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Published in: Discover Oncology 1/2023

Open Access 01-12-2023 | NSCLC | Research

High pre-chemoradiotherapy pan-immune-inflammation value levels predict worse outcomes in patients with stage IIIB/C non-small-cell lung cancer

Authors: Erkan Topkan, Ahmet Kucuk, Emine Elif Ozkan, Duriye Ozturk, Ali Ayberk Besen, Huseyin Mertsoylu, Berrin Pehlivan, Ugur Selek

Published in: Discover Oncology | Issue 1/2023

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Abstract

Background and objectives

We explored the prognostic usefulness of the pan-immune-inflammation value (PIV) in patients with stage IIIB/C non-small-cell lung cancer (NSCLC) who underwent concurrent chemoradiotherapy (CCRT).

Methods and patients

For all patients, the PIV was calculated using platelet (P), monocyte (M), neutrophil (N), and lymphocyte (L) measures obtained on the first day of CCRT: PIV = P × M × N ÷ L. Using receiver operating characteristic (ROC) curve analysis, we searched for the existence of an ideal cutoff that may partition patients into two groups with unique progression-free- (PFS) and overall survival (OS) results. The primary endpoint of this retrospective cohort research was to determine whether there were any significant relationships between pretreatment PIV measures and post-CCRT OS outcomes.

Results

The present research included a total of 807 stage IIIB/C NSCLC patients. According to ROC curve analysis, the ideal PIV cutoff was 516 [area under the curve (AUC): 67.7%; sensitivity: 66.4%; specificity: 66.1%], which divided the whole cohort into two: low PIV (L-PIV: PIV < 516; N = 436) and high PIV (H-PIV: PIV ≥ 516; N = 371). The comparisons between the PIV groups indicated that either the median PFS (9.2 vs. 13.4 months; P < 0.001) or OS (16.7 vs. 32.7 months; P < 0.001) durations in the H-PIV group were substantially inferior to their L-PIV counterpart. Apart from the H-PIV (P < 0.001), the N3 nodal stage (P = 0.006), IIIC disease stage (P < 0.001), and receiving only one cycle of concurrent chemotherapy (P = 0.005) were also determined to be significant predictors of poor PFS (P < 0.05, for each) and OS (P < 0.05, for each) outcomes in univariate analysis. The multivariate analysis findings revealed that all four variables had independent negative impacts on PFS (P < 0.05, for each) and OS (P < 0.05, for each).

