Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 3/2022

Open Access 01-02-2022 | Prostate Cancer | Original Article

The prognostic power of inflammatory indices and clinical factors in metastatic castration-resistant prostate cancer patients treated with radium-223 (BIO-Ra study)

Authors: Matteo Bauckneht, Sara Elena Rebuzzi, Alessio Signori, Viviana Frantellizzi, Veronica Murianni, Elisa Lodi Rizzini, Manlio Mascia, Valentina Lavelli, Maria Isabella Donegani, Marta Ponzano, Angela Gaudiano, Maria Lina Stazza, Maria Licari, Letizia Cavallini, Viola Laghi, Luca Cindolo, Martina Maggi, Alessandro Sciarra, Paolo Mammucci, Gianmario Sambuceti, Renato Patrizio Costa, Angela Spanu, Giuseppe Rubini, Fabio Monari, Giuseppe De Vincentis, Giuseppe Fornarini

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 3/2022

Login to get access

Abstract

Purpose

To combine peripheral blood indices and clinical factors in a prognostic score for metastatic castration-resistant prostate cancer (mCRPC) patients treated with radium-223 dichloride ([223Ra]RaCl2).

Patients and methods

Baseline neutrophil-to-lymphocyte ratio (NLR), derived NLR (donor), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), Eastern Cooperative Oncology Group performance status (ECOG PS), Gleason score (GS) group, number of bone metastases, prostate-specific antigen (PSA), alkaline phosphatase (ALP), line of therapy, previous chemotherapy, and the presence of lymphadenopathies were collected from seven Italian centers between 2013 and 2020. Lab and clinical data were assessed in correlation with the overall survival (OS). Inflammatory indices were then included separately in the multivariable analyses with the prognostic clinical factors. The model with the highest discriminative ability (c-index) was chosen to develop the BIO-Ra score.

Results

Five hundred and nineteen mCRPC patients (median OS: 19.9 months) were enrolled. Higher NLR, dNLR, PLR, and SII and lower LMR predicted worse OS (all with a p < 0.001). The multivariable model including NLR, ECOG PS, number of bone metastases, ALP, and PSA (c-index: 0.724) was chosen to develop the BIO-Ra score. Using the Schneeweiss scoring system, the BIO-Ra score identified three prognostic groups (36%, 27.3%, and 36.6% patients, respectively) with distinct median OS (31, 26.6, and 9.6 months, respectively; hazard ratio: 1.62, p = 0.008 for group 2 vs. 1 and 5.77, p < 0.001 for group 3 vs. 1).

