ORCID Profile
0000-0002-3262-6935
Current Organisations
Melanoma Institute Australia
,
University of Sydney
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Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.C.6489283.V2
Abstract: Abstract The response rates upon neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma are higher as compared to stage IV disease. Given that successful ICB depends on systemic immune response, we hypothesized that systemic immune suppression might be a mechanism responsible for lower response rates in late-stage disease, and also potentially with disease recurrence in early-stage disease. Plasma and serum s les of cohorts of melanoma patients were analyzed for circulating proteins using mass spectrometry proteomic profiling and Olink proteomic assay. A cohort of paired s les of patients with stage III that progressed to stage IV disease (n=64) was used to identify markers associated with higher tumor burden. Baseline patient s les from the OpACIN-neo study (n=83) and PRADO study (n=49 NCT02977052) were used as two independent cohorts to analyze whether the potential identified markers are also associated with disease recurrence after neoadjuvant ICB therapy. When comparing baseline proteins overlapping between patients with progressive disease and patients with recurrent disease, we found leucine-rich alpha-2-glycoprotein 1 (LRG1) to be associated with worse prognosis. Especially non-responder patients to neoadjuvant ICB (OpACIN-neo) with high LRG1 expression had a poor outcome with an estimated 36-month event-free survival of 14% as compared to 83% for non-responders with a low LRG1 expression (P = 0.014). This finding was validated in an independent cohort (P = 0.0021). LRG1 can be used as a biomarker to identify patients with high risk for disease progression and recurrence, and might be a target to be combined with neoadjuvant ICB. /
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.22665684.V1
Abstract: Table S3 shows the patient characteristics PRADO
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2010
Publisher: American Association for Cancer Research (AACR)
Date: 28-03-2023
DOI: 10.1158/2767-9764.C.6489283.V1
Abstract: Abstract The response rates upon neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma are higher as compared to stage IV disease. Given that successful ICB depends on systemic immune response, we hypothesized that systemic immune suppression might be a mechanism responsible for lower response rates in late-stage disease, and also potentially with disease recurrence in early-stage disease. Plasma and serum s les of cohorts of melanoma patients were analyzed for circulating proteins using mass spectrometry proteomic profiling and Olink proteomic assay. A cohort of paired s les of patients with stage III that progressed to stage IV disease (n=64) was used to identify markers associated with higher tumor burden. Baseline patient s les from the OpACIN-neo study (n=83) and PRADO study (n=49 NCT02977052) were used as two independent cohorts to analyze whether the potential identified markers are also associated with disease recurrence after neoadjuvant ICB therapy. When comparing baseline proteins overlapping between patients with progressive disease and patients with recurrent disease, we found leucine-rich alpha-2-glycoprotein 1 (LRG1) to be associated with worse prognosis. Especially non-responder patients to neoadjuvant ICB (OpACIN-neo) with high LRG1 expression had a poor outcome with an estimated 36-month event-free survival of 14% as compared to 83% for non-responders with a low LRG1 expression (P = 0.014). This finding was validated in an independent cohort (P = 0.0021). LRG1 can be used as a biomarker to identify patients with high risk for disease progression and recurrence, and might be a target to be combined with neoadjuvant ICB. /
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.EJCA.2018.02.022
Abstract: In light of the evolving landscape of adjuvant therapy in melanoma and the recently confirmed absent survival benefit of completion lymph node dissection (CLND), it becomes important to explore possible consequences of omitting CLND, and whether it is possible to adequately stratify positive sentinel node (SN) patients solely based on information retrieved from the melanoma up to the sentinel lymph node biopsy (SLNB). A retrospective cohort from nine European Organization for Research and Treatment of Cancer Melanoma Group centres was used. Patients were staged based on SLNB and CLND result according to the American Joint Committee on Cancer (AJCC) criteria and stratified by ulceration and SN tumour burden. These were incorporated in Cox regression models. Predictive ability was assessed using Harrell's concordance index (c-index) and the Akaike information criterion (AIC). In total, 1015 patients were eligible. CLND led to upstaging in N-category in 19% and in AJCC stage in 5-6%. The model incorporating only ulceration and SN tumour burden performed equally well as the model incorporating substages after CLND. The model incorporating substages based on SLNB had the lowest predictive ability. Stratifying by ulceration and SN tumour burden resulted in four positive SN groups from which low-, intermediate- and high-risk prognostic classes could be derived. Adequate stratification of positive SN patients was possible based on ulceration and SN tumour burden category. The identification of low-, intermediate- and high-risk patients could guide adjuvant therapy in clinical practice. Omitting CLND seems to have little consequences.
