scholarly journals OTHR-08. PREDICTION OF RISK OF CENTRAL NERVOUS SYSTEM METASTASIS FOR AJCC 8TH EDITION STAGE III MELANOMA PATIENTS

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i19-i20
Author(s):  
Lauren Haydu ◽  
Serigne Lo ◽  
Jennifer McQuade ◽  
Isabella Glitza ◽  
Hussein Tawbi ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Cumulative Incidence ◽  
Mitotic Rate ◽  
Stage Iii ◽  
Primary Tumor Site ◽  
Cns Metastasis ◽  
Melanoma Patients ◽  
Stage Iii Melanoma ◽  
The Impact ◽  
8Th Edition

Abstract Among common solid tumors, melanoma has the highest risk of CNS metastasis. Improved understanding of the incidence, risk factors, and timing of CNS metastasis is needed to inform surveillance strategies for at-risk patients. Clinical data were extracted from two institutions for AJCC 8th edition stage III melanoma patients, 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 post-diagnosis. The cohort (N=1,918) consisted of patients from major melanoma centers in the US (50.6%) and Australia (49.4%). The first site of distant metastasis was CNS only for 3.9%, CNS and extra-cranial sites (ECS) for 1.9%, and ECS only for 31.2% of patients (N=1918); 15.5% of patients who developed distant metastases (N=708) had CNS involvement at first diagnosis of stage IV disease. Cumulative incidence of CNS metastasis from stage III diagnosis was 3.7% (95% Confidence Interval (CI): 2.9–4.6) at 1-year; 9.6% (95% CI: 8.3–11.0) at 2-years; and 15.9% (95% CI: 14.2–17.7) at 5-years. In multivariable analyses, risk of CNS metastasis was significantly higher for males; younger patients; increasing AJCC stage group; scalp primary tumor site, acral melanoma subtype, and increased primary tumor mitotic rate. Conditional analyses showed that only high primary tumor mitotic rate (>9 per mm2) was significantly associated with risk of subsequent CNS metastasis among patients who survived without CNS recurrence 1-, 2-, and 5-years after the diagnosis of stage III disease. Similar rates of CNS metastasis were observed between these two large, geographically-distinct stage III melanoma patient cohorts. These results provide a framework for developing evidence-based surveillance strategies and for evaluating the impact of contemporary adjuvant therapies on the risk of melanoma CNS metastasis.

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.

The solved and unresolved issues of melanoma staging: A comparison of American Joint Committee on Cancer (AJCC) 7th versus 8th edition.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9578-9578
Author(s):  
Shirin Bajaj ◽  
Anthony Collado ◽  
Una Moran ◽  
Douglas MacArthur Donnelly ◽  
Paul Johannet ◽  
...  
Keyword(s):  
Cox Regression ◽  
Primary Melanoma ◽  
Progression Free Survival ◽  
Stage I ◽  
Added Value ◽  
Stage Iii ◽  
Melanoma Patients ◽  
Ajcc Staging ◽  
The Impact ◽  
8Th Edition

9578 Background: The recently revised (AJCC) Staging Manual, 8th edition, introduced changes including removal of mitotic index and addition of the IIID substage. There is active debate on the utility of this revision, especially, without the inclusion of a novel prognostic biomarker, during an era of major therapeutic shifts and amidst accrual of adjuvant clinical trials for high-risk resected primary melanoma. We examined whether re-staging primary melanoma patients using the new AJCC 8 system yielded improved prognostication as compared to AJCC 7. Methods: We compared the impact of changes in staging criteria in stage I-III melanoma patients who were prospectively enrolled in a NYU clinicopathological database between January 2010 and December 2016 with active protocol-driven follow up (FU). We assessed primary tumor category (T) and nodal status (N) according to both AJCC 7 and 8. Progression free survival (PFS) and overall survival (OS) curves were generated for both editions and then stratified by substage. We analyzed discordance using Cox Regression Models. Results: 1,379 patients (56% male, mean thickness 1.6, median FU 34.8 months) were included in the analyses. All but one patient remained in the same ‘major’ stage using AJCC 7 and 8 (stage I- 998; II- 224, 225; III- 157, 156) whereas 44% of stage III substage classifications were discordant comparing AJCC 7 to 8. Despite removing mitoses as a criterion for Stage I, there was no significant change between editions in PFS/OS when evaluating major and substages of stage I. Stage IIC patients had worse PFS/OS than stage IIIA patients in AJCC 8 (PFS p = 0.04, OS p = 0.02). AJCC 8, which implemented four rather than three substages, had improved PFS prognostication (c-index = 0.59 vs 0.66, p = 0.05 for AJCC 7 vs 8). Conclusions: Our results reinforce the added value of AJCC 8 compared to 7, as removing an operator dependent variable is more practical for stage I, and increased influence of thickness/ulceration and the addition of a new substage is more prognostically informative for stage III. Nevertheless, the poor prognosis of stage IIC patients, despite nodal negative disease, continues to be an unaddressed gap within our current staging framework.