Conclusions

The BIO-Ra score represents an easy and widely applicable tool for the prognostic stratification of mCRPC patients treated with [223Ra]RaCl2 with no additional costs.
Appendix
Available only for authorised users
Literature
1.
Keller ET, Brown J. Prostate cancer bone metastases promote both osteolytic and osteoblastic activity. J Cell Biochem. 2004;91:718–29.PubMed
2.
McDougall JA, Bansal A, Goulart BH, McCune JS, Karnopp A, Fedorenko C, et al. The clinical and economic impacts of skeletal-related events among Medicare enrollees with prostate cancer metastatic to bone. Oncologist. 2016;21:320–6.PubMedPubMedCentral
3.
Harrison MR, Wong TZ, Armstrong AJ, George DJ. Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease. Cancer Manag Res. 2013;5:1–14.PubMedPubMedCentral
4.
Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fosså SD, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23.PubMed
5.
Kluetz PG, Pierce W, Maher VE, Zhang H, Tang S, Song P, et al. Radium Ra 223 dichloride injection: U.S. Food and Drug Administration drug approval summary. Clin Cancer Res. 2014;20:9–14.PubMed
6.
Parikh S, Murray L, Kenning L, Bottomley D, Din O, Dixit S, et al. Real-world outcomes and factors predicting survival and completion of radium 223 in metastatic castrate-resistant prostate cancer. Clin Oncol (R Coll Radiol). 2018;30:548–55.
7.
Wong WW, Anderson EM, Mohammadi H, Daniels TB, Schild SE, Keole SR, et al. Factors associated with survival following radium-223 treatment for metastatic castration-resistant prostate cancer. Clin Genitourin Cancer. 2017;15:e969–75.PubMed
8.
Frantellizzi V, Farcomeni A, Follacchio GA, Pacilio M, Pellegrini R, Pani R, et al. A 3-variable prognostic score (3-PS) for overall survival prediction in metastatic castration-resistant prostate cancer treated with 223Radium-dichloride. Ann Nucl Med. 2018;32:142–8.PubMed
9.
Den RB, George D, Pieczonka C, McNamara M. Ra-223 treatment for bone metastases in castrate-resistant prostate cancer: practical management issues for patient selection. Am J Clin Oncol. 2019;42:399–406.PubMedPubMedCentral
10.
11.
Kuppen MC, Westgeest HM, van der Doelen MJ, van den Eertwegh AJ, Coenen JL, Aben KK, et al. Real-world outcomes of radium-223 dichloride for metastatic castration resistant prostate cancer. Future Oncol. 2020;16:1371–84.PubMed
12.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.PubMed
13.
Templeton AJ, McNamara MG, Šeruga B, Vera-Badillo FE, Aneja P, Ocaña A, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106:dju124.PubMed
14.
Liu R, Zheng S, Yuan Q, Zhu P, Li B, Lin Q, et al. The prognostic significance of combined pretreatment fibrinogen and neutrophil-lymphocyte ratio in various cancers: a systematic review and meta-analysis. Dis Markers. 2020;2020:4565379.PubMedPubMedCentral
15.
Cupp MA, Cariolou M, Tzoulaki I, Aune D, Evangelou E, Berlanga-Taylor AJ. Neutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies. BMC Med. 2020;18:360.PubMedPubMedCentral
16.
Guan Y, Xiong H, Feng Y, Liao G, Tong T, Pang J. Revealing the prognostic landscape of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in metastatic castration-resistant prostate cancer patients treated with abiraterone or enzalutamide: a meta-analysis. Prostate Cancer Prostatic Dis. 2020;23:220–31.PubMed
17.
Man YN, Chen YF. Systemic immune-inflammation index, serum albumin, and fibrinogen impact prognosis in castration-resistant prostate cancer patients treated with first-line docetaxel. Int Urol Nephrol. 2019;51:2189–99.PubMed
18.
Bauckneht M, Rebuzzi SE, Signori A, Donegani MI, Murianni V, Miceli A, et al. The prognostic role of baseline metabolic tumor burden and systemic inflammation biomarkers in metastatic castration-resistant prostate cancer patients treated with radium-223: a proof of concept study. Cancers (Basel). 2020;12:3213.
19.
Poeppel TD, Handkiewicz-Junak D, Andreeff M, Becherer A, Bockisch A, Fricke E, et al. EANM guideline for radionuclide therapy with radium-223 of metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2018;45:824–45.PubMed
20.
Heagerty PJ, Lumley T, Pepe MS. Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics. 2000;56:337–44.PubMed
21.
Cattaneo M, Malighetti P, Spinelli D. Estimating receiver operative characteristic curves for time-dependent outcomes: the stroccurve package. Stand Genomic Sci. 2017;17:1015–23.
22.
Liu X. Classification accuracy and cut point selection. Stat Med. 2012;31:2676–86.PubMed
23.
Liu X, Jin Z. Optimal survival time-related cut-point with censored data. Stat Med. 2015;34:515–24.PubMed
24.
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.
25.
StataCorp. Stata statistical software: release 16. College Station: StataCorp LLC; 2019.
26.
27.
Mehta HB, Mehta V, Girman CJ, Adhikari D, Johnson ML. Regression coefficient-based scoring system should be used to assign weights to the risk index. J Clin Epidemiol. 2016;79:22–8.PubMed
28.
Sartor O, Coleman RE, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, et al. An exploratory analysis of alkaline phosphatase, lactate dehydrogenase, and prostate-specific antigen dynamics in the phase 3 ALSYMPCA trial with radium-223. Ann Oncol. 2017;28:1090–7.PubMedPubMedCentral
29.
Soloway MS, Hardeman SW, Hickey D, Raymond J, Todd B, Soloway S, et al. Stratification of patients with metastatic prostate cancer based on extent of disease on initial bone scan. Cancer. 1988;61:195–202.PubMed
30.
De Vincentis G, Gerritsen W, Gschwend JE, Hacker M, Lewington V, O’Sullivan JM, et al. Advances in targeted alpha therapy for prostate cancer. Ann Oncol. 2019;30:1728–39.PubMedPubMedCentral
31.
McKay RR, Jacobus S, Fiorillo M, Ledet EM, Cotogna PM, Steinberger AE, et al. Radium-223 use in clinical practice and variables associated with completion of therapy. Clin Genitourin Cancer. 2017;15:e289–98.PubMed
