Does volume change of the spleen correlate with the therapy response in uveal melanoma patients with liver metastases undergoing hepatic artery infusion chemotherapy?

Steinberg-Vorhoff, Hannah Luisa; Drews, Marcel; Opitz, Marcel; Landeghem, Natalie van; Salhöfer, Luca; Holtkamp, Mathias; Li, Yan; Haubold, Johannes; Siveke, Jens; Richly, Heike; Forsting, Michael; Schaarschmidt, Benedikt Michael; Zensen, Sebastian

doi:10.2478/raon-2025-0047

Abstract

Background

Uveal melanoma (UM) patients with liver metastases often undergo hepatic artery infusion therapy (HAIC). Due to diffuse metastatic spread in the liver, patients often develop hepatomegaly and secondary, portal hypertension which may lead to splenomegaly. This study aimed to compare spleen volumetry and the change of spleen volume (SV) for the evaluation of HAIC treatment response.

Patients and methods

In this study, 179 UM patients (mean age 64.8 ± 11.0y, 53% female) with liver metastases undergoing HAIC were included. Treatment response was analyzed by RECIST 1.1 and SV on CT imaging before and after first HAIC. The correlation of change in spleen and liver volume was analyzed with Spearman test. Overall survival (OS) was calculated as the time from the first HAIC to patient death using Kaplan-Meier test and multivariate analysis was performed for RECIST 1.1 and SV.

Results

In the study population, OS was 13.8 months (95% CI 10.6-14.7 months). Change in SV before and after first HAIC was +4% (interquartile range [IQR] -4.0%–12.0%, p = 0.49) and showed a weak correlation with OS (r = -0.11, p = 0.18). UM patients with progressive disease (PD) according to RECIST 1.1 showed an increase in SV compared to patients with stable disease (SD) (p = 0.04). Compared to RECIST 1.1, SV was not significant prognostic factor that can identify a change in OS.

Conclusions

In uveal melanoma patients with liver metastases undergoing HAIC, neither the change of SV nor splenomegaly could be identified as prognostic factors for OS.

