Risk Of Melanoma Recurrence Research Articles

Adjuvant Therapy Using Dabrafenib plus Trametinib in Chinese Patients with Resected Stage III Melanoma: A Multicenter Retrospective Cohort Study

Background. In patients with stage III melanoma carrying BRAF mutations, the risk of melanoma recurrence is relatively high even after complete resection of the primary melanoma and regional lymph nodes. Methods. We collected data from patients with stage III cutaneous and acral melanoma who received adjuvant trametinib combined with dabrafenib from three cancer centres in China between August 2019 and December 2022. Results. A total of 55 patients were included in this study. The one-year recurrence-free survival (RFS) rate was 79.8% (95% CI 73.6–86.0%). The one-year RFS rate was 79.8% (95% CI 72.8–86.8%) in the cutaneous melanoma subgroup, while the one-year RFS rate was 74.1% (95% CI 58.0–90.2%) in the acral melanoma subgroup. Six (46.2%) patients experienced recurrence during adjuvant therapy; 7 (53.9%) patients recurred after completion of the regimen. At the time of the first recurrence, distant metastasis occurred in 10 patients, local recurrence occurred in 2 patients, and one patient experienced both distant metastasis and local recurrence. Conclusions. This study confirmed the good tolerability and short-term benefits of adjuvant therapy with dabrafenib and trametinib in Chinese patients with stage III melanoma with BRAF V600 mutation.

Preferences for adjuvant immunotherapy in patients with resected stage III melanoma: A discrete choice experiment.

9558 Background: Adjuvant immunotherapy has revolutionized the management of resectable melanoma, substantially reducing the risk of recurrence but at the risk of immune-related adverse events (AE). This study aimed to quantify patients' preferences for adjuvant immunotherapy, the influence of varying levels of key attributes, and baseline characteristics associated with preferences. Methods: We performed a discrete choice experiment (DCE), including patients with resected stage III melanoma considering or having received adjuvant immunotherapy. Patients chose between twelve randomly presented choice tasks of two alternative options (adjuvant immunotherapy versus observation without adjuvant immunotherapy). The two options varied across two-three levels of six attributes: chance of 3-year melanoma recurrence, mild, permanent, or fatal AE, drug regimen, and out-of-pocket costs. We calculated the marginal rate of substitution (MRS, how much an individual was willing to trade one attribute for preferred levels of another) and willingness-to-pay (WTP, maximum price to trade their preferred attributes) per year. Results: One hundred and sixteen patients completed the DCE. Patients chose adjuvant immunotherapy over observation without adjuvant immunotherapy in 70% of choice tasks. Patients preferred adjuvant immunotherapy with reduced probabilities of recurrence (OR 0.76, 95% CI 0.70-0.83, p<0.001), fatal AE (OR 0.60, 95% CI 0.44-0.80, p=0.006), permanent AE (OR 0.94, 95% CI 0.89-0.99, p=0.046), and lowered out-of-pocket costs, for those with lower incomes (OR 0.63, 95% CI 0.47-0.85, p=0.003) and higher incomes (OR 0.84, 95% CI 0.15-4.86, p=0.064). Patients accepted an increase in their chance of mild AE from 1% to 37% (OR 2.06, 95% CI 1.13-3.78, p=0.019) in return for adjuvant immunotherapy. Willingness-to-pay was lower for patients with incomes that were lower rather than higher: US$595 (95% CI US-$555 to 1,305) and US$1,638 (95% CI US$ -1,235 to 3,419) per year for adjuvant immunotherapy with an absolute reduction of 1% in the 3-year risk of recurrence. Conclusions: Almost three-quarters of patients preferred adjuvant immunotherapy over observation without adjuvant immunotherapy. Patients were more likely to select immunotherapy if the risk of melanoma recurrence and the chance of fatal AE were reduced. Understanding patient preferences and acceptable trade-offs for adjuvant immunotherapy may allow better-informed decisions for individuals and assist policymakers in decisions about access and subsidization of effective and expensive treatments.

