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Annals of Nuclear Medicine
Published in: Annals of Nuclear Medicine 4/2022

Open Access 01-04-2022 | Prostate Cancer | Original Article

Opportunistic skeletal muscle metrics as prognostic tools in metastatic castration-resistant prostate cancer patients candidates to receive Radium-223

Authors: Matteo Bauckneht, Rita Lai, Francesca D’Amico, Alberto Miceli, Maria Isabella Donegani, Cristina Campi, Daniela Schenone, Stefano Raffa, Silvia Chiola, Francesco Lanfranchi, Sara Elena Rebuzzi, Elisa Zanardi, Malvina Cremante, Cecilia Marini, Giuseppe Fornarini, Silvia Morbelli, Michele Piana, Gianmario Sambuceti

Published in: Annals of Nuclear Medicine | Issue 4/2022

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Abstract

Objective

Androgen deprivation therapy alters body composition promoting a significant loss in skeletal muscle (SM) mass through inflammation and oxidative damage. We verified whether SM anthropometric composition and metabolism are associated with unfavourable overall survival (OS) in a retrospective cohort of metastatic castration-resistant prostate cancer (mCRPC) patients submitted to 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) imaging before receiving Radium-223.

Patients and methods

Low-dose CT were opportunistically analysed using a cross-sectional approach to calculate SM and adipose tissue areas at the third lumbar vertebra level. Moreover, a 3D computational method was used to extract psoas muscles to evaluate their volume, Hounsfield Units (HU) and FDG retention estimated by the standardized uptake value (SUV). Baseline established clinical, lab and imaging prognosticators were also recorded.

Results

SM area predicted OS at univariate analysis. However, this capability was not additive to the power of mean HU and maximum SUV of psoas muscles volume. These factors were thus combined in the Attenuation Metabolic Index (AMI) whose power was tested in a novel uni- and multivariable model. While Prostate-Specific Antigen (PSA), Alkaline Phosphatase (ALP), Lactate Dehydrogenase and Hemoglobin, Metabolic Tumor Volume, Total Lesion Glycolysis and AMI were associated with long-term OS at the univariate analyses, only PSA, ALP and AMI resulted in independent prognosticator at the multivariate analysis.

Conclusion

The present data suggest that assessing individual 'patients' SM metrics through an opportunistic operator-independent computational analysis of FDG PET/CT imaging provides prognostic insights in mCRPC patients candidates to receive Radium-223.