Publisher: American Association for Cancer Research (AACR)
Date: 28-03-2023
DOI: 10.1158/2767-9764.22348738.V1
Abstract: Figure S4 shows the serum analysis using Olink proteomic assay
Publisher: American Association for Cancer Research (AACR)
Date: 28-03-2023
DOI: 10.1158/2767-9764.22348744.V1
Abstract: Figure S2 shows a flowchart of patients PRADO study
Publisher: Wiley
Date: 20-03-2019
DOI: 10.1002/IJC.32229
Publisher: Springer Science and Business Media LLC
Date: 17-11-2009
Publisher: Wiley
Date: 07-02-2017
DOI: 10.1002/IJC.30607
Abstract: In the 7
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2018
Publisher: Wiley
Date: 14-02-2019
DOI: 10.1002/HED.25670
Abstract: Parotidectomy in melanoma of the coronal scalp and face with clinically involved cervical lymph node metastasis is based on predicted cervical lymphatic drainage described by O'Brien. In total, 40 parotidectomies with en bloc therapeutic neck dissection were retrospectively analyzed. Lymphatic spread of melanoma to the parotid lymph nodes was observed in 10 of 40 specimens (25%). Eight of the 10 parotid-positive patients developed a recurrence vs 17 of the 30 parotid-negative patients (P = 0.28). There were no differences in overall survival, melanoma-specific survival, and disease-free survival between the parotid-positive and parotid-negative patients. Although in this series no survival differences were found, parotidectomy still merits a sustained role in therapeutic neck dissection procedures to improve regional control and to prevent facial nerve damage after surgery for a second relapse from occult metastases in the parotid.
Publisher: American Association for Cancer Research (AACR)
Date: 06-2010
DOI: 10.1158/1055-9965.EPI-09-1267
Abstract: Background: Reliable population-based incidence and survival data on extracutaneous melanoma (ECM) are sparse. Methods: Incidence data (1989-2006) from the Netherlands Cancer Registry were combined with vital status on January 1, 2008. Age-adjusted annual incidence rates were calculated by direct standardization, and the estimated annual percentage change was estimated to detect changing trends in incidence. Additionally, we carried out cohort-based relative survival analysis. Results: Ocular melanomas were the most common ECM subsite with European standardized incidence rates (ESR) of 10.7 and 8.2 per 1,000,000 person-years for males and females, respectively. In comparison, for cutaneous melanoma (CM), the ESRs for men and women were 122 and 155 per million person-years, respectively. No statistically significant trends in the incidence of ECM were detected, whereas an annual increase of 4.4% for men and 3.6% for women was detected in the incidence of CM. Relative survival for ECM was poor, but differed largely between anatomic subtypes ranging from a 5-year relative survival of 74% for ocular melanomas to 15% for certain subsites of mucosal melanomas. Conclusions: Of all ECM subsites, ocular melanomas had the highest incidence and the best survival. Mucosal melanomas were the second most frequent subsite of ECM. Five-year relative survival for all ECM subtypes was worse if compared with CM. No statistically significant trends in the incidence of (subsites of) ECM were determined. Impact: This study gives insight into the relative sizes of the different subgroups of ECM as well as an estimate of 5-year survival, which varies substantially by subsite. Cancer Epidemiol Biomarkers Prev 19(6) 1453–9. ©2010 AACR.
Publisher: Oxford University Press (OUP)
Date: 11-10-2018
DOI: 10.1002/BJS.10995
Abstract: Patients with melanoma and negative sentinel nodes (SNs) have varying outcomes, dependent on several prognostic factors. Considering all these factors in a prediction model might aid in identifying patients who could benefit from a personalized treatment strategy. The objective was to construct and validate a nomogram for recurrence and melanoma-specific mortality (MSM) in patients with melanoma and negative SNs. A total of 3220 patients with negative SNs were identified from a cohort of 4124 patients from four EORTC Melanoma Group centres who underwent sentinel lymph node biopsy. Prognostic factors for recurrence and MSM were studied with Cox regression analysis. Significant factors were incorporated in the models. Performance was assessed by discrimination (c-index) and calibration in cross-validation across the four centres. A nomogram was developed for graphical presentation. There were 3180 eligible patients. The final prediction model for recurrence and the calibrated model for MSM included three independent prognostic factors: ulceration, anatomical location and Breslow thickness. The c-index was 0·74 for recurrence and 0·76 for the calibrated MSM model. Cross-validation across the four centres showed reasonable model performance. A nomogram was developed based on these models. One-third of the patients had a 5-year recurrence probability of 8·2 per cent or less, and one-third had a recurrence probability of 23·0 per cent or more. A nomogram for predicting recurrence and MSM in patients with melanoma and negative SNs was constructed and validated. It could provide personalized estimates useful for tailoring surveillance strategies (reduce or increase intensity), and selection of patients for adjuvant therapy or clinical trials.
