Prognostic value of pretreatment procalcitonin and neutrophil– lymphocyte ratio in extensive-stage small-cell lung cancer

Prognostic value of pretreatment procalcitonin and neutrophil– lymphocyte ratio in extensive-stage small-cell lung cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prognostic value of pretreatment procalcitonin and neutrophil– lymphocyte ratio in extensive-stage small-cell lung cancer Dongfang Chen, Jianlin Xu, Yizhuo Zhao, Baohui Han, Runbo Zhong This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2518797/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose To investigate the influence of pretreatment neutrophil-to-lymphocyte ratio (NLR) and procalcitonin (PCT) on progression-free survival (PFS) in extensive-stage small-cell lung cancer (SCLC) patients. Methods A total of 100 extensive-stage SCLC patients were enrolled in our study. Patients were stratified according to the median values of pretreatment NLR and PCT levels: low NLR group (NLR ≤ 3.17), high NLR group (NLR༞3.17), low PCT group (PCT ≤ 0.06; ng/ml), high PCT group (PCT༞0.06; ng/ml). The Kaplan-Meier method and multivariable Cox regression model were used to reveal the prognostic effects of pretreatment NLR and PCT on PFS. Results The median PFS of the total extensive-stage SCLC patients was 6.0 months. The median PFS of low pretreatment NLR group (NLR ≤ 3.17) was not significantly different from that of high pretreatment NLR group (6.2 months vs 5.8 months; P = 0.675). Patients with low pretreatment PCT (PCT ≤ 0.06; ng/ml) had significantly better PFS than patients with high pretreatment PCT (PCT༞0.06; ng/ml) (6.9 months vs 5.7 months; P = 0.043). With the multivariable Cox regression analysis, the response to first-line chemotherapy (P ≤ 0.001) and pretreatment PCT (HR = 0.516; 95%CI 0.326–0.817; P = 0.005) were identified as independent factors associated with PFS. Conclusion Pretreatment PCT is an independent factor associated with PFS in extensive-stage SCLC patients treated with first-line chemotherapy, but pretreatment NLR reflects no significant prognostic value in our study. Extensive-stage small-cell lung cancer neutrophil-to-lymphocyte ratio procalcitonin progression-free survival Figures Figure 1 Figure 2 Introduction SCLC accounts for about 15% -20% of lung cancer cases[ 1 ]. SCLC belongs to one of neuroendocrine tumors, which is characterized by rapid tumor proliferation, tendency for early and extensive metastases, and poor prognosis[ 1 ]. About 60% of the SCLC patients are in an extensive stage at the time of diagnosis[ 2 ]. The first-line standard treatment for extensive-stage SCLC patients mainly remains chemotherapy with platinum-etoposide. The responses of posterior-line treatments for extensive-stage SCLC patients are limited and poor, and the median overall survival(OS) is approximately 8 to 12 months[ 3 ]. With the deep understanding of tumor microenvironment, it has been gradually clear that there is a complex relationship among inflammation, immunity, and cancer[ 4 ]. Inflammation has impacts on almost each step of tumorigenesis including tumor initiation, tumor promotion, and metastatic progression[ 4 ]. And immune surveillance plays an important role in preventing or inhibiting tumor growth[ 4 ]. Biochemical markers of inflammatory response have been incorporated in prognostic scores for several types of cancer. Lymphocytes, especially T cells are commonly found within the tumor microenvironment, which mainly engage in anti-tumor immune responses. NLR, a typical marker of inflammation and immune status has been associated with prognosis in various malignant tumors such as gastric cancers, colorectal cancers, pancreatic cancers, and even lung cancers[ 5 ]. A higher pretreatment NLR generally predicts poorer prognosis, but it remains unclear whether pretreatment NLR has influence on the short-term survival of extensive-stage SCLC patients. Serum PCT as a biomarker has been developed over the past two decades for the diagnosis of bacterial infections, including sepsis, community acquired acute pneumonia and exacerbation of chronic obstructive pulmonary diseases (COPD)[ 6 ]. PCT-based strategy is widely used to guide antibiotic therapy clinically. PCT can, however, be elevated in some neoplastic situations while there is no infectious process, particularly in tumorous diseases like medullary thyroid cancer and SCLC, in which PCT is secreted by the tumor cells[ 7 ]. It has also been reported that SCLC cell lines could produce PCT in vitro[ 8 ]. In a study reported by Walter et.al, elevated PCT was present in medullary thyroid cancer patients without infection, besides, the survival analysis indicated that elevated PCT was associated with poor prognosis[ 9 ]. Patout et.al reported that higher PCT levels were detected in the tumors with neuroendocrine component, for example, PCT levels were significantly higher in SCLCs than in pulmonary adenocarcinomas[ 10 ]. A case report also described a phenomenon that the PCT levels were relatively high in a patient with metastatic SCLC but without infection during admission, and surprisingly the PCT levels appeared a trend of decrease after anti-cancer treatment[ 11 ]. As we observed in clinical practice, the elevation of PCT was present in most small-cell carcinoma cases, as well as in large-cell carcinomas with neuroendocrine component. However, few studies reveal the implications of PCT in SCLC patients, especially the prognostic value of PCT. Thus, the aim of our retrospective study is to investigate the influence of pretreatment NLR and PCT on progression-free survival (PFS) in extensive-stage SCLC patients treated with first-line chemotherapy. Materials And Methods Patients A total of 100 patients who had been diagnosed with extensive-stage SCLC histopathologically and clinically at Shanghai Chest Hospital from February 2018 to February 2019 were enrolled in our retrospective study. The follow-up ended on October 15th, 2019. The study protocol was approved by the Ethics Committee of Shanghai Chest Hospital and conducted in accordance with the Declaration of Helsinki (as revised in Fortaleza, Brazil, October 2013). Due to the retrospective nature of this study, the need for informed consent was waived. The key inclusion criteria were as follows: (1) patients whose data on pretreatment NLR and PCT levels were available; (2) patients without any kind of infections at diagnosis or during treatment; (3) patients who had at least one measurable tumor lesion; (4) patients who aged