clinical study pretreatment neutrophil-to-lymphocyte...

Clinical StudyPretreatment Neutrophil-to-Lymphocyte RatioCan Predict the Prognosis in Bladder Cancer Patients WhoReceive Gemcitabine and Nedaplatin Therapy

Shinji Ohtake1 Takashi Kawahara12 Ryo Kasahara1 Hiroki Ito1 Kimito Osaka1

Yusuke Hattori2 Jun-ichi Teranishi2 Kazuhide Makiyama1 Nobuhiko Mizuno3

Susumu Umemoto4 Yasuhide Miyoshi2 Noboru Nakaigawa1 Hiroshi Miyamoto5

Masahiro Yao1 and Hiroji Uemura2

1Department of Urology Yokohama City University Graduate School of Medicine Yokohama Japan2Departments of Urology and Renal Transplantation Yokohama City University Medical Center Yokohama Japan3Department of Urology Yokohama Sakae Kyosai Hospital Yokohama Japan4Department of Urology Hiratsuka Kyosai Hospital Hiratsuka Japan5Departments of Pathology and Urology Johns Hopkins University School of Medicine Baltimore MD USA

Correspondence should be addressed to Takashi Kawahara takashi tk2001yahoocojp

Received 7 April 2016 Accepted 18 August 2016

Academic Editor Tomasz Golabek

Copyright copy 2016 Shinji Ohtake et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Introduction and Objectives Neutrophil-to-lymphocyte ratio (NLR) has been suggested to be a simple marker of the systemicinflammatory response in critical care patientsWe previously assessed the utility ofNLR as a biomarker to predict tumor recurrenceand cancer death in bladder cancer patients who underwent radical cystectomy In this study we evaluated the prognostic impactof NLR in bladder cancer patients who received gemcitabine and nedaplatin (GN) chemotherapy Methods A total of 23 patientswho received GN chemotherapy for advanced bladder cancer were enrolled in this study The cut-off point of NLR accordingto the sensitivity and specificity levels was derived from the area under receiver operator characteristics (AUROC) curve plottedfor disease progression or overall mortality Results The NLR cut-off point was determined as 414 for both tumor progressionand overall mortality Median progression-free survival (PFS)overall survival (OS) in the higher NLR group (NLR ge 414) andlower NLR group (NLR lt 414) were 194468 days versus 73237 days respectively Kaplan-Meier analysis showed that higher NLRsignificantly correlated with poorer PFS (119901 = 0011) andOS (119901 = 0045)Conclusions NLRmay serve as a new biomarker to predictresponses to GN-based chemotherapy in advanced bladder cancer patients andor their prognosis

1 Introduction

Cisplatin alone gemcitabine and cisplatin (GC) and metho-trexate vinblastine doxorubicin and cisplatin (M-VAC)have evolved as the standard first-line systemic therapy forrecurrent or metastatic urothelial carcinoma (UC) Howeverits serious dose-limiting adverse effects include consider-able renal toxicity marked emesis and neurotoxicity Itsnephrotoxic properties particularly make it unsuitable forpatients with renal dysfunction Indeed UC is usually seenin the elderly and due to age-associated impairment in the

renal function and performance status approximately 30ndash50 of patients are ineligible for cisplatin-based chemother-apy [1] Instead nedaplatin a second-generation platinumcomplex with lower renal and gastrointestinal toxicities thancisplatin can be used in patients withmarginal renal function[2]

Neutrophil-to-lymphocyte ratio (NLR) has been sug-gested as a simple marker of the systemic inflammatoryresponse in critical care patients [3] NLR can be easily cal-culated from routine complete blood counts in the peripheralblood [4 5] It has also been reported to be an independent

Hindawi Publishing CorporationBioMed Research InternationalVolume 2016 Article ID 9846823 5 pageshttpdxdoiorg10115520169846823

2 BioMed Research International

prognosticator for some solidmalignancies including bladdercancer [4ndash13]

We previously assessed the utility of NLR as a biomarkerto predict tumor recurrence and cancer death in bladdercancer patients who underwent radical cystectomy [14]In the current study we investigated whether NLR couldpredict the prognosis of bladder cancer patients who receivedgemcitabine and nedaplatin (GN) chemotherapy

