Prognostic significance of children with cutaneous melanoma: Implications for treatment

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8021-8021
Author(s):  
M. A. Kavanagh ◽  
R. Essner ◽  
S. L. Chen ◽  
L. A. Wanek ◽  
R. P. Scheri ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cutaneous Melanoma ◽  
Pediatric Patients ◽  
Prognostic Significance ◽  
Initial Diagnosis ◽  
Adult Patients ◽  
Breslow Thickness ◽  
Superficial Spreading ◽  
Clark Level ◽  
Melanoma Patients

8021 Background: The incidence of melanoma in pediatric patients, particularly teenagers, is increasing. Treatment strategies employed for adult patients with melanoma have been applied to pediatric populations with minimal data to support similar efficacy. We performed a matched-paired analysis to compare the prognosis of pediatric (≤19 yrs old) and adult melanoma patients. Methods: Single institution, prospectively obtained melanoma database containing >14,000 records was queried for children ages 1–19 years treated for cutaneous melanoma. We identified 197 pediatric patients seen at our institute over the last 35 years. After excluding patients not seen within 4 months of initial diagnosis, 115 pediatric patients were matched to adults (age 20–70 years) chosen from the database by gender, stage, primary site and tumor characteristics (Clark level, Breslow thickness, and ulceration). Overall survival was compared between cohorts by the Kaplan-Meier method. Results: For the pediatric patients, median age at diagnosis was 17.7 years (range 7–19 years). Patients were almost equally distributed between girls (47%) and boys. AJCC stage I and II disease at presentation was most common (73%), with stage III and IV occurring much less frequently (25% and 2%). Most pediatric patients had Clark level IV (37%) lesions; Clark level II (25%), III (25%), V (4%), and I (2%) lesions were less common. Breslow thickness ranged between <1.0mm (38%), 1.1–2.0mm (20%), 2.1–4.0mm (17%), and >4.1mm (12%). The two predominant histologic types were superficial spreading (52%) and nodular (22%) melanoma. 14% of the primary lesions were ulcerated. Rates of disease-free and overall survival were 75%± 4% and 84%± 4% at 5 years and 74%± 4% and 77%± 5% at 10 years, respectively, with a median follow up of 5.1 years (range 1–30 years). Matched pediatric and adult patients showed no difference in survival from time of initial diagnosis and stage of presentation (log rank p=0.24). Conclusions: Stage-specific survival in pediatric and adult melanoma patients is similar. In the absence of specific pediatric trials, standard treatment for children with melanoma should be consistent with that for adults. No significant financial relationships to disclose.

Tumor-Infiltrating Lymphocytes Predict Sentinel Lymph Node Positivity in Patients With Cutaneous Melanoma

2007 ◽  
Vol 25 (7) ◽  
pp. 869-875 ◽  
Author(s):  
Rebecca C. Taylor ◽  
Ami Patel ◽  
Katherine S. Panageas ◽  
Klaus J. Busam ◽  
Mary S. Brady
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Cutaneous Melanoma ◽  
Prognostic Significance ◽  
Tumor Infiltrating Lymphocytes ◽  
Breslow Thickness ◽  
Anatomic Site ◽  
Primary Cutaneous Melanoma ◽  
Male Sex ◽  
Infiltrating Lymphocytes

Purpose Tumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response to tumor, but the influence of TILs on outcome remains controversial. Studies evaluating the prognostic significance of TILs were published before routine examination of draining lymph nodes by sentinel lymph node (SLN) biopsy, the most important predictor of survival in patients with melanoma. The prognostic implications of TILs were re-evaluated in a large group of patients undergoing SLN biopsy at our institution. Patients and Methods All patients who underwent SLN mapping for primary cutaneous melanoma between January 1996 and July 2005 were evaluated. Univariate and multivariate analyses were performed to assess factors that predict SLN positivity and survival. Factors analyzed included Breslow thickness, ulceration, anatomic site, sex, Clark level, age, mitotic rate, and the presence (brisk or nonbrisk) or absence of TIL. Results Eight hundred eighty-seven patients underwent SLN mapping, and a SLN was identified in 875 patients (98.8%). The SLN was positive for tumor in 156 patients (17.6%). Multivariate analysis revealed that only Breslow thickness (P < .0001), ulceration (P = .0004), male sex (P = .03), and absent TILs (P = .0003) were independently predictive of the presence of SLN metastases. In melanomas with a brisk TIL infiltrate, the probability of a positive SLN was 3.9% as compared with 26.2% for melanomas in which TILs were absent. TILs were not an independent predictive factor for survival. Conclusion The absence of TILs, together with increasing Breslow thickness, presence of ulceration and male sex, predicts SLN metastasis in patients undergoing SLN biopsy for primary cutaneous melanoma.