between 18 and 70; (5) patients whose Eastern Cooperative Oncology Group performance status were 0 to 1; (6) patients who received cisplatin or carboplatin combined with etoposide as first-line chemotherapy. Data collection The clinical characteristics included gender, age, smoking history, anatomy type, response to first-line chemotherapy, pretreatment NLR and PCT levels. All enrolled patients received response evaluations every two courses of chemotherapy according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The PFS was defined as the time from the initiation of first-line chemotherapy to disease progression or the last follow-up visit. Data on pretreatment NLR and PCT levels were collected at the initiation of first-line chemotherapy. The NLR was defined as the absolute neutrophil count divided by the absolute lymphocyte count. The normal reference value of PCT in our study ranged from 0 to 0.05ng/ml. Statistical analysis Patients were stratified according to the median values of pretreatment NLR and PCT levels. SPSS22.0 statistical software (IBM, Armonk, NY, USA) was used to analyze data. The Chi-squared test was used to identify the clinical characteristics related to pretreatment NLR (or PCT). The Kaplan-Meier method and log-rank test were used to investigate the association between pretreatment NLR (or PCT) and PFS. The multivariable Cox regression model was used to screen out the significant factors related to PFS. All analyses were two-sided, and P values ༜0.05 were defined as statistical significance. Results Patient characteristics Our retrospective study included 100 extensive-stage SCLC patients. The male and female patients accounted for 86% and 14%, respectively. Of the total patients, 84(84%) patients were ever-smokers while 16(16%) patients were never-smokers. Central type(73%) was the main anatomy type of all patients. In terms of response to first-line chemotherapy, 60(60%), 30(30%) and 10(10%) patients achieved partial response (PR), stable disease(SD) and progressive disease(PD), respectively. The median value of pretreatment NLR level was 3.17 (range:1.0-10.1). The median value of pretreatment PCT level was 0.06 (range:0.02–1.49; ng/ml) (Table 1 ). Characteristic N(%) Table 1 Clinical characteristics of the 100 patients Gender Male/Female 86(86%)/14(14%) Age(years) ≤65/＞65 57(57%)/43(43%) Smoking history No/Yes 16(16%)/84(84%) Anatomy type Central type/Peripheral type 73(73%)/27(27%) Response to first-line chemotherapy PD/SD/PR 10(10%)/30(30%)/60(60%) NLR (range:1.0-10.1; median: 3.17) ≤3.17/＞3.17 50(50%)/50(50%) PCT (range:0.02–1.49; median:0.06; ng/ml) ≤0.06/＞0.06 52(52%)/48(48%) PD: progressive disease; SD: stable disease; PR: partial response: NLR: neutrophil-to-lymphocyte ratio; PCT: procalcitonin The association between pretreatment NLR (or PCT) and clinical characteristics The statistical results showed that pretreatment NLR or PCT was not significantly associated with gender, age, smoking history, anatomy type, and response to first-line chemotherapy (Table 2 , Table 3 ). Characteristic NLR ≤ 3.17(n = 50) NLR＞3.17(n = 50) P-value Table 2 The association between pretreatment NLR and clinical characteristics Gender Male 46(92%) 40(80%) 0.084 Female 4(8%) 10(20%) Age(years) ≤ 65 28(56%) 29(58%) 0.840 ＞65 22(44%) 21(42%) Smoking history No 7(14%) 9(18%) 0.585 Yes 43(86%) 41(82%) Anatomy type Central type 40(80%) 33(66%) 0.115 Peripheral type 10(20%) 17(34%) Response to first-line chemotherapy PD 4(8%) 6(12%) 0.465 SD 13(26%) 17(34%) PR 33(66%) 27(54%) PD: progressive disease; SD: stable disease; PR: partial response: NLR: neutrophil-to-lymphocyte ratio Characteristic PCT ≤ 0.06 (n = 52) PCT＞0.06(n = 48) P-value Table 3 The association between pretreatment PCT and clinical characteristics Gender Male 47(90%) 39(81%) 0.188 Female 5(10%) 9(19%) Age(years) ≤ 65 30(58%) 27(56%) 0.884 ＞65 22(42%) 21(44%) Smoking history No 7(14%) 9(19%) 0.471 Yes 45(86%) 39(81%) Anatomy type Central type 34(65%) 39(81%) 0.074 Peripheral type 18(35%) 9(19%) Response to first-line chemotherapy PD 6(11%) 4(8%) 0.829 SD 16(31%) 14(29%) PR 30(58%) 30(63%) PD: progressive disease; SD: stable disease; PR: partial response; PCT: procalcitonin Progression-free survival The median PFS of the total extensive-stage SCLC patients was 6.0 months. The median PFS of male and female patients were 6.0 months and 5.7 months, respectively (P = 0.448). The median PFS of patients with smoking history and patients without smoking history were 6.0 months and 5.7 months, respectively (P = 0.368). The median PFS of low pretreatment NLR group (NLR ≤ 3.17) was longer than that of high pretreatment NLR group (6.2 months vs 5.8 months), however, no significant difference was found (P = 0.675). Most importantly, our study showed that patients with low pretreatment PCT (PCT ≤ 0.06; ng/ml) had significantly better PFS than patients with high pretreatment PCT (PCT＞0.06; ng/ml) (6.9 months vs 5.7 months; P = 0.043)(Fig. 1 ). The same results were observed in subgroups (Fig. 2 ). With the multivariable Cox regression analysis, the response to first-line chemotherapy (P ≤ 0.001) and pretreatment PCT (HR = 0.516; 95%CI 0.326–0.817; P = 0.005) were identified as independent factors associated with PFS (Table 4 ). Characteristic Median PFS (months) Univariate analysis (P-value) Multivariate analysis [HR (95%CI)] P-value Table 4 Univariate and multivariate analyses with regard to PFS Gender Male 6.0 0.448 Female 5.7 Age(years) ≤65 6.2 0.210 ＞65 6.0 Smoking history No 5.7 0.368 Yes 6.0 Anatomy type Central type 6.0 0.915 Peripheral type 6.0 Response to first-line chemotherapy PD 1.7 ≤ 0.001 ≤ 0.001 SD 6.0 SD 6.0 0.056 PR 6.9 NLR ≤ 3.17 6.2 0.675 ＞3.17 5.8 PCT (ng/ml) ≤ 0.06 6.9 0.043 0.516(0.326–0.817) 0.005 ＞0.06 5.7 PD: progressive disease; SD: stable disease; PR: partial response: NLR: neutrophil-to-lymphocyte ratio; PCT: procalcitonin; PFS: progression-free survival; HR: hazard ratio; CI: confidence interval Discussion Our retrospective study investigated the prognostic value of pretreatment NLR and PCT in extensive-stage SCLC patients treated with first-line chemotherapy. To our knowledge, there are few studies about the relationship between pretreatment PCT and survival in extensive-stage SCLC patients. This study shows lower pretreatment PCT is associated with better PFS in extensive-stage SCLC patients treated with first-line chemotherapy. The implications of NLR have been discussed in previous SCLC-related studies. A retrospective study of 139 SCLC patients