The Systemic Inflammatory Response Identifies Patients with Adverse Clinical Outcome from Immunotherapy in Hepatocellular Carcinoma

Muhammed, Ambreen; Fulgenzi, Claudia Angela Maria; Dharmapuri, Sirish; Pinter, Matthias; Balcar, Lorenz; Scheiner, Bernhard; Marron, Thomas U.; Jun, Tomi; Saeed, Anwaar; Hildebrand, Hannah; Muzaffar, Mahvish; Navaid, Musharraf; Naqash, Abdul Rafeh; Gampa, Anuhya; Özbek, Umut; Lin, Junk-Yi; Perone, Ylenia; Vincenzi, Bruno; Silletta, Marianna; Pillai, Anjana; Wang, Yinghong; Khan, Uqba; Huang, Yi Hsiang; Bettinger, Dominik; Abugabal, Yehia I.; Kaseb, Ahmed O.; Pressiani, Tiziana; Personeni, Nicola; Rimassa, Lorenza; Nishida, Naoshi; Tommaso, Luca Di; Kudo, Masatoshi; Vogel, Arndt; Mauri, Francesco; Cortellini, Alessio; Sharma, Rohini; D’Alessio, Antonio; Ang, Celina; Pinato, David J.

doi:10.3390/cancers14010186

Cited by 53 publications

(59 citation statements)

References 31 publications

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“…Therefore, an investigation of the predictive biomarkers of immunotherapy response is important. Recently, several studies have shown that hematological parameters can predict immunotherapy response in various cancers [27][28][29]. Nevertheless, information on the prognostic value of routine blood parameters in cervical cancer after immunotherapy is scarce.…”

Section: Discussionmentioning

confidence: 99%

Pretreatment Neutrophil-to-Lymphocyte Ratio and Lactate Dehydrogenase Predict the Prognosis of Metastatic Cervical Cancer Treated with Combination Immunotherapy

Cheng

Liu

et al. 2022

Journal of Oncology

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Background. Immune checkpoint inhibitors have considerably changed the treatment paradigm for metastatic cervical cancer; nonetheless, only a proportion of patients achieve a durable response. Therefore, exploring the predictive biomarkers of immunotherapy response is of crucial importance. This study aimed to evaluate the predictive and prognostic value of hematological parameters in patients with metastatic cervical cancer treated with combination immunotherapy. Methods. Clinical data of patients with metastatic cervical cancer treated with combination immunotherapy between June 2019 and April 2021 were retrospectively analyzed. Receiver operating characteristic curve analysis was performed to determine the cut-off values of continuous variables, and binary logistic analysis was conducted to compare the treatment response between groups. The Kaplan–Meier method was applied for survival analysis. A Cox proportional hazards regression model was used to identify factors associated with progression-free survival (PFS). Results. Seventy patients were included in this study. The cut-off values for the neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) were 5.33 and 195.00 U/L, respectively. High pretreatment NLR (≥5.33) was correlated with decreased objective response rate (53.19% vs. 78.26%, p = 0.048 ). The survival analysis revealed that high pretreatment NLR (hazard ratio HR = 2.401 , 95% confidence interval [CI]: 1.151–5.009, p = 0.020 ) and LDH level ( HR = 1.987 , 95% CI: 1.029–3.835, p = 0.041 ) were independent prognostic factors associated with short PFS. Conclusions. Our study suggested that high pretreatment NLR and LDH values were independently correlated with poor survival in patients with metastatic cervical cancer treated with combination immunotherapy. Pretreatment NLR and LDH values could serve as potential biomarkers that may aid in the selection of patients who would benefit from combination immunotherapy. Further prospective studies investigating the prognostic value of NLR and LDH are warranted. Trial registration number: UHCT22008.

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Section: Discussionmentioning

confidence: 99%

Pretreatment Neutrophil-to-Lymphocyte Ratio and Lactate Dehydrogenase Predict the Prognosis of Metastatic Cervical Cancer Treated with Combination Immunotherapy

Cheng

Liu

et al. 2022

Journal of Oncology

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“…dNLR can provide more information than NLR because it includes monocytes and other granulocyte subsets in addition to lymphocytes; it is considered an unfavorable prognostic factor in a wide range of malignancies (19,20), whereas LDH can reflect the patient's tumor burden. Several studies have shown the correlation between dNLR and LDH and the prognosis of immunotherapy (18,(21)(22)(23), and in previous studies of nonsmall cell lung cancer, patients with a "good" LIPI score (i.e., dNLR < 3 and normal LDH) had better OS and PFS, regardless of whether they have received immunotherapy, targeted therapy, or chemotherapy (12). To our knowledge, there are no studies that have explored the relationship between the combined indicator of dNLR and LDH and the prognosis of pancreatic cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

A composite indicator of derived neutrophil–lymphocyte ratio and lactate dehydrogenase correlates with outcomes in pancreatic carcinoma patients treated with PD-1 inhibitors

Chen

Guo²,

Gou³

et al. 2022

Front. Oncol.

