Conditional Survival: An Assessment of the Prognosis of Patients at Time Points After Initial Diagnosis and Treatment of Locoregional Melanoma Metastasis

2017 ◽  
Vol 35 (15) ◽  
pp. 1721-1729 ◽  
Author(s):  
Lauren E. Haydu ◽  
Richard A. Scolyer ◽  
Serigne Lo ◽  
Michael J. Quinn ◽  
Robyn P.M. Saw ◽  
...  
Keyword(s):  
Stage Iii ◽  
Melanoma Metastasis ◽  
Conditional Survival ◽  
Time Points ◽  
Melanoma Diagnosis ◽  
Ajcc Stage ◽  
Systemic Treatments ◽  
Increased Risk ◽  
Stage Iii Melanoma

Purpose Standard cancer staging and prognostic estimates are determined at the time of the patient’s initial disease presentation. Conditional survival is an alternative, dynamic assessment from follow-up time points after the initial disease diagnosis and is based on the condition of survivorship. Estimates of conditional survival can provide critical prognostic information for patients and clinicians, guide subsequent cancer follow-up schedules, and influence decisions regarding treatments. The current study presents conditional survival estimates developed from a cohort of 4,540 patients diagnosed with stage III melanoma treated at a single institution. Methods Patients with stage III disease at first melanoma diagnosis (initial; n = 2,042), or who developed locoregional metastasis as a first recurrence some time after primary diagnosis (recurrent; n = 2,498), were assessed. Conditional melanoma-specific survival (MSS) estimates up to 5 years after diagnosis were adjusted for age, sex, and 8th edition American Joint Committee on Cancer (AJCC) stage. Results Older age at diagnosis of stage III disease conveyed a worse prognosis at each conditional survival time point. Males had significantly worse MSS outcomes for up to 2 years of conditional survival, after which males and females had similar MSS. For patients with AJCC stage IIIB and stage IIIC disease, MSS outcomes were similar to those of patients with stage IIIA disease after 3 and 5 years of survivorship, respectively. Conclusion Adjuvant systemic treatments may have the greatest benefit when administered within the first 2 years of stage III melanoma diagnosis, during which period prognosis is significantly worse for male patients of increasing age and AJCC substage. Conditional survival estimates illustrate improved survival prospects for patients with cancer returning for follow-up and may define a finite period of increased risk after diagnosis.

scholarly journals Cumulative Incidence and Predictors of CNS Metastasis for Patients With American Joint Committee on Cancer 8th Edition Stage III Melanoma

2020 ◽  
Vol 38 (13) ◽  
pp. 1429-1441 ◽  
Author(s):  
Lauren E. Haydu ◽  
Serigne N. Lo ◽  
Jennifer L. McQuade ◽  
Rodabe N. Amaria ◽  
Jennifer Wargo ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Cumulative Incidence ◽  
Mitotic Rate ◽  
Stage Iii ◽  
Time Points ◽  
Cns Metastasis ◽  
American Joint Committee ◽  
Stage Iii Melanoma ◽  
8Th Edition

PURPOSE Improved understanding of the incidence, risk factors, and timing of CNS metastasis is needed to inform surveillance strategies for patients with melanoma. PATIENTS AND METHODS Clinical data were extracted from the databases of 2 major melanoma centers in the United States and Australia for 1,918 patients with American Joint Committee on Cancer (AJCC) 8th edition stage III melanoma, diagnosed from 1998-2014, who had (negative) baseline CNS imaging within 4 months of diagnosis. The cumulative incidence of CNS metastasis was calculated in the presence of the competing risk of death, from stage III presentation and at benchmark time points 1, 2, and 5 years postdiagnosis. RESULTS At a median follow-up of 70.2 months, distant recurrence occurred in 711 patients (37.1%). The first site of distant metastasis was CNS only for 3.9% of patients, CNS and extracranial (EC) for 1.8%, and EC only for 31.4%. Overall, 16.7% of patients were diagnosed with CNS metastasis during follow-up. The cumulative incidence of CNS metastasis was 3.6% (95% CI, 2.9% to 4.6%) at 1 year, 9.6% (95% CI, 8.3% to 11.0%) at 2 years, and 15.8% (95% CI, 14.1% to 17.6%) at 5 years. The risk of CNS metastasis was significantly influenced by patient sex, age, AJCC stage, primary tumor site, and primary tumor mitotic rate in multivariable and conditional analyses. High primary tumor mitotic rate was significantly associated with increased risk of CNS metastasis at diagnosis and all subsequent time points examined. CONCLUSION Similar rates of CNS metastasis were observed in 2 large, geographically distinct cohorts of patients with stage III melanoma. The results highlight the importance of primary tumor mitotic rate. Furthermore, they provide a framework for developing evidence-based surveillance strategies and evaluating the impact of contemporary adjuvant therapies on the risk of CNS metastasis development.