Regression Does Not Predict Nodal Metastasis or Survival in Patients with Cutaneous Melanoma

2011 ◽  
Vol 77 (8) ◽  
pp. 1009-1013 ◽  
Author(s):  
Alison L. Burton ◽  
Juliana Gilbert ◽  
Russell W. Farmer ◽  
Arnold J. Stromberg ◽  
Lee Hagendoorn ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cutaneous Melanoma ◽  
Clinical Decision Making ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Nodal Metastasis ◽  
Breslow Thickness ◽  
Significant Prognostic Factor ◽  
Superficial Spreading ◽  
Histologic Subtype

Controversy exists regarding the prognostic implications of regression in patients with cutaneous melanoma. Some consider regression to be an indication for sentinel lymph node (SLN) biopsy because regression may result in underestimation of the true Breslow thickness. Other data support regression as a favorable prognostic indicator, representing immune system recognition of the primary tumor. This analysis was performed to determine whether regression predicts nodal metastasis, disease-free survival (DFS), or overall survival (OS). Post hoc analysis was performed of a multicenter prospective randomized trial that included patients aged 18 to 70 years with cutaneous melanomas 1 mm or greater Breslow thickness. All patients underwent SLN biopsy; those with tumor-positive SLN underwent completion lymphadenectomy. Kaplan-Meier analysis of survival, univariate analysis, and multivariate analysis were performed. A total of 2220 patients (261 with regression; 1959 without regression) were included in this analysis with a median follow-up of 68 months. Patients with regression were more likely to be male, older than 50 years old, and have lower median Breslow thickness, superficial spreading histologic subtype, and a non-extremity anatomic location ( P < 0.05 in all cases). Regression was not significantly associated with Clark level, ulceration, lymphovascular invasion, number of SLNs removed, or SLN metastasis. On multivariate analysis, factors independently predictive of DFS included Breslow thickness, ulceration, and SLN status ( P < 0.05 in all cases); the same factors along with age, gender, and anatomic tumor location were significantly associated with OS ( P < 0.05 in all cases). Regression was not significantly associated with DFS (risk ratio [RR], 0.94; 95% confidence interval [CI], 0.67-1.27; P = 0.68) or OS (RR, 1.01; 95% CI, 0.76-1.32; P = 0.93). These data suggest that regression is not a significant prognostic factor for patients with cutaneous melanoma and should not be used to guide clinical decision-making for such patients.

scholarly journals Immune Parameters in The Prognosis and Therapy Monitoring of Cutaneous Melanoma Patients: Experience, Role, and Limitations

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Monica Neagu ◽  
Carolina Constantin ◽  
Sabina Zurac
Keyword(s):  
Overall Survival ◽  
Cutaneous Melanoma ◽  
Plasma Cells ◽  
Therapy Monitoring ◽  
Good Prognosis ◽  
Immune Parameters ◽  
Advanced Stages ◽  
Melanoma Patients ◽  
Patients Experience ◽  
Peripheral Cells

Cutaneous melanoma is an immune-dependent aggressive tumour. Up to our knowledge, there are no reports regarding immune parameters monitoring in longitudinal followup of melanoma patients. We report a followup for 36 months of the immune parameters of patients diagnosed in stages I–IV. The circulatory immune parameters comprised presurgery and postsurgery immune circulating peripheral cells and circulating intercommunicating cytokines. Based on our analysis, the prototype of the intratumor inflammatory infiltrate in a melanoma with good prognosis is composed of numerous T cells CD3+, few or even absent B cells CD20+, few or absent plasma cells CD138+, and present Langerhans cells CD1a+ or langerin+. Regarding circulatory immune cells, a marker that correlates with stage is CD4+/CD8+ ratio, and its decrease clearly indicates a worse prognosis of the disease. Moreover, even in advanced stages, patients that have an increased overall survival rate prove the increase of this ratio. The decrease in the circulating B lymphocytes with stage is balanced by an increase in circulating NK cells, a phenomenon observed in stage III. Out of all the tested cytokines in the followup, IL-6 level correlated with the patient’s survival, while in our study, IL-8, IL-10, and IL-12 did not correlate statistically in a significant way with overall survival, or relapse-free survival.