showed that high NLR was associated with poor OS[ 12 ]. Ryoko et.al reported higher pretreatment NLR predicted worse OS in extensive-stage SCLC patients[ 13 ]. Another study indicated that NLR could be used as a negative prognostic factor for OS in extensive-stage SCLC patients[ 5 ]. Overall, these findings imply that NLR may predict the long-term survival of SCLC. Besides, a research on extensive-stage SCLC showed that the PFS of first-line chemotherapy was significantly different according to the stratification of baseline NLR, and patients with NLR༜3 could have PFS benefit[ 5 ]. Kang et.al also reported some similar results[ 14 ]. Inflammatory responses to tumors are mediated by the release from neutrophils of inflammatory cytokines, leukocytic and other phagocytic mediators that induce damage to cellular DNA, inhibit apoptosis and promote cancer-associated angiogenesis[ 15 ]. A higher NLR indicates a heavier tumor burden and higher level of inflammation,which may associate with poor prognosis. However, our study found no significant relationship between pretreatment NLR and PFS in extensive-stage SCLC patients, though the median PFS of low NLR group was a bit longer compared with high NLR group. This may be explained by the fact that some extensive-stage SCLC patients are quite sensitive to chemotherapy despite of the heavy tumor load. However, the OS is the gold standard for determining whether the NLR ratio can be used as a predictor. Further investigation is required to increase understanding of the pathophysiology of this relationship and validate these findings with data collected prospectively. PCT is widely used to guide the diagnosis and treatment of bacterial infection. Unlike NLR, we did not know much about the implications of PCT in lung cancer. PCT is secreted by the C-cell of thyroid and neuroendocrine cells located in lung, adrenal, liver, kidney, and muscles[ 16 ]. Biosynthesis of PCT in small cell carcinomas of the lung was firstly reported by Cate et.al[ 8 ], then, neuroendocrine cancers including SCLC are known to be associated with PCT elevation. A previous study showed that pretreatment PCT level above 0.15ng/ml was significantly associated with shorter OS in lung cancer patients[ 7 ]. In our study, extensive-stage SCLC patients with pretreatment PCT level under 0.06 ng/ml could have PFS benefit after first-line chemotherapy. Our results may be explained by the fact that a greater PCT elevation in SCLC patients is associated with a heavier tumor burden especially in extensive stage, which leads to poorer prognosis. Further research is needed to determine the specificity of PCT in SCLC patients and particularly explore the potential usefulness of PCT to monitor the response to chemotherapy. Our study also has some limitations. Firstly, it is a retrospective study: secondly, the data of OS are not available due to the high rate of lost to follow-up. To sum up, we find that pretreatment PCT is an independent factor associated with PFS in extensive-stage SCLC patients treated with first-line chemotherapy, however, pretreatment NLR reflects no significant prognostic value in our study. Declarations Acknowledgments We would like to thank all of the investigators for their involvement in this study. Author contributions (I)Conception and design:Dongfang Chen, Runbo Zhong (II) Administrative support:Baohui Han (III) Provision of study materials or patients: Jianlin Xu (IV) Collection and assembly of data: Yizhuo Zhao (V) Data analysis and interpretation: Dongfang Chen (VI) Manuscript writing: All authors (VII) Final approval of manuscript:All authors Data availability The data used to support the findings of this study are available from the first author and the corresponding author upon request. Funding This work was supported by the Natural Science Foundation of Shanghai（19ZR1449700）. Conflict of interest All authors declare that there is no conflict of interest. References Kahnert K, Kauffmann-Guerrero D, Huber RM. SCLC-State of the Art and What Does the Future Have in Store? Clin Lung Cancer 2016; 17: 325-333. van Meerbeeck JP, Fennell DA, De Ruysscher DK. Small-cell lung cancer. Lancet 2011; 378: 1741-1755. Gong J, Salgia R. Managing Patients With Relapsed Small-Cell Lung Cancer. J Oncol Pract 2018; 14: 359-366. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010; 140: 883-899. Sakin A, Sahin S, Yasar N et al. The Relation between Hemogram Parameters and Survival in Extensive-Stage Small Cell Lung Cancer. Oncol Res Treat 2019; 42: 506-515. Heper Y, Akalin EH, Mistik R et al. Evaluation of serum C-reactive protein, procalcitonin, tumor necrosis factor alpha, and interleukin-10 levels as diagnostic and prognostic parameters in patients with community-acquired sepsis, severe sepsis, and septic shock. Eur J Clin Microbiol Infect Dis 2006; 25: 481-491. Patout M, Salaun M, Brunel V et al. Diagnostic and prognostic value of serum procalcitonin concentrations in primary lung cancers. Clin Biochem 2014; 47: 263-267. Cate CC, Pettengill OS, Sorenson GD. Biosynthesis of procalcitonin in small cell carcinoma of the lung. Cancer Res 1986; 46: 812-818. Walter MA, Meier C, Radimerski T et al. Procalcitonin levels predict clinical course and progression-free survival in patients with medullary thyroid cancer. Cancer 2010; 116: 31-40. Avrillon V, Locatelli-Sanchez M, Folliet L et al. Lung cancer may increase serum procalcitonin level. Infect Disord Drug Targets 2015; 15: 57-63. Pardo-Cabello AJ, Manzano-Gamero V. Small cell lung cancer elevates procalcitonin levels in the absence of infection. Lung Cancer 2019; 134: 272-273. Liu D, Huang Y, Li L et al. High neutrophil-to-lymphocyte ratios confer poor prognoses in patients with small cell lung cancer. BMC Cancer 2017; 17: 882. Suzuki R, Lin SH, Wei X et al. Prognostic significance of pretreatment total lymphocyte count and neutrophil-to-lymphocyte ratio in extensive-stage small-cell lung cancer. Radiother Oncol 2018; 126: 499-505. Kang MH, Go SI, Song HN et al. The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with small-cell lung cancer. Br J Cancer 2014; 111: 452-460. Liew PX, Kubes P. The Neutrophil's Role During Health and Disease. Physiol Rev 2019; 99: 1223-1248. Russwurm S, Stonans I, Stonane E et al. Procalcitonin and CGRP-1 mrna expression in various human tissues. Shock 2001; 16: 109-112. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2518797","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":171042464,"identity":"89324e4a-7f2e-43d8-8f21-d482956d273e","order_by":0,"name":"Dongfang Chen","email":"","orcid":"","institution":"Shanghai Chest Hospital, Shanghai Jiaotong University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Dongfang","middleName":"","lastName":"Chen","suffix":""},{"id":171042465,"identity":"7d8ccdb8-03ca-48ab-90b9-2138eafdab03","order_by":1,"name":"Jianlin Xu","email":"","orcid":"","institution":"Shanghai Chest Hospital, Shanghai Jiaotong University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jianlin","middleName":"","lastName":"Xu","suffix":""},{"id":171042466,"identity":"e02693a7-114f-4dbd-9860-0231cbe74d3d","order_by":2,"name":"Yizhuo Zhao","email":"","orcid":"","institution":"Shanghai Chest Hospital, Shanghai Jiaotong University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yizhuo","middleName":"","lastName":"Zhao","suffix":""},{"id":171042467,"identity":"5be392b5-f6ca-49ff-953a-9194d6c71018","order_by":3,"name":"Baohui Han","email":"","orcid":"","institution":"Shanghai Chest Hospital, Shanghai Jiaotong University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Baohui","middleName":"","lastName":"Han","suffix":""},{"id":171042468,"identity":"3405fde9-01b6-40d0-8f55-ba9114c0f169","order_by":4,"name":"Runbo Zhong","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyklEQVRIiWNgGAWjYJCCA0CcAMSMDxJ+2BBWzoOkhdngYU8acVoYoFrYJB+wHSasxZ699+CBHwx2eQa3269VJPAcZuBv707AbwvPuYSDPQzJxQZ3zpTdSLBIZ5A4c3YDfi0SOQZAxxxI3HAjJ+1GAo81g4FELglaChLYmEnSkn6MIYHNmQgtZ84YgPySOPNGDrNEYk8aD0G/sLf3GH8Ahlhi3430hx9//LCR42/vxa8FDBj/gS00AJOElSNZ+IAU1aNgFIyCUTCCAAC3u0pTeimQXAAAAABJRU5ErkJggg==","orcid":"","institution":"Shanghai Chest Hospital, Shanghai Jiaotong University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Runbo","middleName":"","lastName":"Zhong","suffix":""}],"badges":[],"createdAt":"2023-01-27 03:14:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2518797/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2518797/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":32219516,"identity":"91136d47-5680-43b0-b00e-d9e3f94becb0","added_by":"auto","created_at":"2023-01-30 16:20:41","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":19110,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier analysis of the 100 SCLC patients according to the stratification of pretreatment PCT.\u003c/p\u003e\n\u003cp\u003ePFS: progression-free survival; PCT: procalcitonin\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-2518797/v1/1c49751a5f0b3b2386acdcd7.png"},{"id":32218631,"identity":"0c5cb5a3-886c-4abf-a10c-cca2e6b7a0d7","added_by":"auto","created_at":"2023-01-30 16:12:41","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":340088,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier analysis of subgroups according to the stratification of pretreatment PCT.\u003c/p\u003e\n\u003cp\u003ePFS: progression-free survival; PCT: procalcitonin\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-2518797/v1/eb5a12ab9dca92d61b10996e.png"},{"id":32622807,"identity":"4cbfc81f-5f81-423e-b03a-ddec74bb2458","added_by":"auto","created_at":"2023-02-08 01:59:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":480869,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2518797/v1/d1f60971-5aac-4c33-a2f0-699720574544.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prognostic value of pretreatment procalcitonin and neutrophil– lymphocyte ratio in extensive-stage small-cell lung cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSCLC accounts for about 15% -20% of lung cancer cases[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. SCLC belongs to one of neuroendocrine tumors, which is characterized by rapid tumor proliferation, tendency for early and extensive metastases, and poor prognosis[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. About 60% of the SCLC patients are in an extensive stage at the time of diagnosis[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The first-line standard treatment for extensive-stage SCLC patients mainly remains chemotherapy with platinum-etoposide. The responses of posterior-line treatments for extensive-stage SCLC patients are limited and poor, and the median overall survival(OS) is approximately 8 to 12 months[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWith the deep understanding of tumor microenvironment, it has been gradually clear that there is a complex relationship among inflammation, immunity, and cancer[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Inflammation has impacts on almost each step of tumorigenesis including tumor initiation, tumor promotion, and metastatic progression[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. And immune surveillance plays an important role in preventing or inhibiting tumor growth[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Biochemical markers of inflammatory response have been incorporated in prognostic scores for several types of cancer. Lymphocytes, especially T cells are commonly found within the tumor microenvironment, which mainly engage in anti-tumor immune responses. NLR, a typical marker of inflammation and immune status has been associated with prognosis in various malignant tumors such as gastric cancers, colorectal cancers, pancreatic cancers, and even lung cancers[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. A higher pretreatment NLR generally predicts poorer prognosis, but it remains unclear whether pretreatment NLR has influence on the short-term survival of extensive-stage SCLC patients.\u003c/p\u003e \u003cp\u003eSerum PCT as a biomarker has been developed over the past two decades for the diagnosis of bacterial infections, including sepsis, community acquired acute pneumonia and exacerbation of chronic obstructive pulmonary diseases (COPD)[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. PCT-based strategy is widely used to guide antibiotic therapy clinically. PCT can, however, be elevated in some neoplastic situations while there is no infectious process, particularly in tumorous diseases like medullary thyroid cancer and SCLC, in which PCT is secreted by the tumor cells[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. It has also been reported that SCLC cell lines could produce PCT in vitro[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In a study reported by Walter et.al, elevated PCT was present in medullary thyroid cancer patients without infection, besides, the survival analysis indicated that elevated PCT was associated with poor prognosis[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Patout et.al reported that higher PCT levels were detected in the tumors with neuroendocrine component, for example, PCT levels were significantly higher in SCLCs than in pulmonary adenocarcinomas[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. A case report also described a phenomenon that the PCT levels were relatively high in a patient with metastatic SCLC but without infection during admission, and surprisingly the PCT levels appeared a trend of decrease after anti-cancer treatment[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. As we observed in clinical practice, the elevation of PCT was present in most small-cell carcinoma cases, as well as in large-cell carcinomas with neuroendocrine component. However, few studies reveal the implications of PCT in SCLC patients, especially the prognostic value of PCT.