Prognostic Role of Systemic Inflammatory Indexes in Germ Cell Tumors Treated With High-Dose Chemotherapy

Cursano, Maria Concetta; Kopf, Barbara; Scarpi, Emanuela; Menna, Cecilia; Casadei, Chiara; Schepisi, Giuseppe; Lolli, Cristian; Altavilla, Amelia; Gallà, Valentina; Santini, Daniele; Tonini, Giuseppe; Chovanec, Michal; Mego, Michal; Giorgi, Ugo De

doi:10.3389/fonc.2020.01325

Cited by 14 publications

(22 citation statements)

References 29 publications

(33 reference statements)

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“…The pretreatment neutrophil to lymphocyte ratio (cutoff = 3.3 [25] ) was not prognostic for PFS or OS (data not shown). Similarly, SII [24] was not associated with patient outcome; there was a trend for worse PFS (HR = 3.15, 95% CI 0.47–21.21, p = 0.07) and OS (HR = 3.65, 95% CI 0.50–26.65, p = 0.06) in patients with low SII (cut off = 1003 [24] ).…”

Section: Resultsmentioning

confidence: 98%

“…Numerous studies showed a prognostic value of SII in different types of cancers including GCTs [24] , [25] , [31] , [32] , [33] . However, in this study, SII was not associated with the outcome; surprisingly, there was a trend for worse outcome in patients with low pretreatment SII.…”

Section: Discussionmentioning

confidence: 99%

“…CBC and CBC-derived inflammation-based scores were calculated as described previously [24] , [25] . For CBC-derived inflammation-based scores, identical cutoff values were calculated as published previously [24] , [25] .…”

Section: Methodsmentioning

confidence: 99%

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Paclitaxel, Ifosfamide, and Cisplatin in Patients with Poor-prognosis Disseminated Nonseminomatous Germ Cell Tumors with Unfavorable Serum Tumor Marker Decline After First Cycle of Chemotherapy. The GCT-SK-003 Phase II Trial

Mego

Rejleková

Světlovská

et al. 2021

European Urology Open Science

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Background Germ cell tumors represent highly curable disease even in metastatic stage. However, poor-risk patients with an unfavorable serum tumor marker (STM) decline after the first cycle of chemotherapy represent a subgroup with dismal prognosis, with approximately 50% cure rate using bleomycin, etoposide, and cisplatin (BEP). Objective The aim of this study was to determine the efficacy and safety of paclitaxel, ifosfamide, and cisplatin (TIP) in this patient population. Design, setting, and participants This was an open-labeled, nonrandomized, single-center phase II trial to study the efficacy and toxicity of TIP in the first-line treatment of germ cell tumor patients with an unfavorable decline of STMs. Nineteen patients with a poor prognosis according to the International Germ Cell Cancer Collaboration Group classification and an unfavorable STM decline after the first cycle of chemotherapy were included in this phase II study (NCT02414685). The treatment regimen consisted of paclitaxel 250 mg/m 2 on day 1, ifosfamide 1200 mg/m 2 on days 1–5, and cisplatin 20 mg/m 2 on days 1–5, totally for four cycles. Outcome measurements and statistical analysis The primary endpoint was complete response (CR) rate. An optimal Simon two-stage design was used with a type I error of 5% and study power of 80%. If fewer than six CRs to study therapy have been observed among the first 19 patients, the study was to be terminated. Results and limitations A CR was achieved in four (21.1%) patients; therefore, the study was terminated in the first stage. A favorable response rate (CR or partial remission with negative tumor markers) was observed in 14 (78.9%) patients. At a median follow-up period of 35.2 mo (range, 5.6–62.1 mo), ten (52.6%) patients experienced disease progression and eight patients (42.1%) died. The 2-yr progression-free and overall survival was 41.2% (95% confidence interval [CI] 16.8–65.7) and 72.7% (95% CI 48.9–96.4), respectively. TIP was well tolerated, and no unexpected toxicity was observed. No informative biomarkers, including miR-371a-3p was identified. Conclusions Treatment modification from the BEP to the TIP regimen in patients with an unfavorable STM decline after the first cycle of chemotherapy was not associated with improved outcome, and four cycles of BEP remain the standard treatment option in this patient population. Patient summary Poor-risk patients with an unfavorable serum tumor marker decline after the first cycle of chemotherapy represent a subgroup with dismal prognosis, with an approximately 50% cure rate using bleomycin, etoposide, and cisplatin (BEP). Treatment modification from the BEP regimen to the paclitaxel, ifosfamide, and cisplatin regimen in patients with an unfavorable serum tumor marker decline after the fir...