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.22665690.V1
Abstract: Table S1 shows an overview evaluated immuno-oncology markers by Olink proteomic assay
Publisher: Elsevier BV
Date: 10-2006
Abstract: As only about 20% of sentinel node (SN) positive melanoma patients have additional non-SN lymph node involvement in the Completion Lymph Node Dissection (CLND) specimen, we tried to identify a SN positive patient group, which can be spared CLND. Micro anatomic analyses of metastatic SNs were performed to identify patient/tumor and/or SN factors predicting additional non-SN positivity as well as disease-free and overall survival. SN positivity was found in 77 of 262 stage I/II patients, included into a prospective database (10/97-5/04). Of 74 patients pathology material was available for re-evaluation. Micro anatomic analyses categorized topography of SN-metastases, Starz classification and amount of SN tumor burden. Additional non-SN positivity, DFS, OS and was calculated for all analyses. Mean Breslow thickness was 3.5 mm (0.8-12.0) mean FU was 35 (6-81) months. There was no additional non-SN positivity for SN-micrometastases <0.1 mm. Topography of SN involvement had no impact on OS. Estimated 5-year OS rates for the different groups of 1.0 mm SN tumor burden were 100%, 63% and 35% respectively. Distant metastases were exceedingly rare (1/16 = 6.3%) in <0.1 mm SN-positive patients. On multivariate analysis the SN tumor burden was the most important prognostic factor for DFS (P = 0.005) and OS (P = 0.03). Distant metastasis-free survival was identical (91%) to the 5-yr OS of SN negative patients, the estimated 5-yr OS was 100% for these patients and additional non-SN positivity was not observed. Therefore, our data suggest that patients with sub-micrometastases (<0.1 mm) in the SN may be judged as SN negative, as non-stage III, and are highly unlikely to benefit from CLND, which we no longer recommend.
Publisher: Oxford University Press (OUP)
Date: 18-03-2019
DOI: 10.1002/BJS.11168
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.C.6489283.V3
Abstract: The response rates upon neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma are higher as compared with stage IV disease. Given that successful ICB depends on systemic immune response, we hypothesized that systemic immune suppression might be a mechanism responsible for lower response rates in late-stage disease, and also potentially with disease recurrence in early-stage disease. Plasma and serum s les of cohorts of patients with melanoma were analyzed for circulating proteins using mass spectrometry proteomic profiling and Olink proteomic assay. A cohort of paired s les of patients with stage III that progressed to stage IV disease ( i n /i = 64) was used to identify markers associated with higher tumor burden. Baseline patient s les from the OpACIN-neo study ( i n /i = 83) and PRADO study ( i n /i = 49 NCT02977052) were used as two independent cohorts to analyze whether the potential identified markers are also associated with disease recurrence after neoadjuvant ICB therapy. When comparing baseline proteins overlapping between patients with progressive disease and patients with recurrent disease, we found leucine-rich alpha-2-glycoprotein 1 (LRG1) to be associated with worse prognosis. Especially nonresponder patients to neoadjuvant ICB (OpACIN-neo) with high LRG1 expression had a poor outcome with an estimated 36-month event-free survival of 14% as compared with 83% for nonresponders with a low LRG1 expression ( i P /i = 0.014). This finding was validated in an independent cohort ( i P /i = 0.0021). LRG1 can be used as a biomarker to identify patients with high risk for disease progression and recurrence, and might be a target to be combined with neoadjuvant ICB. Significance: LRG1 could serve as a potential target and as a biomarker to identify patients with high risk for disease recurrence, and consequently benefit from additional therapies and intensive follow-up. /
Publisher: Wiley
Date: 15-01-2019
DOI: 10.1002/CNCR.31924
Abstract: Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue sarcoma for which clinical examination up to 10 years is recommended. The objective of this study was to identify prognostic factors for recurrences and metastases that can be used to evaluate the validity of follow-up schedules after treatment for DFSP. Patients with DFSP who received treatment between 1991 and 2016 at 3 tertiary centers were included. Cox regression analyses were conducted to identify variables associated with the primary endpoints. In total 357 patients were included, with a median age of 38 years (age range, 2-87 years) and a median follow-up of 60 months (interquartile range, 24-115 months). Eighty-one patients developed recurrent disease (22.7%), and the median time to recurrence was 55.5 months (interquartile range, 20-90 months). Of these, 50 tumors (61.7%) were identified by patient self-examination, whereas 3 recurrences (3.7%) were identified at clinical surveillance. For the remaining 28 tumors, no information was available on how the recurrences were identified (34.6%). Fibrosarcomatous change (hazard ratio, 21.865 P < .001), and positive resection margins (hazard ratio, 14.645 P < .001), were independent prognostic factors for recurrence. Metastases occurred in 4 patients (1.1%). All tumors were identified by imaging after patients presented with symptomatic metastases. Fibrosarcomatous change (P 5 cm (P = .014) were associated with the development of metastases. Disease recurrence after resection of DFSP remains a significant issue, whereas metastases are uncommon. The majority of recurrences are identified by patient self-examination. Consideration should be given to in idualized follow-up schedules based on risk factors for recurrences and metastases.