Characterization of Sentinel Lymph Node Immune Signatures and Implications for Risk Stratification for Adjuvant Therapy in Melanoma

Although sentinel lymph node (SLN) biopsy is a standard procedure used to identify patients at risk for melanoma recurrence, it fails to risk-stratify certain patients accurately. Because processes in SLNs regulate anti-tumor immune responses, the authors hypothesized that SLN gene expression may be used for risk stratification. The Nanostring nCounter PanCancer Immune Profiling Panel was used to quantify expression of 730 immune-related genes in 60 SLN specimens (31 positive [pSLNs], 29 negative [nSLNs]) from a retrospective melanoma cohort. A multivariate prediction model for recurrence-free survival (RFS) was created by applying stepwise variable selection to Cox regression models. Risk scores calculated on the basis of the model were used to stratify patients into low- and high-risk groups. The predictive power of the model was assessed using the Kaplan-Meier and log-rank tests. During a median follow-up period of 6.3years, 20 patients (33.3%) experienced recurrence (pSLN, 45.2% [14/31] vs nSLN, 20.7% [6/29]; p = 0.0445). A fitted Cox regression model incorporating 12 genes accurately predicted RFS (C-index, 0.9919). Improved RFS was associated with increased expression of TIGIT (p = 0.0326), an immune checkpoint, and decreased expression of CXCL16 (p = 0.0273), a cytokine important in promoting dendritic and T cell interactions. Independent of SLN status, the model in this study was able to stratify patients into cohorts at high and low risk for recurrence (p < 0.001, log-rank). Expression profiles of the SLN gene are associated with melanoma recurrence and may be able to identify patients as high or low risk regardless of SLN status, potentially enhancing patient selection for adjuvant therapy.

Abstract B16: The immune profile of sentinel lymph nodes in melanoma

Abstract Background: Immune cell composition and immune-mediated processes occurring in the sentinel lymph node (SLN) of melanoma patients regulate generation of tumor-specific effector T-cell responses and ultimately tumor control. We hypothesized that comprehensive analysis of these immune-associated processes in the SLN biopsy may identify patients at high risk of melanoma recurrence. Methods: We analyzed 38 formalin-fixed, paraffin-embedded sentinel lymph nodes from melanoma patients undergoing SLN biopsy from 2009-2012 using the NanoString nCounter® PanCancer Immune Profiling panel. The panel included 770 immune related genes. Results: Of 38 patients, 19 were SLN negative and 19 were SLN positive. Among SLN-negative patients (n=19), the median Breslow depth was 1.25 mm, and 21% (n=4) had developed recurrence at median follow-up of 6.2 years. Among SLN-positive patients, the median Breslow depth was 3.35 mm and 37% (n=7) had developed recurrence at median follow-up of 6.5 years. There were 31 genes significantly differentially expressed (P&amp;lt;0.01) in SLN positive compared to SLN negative, including higher relative expression of B-cell signaling markers (CD19, CD22, Pax5, CXCR5, CD79B). Among all 38 patients, there were 13 genes differentially expressed (P&amp;lt;0.05) between patients with and without recurrence, including higher relative expression of IL6 in patients with recurrence compared to no recurrence. Further analysis is ongoing. Conclusion: In this retrospective series, we found the immunologic gene expression profile of melanoma SLNs was significantly different in SLN negative versus SLN positive. There were also significant differences in the profile between patients who developed melanoma recurrence versus no recurrence regardless of SLN status. We aim to build on these pilot data. The goal is to use this profile to predict patients at high risk of recurrence after SLNB who may benefit from adjuvant therapy. Citation Format: Georgia M. Beasley, Eda K. Holl, Norma E. Farrow, Margaret G. Leddy, April K. Salama, Brent A. Hanks, Smita K. Nair. The immune profile of sentinel lymph nodes in melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr B16.

Skin Self-Examination: Partner Comfort and Support During Examinations as Predictors of Self-Efficacy in Patients At Risk for Melanoma Recurrence.