\u003c/p\u003e \u003cp\u003eThus, the aim of our retrospective study is to investigate the influence of pretreatment NLR and PCT on progression-free survival (PFS) in extensive-stage SCLC patients treated with first-line chemotherapy.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eA total of 100 patients who had been diagnosed with extensive-stage SCLC histopathologically and clinically at Shanghai Chest Hospital from February 2018 to February 2019 were enrolled in our retrospective study. The follow-up ended on October 15th, 2019.\u003c/p\u003e \u003cp\u003e The study protocol was approved by the Ethics Committee of Shanghai Chest Hospital and conducted in accordance with the Declaration of Helsinki (as revised in Fortaleza, Brazil, October 2013). Due to the retrospective nature of this study, the need for informed consent was waived.\u003c/p\u003e \u003cp\u003eThe key inclusion criteria were as follows: (1) patients whose data on pretreatment NLR and PCT levels were available; (2) patients without any kind of infections at diagnosis or during treatment; (3) patients who had at least one measurable tumor lesion; (4) patients who aged between 18 and 70; (5) patients whose Eastern Cooperative Oncology Group performance status were 0 to 1; (6) patients who received cisplatin or carboplatin combined with etoposide as first-line chemotherapy.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003eThe clinical characteristics included gender, age, smoking history, anatomy type, response to first-line chemotherapy, pretreatment NLR and PCT levels. All enrolled patients received response evaluations every two courses of chemotherapy according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The PFS was defined as the time from the initiation of first-line chemotherapy to disease progression or the last follow-up visit. Data on pretreatment NLR and PCT levels were collected at the initiation of first-line chemotherapy. The NLR was defined as the absolute neutrophil count divided by the absolute lymphocyte count. The normal reference value of PCT in our study ranged from 0 to 0.05ng/ml.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003ePatients were stratified according to the median values of pretreatment NLR and PCT levels. SPSS22.0 statistical software (IBM, Armonk, NY, USA) was used to analyze data. The Chi-squared test was used to identify the clinical characteristics\u003c/p\u003e \u003cp\u003erelated to pretreatment NLR (or PCT). The Kaplan-Meier method and log-rank test were used to investigate the association between pretreatment NLR (or PCT) and PFS. The multivariable Cox regression model was used to screen out the significant factors related to PFS. All analyses were two-sided, and P values ༜0.05 were defined as statistical significance.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv class=\"Section2\" id=\"Sec7\"\u003e\n \u003ch2\u003ePatient characteristics\u003c/h2\u003e\n \u003cp\u003eOur retrospective study included 100 extensive-stage SCLC patients. The male and female patients accounted for 86% and 14%, respectively. Of the total patients, 84(84%) patients were ever-smokers while 16(16%) patients were never-smokers. Central type(73%) was the main anatomy type of all patients. In terms of response to first-line chemotherapy, 60(60%), 30(30%) and 10(10%) patients achieved partial response (PR), stable disease(SD) and progressive disease(PD), respectively. The median value of pretreatment NLR level was 3.17 (range:1.0-10.1). The median value of pretreatment PCT level was 0.06 (range:0.02\u0026ndash;1.49; ng/ml) (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). \u0026nbsp;\u003c/p\u003e\n \u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN(%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eClinical characteristics of the 100 patients\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale/Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86(86%)/14(14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge(years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;65/＞65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57(57%)/43(43%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo/Yes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16(16%)/84(84%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnatomy type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCentral type/Peripheral type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73(73%)/27(27%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eResponse to first-line chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePD/SD/PR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(10%)/30(30%)/60(60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNLR (range:1.0-10.1; median: 3.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;3.17/＞3.