Publisher: Springer Science and Business Media LLC
Date: 28-05-2014
Publisher: Elsevier BV
Date: 02-2017
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.EJSO.2018.09.001
Abstract: The purpose of the study was to investigate the time dependent dynamics of wound complications and local control after preoperative radiotherapy (RT) in Extremity Soft Tissue Sarcomas (ESTS). In this retrospective cohort study, all patients treated for an extremity sarcoma with pre-operative radiotherapy followed by surgery were identified from a prospectively maintained database. A wound complication (WC) was defined as any local complication of the surgical area requiring intervention, hospital readmission or significant extension of the initial admission period. A total of 191 preoperatively irradiated ESTS patients were included in this study. WC was seen in 31% of the patients (n = 60). WC started after a median time of 25 days from surgery, with a median duration of 76 days. Adiposity, smoking and a lower extremity or superficial tumor localization were significantly correlated with an increased WC rate. Risk factors for a duration of WC ≥ 120 days are early development of WC (≤21 days after surgery) and smoking. Local control rates after 1, 3 and 5 years were 99%, 93% and 93%, respectively. Approximately one-third of patients selected for preoperative RT develops a WC, typically in smoking, adipose patients with superficial tumor localizations in the lower extremity. Based upon the well-established superior long-term functional outcome, maintained excellent local control rates and the temporary nature of the WC issue, preoperative RT remains our preferred treatment. Although, in patients at high risk of WC, post-operative RT might be considered.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22546891
Abstract: Figure S1 shows a flowchart of patients OpACIN-neo study
Publisher: Elsevier BV
Date: 04-2016
Publisher: Springer Science and Business Media LLC
Date: 08-04-2014
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.22665696
Abstract: Figure S5 shows that complement factor B (CFB), component 7 (C7) and alpha-1B-glycoportein (A1BG) expression are increased upon melanoma progression and recurrence.
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.22665693
Abstract: Figure S6 shows that neutrophil count and neutrophil-to-lymphocyte ratio (NLR) are not associated with recurrence in non-responding patients
Publisher: Springer Science and Business Media LLC
Date: 14-07-2017
DOI: 10.1007/S10689-017-0024-8
Abstract: Gastrointestinal stromal tumors (GISTs) occur mostly sporadically. GISTs associated with a familial syndrome are very rare and are mostly wild type for KIT and platelet-derived growth factor alpha (PDGFRA). To date 35 kindreds and 8 in iduals have been described with GISTs associated with germline KIT mutations. This is the third family described with a germline p.Trp557Arg mutation in exon 11 of the KIT gene. The effect of imatinib in patients harboring a germline KIT mutation has been rarely described. Moreover, in some studies imatinib treatment was withheld considering the lack of evidence for efficacy of this treatment in GIST patients harboring a germline KIT mutation. This paper describes a 52-year old patient with a de novo germline p.Trp557Arg mutation with multiple GISTs throughout the gastrointestinal tract and cutaneous hyperpigmentation. Imatinib treatment showed long-term regression of the GISTs and evident pathological response was seen after resection. Remarkably, the hyperpigmentation of the skin also diminished during imatinib treatment. Genetic screening of the family revealed the same mutation in two daughters, both with similar cutaneous hyperpigmentation. One daughter, aged 23, was diagnosed with multiple small intestine GISTs, which were resected. She was treated with adjuvant imatinib which prompted rapid regression of the cutaneous hyperpigmentation. Imatinib treatment in GIST patients harboring a germline KIT mutation shows favorable and long-term responses in both the tumor and the phenotypical hyperpigmentation.
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.22665690
Abstract: Table S1 shows an overview evaluated immuno-oncology markers by Olink proteomic assay
Publisher: American Roentgen Ray Society
Date: 12-2010
DOI: 10.2214/AJR.10.4833
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.JAAD.2019.01.042
Abstract: Merkel cell carcinoma (MCC) is a rare and potentially lethal skin cancer. MCC is known for its potential rapid growth and its propensity to metastasize. To describe the incidence, treatment, and survival of MCC in a population-based setting. All MCCs diagnosed in The Netherlands between 1993 and 2016 were selected from the Netherlands Cancer Registry. Patient and tumor characteristics, therapy, and vital status were obtained. Cox proportional hazards were computed, and relative survival analyses were performed. Our cohort included 1977 patients with MCC. Incidence increased from 0.17 per 100,000 person-years in 1993 to 0.59 per 100,000 in 2016. The mean age at diagnosis was 75.5. Most MCCs (59.8%) were treated with surgery alone. Relative 5-year survival was low (63.0%) and did not improve. Mortality was higher among males (hazard ratio [HR], 1.24 95% confidence interval [CI], 1.11-1.39), higher age (HR, 1.07 95% CI, 1.06-1.07), and nodal (HR, 1.26 95% CI, 1.08-1.48) and distant spread of disease (HR, 2.44 95% CI, 1.99-2.99). We lacked data on cause of death, comorbidity, and pathologic margins, which may have led to misinterpretation of the data. This study shows continuously increasing incidence rates of MCC in The Netherlands. Survival after a diagnosis of MCC remained low. Our results emphasize the need for implementation of new therapies.
Publisher: Springer International Publishing
Date: 2018
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.22665699
Abstract: Figure S4 shows the serum analysis using Olink proteomic assay
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22546885
Abstract: Figure S3 shows that SAA1, CRP and LDHB are associated with melanoma disease progression.
