Dorsal Root Ganglion Morphometric Changes Under Oxaliplatin Treatment : Longitudinal Assessment by Computed Tomography

Overview

Journal Clin Neuroradiol

Specialties Neurology
Radiology

Date 2021 Sep 9

PMID 34499182

Citations 1

Authors

Leonidas Apostolidis

Lars Kowalscheck

Tim Frederik Weber

Tim Godel

Martin Bendszus

Hans-Ulrich Kauczor

Dirk Jager

Heinz-Peter Schlemmer

Philipp Baumer

Affiliations

Soon will be listed here.

Abstract

Purpose: Magnetic resonance neurography (MRN) can detect dorsal root ganglia (DRG) hypertrophy in patients with oxaliplatin-induced peripheral neuropathy (OXIPN) but is difficult to apply in clinical daily practice. Aims of this study were (i) to assess whether DRG volume is reliably measurable by routine computed tomography (CT) scans, (ii) to measure longitudinal changes in DRG during and after oxaliplatin administration and (iii) to assess correlation between DRG morphometry and individual oxaliplatin dose.

Methods: For comparison of MRN and CT measurements, CT scans of 18 patients from a previous MRN study were analyzed. For longitudinal assessment of DRG size under treatment, 96 patients treated with oxaliplatin between January and December 2014 were enrolled retrospectively. DRG volumetry was performed by analyzing routine CT scans, starting with the last scan before oxaliplatin exposure (t0) and up to four consecutive timepoints after initiation of oxaliplatin therapy (t1-t4) with the following median and ranges in months: 3.1 (0.4-4.9), 6.2 (5.3-7.8), 10.4 (8.2-11.9), and 18.4 (12.8-49.8).

Results: DRG volume measured in CT showed a moderately strong correlation with MRN (r = 0.51, p < 0.001) and a strong correlation between two consecutive CTs (r = 0.77, p < 0.001). DRG volume increased after oxaliplatin administration with a maximum at timepoint t2. Higher cumulative oxaliplatin exposure was associated with significantly higher absolute DRG volumes (p = 0.005). Treatment discontinuation was associated with a nonsignificant trend towards lower relative DRG volume changes (p = 0.08).

Conclusion: CT is a reliable method for continuous DRG morphometry; however, since no standardized assessment of OXIPN was performed in this retrospective study, correlations between DRG size, cumulative oxaliplatin dose and clinical symptoms in future prospective studies are needed to establish DRG size as a potential OXIPN biomarker.

Citing Articles

Dorsal Root Ganglia Volume-Normative Values, Correlation with Demographic Determinants and Reliability of Three Different Methods of Volumetry.

Kronlage M, Fischer T, Behnisch R, Schwarz D, Baumer P, Schwehr V Diagnostics (Basel). 2022; 12(7).

PMID: 35885475 PMC: 9323629. DOI: 10.3390/diagnostics12071570.

References

Park S, Lin C, Krishnan A, Goldstein D, Friedlander M, Kiernan M . Long-term neuropathy after oxaliplatin treatment: challenging the dictum of reversibility. Oncologist. 2011; 16(5):708-16. PMC: 3228192. DOI: 10.1634/theoncologist.2010-0248. View

Cavaletti G, Tredici G, Marmiroli P, Petruccioli M, Barajon I, Fabbrica D . Morphometric study of the sensory neuron and peripheral nerve changes induced by chronic cisplatin (DDP) administration in rats. Acta Neuropathol. 1992; 84(4):364-71. DOI: 10.1007/BF00227662. View

Grothey A . Clinical management of oxaliplatin-associated neurotoxicity. Clin Colorectal Cancer. 2005; 5 Suppl 1:S38-46. DOI: 10.3816/ccc.2005.s.006. View

Holmes J, Stanko J, Varchenko M, Ding H, Madden V, Bagnell C . Comparative neurotoxicity of oxaliplatin, cisplatin, and ormaplatin in a Wistar rat model. Toxicol Sci. 1999; 46(2):342-51. DOI: 10.1006/toxs.1998.2558. View

Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y . FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011; 364(19):1817-25. DOI: 10.1056/NEJMoa1011923. View

Apostolidis L, Schwarz D, Xia A, Weiler M, Heckel A, Godel T . Dorsal root ganglia hypertrophy as in vivo correlate of oxaliplatin-induced polyneuropathy. PLoS One. 2017; 12(8):e0183845. PMC: 5570356. DOI: 10.1371/journal.pone.0183845. View

Al-Batran S, Hartmann J, Hofheinz R, Homann N, Rethwisch V, Probst S . Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2008; 19(11):1882-7. DOI: 10.1093/annonc/mdn403. View

Alejandro L, Behrendt C, Chen K, Openshaw H, Shibata S . Predicting acute and persistent neuropathy associated with oxaliplatin. Am J Clin Oncol. 2012; 36(4):331-7. PMC: 4080710. DOI: 10.1097/COC.0b013e318246b50d. View

Cassidy J, Tabernero J, Twelves C, Brunet R, Butts C, Conroy T . XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer. J Clin Oncol. 2004; 22(11):2084-91. DOI: 10.1200/JCO.2004.11.069. View

10.

Baker S, Verweij J, Rowinsky E, Donehower R, Schellens J, Grochow L . Role of body surface area in dosing of investigational anticancer agents in adults, 1991-2001. J Natl Cancer Inst. 2002; 94(24):1883-8. DOI: 10.1093/jnci/94.24.1883. View

11.

Al-Batran S, Hartmann J, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R . Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008; 26(9):1435-42. DOI: 10.1200/JCO.2007.13.9378. View

12.

Argyriou A, Bruna J, Marmiroli P, Cavaletti G . Chemotherapy-induced peripheral neurotoxicity (CIPN): an update. Crit Rev Oncol Hematol. 2011; 82(1):51-77. DOI: 10.1016/j.critrevonc.2011.04.012. View

13.

Cavaletti G, Petruccioli M, Tredici G, Marmiroli P, Barajon I, Fabbrica D . Effects of repeated administration of low doses of cisplatin on the rat nervous system. Int J Tissue React. 1991; 13(3):151-7. View

14.

de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J . Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000; 18(16):2938-47. DOI: 10.1200/JCO.2000.18.16.2938. View

15.

Kaestner S, Sewell G . Chemotherapy dosing part I: scientific basis for current practice and use of body surface area. Clin Oncol (R Coll Radiol). 2007; 19(1):23-37. DOI: 10.1016/j.clon.2006.10.010. View

16.

Godel T, Mautner V, Farschtschi S, Pham M, Schwarz D, Kronlage M . Dorsal root ganglia volume differentiates schwannomatosis and neurofibromatosis 2. Ann Neurol. 2018; 83(4):854-857. DOI: 10.1002/ana.25191. View

17.

Gregg R, Molepo J, Monpetit V, Mikael N, Redmond D, Gadia M . Cisplatin neurotoxicity: the relationship between dosage, time, and platinum concentration in neurologic tissues, and morphologic evidence of toxicity. J Clin Oncol. 1992; 10(5):795-803. DOI: 10.1200/JCO.1992.10.5.795. View

18.

Godel T, Pham M, Heiland S, Bendszus M, Baumer P . Human dorsal-root-ganglion perfusion measured in-vivo by MRI. Neuroimage. 2016; 141:81-87. DOI: 10.1016/j.neuroimage.2016.07.030. View

19.

Godel T, Baumer P, Pham M, Kohn A, Muschol N, Kronlage M . Human dorsal root ganglion in vivo morphometry and perfusion in Fabry painful neuropathy. Neurology. 2017; 89(12):1274-1282. DOI: 10.1212/WNL.0000000000004396. View

20.

Jamieson S, Liu J, Connor B, McKeage M . Oxaliplatin causes selective atrophy of a subpopulation of dorsal root ganglion neurons without inducing cell loss. Cancer Chemother Pharmacol. 2005; 56(4):391-9. DOI: 10.1007/s00280-004-0953-4. View