scholarly journals S‐100B as an extra selection tool for FDG PET/CT scanning in follow‐up of AJCC stage III melanoma patients

2019 ◽  
Vol 120 (6) ◽  
pp. 1031-1037 ◽  
Author(s):  
Eric A. Deckers ◽  
Kevin P. Wevers ◽  
Anneke C. Muller Kobold ◽  
Samantha Damude ◽  
Otis M. Vrielink ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Ct Scanning ◽  
Stage Iii ◽  
Selection Tool ◽  
Ajcc Stage ◽  
Pet Ct ◽  
Melanoma Patients ◽  
Stage Iii Melanoma ◽  
Fdg Pet Ct

PP 3 S-100B concentrations predict disease specific survival in AJCC Stage III melanoma patients

2011 ◽  
Vol 47 ◽  
pp. S21
Author(s):  
S. Kruijff ◽  
E. Bastiaannet ◽  
M. Speijers ◽  
I. Kema ◽  
R. van Ginkel ◽  
...  
Keyword(s):  
Stage Iii ◽  
Disease Specific Survival ◽  
Ajcc Stage ◽  
Melanoma Patients ◽  
Stage Iii Melanoma ◽  
Disease Specific

Improved survival in stage III melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside.

1994 ◽  
Vol 12 (5) ◽  
pp. 1036-1044 ◽  
Author(s):  
P O Livingston ◽  
G Y Wong ◽  
S Adluri ◽  
Y Tao ◽  
M Padavan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stage Iii ◽  
Disease Free Interval ◽  
Free Interval ◽  
Ajcc Stage ◽  
Melanoma Patients ◽  
Stage Iii Melanoma ◽  
Receive Treatment ◽  
To Receive ◽  
Disease Free

PURPOSE To perform a double-blind randomized trial with American Joint Commission on Cancer (AJCC) stage III melanoma patients for the following reasons: (1) to confirm our previous finding that patients with antibodies against the melanoma differentiation antigen GM2 have an improved prognosis, and (2) to demonstrate clinical benefit from GM2 antibody induction. PATIENTS AND METHODS One hundred twenty-two patients with AJCC stage III melanoma who were free of disease after surgery were randomized: 58 to receive treatment with the GM2/BCG vaccine, and 64 to receive treatment with bacille Calmette-Guèrin (BCG) alone. All patients were pretreated with low-dose cyclophosphamide (Cy). RESULTS GM2 antibody was detected in 50 of 58 patients treated with GM2/BCG and seven of 64 patients treated with BCG alone. With a minimum follow-up period of 51 months, there was a highly significant increase in the disease-free interval (P = .004) and a 17% increase in overall survival (P = .02) in these 57 antibody-positive patients, confirming our earlier experience. Exclusion of all patients with preexisting GM2 antibodies (one in the GM2/BCG group and five in the BCG group) from statistical analysis resulted in a 23% increase in disease-free interval (P = .02) and a 14% increase in overall survival (P = .15) at 51 months for patients treated with the GM2/BCG vaccine. However, when all patients in the two treatment groups were compared as randomized, these increases were 18% for disease-free interval and 11% for survival in the GM2/BCG treatment group, with neither result showing statistical significance. CONCLUSION (1) Vaccination with GM2/BCG induced immunoglobulin M (IgM) antibodies in most patients. (2) GM2 antibody production was associated with a prolonged disease-free interval and survival. (3) Comparison of the two arms of this trial as randomized fails to show a statistically significant improvement in disease-free interval or survival for patients treated with GM2/BCG vaccines.

scholarly journals Longer Follow-Up Confirms Recurrence-Free Survival Benefit of Adjuvant Pembrolizumab in High-Risk Stage III Melanoma: Updated Results From the EORTC 1325-MG/KEYNOTE-054 Trial

2020 ◽  
Vol 38 (33) ◽  
pp. 3925-3936 ◽  
Author(s):  
Alexander M. M. Eggermont ◽  
Christian U. Blank ◽  
Mario Mandala ◽  
Georgina V. Long ◽  
Victoria G. Atkinson ◽  
...  
Keyword(s):  
Lymph Node ◽  
High Risk ◽  
Phase Iii ◽  
Stage Iii ◽  
Recurrence Free Survival ◽  
Meaningful Improvement ◽  
Free Survival ◽  
Stage Iii Melanoma ◽  
The Impact