Conclusions

The findings of this hypothesis-generating retrospective analysis claimed that the novel PIV was an independent and steadfast predictor of PFS and OS in stage IIIB/C NSCLC patients.
Literature
1.
go back to reference Komaki R, Wei X, Allen PK, et al. Phase I study of celecoxib with concurrent irinotecan, cisplatin, and radiation therapy for patients with unresectable locally advanced non-small cell lung cancer. Front Oncol. 2011;1:52.CrossRefPubMedPubMedCentral Komaki R, Wei X, Allen PK, et al. Phase I study of celecoxib with concurrent irinotecan, cisplatin, and radiation therapy for patients with unresectable locally advanced non-small cell lung cancer. Front Oncol. 2011;1:52.CrossRefPubMedPubMedCentral
2.
go back to reference Spigel DR, Faivre-Finn C, Gray JE, et al. Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. J Clin Oncol. 2022;40(12):1301–11.CrossRefPubMedPubMedCentral Spigel DR, Faivre-Finn C, Gray JE, et al. Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. J Clin Oncol. 2022;40(12):1301–11.CrossRefPubMedPubMedCentral
3.
go back to reference Furuse K, Fukuoka M, Kawahara M, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol. 1999;17(9):2692–9.CrossRefPubMed Furuse K, Fukuoka M, Kawahara M, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol. 1999;17(9):2692–9.CrossRefPubMed
4.
go back to reference Curran WJ Jr, Paulus R, Langer CJ, et al. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011;103(19):1452–60.CrossRefPubMedPubMedCentral Curran WJ Jr, Paulus R, Langer CJ, et al. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011;103(19):1452–60.CrossRefPubMedPubMedCentral
5.
go back to reference Crinò L, Weder W, van Meerbeeck J, Felip E, ESMO Guidelines Working Group. Early stage and locally advanced (non-metastatic) non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21:103–15.CrossRef Crinò L, Weder W, van Meerbeeck J, Felip E, ESMO Guidelines Working Group. Early stage and locally advanced (non-metastatic) non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21:103–15.CrossRef
6.
go back to reference Crohns M, Saarelainen S, Laine S, Poussa T, Alho H, Kellokumpu-Lehtinen P. Cytokines in bronchoalveolar lavage fluid and serum of lung cancer patients during radiotherapy—Association of interleukin-8 and VEGF with survival. Cytokine. 2010;50(1):30–6.CrossRefPubMed Crohns M, Saarelainen S, Laine S, Poussa T, Alho H, Kellokumpu-Lehtinen P. Cytokines in bronchoalveolar lavage fluid and serum of lung cancer patients during radiotherapy—Association of interleukin-8 and VEGF with survival. Cytokine. 2010;50(1):30–6.CrossRefPubMed
7.
go back to reference Proctor MJ, Morrison DS, Talwar D, et al. An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumour site: a Glasgow ınflammation outcome study. Br J Cancer. 2011;104:726–34.CrossRefPubMedPubMedCentral Proctor MJ, Morrison DS, Talwar D, et al. An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumour site: a Glasgow ınflammation outcome study. Br J Cancer. 2011;104:726–34.CrossRefPubMedPubMedCentral
8.
go back to reference Naszai M, Kurjan A, Maughan TS. The prognostic utility of pre-treatment neutrophil-to-lymphocyte-ratio (NLR) in colorectal cancer: a systematic review and meta-analysis. Cancer Med. 2021;10(17):5983–97.CrossRefPubMedPubMedCentral Naszai M, Kurjan A, Maughan TS. The prognostic utility of pre-treatment neutrophil-to-lymphocyte-ratio (NLR) in colorectal cancer: a systematic review and meta-analysis. Cancer Med. 2021;10(17):5983–97.CrossRefPubMedPubMedCentral
9.
go back to reference Guo YH, Sun HF, Zhang YB, et al. The clinical use of the platelet/lymphocyte ratio and lymphocyte/monocyte ratio as prognostic predictors in colorectal cancer: a meta-analysis. Oncotarget. 2017;8(12):20011–24.CrossRefPubMedPubMedCentral Guo YH, Sun HF, Zhang YB, et al. The clinical use of the platelet/lymphocyte ratio and lymphocyte/monocyte ratio as prognostic predictors in colorectal cancer: a meta-analysis. Oncotarget. 2017;8(12):20011–24.CrossRefPubMedPubMedCentral
10.