2 Materials and Methods

21 Patients A total of 23 patients (17 men and 6 women)with measurable lesions were treated with GN chemotherapyfor their advanced bladder UC at our institutions from 2005to 2014 Of these patients 4 underwent radical cystectomyprior to GN therapyThe mean age was 630 years (range 46ndash74) the mean creatinine clearance was 805mLmin (range43ndash1571) and the mean follow-up period was 115 months(range 23ndash298) Written informed consent was obtainedfrom all patients and the institutional review board approvedthis study

22 Drug Administration and Evaluation of ResponsesPatients received gemcitabine 1000mgm2 on days 1 and8 plus nedaplatin 80 or 100mgm2 on day 1 Dose modi-fication was allowed depending on the patientrsquos conditionrenal function or bone marrow suppression Twelve patientsreceived at least 3 cycles of GN chemotherapy whereas theremaining 10 received 1 or 2 cycles Tumor response wasassessed according to the Response Evaluation Criteria inSolid Tumor (RECIST) Toxicity was evaluated accordingto the Common Terminology Criteria for Adverse Events(CTCAE) ver 30

23 Clinical and Laboratory Assessments Complete bloodcell counts (CBCs) were performed and NLR was calculatedusing the neutrophil and lymphocyte counts obtained onthe same day or a few days before the initial chemotherapyWe determined the cut-off point of the NLR based on thesensitivity and specificity levels derived from the area underreceiver operator characteristics (AUROC) curve plottedusing disease progression or overall mortality

24 Statistical Analysis The patient characteristics and pre-treatment factors were analyzed using the Mann-Whitney 119880test and chi-square test respectivelyTheKaplan-Meier curvewas used to estimate the progression-free survival (PFS) andoverall survival (OS) The survival duration was defined asthe time between the date of installation of GN chemotherapyand the time of tumor progression or deathThe log-rank testwas performed for comparison of two groups All statisticalanalyses were performed using the GraphPad Prism softwareprogram (GraphPad Software La Jolla CA USA) 119901 lt 005was considered to be statistically significant

3 Results

31 Patients Of 23 patients complete response (CR) andpartial response (PR) were obtained in 2 (87) and 3

(130) patients respectively The median PFS and OS were147 days and 396 days respectively Grade 3 or 4 anemiathrombocytopenia and neutropenia were observed in 10(435) 10 (826) and 21 (913) patients respectivelyNone of these patients died of adverse effects of GN therapy

32TheNLRCut-OffValue Based on the AUROC curve theNLR cut-off point was determined to be 414 for both PFS(AUROC 0618) and OS (AUROC 0717) [Figure 1] Clinico-pathological characteristics of the 23 patients are summarizedin Table 1 There were no statistically significant differencesin the baseline characteristics between high (ge414) and low(lt414) NLRs

33 NLR and Patient Outcomes We compared PFS and OSin patients with high versus lowNLRs Kaplan-Meier analysisshowed that higher NLR strongly correlated with the risks ofdisease progression (119901 = 0006 Figure 2(a)) and mortality(119901 = 0045 Figure 2(b))

4 Discussion

Although advances in chemotherapy have improved the sur-vival of patients with recurrent or metastatic UC a portion ofpatients still die within a few months of disease progressionTherefore more useful and reliable biomarkers that provideadditional prognostic information are needed CBCs aretypically examined during the clinical check-up and theNLR can be applied to all patients virtually either beforeor after surgerymedical treatment We previously reportedNLR as an independent prognosticator in men presentingwith metastatic prostate cancer as well as in bladder cancerpatients who received radical cystectomy [14] Indeed NLRhas been shown to be a prognostic factor in patients withbladder cancer [12 15ndash19] On the other hand the associationbetween NLR and tumor progression remains controversial[12 15ndash19] Several studies have shown a higher NLR topredict a worse prognosis in bladder cancer patients [16 18ndash20] whereas others have concluded that NLR is not stronglycorrelated with OS [12 15ndash18] In the current study higherNLR significantly correlated with a poorer prognosis inpatients who received GN chemotherapy for their advancedbladder cancer