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50(50%)/50(50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePCT (range:0.02\u0026ndash;1.49; median:0.06; ng/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;0.06/＞0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52(52%)/48(48%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003ePD: progressive disease; SD: stable disease; PR: partial response: NLR: neutrophil-to-lymphocyte ratio; PCT: procalcitonin\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec8\"\u003e\n \u003ch2\u003eThe association between pretreatment NLR (or PCT) and clinical characteristics\u003c/h2\u003e\n \u003cp\u003eThe statistical results showed that pretreatment NLR or PCT was not significantly associated with gender, age, smoking history, anatomy type, and response to first-line chemotherapy (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u0026nbsp;\u003c/p\u003e\u0026nbsp;\u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNLR\u0026thinsp;\u0026le;\u0026thinsp;3.17(n\u0026thinsp;=\u0026thinsp;50)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNLR＞3.17(n\u0026thinsp;=\u0026thinsp;50)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe association between pretreatment NLR and clinical characteristics\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46(92%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40(80%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.084\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge(years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;\u0026thinsp;65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28(56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29(58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.840\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e＞65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22(44%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.585\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43(86%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41(82%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnatomy type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCentral type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40(80%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33(66%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.115\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePeripheral type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17(34%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eResponse to first-line chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(12%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.465\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13(26%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17(34%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33(66%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27(54%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003ePD: progressive disease; SD: stable disease; PR: partial response: NLR: neutrophil-to-lymphocyte ratio\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003ctable border=\"1\" id=\"Tab3\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePCT\u0026thinsp;\u0026le;\u0026thinsp;0.06 (n\u0026thinsp;=\u0026thinsp;52)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePCT＞0.06(n\u0026thinsp;=\u0026thinsp;48)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe association between pretreatment PCT and clinical characteristics\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47(90%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39(81%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.188\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(19%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge(years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;\u0026thinsp;65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30(58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27(56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.884\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e＞65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22(42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(44%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(19%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.471\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45(86%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39(81%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnatomy type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCentral type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34(65%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39(81%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.074\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePeripheral type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18(35%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(19%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eResponse to first-line chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(11%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.829\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16(31%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(29%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30(58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30(63%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003ePD: progressive disease; SD: stable disease; PR: partial response; PCT: procalcitonin\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec9\"\u003e\n \u003ch2\u003eProgression-free survival\u003c/h2\u003e\n \u003cp\u003eThe median PFS of the total extensive-stage SCLC patients was 6.0 months. The median PFS of male and female patients were 6.0 months and 5.7 months, respectively (P\u0026thinsp;=\u0026thinsp;0.448). The median PFS of patients with smoking history and patients without smoking history were 6.0 months and 5.7 months, respectively (P\u0026thinsp;=\u0026thinsp;0.368). The median PFS of low pretreatment NLR group (NLR\u0026thinsp;\u0026le;\u0026thinsp;3.17) was longer than that of high pretreatment NLR group (6.2 months vs 5.8 months), however, no significant difference was found (P\u0026thinsp;=\u0026thinsp;0.675). Most importantly, our study showed that patients with low pretreatment PCT (PCT\u0026thinsp;\u0026le;\u0026thinsp;0.06; ng/ml) had significantly better PFS than patients with high pretreatment PCT (PCT＞0.06; ng/ml) (6.9 months vs 5.7 months; P\u0026thinsp;=\u0026thinsp;0.043)(Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The same results were observed in subgroups (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). With the multivariable Cox regression analysis, the response to first-line chemotherapy (P\u0026thinsp;\u0026le;\u0026thinsp;0.001) and pretreatment PCT (HR\u0026thinsp;=\u0026thinsp;0.516; 95%CI 0.326\u0026ndash;0.817; P\u0026thinsp;=\u0026thinsp;0.005) were identified as independent factors associated with PFS (Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u0026nbsp;\u003c/p\u003e\n \u003ctable border=\"1\" id=\"Tab4\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMedian PFS\u003c/p\u003e\n \u003cp\u003e(months)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eUnivariate analysis\u003c/p\u003e\n \u003cp\u003e(P-value)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMultivariate analysis\u003c/p\u003e\n \u003cp\u003e[HR (95%CI)]\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eUnivariate and multivariate analyses with regard to PFS\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.448\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge(years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e6.