scholarly journals Multivariate Analysis of Prognostic Factors Among 2,313 Patients With Stage III Melanoma: Comparison of Nodal Micrometastases Versus Macrometastases

2010 ◽  
Vol 28 (14) ◽  
pp. 2452-2459 ◽  
Author(s):  
Charles M. Balch ◽  
Jeffrey E. Gershenwald ◽  
Seng-jaw Soong ◽  
John F. Thompson ◽  
Shouluan Ding ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Primary Tumor ◽  
Survival Rates ◽  
Mitotic Rate ◽  
Nodal Metastasis ◽  
Stage Iii ◽  
Anatomic Site ◽  
Patient Age ◽  
Patient Âgé ◽  
Stage Iii Melanoma

Purpose To determine the survival rates and independent predictors of survival using a contemporary international cohort of patients with stage III melanoma. Patients and Methods Complete clinicopathologic and follow-up data were available for 2,313 patients with stage III disease in an updated and expanded American Joint Committee on Cancer (AJCC) melanoma staging database. Kaplan-Meier and Cox multivariate survival analyses were performed. Results Among all 2,313 patients with stage III disease, 81% had micrometastases, and 19% had clinically detectable macrometastases. The 5-year overall survival was 63%; it was 67% for patients with nodal micrometastases, and it was 43% for those with nodal macrometastases (P < .001). Tremendous heterogeneity in survival was observed, particularly in the microscopically detected nodal metastasis subset (from 23% to 87% for 5-year survival). Multivariate analysis demonstrated that in patients with nodal micrometastases, number of tumor-containing lymph nodes, primary tumor thickness, patient age, ulceration, and anatomic site of the primary independently predicted survival (all P < .01). When added to the model, primary tumor mitotic rate was the second-most powerful predictor of survival after the number of tumor-containing nodes. In contrast, for patients with nodal macrometastases, the number of tumor-containing nodes, primary ulceration, and patient age independently predicted survival (P < .01). Conclusion In this multi-institutional analysis, we demonstrated remarkable heterogeneity of prognosis among patients with stage III melanoma, especially among those with nodal micrometastases. These results should be incorporated into the design and interpretation of future clinical trials involving patients with stage III melanoma.

Prognostic significance of pathological biomarkers in patients with stage II-III colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14518-14518
Author(s):  
C. Funaioli ◽  
C. Pinto ◽  
C. Ceccarelli ◽  
F. Di Fabio ◽  
D. Cuicchi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Primary Tumor ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Stage Ii ◽  
Stage Iii ◽  
Disease Stage ◽  
Primary Tumor Site ◽  
The Impact

14518 Background: Biopathological colorectal cancer (CRC) studies have provided information on pathogenesis, but it is unclear how important biomarkers actually are in predicting prognosis. The aim of our study was to define the prognostic significance of biomarkers and a biopathological profile that could predict an increase in the disease relapse risk in stage II-III CRC patients (pts). Methods: The primary tumor of the CRC pts treated with surgery was immunohistochemically evaluated on the Ki67, p53, bcl-2, TS, EGFR, MLH1 and MSH2 expressions. All 7 markers were measured using standard immunohistochemical techniques. The biomarker evaluations were scored by just one pathologist. Results: Between March 2001 and October 2006 the primary tumor of 242 consecutive pts was investigated. Pt characteristics were: males 141(58.3%), females 101(41.7%); median age 68.5 (24–88); primary tumor site: right colon 94(38.8%), left colon 148(61.2%); stage II 102(42.1%), stage III 81(33.5%), stage IV 59(24.4%). 5-fluorouracil based adjuvant chemotherapy was performed in 121 (66.1%) pts. After a median follow up of 30 months (1–80), 34 pts (10 pts stage II, 24 pts stage III) of 183 stage II-III pts (18.6%) had a disease recurrence. In a univariate analysis of stage II-III pts, a higher expression of Ki67 (= 50% positive cells) was significantly associated with an improved DFS (p= 0.014) and overall survival (OS) (p=0.010). Expression of p53, bcl-2, TS, EGFR, MLH1 and MSH2 were not significantly associated with DFS and OS. In a multivariate analysis adjusted for the impact of the disease stage and adjuvant chemotherapy, a higher expression of Ki67 was significantly associated with diminished risk of recurrence (HR: 0.395; 95% CI: 0.183–0.855, p=0.018) and death (HR: 0.179; 95% CI: 0.046–0.696, p=0.013). The evaluation of DNA mismatch repair status (MLH1, MSH2) demonstrated that the lack of MLH1 is more frequent in non-relapsed II-III stage pts than in IV stage pts (p= 0.024). Conclusions: This analysis showed a significant correlation between higher Ki67 expression and better DFS and OS in pts with stage II-III CRC. An higher frequency of MLH1 deficiency was observed in non-relapsed pts with stage II-III than in advanced disease. No significant financial relationships to disclose.