In addition to cisplatin various anticancer platinumcomplexes have been developed Carboplatin a cisplatin ana-logue has been shown to exhibit improved toxicity and favor-able antitumor effects resulting in response rates of 184for upper urinary tract UC [20] Additionally nedaplatin wasdeveloped as a second-generation platinum complex withlower renal and gastrointestinal toxicities compared with cis-platin [21] Sasaki et al demonstrated that the pharmacoki-netic behavior of nedaplatin was similar to that of carboplatinbut is strikingly different from that of cisplatin Cisplatineasily binds to serum proteins resulting in a smaller percent-age of platinum excreted into the urine after infusioncompared with nedaplatin or carboplatin [22] Matsumotoet al showed greater activity of GN therapy against lungcancer models than the activity of a combination of gemc-itabine with cisplatin or carboplatin [23] In our institution

BioMed Research International 3

Table 1 Clinicopathological characteristics of the patients

Total NLR lt 414 NLR ≧ 414119901 value

(119899 = 23) (119899 = 9) (119899 = 14)Age (years)lt65 11 (476) 4 (444) 7 (500) 0566ge65 12 (524) 5 (556) 7 (500)

GenderFemale 6 (261) 4 (444) 2 (143) 0131Male 17 (739) 5 (556) 12 (857)

Creatinine clearance (mLmin)lt60 3 (130) 2 (222) 1 (71) 0332ge60 20 (870) 7 (778) 13 (929)

Clinical lymph node metastasisYes 19 (826) 8 (889) 11 (786) 0483No 4 (174) 1 (111) 3 (214)

Neoadjuvant chemotherapyYes 4 (174) 3 (333) 1 (71) 0147No 19 (826) 6 (667) 13 (929)

Clinical T stagele2 6 (261) 2 (222) 4 (286) 0565ge3 17 (739) 7 (778) 10 (714)

02 04 06 08 10False positive fraction

0

02

04

06

08

1

True

pos

itive

frac

tion

(a) Progression-free survival


0

02

04

06

08

1

True

pos

itive

frac

tion

(b) Overall survival

Figure 1 The AUROC for NLR (a) PFS and (b) OS

we have used nedaplatin-based chemotherapy for high-grade UC and have demonstrated good responses with themedian PFS and OS times of 147 and 396 days respectively[2 24]

There are several limitations associated with this studyincluding selection bias and missing data for some of thevariables due to its retrospective nature However this studymay provide supportive data for other studies as well as future

prospective studies Another potential limitation is that wedid not determine the mechanism of NLR for bladder cancerprogression Previous studies showed a correlation betweenNLR as a marker of systemic inflammation in cancer patientsand patient outcomes

In conclusion we demonstrated that NLR might be anew biomarker to predict the prognosis of advanced bladdercancer in patients undergoing GN chemotherapy


200 400 600 8000Follow-up (days)

0

50

100

Prog

ress

ion-

free s

urvi

val (

)

p = 0011

NLR ge 414

NLR lt 415

(a)

0

50

100

Ove

rall

surv

ival

()

200 400 600 800 10000Follow-up (days)

NLR ge 414

NLR lt 415

p = 0045

(b)

Figure 2 The association between NLR and patient outcomes (a) PFS and (b) OS

Competing Interests

The authors declare that they have no competing interests

Acknowledgments

Grants from the Uehara Memorial Foundation the TokyoBiochemical Research Foundation and the Japanese Founda-tion for Research and Promotion of Endoscopy and an Inter-national Exchange Grant from Kato Memorial BioscienceFoundationwere provided to Takashi KawaharaThere are noapplicable grant numbers

References

[1] A Dash M D Galsky A J Vickers et al ldquoImpact of renalimpairment on eligibility for adjuvant cisplatin-based chemo-therapy in patients with urothelial carcinoma of the bladderrdquoCancer vol 107 no 3 pp 506ndash513 2006

[2] T Kawahara H Oshiro Z Sekiguchi et al ldquoHigh-gradeinvasive urothelial carcinoma with focal plasmacytoid differen-tiation successfully treated by transurethral resection followedby chemoradiotherapyrdquo International Journal of Urology vol 18no 12 pp 851ndash853 2011

[3] R Zahorec ldquoRatio of neutrophil to lymphocyte countsmdashrapidand simple parameter of systemic inflammation and stress incritically illrdquo Bratislavske Lekarske Listy vol 102 no 1 pp 5ndash142001

[4] S R Walsh E J Cook F Goulder T A Justin and N JKeeling ldquoNeutrophil-lymphocyte ratio as a prognostic factor incolorectal cancerrdquo Journal of Surgical Oncology vol 91 no 3 pp181ndash184 2005