Skin self-examination (SSE) is an effective method for melanoma survivors to detect potential cancerous growths sooner. The purpose of this study was to examine whether the SSE self-efficacy of patients with melanoma and their partners is affected by their partners' comfort and support during skin examinations. 100 patient-partner dyads completed a 25-item sociodemographic questionnaire. Fifty-two partners attended an education session with the patient on skin examinations and the early detection of melanoma. All patients attended the education session. Having their partners attend the education session, as well as being supportive and comfortable with skin examinations, significantly predicted patients' self-efficacy with SSEs. In addition, male patients were found to be significantly more comfortable with partner-assisted skin examinations and reported feeling more supported by their partner than female patients.

Clinicopathological predictors of recurrence in nodular and superficial spreading cutaneous melanoma: a multivariate analysis of 214 cases

BackgroundNodular melanoma (NM) accounts for most thick melanomas and because of their frequent association with ulceration, fast growth rate and high mitotic rate, contribute substantially to melanoma-related mortality. In a multicentric series of 214 primary melanomas including 96 NM and 118 superficial spreading melanoma (SSM), histopathological features were examined with the aim to identify clinicopathological predictors of recurrence.MethodsAll consecutive cases of histopathologically diagnosed primary invasive SSM and NM during the period 2005–2010, were retrieved from the 12 participating Italian Melanoma Intergroup (IMI) centers. Each center provided clinico-pathological data such as gender, age at diagnosis, anatomical site, histopathological conventional parameters, date of excision and first melanoma recurrence.ResultsResults showed that NM subtype was significantly associated with Breslow thickness (BT) at multivariate analysis: [BT 1.01–2 mm (OR 7.22; 95% CI 2.73–19.05), BT 2.01–4 mm (OR 7.04; 95% CI 2.54–19.56), and BT > 4 mm (OR 51.78; 95% CI 5.65–474.86) (p < 0.0001)]. Furthermore, mitotic rate (MR) was significantly correlated with NM histotype: [(MR 3–5 mitoses/mm2 (OR 2.62; 95% CI 1.01–6.83) and MR > 5 mitoses/mm2 (OR 4.87; 95% CI 1.77–13.40) (p = 0.002)]. The risk of recurrence was not significantly associated with NM histotype while BT [BT 1.01–2.00 mm (HR 1.55; 95% CI 0.51–4.71), BT 2.01–4.00 mm (HR 2.42; 95% CI 0.89–6.54), BT > 4.00 mm. (HR 3.13; 95% CI 0.95–10.28) (p = 0.05)], mitotic rate [MR > 2 mitoses/mm2 (HR 2.34; 95% CI, 1.11–4.97) (p = 0.03)] and the positivity of lymph node sentinel biopsy (SNLB) (HR 2.60; 95% CI 1.19–5.68) (p = 0.007) were significantly associated with an increased risk of recurrence at multivariate analysis.ConclusionsWe found that NM subtype was significantly associated with higher BT and MR but it was not a prognostic factor since it did not significantly correlate with melanoma recurrence rate. Conversely, increased BT and MR as well as SNLB positivity were significantly associated with a higher risk of melanoma recurrence.

Prognostic Role of Multiple Lymphatic Basin Drainage in Sentinel Lymph Node-Negative Trunk Melanoma Patients: A Multicenter Study from the Italian Melanoma Intergroup.

Multiple lymphatic basin drainage (MLBD) is frequently observed in patients with trunk melanoma undergoing sentinel lymph node (SLN) biopsy. Conflicting data regarding the prognostic association of MLBD in SLN-negative patients have been reported. This study aimed to investigate the prognostic role of MLBD in patients with negative SLN biopsy. Retrospective data from 656 melanoma patients who underwent a SLN biopsy (1991-2012) at six Italian centers were gathered in a multicenter database. MLBD was defined as lymphoscintigraphic and intraoperative identification of an SLN in more than one nodal basin. Clinical and pathologic variables were recorded and analyzed for their impact on survival. SLN-negative patients with MLBD were at lower risk of melanoma recurrence [hazard ratio (HR) 0.73, P=0.05) and melanoma-related death (HR 0.68, P=0.001) independent of common staging features. Multivariable Cox analyses of disease-free interval (DFI) and disease-specific survival (DSS) showed that MLBD maintained a favorable role and ulceration an unfavorable role. Histologic regression was independently associated only with DFI. When survival was stratified according to presence of MLBD, histologic regression and Breslow thickness <2mm were associated with improved DFI (5-year DFI: 96.9 vs. 66,1%, respectively; HR 0.48, P<0.001) and DSS (5-year DSS: 96.7 vs. 71.8%, respectively; HR 0.52, P=0.005) compared to patients without these three favorable parameters. Patients with negative SLN biopsy results have better prognosis when two or more lymphatic basins are identified and analyzed. Further research is required to investigate the mechanisms behind this evidence.