Graphical abstract

Literature
1.
Siegel DA, O’Neil ME, Richards TB, Dowling NF, Weir HK. Prostate cancer incidence and survival, by stage and race/ethnicity - United States, 2001–2017. MMWR Morb Mortal Wkly Rep. 2020;69:1473–80.PubMedPubMedCentral
2.
Facchini G, Perri F, Misso G, D’Aniello C, Scarpati GDV, Rossetti S, et al. Optimal management of prostate cancer based on its natural clinical history. Curr Cancer Drug Targets. 2018;18:457–67.PubMed
3.
Morris MJ, Corey E, Guise TA, Gulley JL, Kevin Kelly W, Quinn DI, et al. Radium-223 mechanism of action: implications for use in treatment combinations. Nat Rev Urol. 2019;16:745–56.PubMedPubMedCentral
4.
Nelson BJB, Andersson JD, Wuest F. Targeted alpha therapy: progress in radionuclide production, radiochemistry, and applications. Pharmaceutics. 2020;13:49.PubMedPubMedCentral
5.
Ferrier MG, Radchenko V. An appendix of radionuclides used in targeted alpha therapy. J Med Imaging Radiat Sci. 2019;50:S58–65.PubMed
6.
Cheetham PJ, Petrylak DP. Alpha particles as radiopharmaceuticals in the treatment of bone metastases: mechanism of action of radium-223 chloride (Alpharadin) and radiation protection. Oncology (Williston Park). 2012;26:330–7.
7.
Flux GD. Imaging and dosimetry for radium-223: the potential for personalized treatment. Br J Radiol. 2017;90:20160748.PubMedPubMedCentral
8.
Pacilio M, Ventroni G, De Vincentis G, Cassano B, Pellegrini R, Di Castro E, et al. Dosimetry of bone metastases in targeted radionuclide therapy with alpha-emitting (223)Ra-dichloride. Eur J Nucl Med Mol Imaging. 2016;43:21–33.PubMed
9.
Sciuto R, Rea S, Ungania S, Testa A, Dini V, Tabocchini MA, et al. The role of dosimetry and biological effects in metastatic castration-resistant prostate cancer (mCRPC) patients treated with 223Ra: first in human study. J Exp Clin Cancer Res. 2021;40:281.PubMedPubMedCentral
10.
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
11.
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.
12.
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
13.
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
14.
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
15.
16.
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.
17.
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.
18.
Lee JS, Lee HS, Ha JS, Han KS, Rha KH, Hong SJ, et al. Subcutaneous fat distribution is a prognostic biomarker for men with castration resistant prostate cancer. J Urol. 2018;200:114–20.PubMed
19.
Baracos VE, Arribas L. Sarcopenic obesity: hidden muscle wasting and its impact for survival and complications of cancer therapy. Ann Oncol. 2018;29:ii1-9.PubMed
20.
Ohtaka A, Aoki H, Nagata M, Kanayama M, Shimizu F, Ide H, et al. Sarcopenia is a poor prognostic factor of castration-resistant prostate cancer treated with docetaxel therapy. Prostate Int. 2019;7:9–14.PubMed
21.
Stangl-Kremser J, Suarez-Ibarrola R, Andrea D, Korn SM, Pones M, Kramer G, et al. Assessment of body composition in the advanced stage of castration-resistant prostate cancer: special focus on sarcopenia. Prostate Cancer Prostatic Dis. 2020;23:309–15.PubMed
22.
Fielding RA, Vellas B, Evans WJ, Bhasin S, Morley JE, Newman AB, et al. Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc. 2011;12:249–56.PubMed
23.
Kazemi-Bajestani SM, Mazurak VC, Baracos V. Computed tomography-defined muscle and fat wasting are associated with cancer clinical outcomes. Semin Cell Dev Biol. 2016;54:2–10.PubMed
24.
Deans C, Wigmore SJ. Systemic inflammation, cachexia and prognosis in patients with cancer. Curr Opin Clin Nutr Metab Care. 2005;8:265–9.PubMed
25.
26.
Boellaard R, Delgado-Bolton R, Oyen WJ, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42:328–54.PubMed
27.
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
28.
29.
Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12:489–95.PubMed
30.
Beltrametti MC, Massone AM, Piana M. Hough transform of special classes of functions. SIAM J Imag Sci. 2013;6:391–412.
31.
Bauckneht M, Lai R, Miceli A, Schenone D, Cossu V, Donegani MI, et al. Spinal cord hypermetabolism extends to skeletal muscle in amyotrophic lateral sclerosis: a computational approach to [18F]-fluorodeoxyglucose PET/CT images. EJNMMI Res. 2020;10:23.PubMedPubMedCentral
32.
Kruse V, Mees G, Maes A, D’Asseler Y, Borms M, Cocquyt V, et al. Reproducibility of FDG PET based metabolic tumor volume measurements and of their FDG distribution within. Q J Nucl Med Mol Imaging. 2015;59:462–8.PubMed
33.
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.
34.
van der Zande K, Oyen WJG, Zwart W, Bergman AM. Radium-223 treatment of patients with metastatic castration resistant prostate cancer: biomarkers for stratification and response evaluation. Cancers (Basel). 2021;13:4346.
35.
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
36.
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
37.
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
38.
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
39.
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
40.
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
41.
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
42.
Shachar SS, Williams GR, Muss HB, Nishijima TF. Prognostic value of sarcopenia in adults with solid tumours: a meta-analysis and systematic review. Eur J Cancer. 2016;57:58–67.PubMed
43.