[5] Y Ohno J NakashimaM Ohori T Hatano andM TachibanaldquoPretreatment neutrophil-to-lymphocyte ratio as an indepen-dent predictor of recurrence in patients with nonmetastaticrenal cell carcinomardquoThe Journal of Urology vol 184 no 3 pp873ndash878 2010

[6] P XueMKanai YMori et al ldquoNeutrophil-to-lymphocyte ratiofor predicting palliative chemotherapy outcomes in advanced

pancreatic cancer patientsrdquo Cancer Medicine vol 3 no 2 pp406ndash415 2014

[7] D Gomez G Morris-Stiff G J Toogood J P A Lodge and KR Prasad ldquoImpact of systemic inflammation on outcome fol-lowing resection for intrahepatic cholangiocarcinomardquo Journalof Surgical Oncology vol 97 no 6 pp 513ndash518 2008

[8] W Chua K A Charles V E Baracos and S J Clarke ldquoNeu-trophillymphocyte ratio predicts chemotherapy outcomes inpatients with advanced colorectal cancerrdquo British Journal ofCancer vol 104 no 8 pp 1288ndash1295 2011

[9] B Azab V R Bhatt J Phookan et al ldquoUsefulness of the neutro-phil-to-lymphocyte ratio in predicting short- and long-termmortality in breast cancer patientsrdquoAnnals of Surgical Oncologyvol 19 no 1 pp 217ndash224 2012

[10] O Dalpiaz M Pichler S Mannweiler et al ldquoValidation ofthe pretreatment derived neutrophil-lymphocyte ratio as aprognostic factor in a European cohort of patients with uppertract urothelial carcinomardquo British Journal of Cancer vol 110no 10 pp 2531ndash2536 2014

[11] M R Jung Y K Park O Jeong et al ldquoElevated preoperativeneutrophil to lymphocyte ratio predicts poor survival followingresection in late stage gastric cancerrdquo Journal of Surgical Oncol-ogy vol 104 no 5 pp 504ndash510 2011

[12] A Demirtas V Sabur E C Aknsal et al ldquoCan neutrophil-lymphocyte ratio and lymph node density be used as prognosticfactors in patients undergoing radical cystectomyrdquo The Scien-tific World Journal vol 2013 Article ID 703579 5 pages 2013

[13] L Rosenberg G O Lawlor T Zenlea et al ldquoPredictors of endo-scopic inflammation in patients with ulcerative colitis in clinicalremissionrdquo Inflammatory Bowel Diseases vol 19 no 4 pp 779ndash784 2013

[14] T Kawahara K Furuya M Nakamura et al ldquoNeutrophil-to-lymphocyte ratio is a prognostic marker in bladder cancerpatients after radical cystectomyrdquo BMC Cancer vol 16 no 1article 185 2016

[15] T Hermanns B Bhindi Y Wei et al ldquoPre-treatment neutro-phil-to-lymphocyte ratio as predictor of adverse outcomes inpatients undergoing radical cystectomy for urothelial carci-noma of the bladderrdquo British Journal of Cancer vol 111 no 3pp 444ndash451 2014


[16] T Gondo J Nakashima Y Ohno et al ldquoPrognostic value ofneutrophil-to-lymphocyte ratio and establishment of novel pre-operative risk stratification model in bladder cancer patientstreated with radical cystectomyrdquo Urology vol 79 no 5 pp1085ndash1091 2012

[17] L S Krane K A Richards A K Kader R Davis K C Balajiand A K Hemal ldquoPreoperative neutrophillymphocyte ratiopredicts overall survival and extravesical disease in patientsundergoing radical cystectomyrdquo Journal of Endourology vol 27no 8 pp 1046ndash1050 2013

[18] S TemrazDMukherji Z A A Farhat et al ldquoPreoperative lym-phocyte-to-monocyte ratio predicts clinical outcome in pa-tients undergoing radical cystectomy for transitional cell car-cinoma of the bladder a retrospective analysisrdquo BMC Urologyvol 14 no 1 article 76 2014

[19] B R Viers S A Boorjian I Frank et al ldquoPretreatment neu-trophil-to-lymphocyte ratio is associated with advanced patho-logic tumor stage and increased cancer-specific mortalityamong patients with urothelial carcinoma of the bladder under-going radical cystectomyrdquo European Urology vol 66 no 6 pp1157ndash1164 2014

