Baseline Splenic Volume Outweighs Immuno-Modulated Size Changes with Regard to Survival Outcome in Patients with Hepatocellular Carcinoma under Immunotherapy

Müller, Lukáš; Gairing, Simon Johannes; Kloeckner, Roman; Foerster, Friedrich; Weinmann, Arndt; Mittler, Jens; Stoehr, Fabian; Emrich, Tilman; Düber, Christoph; Galle, Peter R.; Hähn, Felix

doi:10.3390/cancers14153574

Cited by 8 publications

(8 citation statements)

References 31 publications

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“…Again, Lukas Müller at all [ 21 ]. found that a large proportion of hepatocellular carcinoma (HCC) patients who received immunotherapy treatment as first-line therapy had an increase in splenic volume after initiation of immunotherapy, but this was not associated with survival outcomes.…”

Section: Discussionmentioning

confidence: 99%

The role of spleen volume change in predicting immunotherapy response in metastatic renal cell carcinoma

Aslan,

Karabörk Kılıç,

Özet

et al. 2023

BMC Cancer

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Introduction Resistance to immune checkpoint inhibitors (ICI) is a significant issue in metastatic renal cell carcinoma (mRCC), as it is in the majority of cancer types. An important deficiency in immunooncology today is the lack of a predictive factor to identify this patient group. Myeloid-derived suppressor cells (MDSC) are a type of cell that contributes to immunotherapy resistance by inhibiting T cell activity. While it accumulates in the tumor microenvironment and blood, it can also accumulate in lymphoid organs such as the spleen and cause splenomegaly. Therefore we aimed to evaluate the effect of increase in splenic volume, which can be considered as an indirect indicator of increased MDSC cells, on survival outcomes in mRCC patients. Methods We analyzed 45 patients with mRCC who received nivolumab as a second-line or subsequent therapy. Splenic volume was analyzed from baseline imaging before starting nivolumab and from control imaging performed within the first 6 months of treatment initiation. Additionally, we analyzed how patients’ body mass index (BMI), IMDC risk score, ECOG performance status, nephrectomy status, neutrophil-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR) and sites of metastasis. Results Median splenic volume change was 10% (ranging from − 22% to + 117%) during follow-up. Change in splenic volume was found to be associated with overall survival (OS) and progression-free survival (PFS) (p = 0.025, 0.04). The median PFS in patients with increased splenic volume was 5 months, while it was 17 months in patients without increased splenic volume. (HR 2.1, 95% CI (1–4), p = 0.04). The median OS in patients with increased splenic volume was 9 months, while it was 35 months in patients without increased splenic volume (HR 2.7, 95% CI (1.1–6.2), p = 0.025). In four patients with decreased splenic volume, neither PFS nor OS could reach the median value. Log-rank p value in respectively (0.015, 0.035), The group in which an increase in volume was accompanied by a high NLR had the shortest survival rate. Basal splenic volume was analyzed separately. However, neither PFS nor OS differed significantly. Conclusion Our findings suggest that the change in splenic volume throughout immunotherapy regimens may be utilized to predict PFS and OS in mRCC patients undergoing treatment.

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Section: Discussionmentioning

confidence: 99%

The role of spleen volume change in predicting immunotherapy response in metastatic renal cell carcinoma

Aslan,

Karabörk Kılıç,

Özet

et al. 2023

BMC Cancer

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“…In 2022 Müller et al investigated for the first time the change in SV in a cohort of 55 patients with HCC receiving IO [ 17 ]. They demonstrated a significant correlation of high baseline splenic volume (SV) with impaired OS (4.0 months vs. 30.7 months, p = 0.004).…”

Section: Discussionmentioning

confidence: 99%

“…SV was assessed using an established tool for fully automated segmentation and volumetry of the spleen as described previously [ 16 ]. This algorithm employs the open-source MIScnn library, a convolutional neural network with a U-Net architecture, and has previously been trained for spleen segmentation in patients with HCC undergoing transarterial chemoembolization (TACE) [ 20 ] as well as patients with HCC under IO [ 17 ]. Further detailed information on the features of the network, the settings for training and validation, and the model’s performance can be found in the original publication [ 16 ].…”

Section: Methodsmentioning

confidence: 99%

“…A novel and promising method using a simple automated radiological tool was described by Müller L et al in 2022. They used a previously developed fully automated artificial intelligence (AI)-based splenic segmentation software (Version 1) [ 16 ] to predict survival outcomes in patients with hepatocellular carcinoma under IO [ 17 ]. Moreover, SV increase was also described by other research teams in melanoma patients who received immune checkpoint inhibitors [ 14 ] as well as in patients with metastatic non-small cell lung cancer [ 15 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Change in Splenic Volume as a Surrogate Marker for Immunotherapy Response in Patients with Advanced Urothelial and Renal Cell Carcinoma—Evaluation of a Novel Approach of Fully Automated Artificial Intelligence Based Splenic Segmentation