Aberrant lymphatic drainage and risk for melanoma recurrence after negative sentinel node biopsy in middle-aged and older men.

Aberrant lymphatic drainage is believed to contribute to the high recurrence rate of head and neck melanomas. The purpose of this study was to identify the clinical significance of unexpected lymphatic drainage patterns. A single institution retrospective analysis was performed of middle-aged and older men (mean age, 66.2 years; range, 41-87 years) who underwent successful lymphoscintigraphy with sentinel lymph node biopsy (SLNB) from 1997 through 2012. Node status, distribution, and recurrence were assessed comparing patients with expected and unexpected drainage patterns. Sixty-six patients were identified with 55.8 months median follow-up (range, 5.6-206.1 months). Unexpected sentinel lymph node drainage was associated with multiple basin drainage (p < .01) and greater recurrence after negative SLNB (p = .03). Both groups had similar anatomic distribution, sentinel lymph node sampling, histopathologic characteristics, follow-up, and survival. Lymphatic drainage differing from expected patterns is associated with greater recurrence after negative SLNB in middle-aged and older men. © 2015 Wiley Periodicals, Inc. Head Neck 38: E754-E760, 2016.

Does Our “Flight and Fight” Response Have a Link With Cancer?

Does Our “Flight and Fight” Response Have a Link With Cancer?

Highlights from the Current Issue – Audiovisual Summary

Dr Thomas Gerber focuses on the articles featured on the November 2013 cover of Mayo Clinic Proceedings. These include: An Original Article entitled “Effect of Beta-Blockers and Other Antihypertensive Drugs on the Risk of Melanoma Recurrence and Death,” by Dr Vincenzo De Giorgi and colleagues; an accompanying Editorial entitled “Does our ‘Fight and Flight’ Response Have a Link With Cancer?” by Dr Manish Kohli the Original Article entitled “Statins and Cognition: A Systematic Review and Meta-analysis of Shortand Long-term Cognitive Effects,” by Dr Kristopher J. Swiger and colleagues from Johns Hopkins University in Baltimore, Maryland; the Special Article entitled “Guns, Schools, and Mental Illness: Potential Concerns for Physicians and Mental Health Professionals,” by Drs Ryan C. W. Hall and Susan H. Friedman from the University of Central Florida in Orlando, Florida, and Case Western Reserve University in Cleveland, Ohio; the accompanying editorial “A Good Idea Shot Down: Taking Guns Away From the Mentally Ill Won’t Eliminate Mass Shootings,” by Dr J. Michael Bostwick from Mayo Clinic in Rochester, Minnesota; the Concise Review for Clinicians “Maternal and Neonatal Complications of Elective Early-Term Deliveries,” by Dr Jani R. Jensen and colleagues from Mayo Clinic in Rochester, Minnesota; a Review Article entitled “Lipoprotein (a), Cardiovascular Disease, and Contemporary Management,” by Dr Terry A. Jacobson from Emory University in Atlanta, Georgia; the Original Article “International Travel by Persons with Medical Comorbidities: Understanding Risks and Providing Advice,” by Dr Natasha S. Hochberg from Boston University in Boston, Massachusetts, and colleagues from several other national health care institutions; the Original Article “[18F]-Fluorodeoxyglucose Positron Emission Tomography in Patients With Active Myelopathy,” by Dr Eoin P. Flanagan and colleagues from Mayo Clinic in Rochester, Minnesota; the accompanying Editorial “Positron Emission Tomography in Spinal Cord Disease,” by Dr Vivek Gupta from Mayo Clinic in Jacksonville, Florida; and the Symposium on Regenerative Medicine article entitled “Advances in Regenerative Orthopedics,” by Dr Christopher H. Evans from Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiJjY2E0NTc5NGQ3OWQ4NTE1MGZlMGMwODcxNGQ1N2JjNiIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc4NzI0Njk1fQ.YpA5zl5bC9soqVhcLkjmF9JQSvWaz5SNI6S5RD4Vwlvc3MSb2OfYhkss6gNzz0xwovH8htamS5-NmjpcooIrYtDPerRj02TQd39Fyl8m7p9RsK99wVeiXUiC1ToUMbnkmNkWAafSNQ4uufkKcA4bIBlH716oE2iPbXq_ly3pKR6-AqPow2u0IyjCt5wCsgae1U5TIi6fdCLx8drp2SbDFA8IfZEpwCRrZptHyPsaB9ThRqb8uPGvNhp-MyJ2HwssoEHMTFpMfS9HJO__PtUkKb9YbJZPHQ1pXwys5IGJK3qdGKMKrU5LzDHNGyvH5dLjBo46rog7e3Mltkt8SDZFBg Download .mp4 (111.64 MB) Help with .mp4 files Video/cms/asset/ea7557b7-400e-4dd5-bd70-6291b79250eb/mmc2.mp3Loading ... Download .mp3 (21.33 MB) Help with .mp3 files Audio Download .pdf (.04 MB) Help with pdf files Audiovisual Summary Transcript

