Preoperative peripheral blood lymphocyte/monocyte ratio and survival in patients with resected stage IV melanoma.

8600 Background: The prognosis of stage IV melanoma patients remains poor. Published results have suggested that components of the complete blood count have significant prognostic value in several malignancies. Among the most studied were the absolute lymphocyte count (ALC), and absolute monocyte count (AMC) on clinical outcomes of patients with lymphoid malignancies. Thus, we sought to investigate if the pre-operative ALC (ALC-PO), AMC (AMC-PO) and ALC/AMC ratio (ALC/AMC-PO) affects the risk of disease recurrence and survival after complete surgical resection of metastatic melanoma. Methods: We studied 66 stage IV, resected melanoma patients followed at Mayo Clinic from 2000 to 2010. Log rank chi-square analysis was used to determine the best cut-off values for each pre-operative variable, while proportional hazards models were used to compared survival. Results: The median follow-up of the cohort was 24 months (range: 2.3 – 117 months). ALC-PO, AMC-PO and ALC/AMC-PO, as continuous variables, were all identified as prognostic factors for both relapse-free survival (RFS) and overall survival (OS). The best cut-off values for ALC-PO, AMC-PO and ALC/AMC-PO were 1.9; 0.62; and 2.05, respectively. Using Kaplan-Meier analysis, patients with an ALC-PO ≥ 1.9 x 109/L experienced superior OS and RFS compared with ALC-PO < 1.9 x 109/L patients [median OS of 58 months vs. 34 months, p < 0.04; median RFS of 14 months vs. 5 months, p < 0.009]. Conversely, a low AMC-PO (<0.62 x 109/L) was associated with better OS and RFS compared with higher AMC-PO (≥ 0.62 x 109/L): [median OS of 47 months vs. 14 months, p < 0.007; median RFS of 9 months vs. 5 months, p < 0.02]. When the ALC-PO and AMC-PO were combined as an ALC/AMC ratio, the group with an ALC/AMC-PO ≥ 2.05 experienced a superior OS and RFS compared to patients with ALC/AMC-PO < 2.05: [median OS of 49 months vs. 12 months, p < 0.0001; median RFS of 10 months vs. 4 months, p < 0.0001]. Multivariate analysis showed ALC/AMC-PO to be an independent prognostic factor for RFS and OS (HR = 0.32, p < 0.003; HR = 0.23, p < 0.002). Conclusions: Our study showed, that ALC/AMC-PO ratio is an independent prognostic factor for RFS and OS in patients undergoing resection of metastatic (stage IV) melanoma.

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Pretreatment Levels of Peripheral Neutrophils and Leukocytes As Independent Predictors of Overall Survival in Patients With American Joint Committee on Cancer Stage IV Melanoma: Results of the EORTC 18951 Biochemotherapy Trial

Journal of Clinical Oncology ◽

10.1200/jco.2006.09.0274 ◽

2007 ◽

Vol 25 (12) ◽

pp. 1562-1569 ◽

Cited By ~ 136

Author(s):