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BackgroundThere are currently no established biomarkers that can predict whether advanced pancreatic carcinoma (PC) patients would benefit from immune checkpoint inhibitors (ICIs). Our study investigated whether the pretreatment composite biomarker of derived neutrophil–lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) can be used as a reliable prognostic factor for the survival of PC patients receiving PD-1 inhibitor therapy.MethodsPatients with advanced PC treated with PD-1 inhibitors at a single center from September 2015 to September 2020 were included. The high levels of dNLR (≥3) and LDH (≥250 U/L) were considered to be risk factors. Based on these two risk factors, patients in this study were categorized into two risk groups: the good dNLR-LDH group, without risk factors, and the intermediate/poor dNLR-LDH group, with one to two risk factors. Overall survival (OS) and progression-free survival (PFS) served as this study’s primary and secondary endpoints. Cox regression models were used to identify independent prognostic factors for survival benefit.ResultsThere were 98 patients in our study. The good group included 61 (62.2%) patients and the intermediate/poor group included 37 (37.8%). The overall patients with PC who received immunotherapy had a median OS of 12.1 months, and the good dNLR-LDH group had a significantly longer OS compared with the intermediate/poor dNLR-LDH group (44.2 vs. 6.4 months; p < 0.010); median PFS was 3.7 and 2.5 months (p = 0.010). The number of metastatic sites >2 and immunotherapy as third-line or later was associated with worse PFS, and the line of immunotherapy and the dNLR-LDH indicator were independent prognostic factors for OS, according to multivariate analysis.ConclusionThe pretreatment composite biomarker of dNLR and LDH can be used as a prognostic biomarker in patients with advanced PC treated with PD-1 inhibitors.

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“…Another study showed that patients with PLR > or = 300 had reduced OS (6.4 vs. 16.5 months, p < 0.0001) and PFS (1.8 vs. 3.7 months, p = 0.0006). In that study, NLR emerged as an independent prognostic factor for OS in univariate and multivariate analysis (HR 1.95, p < 0.001; HR 1.73, p = 0.002, respectively) and the PLR remained an independent prognostic factor for both OS and PFS in multivariate analysis (HR 1.60, p = 0.020; HR 1.99, p = 0.021) ( 76 ).…”

Section: Blood-based Biomarkers For Immune-based Treatment In Advance...mentioning

confidence: 94%

“…During treatment, the NLR increased rapidly in patients with hyperprogressive disease (HPD) ( 75 ). In addition, a recent study showed that patients treated with various ICIs and ICI-based combination therapies with an NLR ≥ 5 had reduced OS (7.7 vs. 17.6 months, p < 0.0001), reduced PFS (2.1 vs. 3.8 months, p = 0.025), and decreased ORR (12% vs. 22%, p = 0.034), suggesting that systemic inflammation indicated by NLR is an independent negative prognostic factor in patients with HCC undergoing ICI therapy ( 76 ).…”

Section: Blood-based Biomarkers For Immune-based Treatment In Advance...mentioning

confidence: 99%

Blood-based biomarkers for immune-based therapy in advanced HCC: Promising but a long way to go

et al. 2022

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The introduction of immune checkpoint inhibitors (ICIs) represents a key shift in the management strategy for patients with hepatocellular carcinoma (HCC). However, there is a paucity of predictive biomarkers that facilitate the identification of patients that would respond to ICI therapy. Although several researchers have attempted to resolve the issue, the data is insufficient to alter daily clinical practice. The use of minimally invasive procedures to obtain patient-derived specimen, such as using blood-based samples, is increasingly preferred. Circulating tumor DNA (ctDNA) can be isolated from the blood of cancer patients, and liquid biopsies can provide sufficient material to enable ongoing monitoring of HCC. This is particularly significant for patients for whom surgery is not indicated, including those with advanced HCC. In this review, we summarize the current state of understanding of blood-based biomarkers for ICI-based therapy in advanced HCC, which is promising despite there is still a long way to go.

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The Systemic Inflammatory Response Identifies Patients with Adverse Clinical Outcome from Immunotherapy in Hepatocellular Carcinoma

Cited by 53 publications

References 31 publications

Pretreatment Neutrophil-to-Lymphocyte Ratio and Lactate Dehydrogenase Predict the Prognosis of Metastatic Cervical Cancer Treated with Combination Immunotherapy

Pretreatment Neutrophil-to-Lymphocyte Ratio and Lactate Dehydrogenase Predict the Prognosis of Metastatic Cervical Cancer Treated with Combination Immunotherapy

A composite indicator of derived neutrophil–lymphocyte ratio and lactate dehydrogenase correlates with outcomes in pancreatic carcinoma patients treated with PD-1 inhibitors

Blood-based biomarkers for immune-based therapy in advanced HCC: Promising but a long way to go

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