HLA class II alleles predict recurrence and pattern of failure in early-stage melanoma patients

8503 Background: Prior reports have suggested a link between specific HLA class II alleles, including HLA-DRB1*1101, and melanoma recurrence. We therefore investigated the relationship between HLA class II alleles and clinical outcome in a large population of patients who presented with localized melanoma. Methods: HLA class II alleles were determined by typing of genomic DNA from patients who presented with localized melanoma (AJCC stage IA-IIC). Patients found to have occult regional disease by sentinel node biopsy were excluded. Log-rank and Cox analysis of outcome versus standard prognostic factors and common HLA class II alleles (=5% of the population) was performed. Results: 1,241 patients underwent HLA typing. The median primary tumor thickness was 1.1 mm, 16% were ulcerated, and the median follow-up was 56 months. Tumor thickness, ulceration, and Clark level were independent predictors of recurrence. The HLA class II allele HLA-DRB1*1101 (11% of the population) independently predicted a higher risk of recurrence [hazard ratio (HR) 2.04, P=0.004] while HLA-DRB1*0401 (20% of the population) predicted a lower risk of recurrence (HR 0.42, P=0.004). HLA- DRB1*1101 was a particularly strong predictor of recurrence in stage I patients (HR 2.73, P&lt;0.0001). Among patients who recurred, HLA- DRB1*1101 was an independent predictor of local-regional vs. distant recurrence (HR 2.7, P=0.007), and was more common in those whose first recurrence was isolated to the regional nodal basin, compared to those whose first recurrence was elsewhere or in multiple locations (24% HLA-DRB1*1101-positive vs. 14%, P&lt;0.009). Conclusions: These results confirm that HLA-DRB1*1101 is a genetic marker of increased risk of melanoma recurrence, while HLA-DRB1*0401 is a marker of decreased risk of recurrence. HLA-DRB1*1101 is a particularly strong marker among the group of patients predicted clinically to be at the lowest overall risk for recurrence, and independently predicts pattern of recurrence (regional nodal failure). This information is of value in the development of surveillance strategies for melanoma patients, as well as the selection, stratification and randomization of early-stage melanoma patients for clinical trials. No significant financial relationships to disclose.