References

Carvajal RD, Schwartz GK, Tezel T, Marr B, Francis JH, Nathan PD. Metastatic disease from uveal melanoma: treatment options and future prospects. Br J Ophthalmol 2017; 101: 38-44. doi: doi: 10.1136/bjophthalmol-2016-309034
Open DOI Search in Google Scholar Back to article
Singh AD, Turell ME, Topham AK. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology 2011; 118: 1881-5. doi: 10.1016/j.ophtha.2011.01.040
Open DOI Search in Google Scholar Back to article
Rietschel P, Panageas KS, Hanlon C, Patel A, Abramson DH, Chapman PB. Variates of survival in metastatic uveal melanoma. J Clin Oncol 2005; 23: 8076-80. doi: 10.1200/JCO.2005.02.6534
Open DOI Search in Google Scholar Back to article
Diener-West M, Reynolds SM, Agugliaro DJ, Caldwell R, Cumming K, Earle JD, et al. Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26. Arch Ophthalmol 2005; 123: 1639-43. doi: 10.1001/archopht.123.12.1639
Open DOI Search in Google Scholar Back to article
Nathan P, Cohen V, Coupland S, Curtis K, Damato B, Evans J, et al. Uveal Melanoma UK National Guidelines. Eur J Cancer 2015; 51: 2404-12. doi: 10.1016/j.ejca.2015.07.013
Open DOI Search in Google Scholar Back to article
Hassel JC, Piperno-Neumann S, Rutkowski P, Baurain J-F, Schlaak M, Butler MO, et al. Three-year overall survival with tebentafusp in metastatic uveal melanoma. N Engl J Med 2023; 389: 2256-66. doi: doi: 10.1056/NEJMoa2304753
Open DOI Search in Google Scholar Back to article
Buder K, Gesierich A, Gelbrich G, Goebeler M. Systemic treatment of metastatic uveal melanoma: review of literature and future perspectives. Cancer Med 2013; 2: 674-86. doi: 10.1002/cam4.133
Open DOI Search in Google Scholar Back to article
Schelhorn J, Richly H, Ruhlmann M, Lauenstein TC, Theysohn JM. A singlecenter experience in radioembolization as salvage therapy of hepatic metastases of uveal melanoma. Acta Radiol Open 2015; 4: 2047981615570417. doi: 10.1177/2047981615570417
Open DOI Search in Google Scholar Back to article
Heusner TA, Antoch G, Wittkowski-Sterczewski A, Ladd SC, Forsting M, Verhagen R, et al. Transarterial hepatic chemoperfusion of uveal melanoma metastases: survival and response to treatment. Rofo 2011; 183: 1151-60. doi: 10.1055/s-0031-1281743
Open DOI Search in Google Scholar Back to article
Gonsalves CF, Eschelman DJ, Adamo RD, Anne PR, Orloff MM, Terai M, et al. A prospective phase ii trial of radioembolization for treatment of uveal melanoma hepatic metastasis. Radiology 2019; 293: 223-31. doi: 10.1148/radiol.2019190199
Open DOI Search in Google Scholar Back to article
Leyvraz S, Piperno-Neumann S, Suciu S, Baurain JF, Zdzienicki M, Testori A, et al. Hepatic intra-arterial versus intravenous fotemustine in patients with liver metastases from uveal melanoma (EORTC 18021): a multicentric randomized trial. Ann Oncol 2014; 25: 742-6. doi: 10.1093/annonc/mdt585.
Open DOI Search in Google Scholar Back to article
Zimmermann A. Metastatic liver disease: associated liver lesions. In: Zimmermann A, editor. Tumors and tumor-like lesions of the hepatobiliary tract: general and surgical pathology. Cham: Springer International Publishing; 2017. p. 1973-87.
Search in Google Scholar Back to article
Kromrey M, Ittermann T, Plodeck V, Seppelt D, Hoffmann R, Heiss P, et al. Reference values of liver volume in Caucasian population and factors influencing liver size. Eur J Radiol 2018; 106: 32-7. doi: 10.1016/j. ejrad.2018.07.005
Open DOI Search in Google Scholar Back to article
Wu C, Ning H, Liu M, Lin J, Luo S, Zhu W, et al. Spleen mediates a distinct hematopoietic progenitor response supporting tumor-promoting myelopoiesis. J Clin Invest 2018; 128: 3425-38. doi: 10.1172/JCI97973
Open DOI Search in Google Scholar Back to article
Xiao LS, Hu CY, Cui H, Li RN, Hong C, Li QM, et al. Splenomegaly in predicting the survival of patients with advanced primary liver cancer treated with immune checkpoint inhibitors. Cancer Med 2022; 11: 4880-8. doi: 10.1002/cam4.4818
Open DOI Search in Google Scholar Back to article
Fernández-Placencia R, Golse N, Cano L, Allard MA, Pittau G, Ciacio O, et al. Spleen volumetry and liver transient elastography: predictors of persistent posthepatectomy decompensation in patients with hepatocellular carcinoma. Surgery 2020; 168: 17-24. doi: 10.1016/j.surg.2020.02.009
Open DOI Search in Google Scholar Back to article
Prassopoulos P, Daskalogiannaki M, Raissaki M, Hatjidakis A, Gourtsoyiannis N. Determination of normal splenic volume on computed tomography in relation to age, gender and body habitus. Eur Radiol 1997; 7: 246-8. doi: 10.1007/s003300050145
Open DOI Search in Google Scholar Back to article
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228-47. doi: 10.1016/j.ejca.2008.10.026
Open DOI Search in Google Scholar Back to article
Gragoudas ES, Egan KM, Seddon JM, Glynn RJ, Walsh SM, Finn SM, et al. Survival of patents with metastases from uveal melanoma. Ophthalmology 1991; 98: 383-90. doi: 10.1016/s0161-6420(91)32285-1
Open DOI Search in Google Scholar Back to article
Krantz BA, Dave N, Komatsubara KM, Marr BP, Carvajal RD. Uveal melanoma: epidemiology, etiology, and treatment of primary disease. Clin Ophthalmol 2017; 11: 279-89. doi: 10.2147/OPTH.S89591
Open DOI Search in Google Scholar Back to article
Kujala E, Mäkitie T, Kivelä T. Very long-term prognosis of patients with malignant uveal melanoma. Invest Ophthalmol Vis Sci 2003; 44: 4651-9. doi: 10.1167/iovs.03-0538
Open DOI Search in Google Scholar Back to article
Kuk D, Shoushtari AN, Barker CA, Panageas KS, Munhoz RR, Momtaz P, et al. Prognosis of mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma from the time of first metastasis. Oncologist 2016; 21: 848-54. doi: 10.1634/theoncologist.2015-0522
Open DOI Search in Google Scholar Back to article
Müller L, Kloeckner R, Mähringer-Kunz A, Stoehr F, Düber C, Arnhold G, et al. Fully automated AI-based splenic segmentation for predicting survival and estimating the risk of hepatic decompensation in TACE patients with HCC. Eur Radiol 2022; 32: 6302-13. doi: 10.1007/s00330-022-08737-z
Open DOI Search in Google Scholar Back to article
Müller L, Gairing SJ, Kloeckner R, Foerster F, Weinmann A, Mittler J, et al. Baseline splenic volume outweighs immuno-modulated size changes with regard to survival outcome in patients with hepatocellular carcinoma under immunotherapy. Cancers (Basel) 2022; 14: 3574. doi: 10.3390/cancers14153574
Open DOI Search in Google Scholar Back to article
Wu WC, Chiou YY, Hung HH, Kao WY, Chou YH, Su CW, et al. Prognostic significance of computed tomography scan-derived splenic volume in hepatocellular carcinoma treated with radiofrequency ablation. J Clin Gastroenterol 2012; 46: 789-95. doi: 10.1097/MCG.0b013e31825ceeb5
Open DOI Search in Google Scholar Back to article
Galland L, Lecuelle J, Favier L, Fraisse C, Lagrange A, Kaderbhai C, et al. Splenic volume as a surrogate marker of immune checkpoint inhibitor efficacy in metastatic non small cell lung cancer. Cancers (Basel) 2021; 13: 3020. doi: 10.3390/cancers13123020
Open DOI Search in Google Scholar Back to article
Castagnoli F, Doran S, Lunn J, Minchom A, O’Brien M, Popat S, et al. Splenic volume as a predictor of treatment response in patients with non-small cell lung cancer receiving immunotherapy. PLoS One 2022; 17: e0270950. doi: 10.1371/journal.pone.0270950
Open DOI Search in Google Scholar Back to article
Feucht HE, Schneeberger H, Hillebrand G, Burkhardt K, Weiss M, Riethmüller G, et al. Capillary deposition of C4d complement fragment and early renal graft loss. Kidney Int 1993; 43: 1333-8. doi: 10.1038/ki.1993.187
Open DOI Search in Google Scholar Back to article
Theophilidou E, Waraich N, Raza T, Agarwal PK. Liver metastases, a rare cause of portal hypertension and stoma bleeding. Brief review of literature. Int J Surg Case Rep 2012; 3: 173-6. doi: 10.1016/j.ijscr.2011.11.008
Open DOI Search in Google Scholar Back to article