Publisher: Elsevier BV
Date: 11-2017
Publisher: Elsevier BV
Date: 02-2018
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22546882
Abstract: Figure S4 shows the serum analysis using Olink proteomic assay
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22546888
Abstract: Figure S2 shows a flowchart of patients PRADO study
Publisher: Elsevier BV
Date: 03-2023
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.EJSO.2016.05.012
Abstract: Worldwide, sentinel node biopsy (SNB) is the recommended staging procedure for stage I/II melanoma. Most melanoma guidelines recommend re-excision plus SNB as soon as possible after primary excision. To date, there is no evidence to support this timeframe. To determine melanoma specific survival (MSS) for time intervals between excisional biopsy and SNB in SNB positive patients. Between 1993 and 2008, 1080 patients were diagnosed with a positive SNB in nine Melanoma Group centers. We selected 1015 patients (94%) with known excisional biopsy date. Time interval was calculated from primary excision until SNB. Kaplan-Meier estimated MSS was calculated for different cutoff values. Multivariable analysis was performed to correct for known prognostic factors. Median age was 51 years (Inter Quartile Range (IQR) 40-62 years), 535 (53%) were men, 603 (59%) primary tumors were located on extremities. Median Breslow thickness was 3.00 mm (IQR 1.90-4.80 mm), 442 (44%) were ulcerated. Median follow-up was 36 months (IQR 20-62 months). Median time interval was 47 days (IQR 32-63 days). Median Breslow thickness was equal for both <47 days and ≥47 days interval: 3.00 mm (1.90-5.00 mm) vs 3.00 mm (1.90-4.43 mm) (p = 0.402). Sentinel node tumor burden was significantly higher in patients operated ≥47 days (p = 0.005). Univariate survival was not significantly different for median time interval. Multivariable analysis confirmed that time interval was no independent prognostic factor for MSS. Time interval from primary melanoma excision until SNB was no prognostic factor for MSS in this SNB positive cohort. This information can be used to counsel patients.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2018
Publisher: American Association for Cancer Research (AACR)
Date: 28-03-2023
DOI: 10.1158/2767-9764.22348726.V1
Abstract: Table S2 shows the patient characteristics OpACIN-neo
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2018
Publisher: MDPI AG
Date: 07-05-2020
Abstract: Opportunities for surgical treatment in metastatic melanoma patients have re-emerged due to the development of novel systemic therapeutics over the past decade. The aim of this study is to present data on outcomes of surgery in patients with unresectable stage IIIC and IV melanoma, who have previously been treated with immunotherapy or targeted therapy. Data was extracted from the Dutch Melanoma Treatment Registry (DMTR) on 154 patients obtaining disease control to systemic therapy and undergoing subsequent surgery. Disease control was defined as a complete response (CR), which was seen in 3.2% of patients a partial response (PR), seen in 46.1% of patients or stable disease (SD), seen in 44.2% of patients. At a median follow-up of 10.0 months (interquartile range 4–22) after surgery, the median overall survival (OS) had not been reached in our cohort and median progression-free survival (PFS) was 9.0 months (95% CI 6.3–11.7). A CR or PR at first follow-up after surgery was associated with both a better OS and PFS compared to stable or progressive disease (p 0.001). We conclude that selected patients can benefit from surgery after achieving disease control with systemic therapy.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22546873
Abstract: Table S1 shows an overview evaluated immuno-oncology markers by Olink proteomic assay
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.EJCA.2010.06.003
Abstract: Sentinel node (SN) status is the most important prognostic factor for disease-free survival (DFS) and overall survival (OS) in stages I-II melanoma. We evaluated the positive sentinel node identification rate of the EORTC Melanoma Group (MG) protocol as well as its capacity to identify minimal tumour burden, according to the Rotterdam Criteria in 421 consecutive patients. Correlations between primary tumour characteristics and SN tumour burden were investigated. The same 2 pathologists worked up all SNs according to the EORTC MG protocol and tumour burden was scored according to the Rotterdam Criteria ( 1.0 mm for the largest diameter of the largest metastasis in the SN). The positive SN detection rate was 28.7% with a false negative rate of 10.4% at a median Breslow thickness of 2.1 mm. The high positive identification rate of about 30% of the EORTC MG protocol has been confirmed in this study. The protocol is sensitive and identifies submicrometastases (<0.1 mm) in a high percentage (18%). The variables SN tumour load, non-SN (NSN) status and ulceration of the primary were independent prognostic factors for DFS and OS in the multivariate analysis. At a median follow-up time of 4.3 years patients with minimal tumour burden (<0.1 mm) had a 5 year OS rate of 91%, virtually identical to 90% for SN-negative patients. The NSN positivity rate of 0% in these patients indicates that they may be spared a completion lymph node dissection (CLND) and its morbidity.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22546870
Abstract: Table S2 shows the patient characteristics OpACIN-neo
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22546867.V1
Abstract: Table S3 shows the patient characteristics PRADO
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22546879
Abstract: Figure S5 shows that complement factor B (CFB), component 7 (C7) and alpha-1B-glycoportein (A1BG) expression are increased upon melanoma progression and recurrence.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22546876