PURPOSE We conducted the phase III double-blind European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial to evaluate pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. On the basis of 351 recurrence-free survival (RFS) events at a 1.25-year median follow-up, pembrolizumab prolonged RFS (hazard ratio [HR], 0.57; P < .0001) compared with placebo. This led to the approval of pembrolizumab adjuvant treatment by the European Medicines Agency and US Food and Drug Administration. Here, we report an updated RFS analysis at the 3.05-year median follow-up. PATIENTS AND METHODS A total of 1,019 patients with complete lymph node dissection of American Joint Committee on Cancer Staging Manual (seventh edition; AJCC-7), stage IIIA (at least one lymph node metastasis > 1 mm), IIIB, or IIIC (without in-transit metastasis) cutaneous melanoma were randomly assigned to receive pembrolizumab at a flat dose of 200 mg (n = 514) or placebo (n = 505) every 3 weeks for 1 year or until disease recurrence or unacceptable toxicity. The two coprimary end points were RFS in the overall population and in those with programmed death-ligand 1 (PD-L1)–positive tumors. RESULTS Pembrolizumab (190 RFS events) compared with placebo (283 RFS events) resulted in prolonged RFS in the overall population (3-year RFS rate, 63.7% v 44.1% for pembrolizumab v placebo, respectively; HR, 0.56; 95% CI, 0.47 to 0.68) and in the PD-L1–positive tumor subgroup (HR, 0.57; 99% CI, 0.43 to 0.74). The impact of pembrolizumab on RFS was similar in subgroups, in particular according to AJCC-7 and AJCC-8 staging, and BRAF mutation status (HR, 0.51 [99% CI, 0.36 to 0.73] v 0.66 [99% CI, 0.46 to 0.95] for V600E/K v wild type). CONCLUSION In resected high-risk stage III melanoma, pembrolizumab adjuvant therapy provided a sustained and clinically meaningful improvement in RFS at 3-year median follow-up. This improvement was consistent across subgroups.

scholarly journals Protein signatures correspond to survival outcomes of AJCC stage III melanoma patients

2014 ◽  
Vol 27 (6) ◽  
pp. 1106-1116 ◽  
Author(s):  
Swetlana Mactier ◽  
Kimberley L. Kaufman ◽  
Penghao Wang ◽  
Ben Crossett ◽  
Gulietta M. Pupo ◽  
...  
Keyword(s):  
Stage Iii ◽  
Survival Outcomes ◽  
Ajcc Stage ◽  
Protein Signatures ◽  
Melanoma Patients ◽  
Stage Iii Melanoma

Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: New recurrence-free survival results from the EORTC 1325-MG/Keynote 054 double-blinded phase III trial at three-year median follow-up.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10000-10000 ◽  
Author(s):  
Alexander M. Eggermont ◽  
Christian U. Blank ◽  
Mario Mandalà ◽  
Georgina V. Long ◽  
Victoria Atkinson ◽  
...  
Keyword(s):  
Lymph Node ◽  
High Risk ◽  
Complete Resection ◽  
Phase Iii ◽  
Stage Iii ◽  
Recurrence Free Survival ◽  
Stage Iiia ◽  
Free Survival ◽  
Stage Iii Melanoma

10000 Background: We conducted the phase 3 double-blind EORTC 1325/KEYNOTE-054 trial to evaluate pembrolizumab vs placebo in patients (pts) with resected high-risk stage III melanoma. Based on 351 recurrence-free survival (RFS) events and at a median follow-up of 1.25 years (yrs), pembrolizumab improved RFS (hazard ratio (HR) 0.57, P<0.0001) as compared to placebo (Eggermont, NEJM 2018). This led to the approval of pembrolizumab adjuvant treatment by EMA and FDA. Methods: Eligible pts included those ≥18 yrs of age with complete resection of cutaneous melanoma metastatic to lymph node(s), classified as AJCC-7 stage IIIA (at least one lymph node metastasis >1 mm), IIIB or IIIC (without in-transit metastasis). A total of 1019 pts were randomized (stratification by stage and region) to pembrolizumab at a flat dose of 200 mg (N=514) or placebo (N=505) every 3 weeks for a total of 18 doses (~1 year) or until disease recurrence or unacceptable toxicity. The 2 co-primary endpoints were RFS in the intention-to-treat overall population and in pts with PD-L1-positive tumors. Here, we report an updated RFS analysis based on a longer follow-up. Results: Overall, 15%/46%/39% of pts had stage IIIA/IIIB/IIIC. At 3.05-yr median follow-up, pembrolizumab (190 RFS events) compared with placebo (283 RFS events) prolonged RFS, in the overall population and in the PD-L1 positive tumor subgroup (see Table). RFS was consistently prolonged across subgroups, in particular according to AJCC-7 staging, BRAF-V600 E/K mutation status. Conclusions: Pembrolizumab, administered at 200 mg every 3 weeks for up to 1 year as adjuvant therapy, provided, at a 3-yr median follow-up, a sustained improvement in RFS, which was clinically meaningful, in resected high-risk stage III melanoma. This improvement was consistent across subgroups. In the overall population, the 3-yr cumulative incidence of distant metastasis being the first recurrence was 22.3% (pembrolizumab group) vs 37.3% (placebo group) (HR 0.55, 95% CI 0.44-0.69). Clinical trial information: NCT02362594. [Table: see text]