go back to reference Zhang Y, Xiao G, Wang R. Clinical significance of systemic immune-inflammation index (SII) and C-reactive protein-to-albumin ratio (CAR) in patients with esophageal cancer: a meta-analysis. Cancer Manag Res. 2019;11:4185–200.CrossRefPubMedPubMedCentral Zhang Y, Xiao G, Wang R. Clinical significance of systemic immune-inflammation index (SII) and C-reactive protein-to-albumin ratio (CAR) in patients with esophageal cancer: a meta-analysis. Cancer Manag Res. 2019;11:4185–200.CrossRefPubMedPubMedCentral
11.
go back to reference Zhou Q, Su S, You W, Wang T, Ren T, Zhu L. Systemic inflammation response index as a prognostic marker in cancer patients: a systematic review and meta-analysis of 38 cohorts. Dose Response. 2021;19(4):15593258211064744.CrossRefPubMedPubMedCentral Zhou Q, Su S, You W, Wang T, Ren T, Zhu L. Systemic inflammation response index as a prognostic marker in cancer patients: a systematic review and meta-analysis of 38 cohorts. Dose Response. 2021;19(4):15593258211064744.CrossRefPubMedPubMedCentral
12.
go back to reference Abravan A, Salem A, Price G, Faivre-Finn C, van Herk M. Effect of systemic inflammation biomarkers on overall survival after lung cancer radiotherapy: a single-center large-cohort study. Acta Oncol. 2022;61(2):163–71.CrossRefPubMed Abravan A, Salem A, Price G, Faivre-Finn C, van Herk M. Effect of systemic inflammation biomarkers on overall survival after lung cancer radiotherapy: a single-center large-cohort study. Acta Oncol. 2022;61(2):163–71.CrossRefPubMed
13.
go back to reference Biswas T, Gawdi R, Jindal C, et al. Pretreatment neutrophil-to-lymphocyte ratio as an important prognostic marker in stage III locally advanced non-small cell lung cancer: confirmatory results from the PROCLAIM phase III clinical trial. J Thorac Dis. 2021;13(10):5617–26.CrossRefPubMedPubMedCentral Biswas T, Gawdi R, Jindal C, et al. Pretreatment neutrophil-to-lymphocyte ratio as an important prognostic marker in stage III locally advanced non-small cell lung cancer: confirmatory results from the PROCLAIM phase III clinical trial. J Thorac Dis. 2021;13(10):5617–26.CrossRefPubMedPubMedCentral
14.
go back to reference Topkan E, Selek U, Kucuk A, et al. Prechemoradiotherapy systemic inflammation response index stratifies stage IIIB/C non-small-cell lung cancer patients into three prognostic groups: a propensity score-matching analysis. J Oncol. 2021;2021:6688138.CrossRefPubMedPubMedCentral Topkan E, Selek U, Kucuk A, et al. Prechemoradiotherapy systemic inflammation response index stratifies stage IIIB/C non-small-cell lung cancer patients into three prognostic groups: a propensity score-matching analysis. J Oncol. 2021;2021:6688138.CrossRefPubMedPubMedCentral
15.
go back to reference Ozdemir Y, Topkan E, Mertsoylu H, Selek U. Low prognostic nutritional index predicts poor clinical outcomes in patients with stage IIIB non-small-cell lung carcinoma undergoing chemoradiotherapy. Cancer Manag Res. 2020;12:1959–67.CrossRefPubMedPubMedCentral Ozdemir Y, Topkan E, Mertsoylu H, Selek U. Low prognostic nutritional index predicts poor clinical outcomes in patients with stage IIIB non-small-cell lung carcinoma undergoing chemoradiotherapy. Cancer Manag Res. 2020;12:1959–67.CrossRefPubMedPubMedCentral
16.
go back to reference Fucà G, Guarini V, Antoniotti C, et al. The pan-immune-inflammation value is a new prognostic biomarker in metastatic colorectal cancer: results from a pooled-analysis of the Valentino and TRIBE first-line trials. Br J Cancer. 2020;123(3):403–9.CrossRefPubMedPubMedCentral Fucà G, Guarini V, Antoniotti C, et al. The pan-immune-inflammation value is a new prognostic biomarker in metastatic colorectal cancer: results from a pooled-analysis of the Valentino and TRIBE first-line trials. Br J Cancer. 2020;123(3):403–9.CrossRefPubMedPubMedCentral
17.