scholarly journals Association of Socioeconomic Status With Breslow Thickness and Disease-Free and Overall Survival in Stage I-II Primary Cutaneous Melanoma

2011 ◽  
Vol 86 (2) ◽  
pp. 113-119 ◽  
Author(s):  
Mario Mandalà ◽  
Gian Lorenzo Imberti ◽  
Dario Piazzalunga ◽  
Maurizio Belfiglio ◽  
Giuseppe Lucisano ◽  
...  
Keyword(s):  
Socioeconomic Status ◽  
Overall Survival ◽  
Cutaneous Melanoma ◽  
Stage I ◽  
Breslow Thickness ◽  
Primary Cutaneous Melanoma ◽  
Disease Free

XPG D1104 single-nucleotide polymorphisms and the prognosis of melanoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11096-11096
Author(s):  
J. C. Becker ◽  
M. Schneider ◽  
D. Scherer ◽  
S. Ugurel ◽  
M. Zapatka ◽  
...  
Keyword(s):  
Overall Survival ◽  
Dna Repair ◽  
Cutaneous Melanoma ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Dna Repair Enzymes ◽  
Repair Enzymes ◽  
Melanoma Patients ◽  
T Classification ◽  
The Impact

11096 Background: Sunlight is a major risk factor for melanoma. Since UV radiation causes DNA damage, it is not surprisingly, that genetic variants in DNA repair enzymes contribute to the susceptibility to cutaneous melanoma. Methods: Presence of common non-synonymous single-nucleotide polymorphism in different DNA repair enzymes were established and correlated with overall survival of melanoma patients. To this end, the SNPs of 6 different DNA repair enzymes were evaluated in a cohort of 742 melanoma patients. The impact of these polymorphisms on overall survival was subsequently calculated by the cox hazard model. Results: This analysis demonstrated that after adjustment to gender and primary tumor T classification XPG 1104 His/His as well as XPD 751 Lys/Lys genotypes were significantly associated with improved survival. Cox hazard coefficients were 0.744 for XPG 1104 His/His (p = 0.0059) and 0.651 for XPD 751 Lys/Lys (p = 0.017). Importantly, bootstrapping confirmed theses results for subpopulations. Furthermore, multivariate analysis demonstrated that XPG 1104 His/His is an independent factor affecting overall survival (cox coefficient 0.95788; p = 0.0011). Conclusions: XPG codon 1104 polymorphism may be predictive of survival outcome in patients with cutaneous melanoma. No significant financial relationships to disclose.

Second primary melanoma: Risk factors, histopathologic features, and survival

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9073-9073
Author(s):  
H. F. Schoellhammer ◽  
H. Torisu-Itakura ◽  
Y. Huynh ◽  
M. Sim ◽  
M. B. Faries ◽  
...  
Keyword(s):  
Primary Melanoma ◽  
Breslow Thickness ◽  
Second Primary ◽  
Clark Level ◽  
Ajcc Stage ◽  
Melanoma Patients ◽  
Level I ◽  
Second Primaries