Long-term follow-up of patients treated by adoptive transfer of melanoma tumor-infiltrating lymphocytes as adjuvant therapy for stage III melanoma

2007 ◽  
Vol 56 (11) ◽  
pp. 1853-1860 ◽  
Author(s):  
Amir Khammari ◽  
Jean-Michel Nguyen ◽  
Marie Christine Pandolfino ◽  
Gaëlle Quereux ◽  
Anabelle Brocard ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Adoptive Transfer ◽  
Tumor Infiltrating Lymphocytes ◽  
Stage Iii ◽  
Melanoma Tumor ◽  
Long Term Follow Up ◽  
Stage Iii Melanoma ◽  
Infiltrating Lymphocytes

scholarly journals Site and Timing of First Relapse in Stage III Melanoma Patients: Implications for Follow-Up Guidelines

2010 ◽  
Vol 28 (18) ◽  
pp. 3042-3047 ◽  
Author(s):  
Emanuela Romano ◽  
Michael Scordo ◽  
Stephen W. Dusza ◽  
Daniel G. Coit ◽  
Paul B. Chapman
Keyword(s):  
Stage Iii ◽  
Cancer Center ◽  
Stage Iiia ◽  
Stage Iiic ◽  
Relapse Time ◽  
First Relapse ◽  
Stage Iii Melanoma ◽  
Clinical Records ◽  
In Transit

Purpose Stage III melanoma is associated with a high risk of relapse and mortality. Nevertheless, follow-up guidelines have largely been empirical rather than evidence-based. Patients and Methods Clinical records of stage III patients with no evidence of disease seen at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1992 and 2004, who ultimately relapsed, were reviewed retrospectively to evaluate date of first relapse, time to first relapse, method of first relapse detection, and survival. We also determined overall 5-year relapse-free survival (RFS) of all stage III patients seen at MSKCC during this period. Results The overall 5-year RFS for stage IIIA, IIIB, and IIIIC patients was 63%, 32%, and 11%, respectively. Among relapsing patients, 340 had adequate follow-up to be evaluable for all parameters. Site of first relapse was local/in-transit (28%), regional nodal (21%), or systemic (51%). First relapses were detected by the patient or family, physician, or by screening radiologic tests in 47%, 21%, and 32% of patients, respectively. Multivariate analysis revealed that better overall survival was associated with younger age and first relapse being local/in-transit or nodal, asymptomatic, or resectable. For each substage, we estimated site-specific risk of first relapse. Conclusion Patients detected almost half of first relapses. Our data suggest that routine physical examinations beyond 3 years for stage IIIA, 2 years for stage IIIB, and 1 year for stage IIIC patients and radiologic imaging beyond 3 years for stages IIIA and IIIB and 2 years for stage IIIC patients would be expected to detect few first systemic relapses.

scholarly journals Double venipuncture is not required for adequate S-100B determination in melanoma patients

BioTechniques ◽  
2020 ◽  
Vol 69 (5) ◽  
pp. 371-378
Author(s):  
Samantha Damude ◽  
Anneke C Muller Kobold ◽  
Esther Bastiaannet ◽  
Schelto Kruijff ◽  
Harald J Hoekstra ◽  
...  
Keyword(s):  
Cancer Staging ◽  
Stage Iii ◽  
Tube System ◽  
Serum Samples ◽  
Blood Samples ◽  
Significant Difference ◽  
Melanoma Patients ◽  
The Mean ◽  
Stage Iii Melanoma

S-100B is used in melanoma follow-up. This serum biomarker is also present in adipocytes; therefore, subcutaneous adipocytes trapped in the needle before performing a venipuncture could contaminate the serum. The aim was to study the influence of adipocyte contamination on blood samples used for S-100B analysis, possibly resulting in falsely elevated S-100B values. A total of 294 serum samples were collected from 147 American Joint Committee on Cancer staging stage III melanoma patients. The mean difference between the first (dummy) and second tubes was 0.003 μg/l (p = 0.077), with a decrease in the second tube. Compared with the second tube, the S-100B level was higher in the first tube in 33.3% of the samples, equal in 36.8% of the samples and lower in 29.9% of the samples. No significant difference between the two consecutively drawn tubes was found. There seems to be no necessity of implementing a dummy tube system for accurate S-100B determination in melanoma patients.

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