[20] H Akaza M Hagiwara N Deguchi et al ldquoPhase II trial of car-boplatin in patients with advanced germ-cell testicular tumorsand transitional cell carcinomas of the urinary tractrdquo Can-cer Chemotherapy and Pharmacology vol 23 no 3 pp 181ndash1851989

[21] W Cao C Xu G Lou et al ldquoA phase II study of paclitaxel andnedaplatin as first-line chemotherapy in patients with advancedesophageal cancerrdquo Japanese Journal of Clinical Oncology vol39 no 9 pp 582ndash587 2009

[22] Y Sasaki T Tamura K Eguchi et al ldquoPharmacokineticsof (glycolato-001015840)-diammine platinum (II) a new platinumderivative in comparison with cisplatin and carboplatinrdquo Can-cer Chemotherapy andPharmacology vol 23 no 4 pp 243ndash2461989

[23] M Matsumoto Y Takeda H Maki et al ldquoPreclinical invivo antitumor efficacy of nedaplatin with gemcitabine againsthuman lung cancerrdquo Japanese Journal of Cancer Research vol92 no 1 pp 51ndash58 2001

[24] S Umemoto Y Miyoshi Y Yokomizo et al ldquoA case of salvagecombination chemotherapy of gemcitabine plus nedaplatin forsquamous cell carcinoma of the ureterrdquoHinyokika Kiyo vol 52no 1 pp 35ndash39 2006

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


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of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


prognosticator for some solidmalignancies including bladdercancer [4ndash13]

We previously assessed the utility of NLR as a biomarkerto predict tumor recurrence and cancer death in bladdercancer patients who underwent radical cystectomy [14]In the current study we investigated whether NLR couldpredict the prognosis of bladder cancer patients who receivedgemcitabine and nedaplatin (GN) chemotherapy

2 Materials and Methods

21 Patients A total of 23 patients (17 men and 6 women)with measurable lesions were treated with GN chemotherapyfor their advanced bladder UC at our institutions from 2005to 2014 Of these patients 4 underwent radical cystectomyprior to GN therapyThe mean age was 630 years (range 46ndash74) the mean creatinine clearance was 805mLmin (range43ndash1571) and the mean follow-up period was 115 months(range 23ndash298) Written informed consent was obtainedfrom all patients and the institutional review board approvedthis study

22 Drug Administration and Evaluation of ResponsesPatients received gemcitabine 1000mgm2 on days 1 and8 plus nedaplatin 80 or 100mgm2 on day 1 Dose modi-fication was allowed depending on the patientrsquos conditionrenal function or bone marrow suppression Twelve patientsreceived at least 3 cycles of GN chemotherapy whereas theremaining 10 received 1 or 2 cycles Tumor response wasassessed according to the Response Evaluation Criteria inSolid Tumor (RECIST) Toxicity was evaluated accordingto the Common Terminology Criteria for Adverse Events(CTCAE) ver 30

23 Clinical and Laboratory Assessments Complete bloodcell counts (CBCs) were performed and NLR was calculatedusing the neutrophil and lymphocyte counts obtained onthe same day or a few days before the initial chemotherapyWe determined the cut-off point of the NLR based on thesensitivity and specificity levels derived from the area underreceiver operator characteristics (AUROC) curve plottedusing disease progression or overall mortality

24 Statistical Analysis The patient characteristics and pre-treatment factors were analyzed using the Mann-Whitney 119880test and chi-square test respectivelyTheKaplan-Meier curvewas used to estimate the progression-free survival (PFS) andoverall survival (OS) The survival duration was defined asthe time between the date of installation of GN chemotherapyand the time of tumor progression or deathThe log-rank testwas performed for comparison of two groups All statisticalanalyses were performed using the GraphPad Prism softwareprogram (GraphPad Software La Jolla CA USA) 119901 lt 005was considered to be statistically significant

3 Results

31 Patients Of 23 patients complete response (CR) andpartial response (PR) were obtained in 2 (87) and 3

(130) patients respectively The median PFS and OS were147 days and 396 days respectively Grade 3 or 4 anemiathrombocytopenia and neutropenia were observed in 10(435) 10 (826) and 21 (913) patients respectivelyNone of these patients died of adverse effects of GN therapy