9073 Background: Melanoma incidence in the United States is expected to be 4.3% of all cancers in 2008. Cutaneous melanoma patients are at risk for second primary melanoma development. Our goal was to characterize the histopathologic features, risk factors, and patient survival for second primary melanoma. Methods: A review of the melanoma database established in 1971 at John Wayne Cancer Institute was conducted identifying patients with American Joint Committee on Cancer (AJCC) stage I and II cutaneous melanoma who later developed a second primary melanoma. Patients were grouped by Breslow thickness, Clark level, and histopathologic subtype (superficial spreading [SSM], nodular, acral lentiginous, lentigo maligna, and in situ). Multivariate analysis involving age, gender, Breslow thickness, Clark level, and ulceration status was performed to determine an effect on development of second primary. Kaplan-Meier survival curves were plotted for single primary and second primary melanoma patients. Results: Second primary melanoma was identified in 411 (3.7%) of 10,968 patients with AJCC stage I-II melanoma. The most common first primary subtype was SSM, and 93% of these patients had in situ or SSM as the second primary. Sixty-five percent of first primaries had a Breslow thickness of ≤1 mm, and 75% of second primaries had a thickness ≤1 mm. Forty-nine percent of first primaries had Clark level I or II, but 68% of second primaries had Clark level I or II. In multivariate analysis, only increasing age was significantly associated with the likelihood of second primary melanoma (p<0.0001). With increasing follow-up time the hazard ratio of second primary melanoma was 1.31 for every decade. Overall survival for second primary melanoma patients was better than for single primary patients (p<0.0001). Conclusions: Most second primary melanoma patients will have SSM or in situ, with a decreased Clark level and Breslow thickness. Contrary to expectations, patients developing second primary melanoma did not exhibit decreased overall survival. Increased follow-up time after first primary melanoma is a significant risk factor for second primary development, thus illustrating the importance of lifelong patient follow-up. No significant financial relationships to disclose.

Prognostic Significance of CD20 in Children with B-Precursor Acute Lymphoblastic Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1452-1452
Author(s):  
Sima Jeha ◽  
Cheng Cheng ◽  
John Sandlund ◽  
Raul Ribeiro ◽  
Bassem Razzouk ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Prognostic Impact ◽  
Cell Precursor ◽  
Improve Outcome ◽  
Cd20 Expression ◽  
Total Therapy ◽  
Therapy Studies

Abstract CD20 expression is associated with inferior survival in adults with ALL. Preliminary reports indicate that regimens incorporating rituximab improve outcome in this subgroup. We analyzed the prognostic impact of CD20 in 353 children with B-cell precursor ALL treated between 12/20/91 and 5/17/99 on three consecutive St. Jude Total Therapy studies. CD20 expression (>20%) was found in 169 patients (48%). Expression was higher in patients between 1 and 10 years (51% of 252 patients), as compared to those less than 1 year of age (7% of 15 patients) or more than 10 year old (43% of 86 patients), p=0.0008. African American patients were more likely to express CD20 (66%), as compared to Caucasians (45%) or other ethnic groups (45%), p=0.047. None of 14 patients with MLL-AF4 expressed CD20. There was no association between CD20 expression and E2A-PBX, TEL-AML1, ploidy, WBC at diagnosis, or gender. In contrast to the experience in adult ALL, our patients with CD20 expression tended to have a better treatment outcome than those without the expression: 5-year EFS 84% ± 2.9% versus 78% ± 3.1% (p=0.08); 5-year overall survival 88% ± 2.5% versus 83% ± 2.8% (p=0.13). This data suggest that CD20 expression is not associated with inferior outcome in pediatric patients treated with contemporary regimens.

scholarly journals PARP1 as a Marker of an Aggressive Clinical Phenotype in Cutaneous Melanoma—A Clinical and an In Vitro Study

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 286
Author(s):  
Piotr Kupczyk ◽  
Aleksandra Simiczyjew ◽  
Jakub Marczuk ◽  
Ewelina Dratkiewicz ◽  
Artur Beberok ◽  
...  
Keyword(s):  
Cutaneous Melanoma ◽  
Prognostic Significance ◽  
In Vitro Study ◽  
Nodal Metastases ◽  
Node Negative ◽  
Protein Levels ◽  
Melanoma Patients ◽  
Melanoma Cell Lines

