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

2007 ◽  
Vol 25 (12) ◽  
pp. 1562-1569 ◽  
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.

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

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8600-8600
Author(s):  
Nicole M. Rochet ◽  
Luis F. Porrata ◽  
Lisa A. Kottschade ◽  
Travis Edward Grotz ◽  
Svetomir Markovic
Keyword(s):  
Prognostic Factor ◽  
Proportional Hazards ◽  
Complete Blood Count ◽  
Stage Iv ◽  
Independent Prognostic Factor ◽  
Monocyte Count ◽  
Continuous Variables ◽  
Melanoma Patients ◽  
Chi Square Analysis ◽  
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.

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

2004 ◽  
Vol 22 (13) ◽  
pp. 2671-2680 ◽  
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.

Immune gene polymorphisms predict overall survival for stage IV melanoma patients treated with biochemotherapy

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 7550-7550
Author(s):  
D. Liu ◽  
S. J. O'Day ◽  
D. Yang ◽  
P. Boasberg ◽  
R. Milford ◽  
...  
Keyword(s):  
Overall Survival ◽  
Gene Polymorphisms ◽  
Stage Iv ◽  
Immune Gene ◽  
Melanoma Patients ◽  
Stage Iv Melanoma

Serum-sodium as an independent prognostic factor in metastatic renal cell carcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5102-5102
Author(s):  
A. N. Jeppesen ◽  
H. K. Jensen ◽  
F. Donskov ◽  
N. Marcussen ◽  
H. von der Maase
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factor ◽  
Serum Sodium ◽  
Interleukin 2 ◽  
Independent Prognostic Factor ◽  
Normal Range ◽  
Metastatic Rcc ◽  
Low Serum

5102 Background: Recently, low serum sodium has been associated with poor disease-free and overall survival in localized renal cell carcinoma (RCC) (Vasudev, Clin Can Res. 2008). The present study investigated the prognostic impact of serum-sodium values below normal in patients with metastatic RCC (mRCC). Methods: A cohort of 120 consecutive patients with mRCC received subcutaneous, low-dose Interleukin-2 and Interferon-α at Dept. of Oncology, Aarhus University Hospital, from 2002 to 2004 (Cohort A). Baseline variables were collected retrospectively. Follow up was at least 4 years. Potential prognostic factors were analyzed by univariate and multivariate analyses. Endpoint was overall survival. An independent cohort of 120 consecutive patients with mRCC was used for validation. These patients were treated with interleukin-2 based regimens at the same institution from 1999 to 2002 (Cohort B). Data in this cohort were prospectively collected. Results: In cohort A, the estimated 5-year survival rate was 15% and the median survival was 15.1 months. Serum-sodium ranged between 126 and 144 mmol/l. Twenty-four patients (20%) had serum-sodium levels below normal range (<136 mmol/l). In the multivariate analysis, significant independent risk factors of short survival were serum-sodium below normal value (HR 1.90, CI 1.1–3.2, p = 0.014), high neutrophile count (>7) (HR 1.75, CI 1.1–2.8, p = 0.018), lactate dehydrogenase >1.5 upper normal level (HR 2.09, CI 1.3–3.3, p = 0.002), and number of sites (+3) (HR 1.92; CI 1.3–2.9, p = 0.003). In cohort B, the observed 5-year survival rate was 15% and the median survival was 15 months. Serum-sodium ranged between 128 mmol/l and 146 mmol/l. Seventeen patients (14%) had sodium levels below normal range. In the multivariate analysis, serum-sodium was validated as an independent prognostic factor (HR 2.98, CI 1.54–5.77, p = 0.001). Conclusions: Low serum-sodium is a new, validated, independent prognostic factor in patients with metastatic RCC. No significant financial relationships to disclose.

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

Dermatology ◽  
2013 ◽  
Vol 227 (1) ◽  
pp. 55-61 ◽  
Author(s):  
V. Panasiti ◽  
M. Curzio ◽  
V. Roberti ◽  
P. Lieto ◽  
V. Devirgiliis ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Stage Iv ◽  
Melanoma Patients ◽  
Stage Iv Melanoma

Phase III Comparison of Vitespen, an Autologous Tumor-Derived Heat Shock Protein gp96 Peptide Complex Vaccine, With Physician's Choice of Treatment for Stage IV Melanoma: The C-100-21 Study Group

2008 ◽  
Vol 26 (6) ◽  
pp. 955-962 ◽  
Author(s):  
Alessandro Testori ◽  
Jon Richards ◽  
Eric Whitman ◽  
G. Bruce Mann ◽  
Jose Lutzky ◽  
...  
Keyword(s):  
Overall Survival ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Interleukin 2 ◽  
Stage Iv ◽  
Phase Iii ◽  
Autologous Tumor ◽  
Heat Shock Protein Gp96 ◽  
To Receive ◽  
Stage Iv Melanoma