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.210\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e＞65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoking history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.368\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnatomy type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCentral type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.915\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePeripheral type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eResponse to first-line chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.056\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e6.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;\u0026thinsp;3.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e6.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.675\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e＞3.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePCT (ng/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;\u0026thinsp;0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e6.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.043\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.516(0.326\u0026ndash;0.817)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e＞0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003ePD: progressive disease; SD: stable disease; PR: partial response: NLR: neutrophil-to-lymphocyte ratio; PCT: procalcitonin; PFS: progression-free survival; HR: hazard ratio; CI: confidence interval\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur retrospective study investigated the prognostic value of pretreatment NLR and PCT in extensive-stage SCLC patients treated with first-line chemotherapy. To our knowledge, there are few studies about the relationship between pretreatment PCT and survival in extensive-stage SCLC patients. This study shows lower pretreatment PCT is associated with better PFS in extensive-stage SCLC patients treated with first-line chemotherapy.\u003c/p\u003e \u003cp\u003eThe implications of NLR have been discussed in previous SCLC-related studies. A retrospective study of 139 SCLC patients showed that high NLR was associated with poor OS[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Ryoko et.al reported higher pretreatment NLR predicted worse OS in extensive-stage SCLC patients[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Another study indicated that NLR could be used as a negative prognostic factor for OS in extensive-stage SCLC patients[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Overall, these findings imply that NLR may predict the long-term survival of SCLC. Besides, a research on extensive-stage SCLC showed that the PFS of first-line chemotherapy was significantly different according to the stratification of baseline NLR, and patients with NLR༜3 could have PFS benefit[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Kang et.al also reported some similar results[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Inflammatory responses to tumors are mediated by the release from neutrophils of inflammatory cytokines, leukocytic and other phagocytic mediators that induce damage to cellular DNA, inhibit apoptosis and promote cancer-associated angiogenesis[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. A higher NLR indicates a heavier tumor burden and higher level of inflammation,which may associate with poor prognosis. However, our study found no significant relationship between pretreatment NLR and PFS in extensive-stage SCLC patients, though the median PFS of low NLR group was a bit longer compared with high NLR group. This may be explained by the fact that some extensive-stage SCLC patients are quite sensitive to chemotherapy despite of the heavy tumor load. However, the OS is the gold standard for determining whether the NLR ratio can be used as a predictor. Further investigation is required to increase understanding of the pathophysiology of this relationship and validate these findings with data collected prospectively.\u003c/p\u003e \u003cp\u003ePCT is widely used to guide the diagnosis and treatment of bacterial infection. Unlike NLR, we did not know much about the implications of PCT in lung cancer. PCT is secreted by the C-cell of thyroid and neuroendocrine cells located in lung, adrenal, liver, kidney, and muscles[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Biosynthesis of PCT in small cell carcinomas of the lung was firstly reported by Cate et.al[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], then, neuroendocrine cancers including SCLC are known to be associated with PCT elevation. A previous study showed that pretreatment PCT level above 0.15ng/ml was significantly associated with shorter OS in lung cancer patients[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In our study, extensive-stage SCLC patients with pretreatment PCT level under 0.06 ng/ml could have PFS benefit after first-line chemotherapy. Our results may be explained by the fact that a greater PCT elevation in SCLC patients is associated with a heavier tumor burden especially in extensive stage, which leads to poorer prognosis. Further research is needed to determine the specificity of PCT in SCLC patients and particularly explore the potential usefulness of PCT to monitor the response to chemotherapy.\u003c/p\u003e \u003cp\u003eOur study also has some limitations. Firstly, it is a retrospective study: secondly, the data of OS are not available due to the high rate of lost to follow-up.\u003c/p\u003e \u003cp\u003eTo sum up, we find that pretreatment PCT is an independent factor associated with PFS in extensive-stage SCLC patients treated with first-line chemotherapy, however, pretreatment NLR reflects no significant prognostic value in our study.