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Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Paclitaxel, Ifosfamide, and Cisplatin in Patients with Poor-prognosis Disseminated Nonseminomatous Germ Cell Tumors with Unfavorable Serum Tumor Marker Decline After First Cycle of Chemotherapy. The GCT-SK-003 Phase II Trial

Mego

Rejleková

Světlovská

et al. 2021

European Urology Open Science

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“…Therefore, for many of these patients a second line of chemotherapy is envisaged, with respect to which, in the international guidelines, no specific regimen seems to prevail over the others, both at standard and high doses [54][55][56][57][58][59]. In order to optimize care for these patients, several potential prognostic and predictive factors have been analyzed in recent years, including systemic inflammatory index (SII) [60][61][62], neutrophil-to-lymphocyte ratio (NLR) [63,64], platelet-to-lymphocyte ratio (PLR) [60]. However, whatever the choice, the response rate is currently very low, and is between 5 and 10% [42].…”

Section: Mgct: Clinico-pathological Features and Treatmentmentioning

confidence: 99%

Primary Mediastinal and Testicular Germ Cell Tumors in Adolescents and Adults: A Comparison of Genomic Alterations and Clinical Implications

Urbini

Schepisi

Bleve

et al. 2021

Cancers

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Mediastinal germ cell tumors (MGCTs) share histologic, molecular and biomarkers features with testicular GCTs; however, nonseminomatous MGCTs are usually more aggressive and have poorer prognosis than nonseminomatous TGCTs. Most nonseminomatous MGCT cases show early resistance to platinum-based therapies and seldom have been associated with the onset of one or more concomitant somatic malignancies, in particular myeloid neoplasms with recent findings supporting a common, shared genetic precursor with the primary MGCT. Genomic, transcriptomic and epigenetic features of testicular GCTs have been extensively studied, allowing for the understanding of GCT development and transformation of seminomatous and nonseminomatous histologies. However, MGCTs are still lacking proper multi-omics analysis and only few data are reported in the literature. Understanding of the mechanism involved in the development, in the progression and in their higher resistance to common therapies is still poorly understood. With this review, we aim to collect all molecular findings reported in this rare disease, resuming the similarities and disparities with the gonadal counterparts.

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“…Furthermore, the SII and neutrophil-to-lymphocyte ratio (NLR) were reported as independent predictors of progression-free survival (PFS) and overall survival (OS) in a cohort of 62 relapsed/refractory GCT patients undergoing high-dose chemotherapy (HDCT). The SII, NLR and platelet-to-lymphocyte ratio (PLR) were also significantly associated with the overall response to HDCT [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Are Changes in the Percentage of Specific Leukocyte Subpopulations Associated with Endogenous DNA Damage Levels in Testicular Cancer Patients?

Kalavska

Šestáková

Mlcakova³

et al. 2021

IJMS

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Chemoresistance of germ cell tumors (GCTs) represents an intensively studied property of GCTs that is the result of a complicated multifactorial process. One of the driving factors in this process is the tumor microenvironment (TME). Intensive crosstalk between the DNA damage/DNA repair pathways and the TME has already been reported. This study aimed at evaluating the interplay between the immune TME and endogenous DNA damage levels in GCT patients. A cocultivation system consisting of peripheral blood mononuclear cells (PBMCs) from healthy donors and GCT cell lines was used in an in vitro study. The patient cohort included 74 chemotherapy-naïve GCT patients. Endogenous DNA damage levels were measured by comet assay. Immunophenotyping of leukocyte subpopulations was performed using flow cytometry. Statistical analysis included data assessing immunophenotypes, DNA damage levels and clinicopathological characteristics of enrolled patients. The DNA damage level in PBMCs cocultivated with cisplatin (CDDP)-resistant GCT cell lines was significantly higher than in PBMCs cocultivated with their sensitive counterparts. In GCT patients, endogenous DNA damage levels above the cutoff value were independently associated with increased percentages of natural killer cells, CD16-positive dendritic cells and regulatory T cells. The crosstalk between the endogenous DNA damage level and specific changes in the immune TME reflected in the blood of GCT patients was revealed. The obtained data contribute to a deeper understanding of ongoing interactions in the TME of GCTs.

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Prognostic Role of Systemic Inflammatory Indexes in Germ Cell Tumors Treated With High-Dose Chemotherapy

Cited by 14 publications

References 29 publications

Paclitaxel, Ifosfamide, and Cisplatin in Patients with Poor-prognosis Disseminated Nonseminomatous Germ Cell Tumors with Unfavorable Serum Tumor Marker Decline After First Cycle of Chemotherapy. The GCT-SK-003 Phase II Trial

Paclitaxel, Ifosfamide, and Cisplatin in Patients with Poor-prognosis Disseminated Nonseminomatous Germ Cell Tumors with Unfavorable Serum Tumor Marker Decline After First Cycle of Chemotherapy. The GCT-SK-003 Phase II Trial

Primary Mediastinal and Testicular Germ Cell Tumors in Adolescents and Adults: A Comparison of Genomic Alterations and Clinical Implications

Are Changes in the Percentage of Specific Leukocyte Subpopulations Associated with Endogenous DNA Damage Levels in Testicular Cancer Patients?

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