go back to reference Corti F, Lonardi S, Intini R, et al. The pan-immune-inflammation value in microsatellite instability-high metastatic colorectal cancer patients treated with immune checkpoint inhibitors. Eur J Cancer. 2021;150:155–67.CrossRefPubMed Corti F, Lonardi S, Intini R, et al. The pan-immune-inflammation value in microsatellite instability-high metastatic colorectal cancer patients treated with immune checkpoint inhibitors. Eur J Cancer. 2021;150:155–67.CrossRefPubMed
19.
go back to reference Ligorio F, Fucà G, Zattarin E, et al. The pan-immune-inflammation-value predicts the survival of patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer treated with first-line taxane-trastuzumab-pertuzumab. Cancers (Basel). 2021;13(8):1964.CrossRefPubMed Ligorio F, Fucà G, Zattarin E, et al. The pan-immune-inflammation-value predicts the survival of patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer treated with first-line taxane-trastuzumab-pertuzumab. Cancers (Basel). 2021;13(8):1964.CrossRefPubMed
20.
go back to reference Sahin AB, Cubukcu E, Ocak B, et al. Low pan-immune-inflammation-value predicts better chemotherapy response and survival in breast cancer patients treated with neoadjuvant chemotherapy. Sci Rep. 2021;11(1):14662.CrossRefPubMedCentral Sahin AB, Cubukcu E, Ocak B, et al. Low pan-immune-inflammation-value predicts better chemotherapy response and survival in breast cancer patients treated with neoadjuvant chemotherapy. Sci Rep. 2021;11(1):14662.CrossRefPubMedCentral
21.
go back to reference Demir H, Demirci A, Eren SK, Beypinar I, Davarcı SE, Baykara M. A new prognostic index in young breast cancer patients. J Coll Physicians Surg Pak. 2022;32(1):86–91.CrossRefPubMed Demir H, Demirci A, Eren SK, Beypinar I, Davarcı SE, Baykara M. A new prognostic index in young breast cancer patients. J Coll Physicians Surg Pak. 2022;32(1):86–91.CrossRefPubMed
22.
go back to reference Yoshifumi B, Shigeki N, Tasuku T, et al. Pan-immune-inflammation value and prognosis in patients with esophageal cancer. Ann Surg. 2022;3(1):e113.CrossRef Yoshifumi B, Shigeki N, Tasuku T, et al. Pan-immune-inflammation value and prognosis in patients with esophageal cancer. Ann Surg. 2022;3(1):e113.CrossRef
23.
go back to reference Zeng R, Liu F, Fang C, et al. PIV and PILE Score at baseline predict clinical outcome of anti-PD-1/PD-L1 inhibitor combined with chemotherapy in extensive-stage small cell lung cancer patients. Front Immunol. 2021;12:724443.CrossRefPubMedPubMedCentral Zeng R, Liu F, Fang C, et al. PIV and PILE Score at baseline predict clinical outcome of anti-PD-1/PD-L1 inhibitor combined with chemotherapy in extensive-stage small cell lung cancer patients. Front Immunol. 2021;12:724443.CrossRefPubMedPubMedCentral
24.
go back to reference Chen X, Hong X, Chen G, et al. The Pan-Immune-Inflammation Value predicts the survival of patients with anaplastic lymphoma kinase-positive non-small cell lung cancer treated with first-line ALK inhibitor. Transl Oncol. 2022;17:101338.CrossRefPubMedPubMedCentral Chen X, Hong X, Chen G, et al. The Pan-Immune-Inflammation Value predicts the survival of patients with anaplastic lymphoma kinase-positive non-small cell lung cancer treated with first-line ALK inhibitor. Transl Oncol. 2022;17:101338.CrossRefPubMedPubMedCentral
26.
go back to reference Fucà G, Beninato T, Bini M, et al. The pan-immune-inflammation value in patients with metastatic melanoma receiving first-line therapy. Target Oncol. 2021;16(4):529–36.CrossRefPubMed Fucà G, Beninato T, Bini M, et al. The pan-immune-inflammation value in patients with metastatic melanoma receiving first-line therapy. Target Oncol. 2021;16(4):529–36.CrossRefPubMed
27.
go back to reference Guven DC, Sahin TK, Erul E, Kilickap S, Gambichler T, Aksoy S. The association between the pan-immune-inflammation value and cancer prognosis: a systematic review and meta-analysis. Cancers (Basel). 2022;14(11):2675.CrossRefPubMed Guven DC, Sahin TK, Erul E, Kilickap S, Gambichler T, Aksoy S. The association between the pan-immune-inflammation value and cancer prognosis: a systematic review and meta-analysis. Cancers (Basel). 2022;14(11):2675.CrossRefPubMed
28.