Duwe,

Müller,

Ruckes

et al. 2023

Biomedicines

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Background: In the treatment of advanced urothelial (aUC) and renal cell carcinoma (aRCC), biomarkers such as PD-1 and PD-L1 are not robust prognostic markers for immunotherapy (IO) response. Previously, a significant association between IO and a change in splenic volume (SV) was described for several tumour entities. To the best of our knowledge, this study presents the first correlation of SV to IO in aUC and aRCC. Methods: All patients with aUC (05/2017–10/2021) and aRCC (01/2012–05/2022) treated with IO at our academic centre were included. SV was measured at baseline, 3 and 9 months after initiation of IO using an in-house developed convolutional neural network-based spleen segmentation method. Uni- and multivariate Cox regression models for overall survival (OS) and progression-free survival (PFS) were used. Results: In total, 35 patients with aUC and 30 patients with aRCC were included in the analysis. Lower SV at the three-month follow-up was significantly associated with improved OS in the aRCC group. Conclusions: We describe a new, innovative artificial intelligence-based approach of a radiological surrogate marker for IO response in aUC and aRCC which presents a promising new predictive imaging marker. The data presented implicate improved OS with lower follow-up SV in patients with aRCC.

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“…By contrast, Castagnoli et al 20 negated the predictive value of SV in treatment response among patients who underwent immunotherapy for non–small-cell lung cancer. Muller et al 21 noted that an increase in SV before and throughout immunotherapy served as a major predictive factor of poor overall survival (OS) in patients with advanced HCC. However, few studies have compared the role of SV changes in patients undergoing treatment with ICIs or sorafenib for advanced HCC.…”

Section: Introductionmentioning

confidence: 99%

Changes in Posttreatment Spleen Volume Associated with Immunotherapy Outcomes for Advanced Hepatocellular Carcinoma

Chen,

Liang,

Shih

et al. 2024

JHC

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Purpose We investigated whether spleen volume (SV) changes were associated with treatment outcomes in advanced hepatocellular carcinoma (HCC) patients who received immunotherapy or first-line sorafenib. Patients and Methods Patients with advanced HCC who underwent immunotherapy or first-line sorafenib at our institute were retrospectively analyzed. CT was used to measure SV before and within 3 months of treatment initiation. Tumor assessment followed Response Evaluation Criteria in Solid Tumors version 1.1. The association between SV change and tumor response or progression-free survival (PFS) was analyzed. The inverse probability of treatment weighting (IPTW) was used to adjust for differences in baseline characteristics. Results The immunotherapy group comprised 143 patients (124 men, mean age, 59.8 years ± 11.2 [standard deviation]), while the sorafenib group had 57 (47 men, mean age, 59.6 years ± 9.9). SV increased in 108 (75.5%) immunotherapy and 21 (36.8%) sorafenib patients. In the immunotherapy group, patients with increased SV were more likely than those with decreased SV to have a higher disease control rate (76.9% vs 57.1%, p = 0.024) and durable clinical benefit (52.8% vs 25.7%, p = 0.005). It was also associated with extended PFS in the immunotherapy group in both the univariate ( p = 0.028) and multivariate ( p = 0.014) analysis. By contrast, in the sorafenib group, an increased in SV was not associated with treatment response but was presumably associated with reduced PFS ( p = 0.072) in the multivariate analysis. After IPTW adjustment, the increase in SV remained a significant predictor for DCB and PFS in the immunotherapy group. Conclusion Most patients exhibited an increase in SV after the initiation of immunotherapy, which may be used to predict response and prognosis. However, this association was not observed in patients who received sorafenib.

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Baseline Splenic Volume Outweighs Immuno-Modulated Size Changes with Regard to Survival Outcome in Patients with Hepatocellular Carcinoma under Immunotherapy

Cited by 8 publications

References 31 publications

The role of spleen volume change in predicting immunotherapy response in metastatic renal cell carcinoma

The role of spleen volume change in predicting immunotherapy response in metastatic renal cell carcinoma

Change in Splenic Volume as a Surrogate Marker for Immunotherapy Response in Patients with Advanced Urothelial and Renal Cell Carcinoma—Evaluation of a Novel Approach of Fully Automated Artificial Intelligence Based Splenic Segmentation

Changes in Posttreatment Spleen Volume Associated with Immunotherapy Outcomes for Advanced Hepatocellular Carcinoma

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