A phase III randomized trial of adjuvant biochemotherapy (BC) versus interferon-α-2b (IFN) in patients (pts) with high risk for melanoma recurrence

8003 Background: High-dose IFN (HDI) is associated with significant toxicity, and its clinical benefit as an adjuvant therapy for melanoma has been often debated. BC is associated with higher response rates than other regimens, but it has never been tested in an adjuvant setting. Methods: We conducted a prospective randomized phase III study comparing the clinical benefit of IFN and BC in pts who had undergone lymphadenectomy within 56 days for melanoma metastatic to regional lymph nodes. Pts were randomized to receive BC (Cisplatin 20 mg/m2 IV [d1–4]; Vinblastine 1.5 mg/m2 IV [d1–4]; DTIC 800 mg/m2 IV [d1]; IFN 5 MU/m2 SQ [d1–5]; IL-2 9 MU/m2 continuous IV infusion [d1–4] every 3 wks for 4 courses) or IFN, and those who were randomized to IFN were further randomized to either HDI (20 MU/m2 IV for 5 d/week for 4 wks and 10 MU/m2 SQ 3 times a wk for 48 wks) or intermediate-dose IFN (IDI) (10 MU/m2 SQ 3 times a wk for 1 year). The primary end points were overall survival (OS) and relapse-free survival (RFS). Using 80% power and 5% significance level, 200 pts would be required to detect the difference in median RFS of 18 vs. 36 months and in OS of 40 vs. 80 months between IFN and BC groups. Results: An interim analysis was performed because of slow accrual. 138 pts were enrolled between 1995 and 2003, with 71, 33 and 33 in the BC, HDI and IDI group, respectively. There were no significant differences in both RFS and OS between HDI and IDI groups. With median follow up of 49.3 months, neither the BC or IFN had reached the median RFS and OS. Log-rank test was used to compare RFS (p=0.96) and OS (p=0.52) between 2 groups. RFS and OS data are presented below. Pts in the BC arm had more grade 3–4 fatigue, nausea, anorexia, capillary leak syndrome, diarrhea and myelosuppression. Conclusions: There were no significant differences in both OS and RFS between the BC and IFN groups. This interim analysis supports terminating this trial before achieving the specified target for patient accrual. Supported in part by Schering-Plough. [Table: see text] [Table: see text]

Outcome of patients with melanoma and histologically negative sentinel lymph nodes.

Patients with melanoma and histologically negative sentinel lymph nodes identified by lymphatic mapping have a very good prognosis. Cohort study with follow-up information obtained from medical records and telephone interviews. Of all patients with cutaneous melanoma who underwent intraoperative sentinel lymph node mapping between November 15, 1993, and April 18, 1997, at the Massachusetts General Hospital, Boston, 89 were found to have no evidence of melanoma in their sentinel nodes. Forty-six lesions (51%) were on an extremity and 44 (49%) were of axial location. The median tumor thickness was 1.8 mm (range, 0.36-12.0 mm) and 11 tumors (12%) were ulcerated. Patients underwent intraoperative sentinel lymph node mapping with lymphazurin and radiolabeled sulfur colloid. Sentinel lymph nodes were analyzed by standard hematoxylin-eosin staining. Only 2 patients received adjuvant therapy following wide excision of the primary lesion. Site of initial recurrence and time to initial recurrence. The median follow-up for all patients was 23 months (range, 2-54 months). Eleven patients (12%) developed melanoma recurrences, and 78 (88%) patients remain disease free. Regional lymph nodes were the initial site of recurrence in 7 (8%) of 89 patients, and 7 (7%) of 106 mapped basins. Four patients had recurrence without involvement of regional lymph nodes: 2 with distant metastases and 2 with in transit metastases. The median time to recurrence was 12 months (range, 2-35 months). Sentinel lymph nodes were reanalyzed using serial sections and immunoperoxidase stains in 7 patients with recurrence and metastatic melanoma was identified in 3 (43%). The risk for melanoma recurrence is relatively low in patients with histologically negative sentinel nodes identified by lymphatic mapping. Longer follow-up will improve our understanding of the prognostic value of this procedure.