scholarly journals PTENP1-AS contributes to BRAF inhibitor resistance and is associated with adverse clinical outcome in stage III melanoma

2020 ◽  
Author(s):  
Linda Vidarsdottir ◽  
Alireza Azimi ◽  
Ingibjorg Sigvaldadottir ◽  
Aldwin Suryo Rahmanto ◽  
Andreas Petri ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Transcriptional Repression ◽  
Regional Lymph Node ◽  
Braf Inhibitor ◽  
Suppressor Gene ◽  
Stage Iii ◽  
Activating Mutations ◽  
Melanoma Patients ◽  
Stage Iii Melanoma ◽  
The Impact

ABSTRACTApproximately 50% of human cutaneous melanomas carry activating mutations in the serine/threonine protein kinase BRAF. BRAF inhibitors (BRAFi) selectively target the oncogenic BRAFV600E/K and are effective in approximately 80% of patients carrying the mutation. However, resistance to BRAFi is common and emerges within a median time of 6-7 months of treatment and is prolonged to 11 months when combined with MEK inhibitors. Better characterization of the underlying molecular processes is therefore needed to further improve treatments. Inactivation of the tumor suppressor gene PTEN has been suggested to occur during melanomagenesis and drug resistance development. We recently demonstrated that transcription of PTEN is negatively regulated by an antisense RNA from the PTEN pseudogene (PTENP1-AS) and here set out to investigate the impact of this molecular pathway on the resistance to BRAFi and clinical outcome. We used a panel of BRAFi resistant A375 sublines, and observed increased levels of PTENP1-AS associated with reduced expression of PTEN. Furthermore, this loss of PTEN expression was correlated to increased recruitment of Enhancer of zeste homolog 2 (EZH2) and formation of the transcriptional repression mark H3K27me3 at the PTEN promoter in the resistant cells. We demonstrated that targeting of PTENP1-AS was able to re-activate the expression of PTEN and sensitize resistant melanoma cells to BRAFi. Finally, we showed that PTENP1-AS is a promising prognostic marker for clinical outcome in melanoma patients as high expression of PTENP1-AS in regional lymph node metastases from stage III melanoma patients correlated with poor survival.

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

Incidence, timing, and predictors of CNS metastasis in patients (Pts) with clinically localized cutaneous melanoma (CM).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9580-9580
Author(s):  
Merve Hasanov ◽  
Denai R. Milton ◽  
Sapna Pradyuman Patel ◽  
Hussein Abdul-Hassan Tawbi ◽  
Isabella Claudia Glitza ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Cumulative Incidence ◽  
Tumor Location ◽  
Initial Diagnosis ◽  
Stage I ◽  
Acral Lentiginous Melanoma ◽  
Primary Tumor Location ◽  
Cns Metastasis ◽  
Increased Risk