Henrik Schmidt ◽

Stefan Suciu ◽

Cornelis J.A. Punt ◽

Martin Gore ◽

Wim Kruit ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factor ◽

Interleukin 2 ◽

Stage Iv ◽

Progression Free Survival ◽

Independent Prognostic Factor ◽

Short Overall Survival ◽

Leukocyte Counts ◽

Melanoma Patients ◽

Stage Iv Melanoma

Purpose An elevated count of blood neutrophils and monocytes recently was shown independently to predict short survival in patients with stage IV melanoma undergoing interleukin-2–based immunotherapy. In this study, we aimed to validate this finding in a large cohort of stage IV melanoma patients. Patients and Methods For this retrospective prognostic study, the data from the European Organisation for the Research and Treatment of Cancer 18951 study were used. Patients were randomly assigned between treatment with dacarbazine, cisplatin, and interferon alfa with or without interleukin-2. Counts of neutrophils and leukocytes were analyzed together with other known prognostic factors: serum lactate dehydrogenase, performance status, metastatic site, and sex. Two multivariate prognostic factor analyses were carried out in the model: one with leukocyte counts and one with neutrophil counts. Results A total of 363 patients were randomly assigned and baseline blood neutrophil and leukocyte counts were available from 316 and 350 patients, respectively. A high neutrophil count (> 7.5 × 109/L) was an independent prognostic factor for short overall survival (hazard ratio [HR], 1.5; 95% CI, 1.1 to 2.1; P = 0.02), and a high leukocyte count (> 10 × 109/L) was an independent prognostic factor of both short overall survival (HR, 1.7; 95% CI, 1.3 to 2.4; P = 0.0005) and short progression-free survival (HR, 1.5; 95% CI, 1.1 to 2.1; P = 0.008). Conclusion A high pretreatment count of neutrophils in blood was confirmed as an independent prognostic factor for short overall survival in stage IV melanoma patients undergoing interleukin-2–based immunotherapy. Furthermore, a high count of leukocytes was an independent prognostic factor for short overall survival and progression-free survival. Both parameters should be useful as stratification factors in clinical trials.

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Metastatic Volume: An Old Oncologic Concept and a New Prognostic Factor for Stage IV Melanoma Patients

Dermatology ◽

10.1159/000351713 ◽

2013 ◽

Vol 227 (1) ◽

pp. 55-61 ◽

Cited By ~ 10

Author(s):

V. Panasiti ◽

M. Curzio ◽

V. Roberti ◽

P. Lieto ◽

V. Devirgiliis ◽

...

Keyword(s):

Prognostic Factor ◽

Stage Iv ◽

Melanoma Patients ◽

Stage Iv Melanoma

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Validation of a multimarker blood assay for postoperative assessment of stage IV melanoma patients in a prospective international phase III trial

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.9045 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 9045-9045

Author(s):

S. Hoshimoto ◽

T. Shingai ◽

H. Wang ◽

R. M. Elashhoff ◽

D. L. Morton ◽

...

Keyword(s):

Prognostic Factor ◽

Risk Ratio ◽

Clinical Utility ◽

Stage Iv ◽

Molecular Biomarkers ◽

Phase Iii ◽

Phase Iii Trial ◽

Qrt Pcr ◽

Melanoma Patients ◽

Stage Iv Melanoma

9045 Background: Currently there are no validated prognostic molecular biomarkers for assessment of outcome after complete resection of stage IV melanoma patients. To validate blood molecular biomarkers for prognostic value and monitoring of these patients, we evaluated the clinical utility of a multimarker quantitative reverse-transcription PCR (qRT-PCR) for detecting circulating tumor cells (CTC) of patients blood enrolled in a multicenter international (29 sites) phase III trial of postoperative adjuvant therapy. After complete metastasectomy, AJCC stage IV patients underwent immunotherapy with bacille Calmette-Guerin (BCG) plus placebo or BCG plus melanoma vaccine. Methods: Bleeds were taken before and during treatment in both randomized treatment arms. Pre- and during treatment bleeds from patients were assessed by an optimized qRT-PCR assay for MART1, MAGEA3, and PAX3 genes mRNA. Median clinical follow-up time was 21.8 and 24.2 mos. for disease-free survival (DFS) and overall survival (OS), respectively. Results: MART1, MAGEA3, and PAX3 were detected in 64 (26%), 56 (23%), 73 (29%) of 244 post-operative pretreatment patients, respectively. Multivariate Cox analysis showed that biomarker-negative patients had significantly higher DFS than biomarker- positive patients (risk ratio 1.56, 95% CI, 1.14 - 2.15; P=0.0062). In serial-bleeds (pretreatment, mos 1 and 3) analysis of 214 patients, biomarker-negative patients had significantly higher OS than patients with 1–2 positive- or 3 positive-biomarkers (risk ratio 2.37, 95% CI 1.14 - 4.94, P=0.021; and risk ratio 2.90, 95% CI 1.28 - 6.53, P=0.01, respectively). Multivariate analysis confirmed that 1–2 positive- and 3 positive-biomarkers were significant independent prognostic factors for poor OS (risk ratio 2.44, 95% CI 1.16 - 5.12, P=0.019; and risk ratio 3.08, 95% CI 1.36 to 6.98, P=0.007, respectively). Conclusions: This prospective multicenter blood biomarker validation study demonstrates that multimarker qRT-PCR analysis of CTC has significant clinical utility as a prognostic factor of disease outcome at pretreatment, and as a treatment monitoring prognostic factor in stage IV melanoma patients. No significant financial relationships to disclose.