Abstract: Figure S6 shows that neutrophil count and neutrophil-to-lymphocyte ratio (NLR) are not associated with recurrence in non-responding patients
Publisher: American Association for Cancer Research (AACR)
Date: 28-03-2023
DOI: 10.1158/2767-9764.22348732.V1
Abstract: Figure S6 shows that neutrophil count and neutrophil-to-lymphocyte ratio (NLR) are not associated with recurrence in non-responding patients
Publisher: Oxford University Press (OUP)
Date: 07-12-2011
DOI: 10.1093/JNCI/DJR381
Abstract: Fine needle aspiration cytology (FNAC) is usually used to evaluate palpable nodes in patients with melanoma. The goal of our study is to review the sensitivity and specificity of this technique when applied to palpable but also to nonpalpable nodes. FNAC was performed during 1984-2007 in 1279 patients with suspicious lesions and/or lymph nodes. Indications for biopsy included increased size and/or palpability of nodes or abnormal ultrasound findings such as increased perfusion or focal lesions within the lymph nodes. The sensitivity, specificity, and positive and negative predictive values of FNACs guided by palpation or ultrasound were calculated for all patients and for subgroups of patients with palpable nodes or nonpalpable but sonomorphologically suspicious nodes. A total of 2446 FNACs were performed in 1279 melanoma patients, of which 2011 (82.2%) FNACs had clinically or histologically confirmed results. Increased size and/or palpability of nodes was observed in 376 (29.4%) of 1279 patients, and abnormal ultrasound findings occurred for 903 (70.6%), indicating that a biopsy was needed. FNACs guided by palpation had sensitivity, specificity, and positive and negative predictive values similar to that of FNACs guided by ultrasound (sensitivity = 98.4% vs 97.2%, specificity = 100% vs 99.8%, positive predictive value = 100% vs 99.9%, and negative predictive value = 95.2% vs 96.4%, for palpation-guided FNACs vs ultrasound-guided FNACs, respectively). Results did not differ between patients with the palpable nodes and patients with nonpalpable but sonomorphologically suspicious nodes. Ultrasound-guided FNAC of suspicious lymph nodes and lesions in melanoma patients has a high sensitivity and specificity, and FNAC should not be limited to palpable nodes. FNAC of normal-sized nodes and/or lymph nodes with abnormal ultrasound findings can be used to identify early metastatic disease.
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.EJSO.2017.07.015
Abstract: Merkel cell carcinoma (MCC) is a rare and potentially aggressive neuroendocrine tumor of the skin, with a propensity for locoregional metastases. In two expert referral centers, isolated limb perfusion (ILP) is used to obtain locoregional control in selected locoregionally advanced MCC patients. This study describes our experience. Patients who underwent ILP for MCC were analyzed. ILP was performed with melphalan and tumor necrosis factor (TNF) combination therapy. Depending on the institution, either a normothermic or a hyperthermic temperature regimen was used. Baseline characteristics, toxicity data, locoregional progression-free survival (LPFS) and overall survival (OS) were assessed. Four males and 6 females with a median age of 78 years (IQR 61-84 years) were included. Four patients underwent ILP for upper extremity disease and 6 for lower extremity disease. All patients received combination therapy with Melphalan and TNF, one patient with the addition of interferon-gamma. No signs of systemic toxicity were present post-ILP. Severe locoregional toxicity (compartment syndrome) occurred in 1 patient and 1 elderly patient with extensive atherosclerosis had to undergo transfemoral utation due to critical ischemia. Eight patients could be included for response evaluation. The overall response rate (ORR) was 87.5% with a complete response (CR) rate of 62.5%. Two long-term responses of 53 months and 71 months were observed. Median LPFS was 5 months and median OS was 54 months. ILP shows a high CR rate that can be durable. Therefore, ILP should be considered an effective treatment modality for locally advanced MCC.
Publisher: Georg Thieme Verlag KG
Date: 24-04-2014
Abstract: Ultrasound-guided fine needle aspiration cytology (US-FNAC) prior to surgical excision of a sentinel lymph node (SLN) is a new microinvasive approach for detecting micrometastases in melanoma patients. The aim of the current prospective study was to determine the sensitivity and specificity of the method and to define new diagnostic generally applicable ultrasound criteria. In 800 consecutive patients suffering from malignant melanoma of stage I/II, the SNs were examined sonographically after lymphoscintigraphy. US-FNAC was performed in all suspicious lesions in 302 patients. All patients underwent surgical removal of the SLN. The final histopathology and sonographic findings were correlated. After a follow-up of 37 months and a given median tumor thickness of 1.6 mm in our cohort, 21 % of the patients had a positive SLN in the histologic examination. We calculated a sensitivity and specificity of US-FNAC of 56 % and 99 %, respectively. The positive and negative predictive values were 92 % and 89 %, respectively. The highest positive predictive values were achieved using the ultrasound criterion of peripheral perfusion in power mode. The sensitivity of US-FNAC increased in parallel with an increasing pT stage of the primary tumor and increasing size of the largest diameter of the involved SN nest. Our prospective study shows the impact of ultrasound-guided FNAC in the staging of the SN prior to a planned SLNB. It proved to be an additional, cost-effective diagnostic tool that enhances the discriminatory power for the indication to perform SLNB and spares both the patient and the surgeon a second surgical procedure. Among the tested ultrasound criteria, peripheral perfusion (PP) showed the highest sensitivity for detecting early SN.