9580 Background: Surveillance for CNS metastasis (mets) is not routinely performed in pts with clinically localized CM. Improved understanding of the incidence, timing and risk factors for the development of CNS metastasis in these pts may inform surveillance strategies. Methods: Under an IRB-approved protocol, demographics, tumor characteristics, and clinical events were collected for pts diagnosed from 1998 to 2019 with AJCC 8th edition stage I or II CM at MD Anderson Cancer Center. Dates of initial diagnosis, regional, distant non-CNS, and CNS mets were recorded. Symptoms and the extent of disease (brain, LMD, both) were recorded for pts with CNS mets. Cumulative incidence of distant mets (CNS and non-CNS) was determined using the competing risks method, including death; pts without CNS mets and alive at last follow-up were censored. Differences in cumulative incidence between groups were assessed using Gray’s test. Associations between measures of interest and cumulative incidence were determined using proportional subdistribution hazards regression models. All statistical tests used a significance level of 5%. Results: 5,179 Stage I-II CM pts were identified. At a median follow up of 82 (0.0-268.8) months, 703 (13.6%) pts were diagnosed with distant mets, including 355 (6.9%) with CNS mets. Cumulative incidence of CNS mets was 0%, 2%, and 5% at 1, 2, and 5 years, respectively. Among pts with distant mets, the first site of distant mets was CNS only for 29 (4%), non-CNS only for 557 (79%), and both for 116 (17%) pts. At initial diagnosis of CNS mets, 195 (55%) pts were asymptomatic, and 46 (13%) had no active extracranial disease. Median time to any distant met was longer for pts who were diagnosed with CNS mets [40.0 (1.9-238.0) months] vs pts diagnosed with non-CNS mets only [31.4 (1.1-185.7) months, p < 0.001]. On multivariable analysis, risk of CNS mets was significantly associated with primary tumor location of scalp [Hazard Ratio (HR) 3.4, 95% Confidence interval (CI) 1.9-5.9], head/neck (HR 3.3, 95% CI 2.0-5.3), or trunk (HR 2.3, 95% CI 1.5-3.5) (vs upper extremity); acral lentiginous melanoma subtype (HR 2.0, 95% CI 1.2-3.6) (vs superficial spreading); increased T category (T2 HR 1.5, 95% CI 1.1-2.2; T3 HR 1.9, 95% CI 1.2-3.0; T4 HR 2.1, 95% CI 1.1-3.8; vs T1), Clark level (CL) (CL4 HR 2.1, 95% CI 1.2-3.7 vs CL2), and mitotic rate (MR) (MR 5-9/mm2 HR 2.1, 95% CI 1.5-3.0; MR > 9/mm2 HR 2.0, 95% CI 1.3-3.0; vs MR 0-4/mm2). While high ( > 9/mm2) MR was associated with increased risk of CNS and non-CNS mets, intermediate (5-9/mm2) was associated with CNS mets only. Conclusions: Primary tumor location, tumor thickness, and MR were strongly associated with risk of CNS mets. MR rate was more strongly associated with risk of CNS than non-CNS mets. Validation in independent cohorts may provide evidence to support CNS surveillance strategies in select pts with stage I-II CM who are deemed high risk for CNS mets.

scholarly journals Long-term follow-up of children with neuroblastoma receiving radiotherapy to metastatic lesions within the German Neuroblastoma Trials NB97 and NB 2004

2020 ◽  
Author(s):  
Danny Jazmati ◽  
Sarina Butzer ◽  
Barbara Hero ◽  
Jerome Doyen ◽  
Dalia Ahmad Khalil ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Primary Tumor ◽  
Secondary Malignancy ◽  
Primary Tumor Site ◽  
Free Survival ◽  
Stage 4 ◽  
Metastatic Sites ◽  
The Impact

Abstract Purpose Neuroblastoma (NB) is the most common extracranial solid malignancy during childhood. Despite a multimodal treatment approach, the prognosis of patients with metastatic NB is not satisfactory. Although radiotherapy (RT) has become an integral part of treatment of the primary tumor, the role of RT in osteomedullary lesions is not well defined. A retrospective analysis was conducted to evaluate the impact of RT for metastatic sites in children with high-risk NB. Methods All patients with stage 4 NB from the prospective, multicenter NB trials NB97 and NB2004 who received RT to metastatic sites during frontline treatment were included in this retrospective analysis. Results A total of 18 children were irradiated with a median dose of 36 Gray (Gy; range 20–45 Gy) to one or more (range 1–3) osteomedullary metastases with or without concomitant RT to the primary tumor site. The median follow-up time was 149 months (range 55–220) in survivors. At 5 years, local relapse-free survival (LRFS) at irradiated metastatic sites and metastases-free survival (MFS) at distant, non-irradiated site rates were 51.4 and 39.9%, respectively. The estimated overall survival (OS) rate at 5 years was 49.4%. No high-grade acute or late toxicity and no secondary malignancy was reported. Conclusion RT to metastases is feasible for patients with stage 4 NB. However, an impact of RT to residual metastatic sites on outcome was not found. Studies with larger cohorts or prospective trials would be desirable in order to elucidate the role of RT for metastases.

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.

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