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Long-term Survival of Stage IV Melanoma Patients Treated with BOLD Combination Chemotherapy and Intermediate-dose Subcutaneous Interferon-alpha

Anticancer Research ◽

10.21873/anticanres.12999 ◽

2018 ◽

Vol 38 (11) ◽

pp. 6393-6397 ◽

Cited By ~ 1

Author(s):

KALLE MATTILA ◽

PIRITA RAANTA ◽

VALTTERI LAHTELA ◽

SEPPO PYRHÖNEN ◽

ILKKA KOSKIVUO ◽

...

Keyword(s):

Interferon Alpha ◽

Combination Chemotherapy ◽

Stage Iv ◽

Term Survival ◽

Long Term Survival ◽

Melanoma Patients ◽

Stage Iv Melanoma ◽

Intermediate Dose

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Prognostic Significance of Molecular Upstaging of Paraffin-Embedded Sentinel Lymph Nodes in Melanoma Patients

Journal of Clinical Oncology ◽

10.1200/jco.2004.12.009 ◽

2004 ◽

Vol 22 (13) ◽

pp. 2671-2680 ◽

Cited By ~ 109

Author(s):

Hiroya Takeuchi ◽

Donald L. Morton ◽

Christine Kuo ◽

Roderick R. Turner ◽

David Elashoff ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factor ◽

Lymph Nodes ◽

Risk Ratio ◽

Disease Recurrence ◽

Sentinel Lymph Nodes ◽

Independent Prognostic Factor ◽

Number Of Patients ◽

Significant Independent Prognostic Factor ◽

Melanoma Patients

PurposeDetection of micrometastases in sentinel lymph nodes (SLNs) is important for accurate staging and prognosis in melanoma patients. However, a significant number of patients with histopathology-negative SLNs subsequently develop recurrent disease. We hypothesized that a quantitative realtime reverse transcriptase polymerase chain reaction (qRT) assay using multiple specific mRNA markers could detect occult metastasis in paraffin-embedded (PE) SLNs to upstage and predict disease outcome.Patients and MethodsqRT was performed on retrospectively collected PE SLNs from 215 clinically node-negative patients who underwent lymphatic mapping and sentinel lymphadenectomy for melanoma and were followed up for at least 8 years. PE SLNs (n = 308) from these patients were sectioned and assessed by qRT for mRNA of four melanoma-associated genes: MART-1 (antigen recognized by T cells-1), MAGE-A3 (melanoma antigen gene-A3 family), GalNAc-T (β1→4-N-acetylgalactosaminyl-transferase), and Pax3 (paired-box homeotic gene transcription factor 3).ResultsFifty-three (25%) patients had histopathology-positive SLNs by hemotoxylin and eosin and/or immunohistochemistry. Of the 162 patients with histopathology-negative SLNs, 48 (30%) had nodes that expressed at least one of the four qRT markers, and these 48 patients also had a significantly increased risk of disease recurrence by a Cox proportional hazards model analysis (P < .0001; risk ratio, 7.48; 95% CI, 3.70 to 15.15). The presence of ≥ one marker in histopathology-negative SLNs was also a significant independent prognostic factor by multivariate analysis for overall survival (P = .0002; risk ratio, 11.42; 95% CI, 3.17 to 41.1).ConclusionMolecular upstaging of PE histopathology-negative SLNs by multiple-marker qRT assay is a significant independent prognostic factor for long-term disease recurrence and overall survival of patients with early-stage melanoma.

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