(1) Background: Poly(ADP-ribose) polymerase 1) (PARP1) is a pleiotropic enzyme involved in several cellular processes, e.g., DNA damage repair, regulation of mitosis, and immune response. Little is known about the role of PARP1 in melanoma development and progression. We aimed to investigate the prognostic significance of PARP1 expression in cutaneous melanoma through evaluation of mRNA and protein levels of PARP1 in normal melanocytes and melanoma cell lines, as well as in patients’ tissue material from surgical resections. (2) Methods: An in vitro model was based on two types of normal human melanocytes (HEMn-DP and HEMn-LP) and four melanoma cell lines (A375, WM1341D, Hs294T, and WM9). PARP1 mRNA gene expression was estimated using real-time polymerase chain reaction (RT-PCR), whereas the protein level of PARP1 was evaluated by fluorescence confocal microscopy and then confirmed by Western Blotting analysis. The expression of PARP1 was also assessed by immunohistochemistry in formalin-fixed paraffin-embedded tissues of 128 primary cutaneous melanoma patients and correlated with follow-up and clinicopathologic features. (3) Results: The in vitro study showed that melanoma cells exhibited significantly higher PARP1 expression at mRNA and protein levels than normal melanocytes. High PARP1 expression was also associated with the invasiveness of tumor cells. Elevated nuclear PARP1 expression in patients without nodal metastases strongly correlated with significantly shorter disease-free survival (p = 0.0015) and revealed a trend with shorter cancer-specific overall survival (p = 0.05). High PARP1 immunoreactivity in the lymph node-negative group of patients was significantly associated with higher Breslow tumor thickness, presence of ulceration, and a higher mitotic index (p = 0.0016, p = 0.023, and p < 0.001, respectively). In patients with nodal metastases, high PARP1 expression significantly correlated with the presence of microsatellitosis (p = 0.034), but we did not confirm the prognostic significance of PARP1 expression in these patients. In the entire analyzed group of patients (with and without nodal metastases at the time of diagnosis), PARP1 expression was associated with a high mitotic index (p = 0.001) and the presence of ulceration (p = 0.036). Moreover, in patients with elevated PARP1 expression, melanoma was more frequently located in the skin of the head and neck region (p = 0.015). In multivariate analysis, high PARP1 expression was an independent unfavorable prognosticator in lymph node-negative cutaneous melanoma patients. (4) Conclusions: In vitro molecular biology approaches demonstrated enhanced PARP1 expression in cutaneous melanoma. These results were confirmed by the immunohistochemical study with clinical parameter analysis, which showed that a high level of PARP1 correlated with unfavorable clinical outcome. These observations raise the potential role of PARP1 inhibitor-based therapy in cutaneous melanoma.

scholarly journals Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma. Austrian Malignant Melanoma Cooperative Group.

1998 ◽  
Vol 16 (4) ◽  
pp. 1425-1429 ◽  
Author(s):  
H Pehamberger ◽  
H P Soyer ◽  
A Steiner ◽  
R Kofler ◽  
M Binder ◽  
...  
Keyword(s):  
Cutaneous Melanoma ◽  
Primary Tumor ◽  
Disease Free Survival ◽  
Interferon Alfa ◽  
Breslow Thickness ◽  
Stage Ii ◽  
Primary Stage ◽  
Free Survival ◽  
Melanoma Patients ◽  
Disease Free

PURPOSE Patients with primary cutaneous melanoma with a Breslow thickness > or = 1.5 mm have only a 30% to 70% probability of survival after surgery, and no adjuvant therapy has so far improved this outcome. Since interferon alfa-2a (IFNalpha2a) exhibits antitumor activity in metastatic melanoma, we investigated whether adjuvant IFNalpha2a diminishes the occurrence of metastases and thus prolongs disease-free survival in melanoma patients after excision of the primary tumor. PATIENTS AND METHODS In a prospective randomized study, 311 melanoma patients with a Breslow thickness > or = 1.5 mm were assigned to either adjuvant IFNalpha2a treatment (n = 154) or observation (n = 157) after excision of the primary tumor. IFNalpha2a was given daily at a dose of 3 mIU subcutaneously (s.c.) for 3 weeks (induction phase), after which a dose of 3 mIU s.c. three times per week was given over 1 year (maintenance phase). RESULTS Prolonged disease-free survival was observed in patients treated with IFNalpha2a versus those who underwent surgery alone. This difference was significant (P = .02) for all patients enrolled onto the study (intention-to-treat analysis) at a mean observation time of 41 months. Subgroup analysis showed that Breslow tumor thickness had no influence on treatment results in the groups of patients investigated. CONCLUSION Adjuvant IFNalpha2a treatment diminishes the occurrence of metastases and thus prolongs disease-free survival in resected primary stage II cutaneous melanoma patients.

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