32TheNLRCut-OffValue Based on the AUROC curve theNLR cut-off point was determined to be 414 for both PFS(AUROC 0618) and OS (AUROC 0717) [Figure 1] Clinico-pathological characteristics of the 23 patients are summarizedin Table 1 There were no statistically significant differencesin the baseline characteristics between high (ge414) and low(lt414) NLRs

33 NLR and Patient Outcomes We compared PFS and OSin patients with high versus lowNLRs Kaplan-Meier analysisshowed that higher NLR strongly correlated with the risks ofdisease progression (119901 = 0006 Figure 2(a)) and mortality(119901 = 0045 Figure 2(b))

4 Discussion

Although advances in chemotherapy have improved the sur-vival of patients with recurrent or metastatic UC a portion ofpatients still die within a few months of disease progressionTherefore more useful and reliable biomarkers that provideadditional prognostic information are needed CBCs aretypically examined during the clinical check-up and theNLR can be applied to all patients virtually either beforeor after surgerymedical treatment We previously reportedNLR as an independent prognosticator in men presentingwith metastatic prostate cancer as well as in bladder cancerpatients who received radical cystectomy [14] Indeed NLRhas been shown to be a prognostic factor in patients withbladder cancer [12 15ndash19] On the other hand the associationbetween NLR and tumor progression remains controversial[12 15ndash19] Several studies have shown a higher NLR topredict a worse prognosis in bladder cancer patients [16 18ndash20] whereas others have concluded that NLR is not stronglycorrelated with OS [12 15ndash18] In the current study higherNLR significantly correlated with a poorer prognosis inpatients who received GN chemotherapy for their advancedbladder cancer

In addition to cisplatin various anticancer platinumcomplexes have been developed Carboplatin a cisplatin ana-logue has been shown to exhibit improved toxicity and favor-able antitumor effects resulting in response rates of 184for upper urinary tract UC [20] Additionally nedaplatin wasdeveloped as a second-generation platinum complex withlower renal and gastrointestinal toxicities compared with cis-platin [21] Sasaki et al demonstrated that the pharmacoki-netic behavior of nedaplatin was similar to that of carboplatinbut is strikingly different from that of cisplatin Cisplatineasily binds to serum proteins resulting in a smaller percent-age of platinum excreted into the urine after infusioncompared with nedaplatin or carboplatin [22] Matsumotoet al showed greater activity of GN therapy against lungcancer models than the activity of a combination of gemc-itabine with cisplatin or carboplatin [23] In our institution




(119899 = 23) (119899 = 9) (119899 = 14)Age (years)lt65 11 (476) 4 (444) 7 (500) 0566ge65 12 (524) 5 (556) 7 (500)







0

02

04

06

08

1

True

pos

itive

frac

tion



0

02

04

06

08

1

True

pos

itive

frac

tion








200 400 600 8000Follow-up (days)

0

50

100

Prog

ress

ion-

free s

urvi

val (

)

p = 0011

NLR ge 414

NLR lt 415

(a)

0

50

100

Ove

rall

surv

ival

()

200 400 600 800 10000Follow-up (days)

NLR ge 414

NLR lt 415

p = 0045

(b)


Competing Interests


Acknowledgments


References
































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















(119899 = 23) (119899 = 9) (119899 = 14)Age (years)lt65 11 (476) 4 (444) 7 (500) 0566ge65 12 (524) 5 (556) 7 (500)







0

02

04

06

08

1

True

pos

itive

frac

tion



0

02

04

06

08

1

True

pos

itive

frac

tion








200 400 600 8000Follow-up (days)

0

50

100

Prog

ress

ion-

free s

urvi

val (

)

p = 0011

NLR ge 414

NLR lt 415

(a)

0

50

100

Ove

rall

surv

ival

()

200 400 600 800 10000Follow-up (days)

NLR ge 414

NLR lt 415

p = 0045

(b)


Competing Interests


Acknowledgments


References
































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















200 400 600 8000Follow-up (days)

0

50

100

Prog

ress

ion-

free s

urvi

val (

)

p = 0011

NLR ge 414

NLR lt 415

(a)

0

50

100

Ove

rall

surv

ival

()

200 400 600 800 10000Follow-up (days)

NLR ge 414

NLR lt 415

p = 0045

(b)


Competing Interests


Acknowledgments


References
































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















clinical study pretreatment neutrophil-to-lymphocyte...

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