Simonsen C, de Heer P, Bjerre ED, Suetta C, Hojman P, Pedersen BK, et al. Sarcopenia and postoperative complication risk in gastrointestinal surgical oncology: a meta-analysis. Ann Surg. 2018;268:58–69.PubMed
44.
45.
Meyer HJ, Wienke A, Surov A. CT-defined low-skeletal muscle mass as a prognostic marker for survival in prostate cancer: a systematic review and meta-analysis. Urol Oncol. 2021;S1078–1439(21):00368–9.
46.
Jahrreiss V, Laukhtina E, D’Andrea D, Shariat SF. The prognostic value of sarcopenia in patients with prostate cancer: a systematic review. Curr Opin Urol. 2021;31:315–23.PubMed
47.
Frenette A, Morrell J, Bjella K, Fogarty E, Beal J, Chaudhary V. Do Diametric measurements provide sufficient and reliable tumor assessment? An evaluation of diametric, areametric, and volumetric variability of lung lesion measurements on computerized tomography scans. J Oncol. 2015;2015:632943.PubMedPubMedCentral
48.
Foster B, Boutin RD, Lenchik L, Gedeon D, Liu Y, Nittur V, et al. Skeletal muscle metrics on clinical 18F-FDG PET/CT predict health outcomes in patients with sarcoma. J Nat Sci. 2018;4:e502.PubMedPubMedCentral
49.
Saylor PJ, Smith MR. Metabolic complications of androgen deprivation therapy for prostate cancer. J Urol. 2013;189:S34-42.PubMed
50.
51.
Schaap LA, Pluijm SM, Deeg DJ, Harris TB, Kritchevsky SB, Newman AB, et al. Higher inflammatory marker levels in older persons: associations with 5-year change in muscle mass and muscle strength. J Gerontol A Biol Sci Med Sci. 2009;64:1183–9.PubMed
52.
Kim JY, Jun DW, Choi J, Nam E, Son D, Choi YY. Psoas muscle fluorine-18-labelled fluoro-2-deoxy-d-glucose uptake associated with the incidence of existing and incipient metabolic derangement. J Cachexia Sarcopenia Muscle. 2019;10:894–902.PubMedPubMedCentral
53.
Zoico E, Corzato F, Bambace C, Rossi AP, Micciolo R, Cinti S, et al. Myosteatosis and myofibrosis: relationship with aging, inflammation and insulin resistance. Arch Gerontol Geriatr. 2013;57:411–6.PubMedPubMedCentral
54.
Tateyama M, Fujihara K, Misu T, Arai A, Kaneta T, Aoki M. Clinical values of FDG PET in polymyositis and dermatomyositis syndromes: imaging of skeletal muscle inflammation. BMJ Open. 2015;5:e006763.PubMedPubMedCentral
55.
Tanaka S, Ikeda K, Uchiyama K, Iwamoto T, Sanayama Y, Okubo A, et al. [18F]FDG uptake in proximal muscles assessed by PET/CT reflects both global and local muscular inflammation and provides useful information in the management of patients with polymyositis/dermatomyositis. Rheumatology (Oxford). 2013;52:1271–8.
56.
Foreman NA, Hesse AS, Ji LL. Redox signaling and sarcopenia: searching for the primary suspect. Int J Mol Sci. 2021;22:9045.PubMedPubMedCentral
57.
Marini C, Ravera S, Buschiazzo A, Bianchi G, Orengo AM, Bruno S, et al. Discovery of a novel glucose metabolism in cancer: the role of endoplasmic reticulum beyond glycolysis and pentose phosphate shunt. Sci Rep. 2016;6:25092.PubMedPubMedCentral
58.
Scussolini M, Bauckneht M, Cossu V, Bruno S, Orengo AM, Piccioli P, et al. G6Pase location in the endoplasmic reticulum: implications on compartmental analysis of FDG uptake in cancer cells. Sci Rep. 2019;9:2794.PubMedPubMedCentral
59.
Cossu V, Marini C, Piccioli P, Rocchi A, Bruno S, Orengo AM, et al. Obligatory role of endoplasmic reticulum in brain FDG uptake. Eur J Nucl Med Mol Imaging. 2019;46:1184–96.PubMed
60.
Marini C, Cossu V, Kumar M, Milanese M, Cortese K, Bruno S, et al. The role of endoplasmic reticulum in the differential endurance against Redox stress in cortical and spinal astrocytes from the newborn SOD1G93A mouse model of amyotrophic lateral sclerosis. Antioxidants (Basel). 2021;10:1392.
61.
Bauckneht M, Pastorino F, Castellani P, Cossu V, Orengo AM, Piccioli P, et al. Increased myocardial 18F-FDG uptake as a marker of Doxorubicin-induced oxidative stress. J Nucl Cardiol. 2020;27:2183–94.PubMed
62.
Bauckneht M, Cossu V, Castellani P, Piccioli P, Orengo AM, Emionite L, et al. FDG uptake tracks the oxidative damage in diabetic skeletal muscle: an experimental study. Mol Metab. 2020;31:98–108.PubMed
63.
Marini C, Cossu V, Bonifacino T, Bauckneht M, Torazza C, Bruno S, et al. Mechanisms underlying the predictive power of high skeletal muscle uptake of FDG in amyotrophic lateral sclerosis. EJNMMI Res. 2020;10:76.PubMedPubMedCentral
64.
65.
Albano D, Camoni L, Rinaldi R, Tucci A, Zilioli VR, Muzi C, et al. Comparison between skeletal muscle and adipose tissue measurements with high-dose CT and low-dose attenuation correction CT of 18F-FDG PET/CT in elderly Hodgkin lymphoma patients: a two-centre validation. Br J Radiol. 2021;94:20200672.PubMedPubMedCentral
Metadata
Title
Opportunistic skeletal muscle metrics as prognostic tools in metastatic castration-resistant prostate cancer patients candidates to receive Radium-223
Authors
Matteo Bauckneht
Rita Lai
Francesca D’Amico
Alberto Miceli
Maria Isabella Donegani
Cristina Campi
Daniela Schenone
Stefano Raffa
Silvia Chiola
Francesco Lanfranchi
Sara Elena Rebuzzi
Elisa Zanardi
Malvina Cremante
Cecilia Marini
Giuseppe Fornarini
Silvia Morbelli
Michele Piana
Gianmario Sambuceti
Publication date
01-04-2022
Publisher
Springer Singapore
Published in
Annals of Nuclear Medicine / Issue 4/2022
Print ISSN: 0914-7187
Electronic ISSN: 1864-6433
DOI
https://doi.org/10.1007/s12149-022-01716-w

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