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.22665708
Abstract: Figure S1 shows a flowchart of patients OpACIN-neo study
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-09-2011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2011
Publisher: Springer Science and Business Media LLC
Date: 19-11-2018
DOI: 10.1245/S10434-018-7038-9
Abstract: Non-sentinel node (NSN) positivity impacts the prognosis of melanoma patients however, the benefits of completion lymph node dissection in patients with positive sentinel nodes (SNs) are limited. We aimed to present a predictive nomogram for NSN positivity in melanoma patients with a positive SN biopsy. This retrospective analysis from patients who underwent SN biopsy in a Brazilian institution from 2000 to 2015 was used for the construction and internal validation of the nomogram. This nomogram was then externally validated in a cohort of Dutch patients. The Brazilian cohort comprised 1213 patients, with a mean follow-up of 5.11 years. Breslow thickness (odds ratio [OR] 1.170, 95% confidence interval [CI] 1.043-1.314] p = 0.008), number of positive SNs (OR 1.092, 95% CI 1.034-1.153 p = 0.001), and largest diameter of the metastatic deposit (OR 3.217, 95% CI 1.551-6.674 p = 0.002) were statistically significant for NSN positivity. Internal validation was performed using a bootstrapping technique. A good performance was observed (Brier score 0.097) and an excellent power of discrimination was achieved (area under the curve [AUC] 0.822). The nomogram was then applied to the Dutch cohort, and its overall performance (Brier score 0.085), calibration (Hosmer-Lemeshow goodness-of-fit test p = 0.198), and discriminatory power (AUC 0.752, 95% CI 0.615-0.890) were all adequate. We presented a nomogram for assessing NSN probability that should not only be used for surgical considerations but also for risk stratification and clinical decisions. Internal validation has shown that this is an adequate model, while external validation increases the model's reliability and suggests that it can be globally incorporated.
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.EJSO.2016.08.007
Abstract: Sentinel node biopsy (SNB) is the most accurate staging tool for melanoma patients. The procedure is indicated especially for intermediate thickness melanoma (pT2/3). SNB can be of value in thin melanoma (>0.75 mm in thickness), with adverse prognostic factors, and in thick melanomas (pT4), although T4 patients are already at high risk of disease progression. Completion lymph node dissection (CLND) after positive SN yields additional non-sentinel lymph nodes (NSNs) in 20% of cases. Several factors are predictive for NSN positivity, such as primary tumor characteristics and SN tumor burden. The most used and best validated tumor burden parameter is the maximum diameter of the SN metastasis. Others are the microanatomic location of the metastasis in the SN and tumor penetrative depth. These parameters might be used to stratify risk and select patients for either adjuvant treatment trials (diameter >1 mm), or refraining from treatment (minimal SN tumor burden). There is no undisputed evidence for an overall treatment-related benefit for SNB-based management, although benefit has been suggested for a subgroup of node positive patients with intermediate-thickness melanomas. The DeCOG-SLT study failed to demonstrate a survival benefit for CLND after a positive SN. Results of the MSLT-2 and EORTC 1208 (MINITUB) trial, that both assess the role of CLND in SN positive patients have to be awaited. There might be a role for US-FNAC in melanoma staging. New SN visualization techniques can help allow easier identification of SNs in complex areas, shorten operation time and possibly reduce the amount of false-negative SNBs.
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.22665705
Abstract: Figure S2 shows a flowchart of patients PRADO study
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-10-2009
Abstract: Sentinel node (SN) status is the most important prognostic factor for overall survival (OS) for patients with stage I/II melanoma, and the role of the SN procedure as a staging procedure has long been established. However, a less invasive procedure, such as ultrasound (US) -guided fine-needle aspiration cytology (FNAC), would be preferred. The aim of this study was to evaluate the accuracy of US-guided FNAC and compare the results with histology after SN surgery was performed in all patients. Four hundred consecutive patients who underwent lymphoscintigraphy subsequently underwent a US examination before the SN procedure. When the US examination showed a suspicious or malignant pattern, patients underwent an FNAC. Median Breslow thickness was 1.8 mm mean follow-up was 42 months (range, 4 to 82 months). We considered the US-guided FNAC positive if either US and/or FNAC were positive. If US was suggestive of abnormality, but FNAC was negative, the US-guided FNAC was considered negative. US-guided FNAC identified 51 (65%) of 79 SN metastases. Specificity was 99% (317 of 321), with a positive predictive value of 93% and negative predictive value of 92%. SN-positive identification rate by US-guided FNAC increased from 40% in stage pT1a/b disease to 79% in stage pT4a/b disease. US-guided FNAC detected SN tumors more than 1.0 mm in 86% of cases, SN tumors of 0.1 to 1.0 mm in 46% of cases, and SN tumors less than 0.1 mm in 23% of cases. Estimated 5-year OS rates were 92% for patients with negative US-guided FNAC results and 51% for patients with positive results. US-guided FNAC of SNs is highly accurate. Up to 65% of the patients with SN-positive results in our institution could have been spared an SN procedure.