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank all of the investigators for their involvement in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(I)Conception and design:Dongfang Chen, Runbo Zhong\u003c/p\u003e\n\u003cp\u003e(II) Administrative support:Baohui Han\u003c/p\u003e\n\u003cp\u003e(III) Provision of study materials or patients: Jianlin Xu\u003c/p\u003e\n\u003cp\u003e(IV) Collection and assembly of data:\u0026nbsp;Yizhuo Zhao\u003c/p\u003e\n\u003cp\u003e(V) Data analysis and interpretation: Dongfang Chen\u003c/p\u003e\n\u003cp\u003e(VI) Manuscript writing: All authors\u003c/p\u003e\n\u003cp\u003e(VII) Final approval of manuscript:All authors\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data used to support the findings of this study are available from the first author and the corresponding author upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported\u0026nbsp;by the Natural Science Foundation of Shanghai（19ZR1449700）.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that there is no conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKahnert K, Kauffmann-Guerrero D, Huber RM. SCLC-State of the Art and What Does the Future Have in Store? Clin Lung Cancer 2016; 17: 325-333.\u003c/li\u003e\n\u003cli\u003evan Meerbeeck JP, Fennell DA, De Ruysscher DK. Small-cell lung cancer. Lancet 2011; 378: 1741-1755.\u003c/li\u003e\n\u003cli\u003eGong J, Salgia R. Managing Patients With Relapsed Small-Cell Lung Cancer. J Oncol Pract 2018; 14: 359-366.\u003c/li\u003e\n\u003cli\u003eGrivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010; 140: 883-899.\u003c/li\u003e\n\u003cli\u003eSakin A, Sahin S, Yasar N et al. The Relation between Hemogram Parameters and Survival in Extensive-Stage Small Cell Lung Cancer. Oncol Res Treat 2019; 42: 506-515.\u003c/li\u003e\n\u003cli\u003eHeper Y, Akalin EH, Mistik R et al. Evaluation of serum C-reactive protein, procalcitonin, tumor necrosis factor alpha, and interleukin-10 levels as diagnostic and prognostic parameters in patients with community-acquired sepsis, severe sepsis, and septic shock. Eur J Clin Microbiol Infect Dis 2006; 25: 481-491.\u003c/li\u003e\n\u003cli\u003ePatout M, Salaun M, Brunel V et al. Diagnostic and prognostic value of serum procalcitonin concentrations in primary lung cancers. Clin Biochem 2014; 47: 263-267.\u003c/li\u003e\n\u003cli\u003eCate CC, Pettengill OS, Sorenson GD. Biosynthesis of procalcitonin in small cell carcinoma of the lung. Cancer Res 1986; 46: 812-818.\u003c/li\u003e\n\u003cli\u003eWalter MA, Meier C, Radimerski T et al. Procalcitonin levels predict clinical course and progression-free survival in patients with medullary thyroid cancer. Cancer 2010; 116: 31-40.\u003c/li\u003e\n\u003cli\u003eAvrillon V, Locatelli-Sanchez M, Folliet L et al. Lung cancer may increase serum procalcitonin level. Infect Disord Drug Targets 2015; 15: 57-63.\u003c/li\u003e\n\u003cli\u003ePardo-Cabello AJ, Manzano-Gamero V. Small cell lung cancer elevates procalcitonin levels in the absence of infection. Lung Cancer 2019; 134: 272-273.\u003c/li\u003e\n\u003cli\u003eLiu D, Huang Y, Li L et al. High neutrophil-to-lymphocyte ratios confer poor prognoses in patients with small cell lung cancer. BMC Cancer 2017; 17: 882.\u003c/li\u003e\n\u003cli\u003eSuzuki R, Lin SH, Wei X et al. Prognostic significance of pretreatment total lymphocyte count and neutrophil-to-lymphocyte ratio in extensive-stage small-cell lung cancer. Radiother Oncol 2018; 126: 499-505.\u003c/li\u003e\n\u003cli\u003eKang MH, Go SI, Song HN et al. The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with small-cell lung cancer. Br J Cancer 2014; 111: 452-460.\u003c/li\u003e\n\u003cli\u003eLiew PX, Kubes P. The Neutrophil\u0026apos;s Role During Health and Disease. Physiol Rev 2019; 99: 1223-1248.\u003c/li\u003e\n\u003cli\u003eRusswurm S, Stonans I, Stonane E et al. Procalcitonin and CGRP-1 mrna expression in various human tissues. Shock 2001; 16: 109-112.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Extensive-stage small-cell lung cancer, neutrophil-to-lymphocyte ratio, procalcitonin, progression-free survival","lastPublishedDoi":"10.21203/rs.3.rs-2518797/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2518797/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTo investigate the influence of pretreatment neutrophil-to-lymphocyte ratio (NLR) and procalcitonin (PCT) on progression-free survival (PFS) in extensive-stage small-cell lung cancer (SCLC) patients.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA total of 100 extensive-stage SCLC patients were enrolled in our study. Patients were stratified according to the median values of pretreatment NLR and PCT levels: low NLR group (NLR\u0026thinsp;\u0026le;\u0026thinsp;3.17), high NLR group (NLR༞3.17), low PCT group (PCT\u0026thinsp;\u0026le;\u0026thinsp;0.06; ng/ml), high PCT group (PCT༞0.06; ng/ml). The Kaplan-Meier method and multivariable Cox regression model were used to reveal the prognostic effects of pretreatment NLR and PCT on PFS.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe median PFS of the total extensive-stage SCLC patients was 6.0 months. The median PFS of low pretreatment NLR group (NLR\u0026thinsp;\u0026le;\u0026thinsp;3.17) was not significantly different from that of high pretreatment NLR group (6.2 months vs 5.8 months; P\u0026thinsp;=\u0026thinsp;0.675). Patients with low pretreatment PCT (PCT\u0026thinsp;\u0026le;\u0026thinsp;0.06; ng/ml) had significantly better PFS than patients with high pretreatment PCT (PCT༞0.06; ng/ml) (6.9 months vs 5.7 months; P\u0026thinsp;=\u0026thinsp;0.043). With the multivariable Cox regression analysis, the response to first-line chemotherapy (P\u0026thinsp;\u0026le;\u0026thinsp;0.001) and pretreatment PCT (HR\u0026thinsp;=\u0026thinsp;0.516; 95%CI 0.326\u0026ndash;0.817; P\u0026thinsp;=\u0026thinsp;0.005) were identified as independent factors associated with PFS.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003ePretreatment PCT is an independent factor associated with PFS in extensive-stage SCLC patients treated with first-line chemotherapy, but pretreatment NLR reflects no significant prognostic value in our study.\u003c/p\u003e","manuscriptTitle":"Prognostic value of pretreatment procalcitonin and neutrophil– lymphocyte ratio in extensive-stage small-cell lung cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-01-30 16:12:36","doi":"10.21203/rs.3.rs-2518797/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f59fa35a-2529-4b4f-bcbf-7f18a5ce7763","owner":[],"postedDate":"January 30th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-02-08T01:59:29+00:00","versionOfRecord":[],"versionCreatedAt":"2023-01-30 16:12:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2518797","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2518797","identity":"rs-2518797","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}