariate survival analyses in patients with advanced non-small cell lung cancer (NCSLC)

Jiang and Lu Glasgow prognostic score as a prognostic factor

Jiang and Lu

Figure 1 Glasgow prognostic score and its prognostic effects in advanced NSCLC. (A) Kaplan–Meier survival analysis for the progression free survival (PFS). (B) Kaplan–Meier survival analysis for the overall survival (OS).

system, is a simple and useful factor predicting prognosis in patients with advanced NSCLC. The GPS can be used to individualize treatment strategies and the follow-up of patients with advanced NSCLC treated with cisplatin-based first-line chemotherapy.

Disclaimer Statements Contributors Ai-Gui Jiang contributed to study design, data collection, and preparation of the manuscript. HuiYu Lu contributed to study design and data collection. Funding None. Conflict of interest The authors have no conflict of interest concerning this study. Ethics approval This study was approved by the Ethics Committee of our hospital.

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Glasgow prognostic score as a prognostic factor

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The Glasgow prognostic score as a prognostic factor in patients with advanced non-small cell lung cancer treated with cisplatin-based first-line chemotherapy.

The aim of this study was to assess the predictive value of survival in patients with advanced non-small cell lung cancer (NSCLC) treated with cisplat...
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