go back to reference Topkan E, Parlak C, Selek U. Impact of weight change during the course of concurrent chemoradiation therapy on outcomes in stage IIIB non-small cell lung cancer patients: retrospective analysis of 425 patients. Int J Radiat Oncol Biol Phys. 2013;87(4):697–704.CrossRefPubMed Topkan E, Parlak C, Selek U. Impact of weight change during the course of concurrent chemoradiation therapy on outcomes in stage IIIB non-small cell lung cancer patients: retrospective analysis of 425 patients. Int J Radiat Oncol Biol Phys. 2013;87(4):697–704.CrossRefPubMed
29.
go back to reference Crusz SM, Balkwill FR. Inflammation and cancer: advances and new agents. Nat Rev Clin Oncol. 2015;12:584–96.CrossRefPubMed Crusz SM, Balkwill FR. Inflammation and cancer: advances and new agents. Nat Rev Clin Oncol. 2015;12:584–96.CrossRefPubMed
30.
go back to reference Diakos CI, Charles KA, McMillan DC, Clarke SJ. Cancer-related inflammation and treatment effectiveness. Lancet Oncol. 2014;15:e493–503.CrossRefPubMed Diakos CI, Charles KA, McMillan DC, Clarke SJ. Cancer-related inflammation and treatment effectiveness. Lancet Oncol. 2014;15:e493–503.CrossRefPubMed
31.
go back to reference Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;30(7):1073–81.CrossRefPubMed Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;30(7):1073–81.CrossRefPubMed
32.
go back to reference Tang Y, Ji Y, Yang M. Prognostic value of pre-treatment advanced lung cancer inflammation index in non-small cell lung cancer: a meta-analysis. Biomarkers. 2022;27:1–7.CrossRef Tang Y, Ji Y, Yang M. Prognostic value of pre-treatment advanced lung cancer inflammation index in non-small cell lung cancer: a meta-analysis. Biomarkers. 2022;27:1–7.CrossRef
33.
go back to reference Huang T, Zhang H, Zhao Y, et al. Systemic immune-inflammation index changes predict outcome in stage III non-small-cell lung cancer patients treated with concurrent chemoradiotherapy. Future Oncol. 2021;17(17):2141–9.CrossRefPubMed Huang T, Zhang H, Zhao Y, et al. Systemic immune-inflammation index changes predict outcome in stage III non-small-cell lung cancer patients treated with concurrent chemoradiotherapy. Future Oncol. 2021;17(17):2141–9.CrossRefPubMed
34.
go back to reference Topkan E, Selek U, Kucuk A, et al. Prechemoradiotherapy systemic inflammation response index stratifies stage IIIB/C non-small-cell lung cancer patients into three prognostic groups: a propensity score-matching analysis. J Oncol. 2021;2021:6688138.CrossRefPubMedPubMedCentral Topkan E, Selek U, Kucuk A, et al. Prechemoradiotherapy systemic inflammation response index stratifies stage IIIB/C non-small-cell lung cancer patients into three prognostic groups: a propensity score-matching analysis. J Oncol. 2021;2021:6688138.CrossRefPubMedPubMedCentral
35.
go back to reference Tong YS, Tan J, Zhou XL, et al. Systemic immune-inflammation index predicting chemoradiation resistance and poor outcome in patients with stage III non-small cell lung cancer. J Transl Med. 2017;15:221.CrossRefPubMedPubMedCentral Tong YS, Tan J, Zhou XL, et al. Systemic immune-inflammation index predicting chemoradiation resistance and poor outcome in patients with stage III non-small cell lung cancer. J Transl Med. 2017;15:221.CrossRefPubMedPubMedCentral
36.
go back to reference Goldstraw P, Chansky K, Crowley J, et al. The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. J Thorac Oncol. 2016;11(1):39–51.CrossRefPubMed Goldstraw P, Chansky K, Crowley J, et al. The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. J Thorac Oncol. 2016;11(1):39–51.CrossRefPubMed
Metadata
Title
High pre-chemoradiotherapy pan-immune-inflammation value levels predict worse outcomes in patients with stage IIIB/C non-small-cell lung cancer
Authors
Erkan Topkan
Ahmet Kucuk
Emine Elif Ozkan
Duriye Ozturk
Ali Ayberk Besen
Huseyin Mertsoylu
Berrin Pehlivan
Ugur Selek
Publication date
01-12-2023
Publisher
Springer US
Published in
Discover Oncology / Issue 1/2023
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI
https://doi.org/10.1007/s12672-023-00851-8

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