32.
Saad F, Carles J, Gillessen S, Heidenreich A, Heinrich D, Gratt J, et al. Radium-223 and concomitant therapies in patients with metastatic castration-resistant prostate cancer: an international, early access, open-label, single-arm phase 3b trial. Lancet Oncol. 2016;17:1306–16.PubMed
33.
Naito M, Ukai R, Hashimoto K. Bone scan index can be a useful biomarker of survival outcomes in patients with metastatic castration-resistant prostate cancer treated with radium-223. Cancer Rep (Hoboken). 2019;2:e1203.
34.
Prelaj A, Rebuzzi SE, Buzzacchino F, Pozzi C, Ferrara C, Frantellizzi V, et al. Radium-223 in patients with metastatic castration-resistant prostate cancer: efficacy and safety in clinical practice. Oncol Lett. 2019;17:1467–76.PubMed
35.
Maruzzo M, Basso U, Borsatti E, Evangelista L, Alongi F, Caffo O, et al. Results from a large, multicenter, retrospective analysis on radium223 use in metastatic castration-resistant prostate cancer (mCRPC) in the Triveneto Italian Region. Clin Genitourin Cancer. 2019;17:e187–94.PubMed
36.
Parimi S, Tsang E, Alexander A, Mckenzie M, Bachand F, Sunderland K, et al. A population-based study of the use of radium 223 in metastatic castration-resistant prostate cancer: factors associated with treatment completion. Can Urol Assoc J. 2017;11:350–5.PubMedPubMedCentral
37.
De Luca R, Costa RP, Tripoli V, Murabito A, Cicero G. the clinical efficacy of radium-223 for bone metastasis in patients with castration-resistant prostate cancer: an Italian clinical experience. Oncology. 2018;94:161–6.PubMed
38.
Vidal M, Delgado A, Martinez C, Correa JJ, Durango IC. Overall survival prediction in metastatic castration-resistant prostate cancer treated with radium-223. Int Braz J Urol. 2020;46:599–611.PubMedPubMedCentral
39.
Bauckneht M, Capitanio S, Donegani MI, Zanardi E, Miceli A, Murialdo R, et al. Role of baseline and post-therapy 18F-FDG PET in the prognostic stratification of metastatic castration-resistant prostate cancer (mCRPC) patients treated with radium-223. Cancers (Basel). 2019;12:31.
40.
Filippi L, Spinelli GP, Chiaravalloti A, Schillaci O, Equitani F, Bagni O. Prognostic value of 18F-Choline PET/CT in Patients with metastatic castration-resistant prostate cancer treated with radium-223. Biomedicines. 2020;8:555.PubMedCentral
41.
Roque V, Jessop M, Pereira L, Gape P, Dizdarevic S, Sousa E, et al. Bone scan index as metastatic bone disease quantifier and predictor of radium-223-dichloride biochemical response. Nucl Med Commun. 2019;40:588–96.PubMed
42.
Frantellizzi V, Pani A, Ippoliti MD, Farcomeni A, Aloise I, Colosi M, et al. Scintigraphic load of bone disease evaluated by DASciS software as a survival predictor in metastatic castration-resistant prostate cancer patients candidates to 223RaCl treatment. Radiol Oncol. 2019;54:40–7.PubMedPubMedCentral
43.
44.
Ricci M, Frantellizzi V, Bulzonetti N, De Vincentis G. Reversibility of castration resistance status after Radium-223 dichloride treatment: clinical evidence and review of the literature. Int J Radiat Biol. 2019;95:554–61.PubMed
45.
Frantellizzi V, Monari F, Mascia M, Costa R, Rubini G, Spanu A, et al. Validation of the 3-variable prognostic score (3-PS) in mCRPC patients treated with 223Radium-dichloride: a national multicenter study. Ann Nucl Med. 2020;34:772–80.PubMedPubMedCentral
46.
Akimoto S, Furuya Y, Akakura K, Shimazaki J, Ito H. Relationship between prostate-specific antigen, clinical stage, and degree of bone metastasis in patients with prostate cancer: comparison with prostatic acid phosphatase and alkaline phosphatase. Int J Urol. 1997;4:572–5.PubMed
47.
Saad F, Gillessen S, Heinrich D, Keizman D, O’Sullivan JM, Nilsson S, et al. Disease characteristics and completion of treatment in patients with metastatic castration-resistant prostate cancer treated with radium-223 in an international early access program. Clin Genitourin Cancer. 2019;17:348-355.e5.PubMed
48.
Metadata
Title
The prognostic power of inflammatory indices and clinical factors in metastatic castration-resistant prostate cancer patients treated with radium-223 (BIO-Ra study)
Authors
Matteo Bauckneht
Sara Elena Rebuzzi
Alessio Signori
Viviana Frantellizzi
Veronica Murianni
Elisa Lodi Rizzini
Manlio Mascia
Valentina Lavelli
Maria Isabella Donegani
Marta Ponzano
Angela Gaudiano
Maria Lina Stazza
Maria Licari
Letizia Cavallini
Viola Laghi
Luca Cindolo
Martina Maggi
Alessandro Sciarra
Paolo Mammucci
Gianmario Sambuceti
Renato Patrizio Costa
Angela Spanu
Giuseppe Rubini
Fabio Monari
Giuseppe De Vincentis
Giuseppe Fornarini
Publication date
01-02-2022
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 3/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-021-05550-6

Other articles of this Issue 3/2022

European Journal of Nuclear Medicine and Molecular Imaging 3/2022 Go to the issue

Original Article

177 Lu-PSMA-617 radioligand therapy of metastatic castration-resistant prostate cancer: Initial 254-patient results from a prospective registry (REALITY Study)

Original Article

Peripheral inflammation is associated with brain SPECT perfusion changes in schizophrenia

Editorial

Patients’ findings after COVID-19 infection and vaccinations: what to expect from [18F]FDG PET/CT

Original Article

18F-FDG PET baseline radiomics features improve the prediction of treatment outcome in diffuse large B-cell lymphoma

Original Article

The potential utility of [68 Ga]Ga-DOTA-FAPI-04 as a novel broad-spectrum oncological and non-oncological imaging agent—comparison with [18F]FDG

Guidelines

International consensus on the use of tau PET imaging agent 18F-flortaucipir in Alzheimer’s disease