Purpose To assess the antitumor activity of vitespen (autologous, tumor- derived heat shock protein gp96 peptide complexes) by determining whether patients with stage IV melanoma treated with vitespen experienced longer overall survival than patients treated with physician's choice. Patients and Methods Patients (N = 322) were randomly assigned 2:1 to receive vitespen or physician's choice (PC) of a treatment containing one or more of the following: dacarbazine, temozolomide, interleukin-2, or complete tumor resection. This open-label trial was conducted at 71 centers worldwide. Patients were monitored for safety and overall survival. Results Therapy with vitespen is devoid of significant toxicity. Patients randomly assigned to the vitespen arm received variable number of injections (range, 0 to 87; median, 6) in part because of the autologous nature of vitespen therapy. Intention-to-treat analysis showed that overall survival in the vitespen arm is statistically indistinguishable from that in the PC arm. Exploratory landmark analyses show that patients in the M1a and M1b substages receiving a larger number of vitespen immunizations survived longer than those receiving fewer such treatments. Such difference was not detected for substage M1c patients. Conclusion These results are consistent with the immunologic mechanism of action of vitespen, indicating delayed onset of clinical activity after exposure to the vaccine. The results suggest patients with M1a and M1b disease who are able to receive 10 or more doses of vitespen as the candidate population for a confirmatory study.

scholarly journals Primary Resistance to PD-1-Based Immunotherapy—A Study in 319 Patients with Stage IV Melanoma

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1027 ◽  
Author(s):  
Teresa Amaral ◽  
Olivia Seeber ◽  
Edgar Mersi ◽  
Stephanie Sanchez ◽  
Ioannis Thomas ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Checkpoint Inhibitors ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Primary Resistance ◽  
Dismal Prognosis ◽  
Significant Difference ◽  
Melanoma Patients ◽  
Stage Iv Melanoma

Background: Primary resistance to immunotherapy can be observed in approximately 40–65% of the stage IV melanoma patients treated with immune checkpoint inhibitors. A minority of the patients receive a second-line therapy, and the clinical benefit is small. Patients and methods: Stage IV melanoma patients treated with first-line PD-1-based immunotherapy between January 2015 and December 2018 were investigated. Primary resistance was defined as progressive disease (PD) at the time of the first tumor assessment after starting immunotherapy. Patients with complete response, partial response, and stable disease were classified as having disease control (DC). Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan–Meier estimator. Univariate and multivariate logistic regression analyses were performed to determine prognostic factors associated with OS. Results: Three hundred and nineteen patients were included, and 40% had primary resistance to immunotherapy. The median follow-up time was 22 months. Patients with primary resistance had 1-, 2-, and 3-year OS rates of 41%, 15%, and 10%, respectively, compared to 91%, 81%, and 65% for the patients who achieved DC. The following independently significant prognostic factors for OS were identified: protein S100B level and primary tumor localization. There was a statistically significant difference for OS (p < 0.0001) but not for PFS (p = 0.230) when analyzing risk groups formed with a combination of these two variables (low-, intermediate-, and high-risk subgroups). Conclusions: Melanoma patients with primary resistance to immunotherapy have a dismal prognosis. Response at the first tumor assessment after starting immunotherapy is a stronger prognostic factor for the further course of the disease than pretreatment risk factors.

A Phase II Study of the Administration of Recombinant Interleukin 2 (rIL-2) Plus Lymphokine Activated Killer (LAK) Cells in Stage IV Melanoma Patients

1989 ◽  
Vol 75 (3) ◽  
pp. 233-244 ◽  
Author(s):  
Natale Cascinelli ◽  
Filiberto Belli ◽  
Silvana Marchini ◽  
Raffaele Marolda ◽  
Augusto Prada ◽  
...  
Keyword(s):  
Total Dose ◽  
Bolus Injection ◽  
Interleukin 2 ◽  
Stage Iv ◽  
Lak Cells ◽  
Duration Of Treatment ◽  
Recombinant Interleukin 2 ◽  
Melanoma Patients ◽  
A Minor ◽  
Stage Iv Melanoma

From January 1987 to February 1988, 15 stage IV melanoma patients were treated with two courses of bolus injection of rIL-2 plus LAK cell infusions at the National Cancer Institute of Milan. The original treatment regimen included a first course of rIL-2 administration (400 μg/m5 bolus injection 3 times a day [TID] for 4 days) and a second course of rIL-2 administration (800 μg/m2 bolus injection TID for 7 days) separated by 4 consecutive daily leukaphereses. Autologous lymphokine activated killer (LAK) cells were reinfused into each patient on three occasions during the second period of rIL-2 administration. Due to the appearance of grade III–IV neurological, hepatic and cardiopulmonary toxicity, 7 patients discontinued dosing before the end of treatment, one patient desired to be withdrawn and one patient died from rapidly progressive disease, although complications of rIL-2 administration may have contributed to her death. Only 6 patients completed the schedule without evidence of major intolerance, even though the planned dose during the second course of rIL-2 was reduced to 400 μg/m2. The complete duration of treatment ranged from 11 to 19 days. The total dose of rIL-2 injected ranged from 12.6 to 30.4 mg. The number of infused LAK cells ranged from 15.5x109 to 60x109/patient. Two of the 14 evaluable patients showed a minor anti-tumor response. In 5 patients new metastases in other sites were documented from 2 to 5 months after completion of dosing. No apparent association was found between progression of the disease (or the appearance of new metastases) and the total dose of rIL-2 injected, the number of LAK cells administered or the number of days of treatment. By December 1988, all patients had died of their disease in a period ranging from 3 to 14 months from the last injection of rIL-2. The lack of significant clinical responses in this study and the high toxicity of this treatment lead us to conclude that at least as far as melanoma patients are concerned, adoptive immunotherapy with rIL-2 plus LAK cells (as described here) is not a justifiable treatment option unless new evidence presents itself.

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