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.22665702
Abstract: Figure S3 shows that SAA1, CRP and LDHB are associated with melanoma disease progression.
Publisher: Springer Science and Business Media LLC
Date: 20-11-2017
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.EJCA.2014.05.027
Abstract: Ultrasound guided fine needle aspiration cytology (US-guided FNAC) can identify microscopic involvement of lymph nodes as in breast cancer and avoid surgical sentinel node (SN). Its utility in melanoma patients is controversial and subject of this study. Between 2001 and 2010 over 1000 stage I/II consecutive melanoma patients prospectively underwent US-FNAC prior to SN biopsy. All patients underwent lymphoscintigraphy prior to US-FNAC. The Berlin US morphology criteria: Peripheral perfusion (PP), loss of central echoes (LCE) and balloon shaped (BS) were registered. FNAC was performed in case of presence of any of these factors. SN tumour burden was measured according to the Rotterdam criteria. All patients underwent SN or lymph node dissection (LND) in case of positive FNAC. Mean/median Breslow thickness was 2.58/1.57 mm. Mean/median follow-up was 56/53 months (1-132). SN positivity rate was 21%. US-FNAC Sensitivity was 71% (US only) and 51% (US-FNAC). Sensitivity of US-FNAC was highest for T4 (76%) and ulcerated melanomas (63%). PP, LCE and BS had sensitivity of 69%, 24% and 24% respectively. Sensitivity of US-FNAC increased with increasing SN tumour burden. PP was an early sign of metastasis (58% in <0.1mm metastases). Threshold size of a metastasis for FNAC was 0.3mm. Five-year survival correlated to US-FNAC status (95% in negative and 59% in positive). Ultrasound guided FNAC (US-FNAC) according to the Berlin morphology criteria could correctly identify at least half of all tumour positive sentinel nodes, prior to the surgical SN procedure. Peripheral perfusion is an early sign of metastasis, which is very sensitive, but with lower positive predictive value (PPV). It is responsible for the sensitivity of the procedure. Balloon shape is a sign of advanced metastases, with lower sensitivity, but high PPV. US-FNAC sensitivity correlated with increasing T-stage, ulceration of the primary and increasing SN tumour burden. US-FNAC status accurately predicts survival.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22546873.V1
Abstract: Table S1 shows an overview evaluated immuno-oncology markers by Olink proteomic assay
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-12-2008
Abstract: This study analyzes (1) the value of tyrosinase reverse-transcriptase polymerase chain reaction (RT-PCR) of aspirates obtained by ultrasound-guided fine-needle aspiration cytology (US-FNAC) of sentinel nodes (SNs) in patients with melanoma before sentinel lymph node biopsy (SLNB) and (2) the value of RT-PCR of blood s les of all SLNB patients. Between 2001 and 2003, 127 patients with melanoma (median Breslow depth, 2.1 mm) underwent SLNB. FNAC was performed in all SNs of all patients pre- and post-SLNB. The aspirates were partly shock-frozen for RT-PCR and were partly used for standard cytology. Peripheral blood was collected at the time of SLNB and at every outpatient visit thereafter. Thirty-four (23%) of 120 SNs were positive for melanoma. SN involvement was predicted by US-FNAC with a sensitivity of 82% and a specificity of 72%. Additional tyrosinase RT-PCR revealed the same sensitivity of 82% and a specificity of 72%. At a median follow-up time of 40 months from first blood s le, peripheral-blood RT-PCR was a significant independent predictor of disease-free survival (DFS) and overall survival (OS P .001). US-FNAC is highly accurate and eliminates the need for SLNB in 16% of all SLNB patients. RT-PCR of the aspirate or excised SN does not improve sensitivity or specificity. RT-PCR of blood s les predicts DFS and OS.
Publisher: S. Karger AG
Date: 2016
DOI: 10.1159/000453592
Abstract: b i Background: /i /b How to deal with melanoma of unknown primary (MUP) origin is a debated topic in the literature. b i Objective: /i /b We performed a worldwide survey to inquire what clinical and investigational workup is performed as well as the physicians' perception of this disease. b i Methods: /i /b A questionnaire was sent via mail to clinicians involved in melanoma care from December 2015 to April 2016 using the International Dermoscopy Society website. b i Results: /i /b 119 physicians from 47 different countries answered the questionnaire. The most reported examination was skin examination followed by CT and/or PET scans. All the participants declared asking about previous excisions of skin lesions with 81% of them asking for a histopathological slide review of previous biopsies. Half of the participants checked for a possible vitiligo phenomenon that may explain regression of the primary lesion. i BRAF, cKIT, /i and i GNAQ /i mutations were screened by 32% of participants. The majority of participants (76%) applied the same treatment protocols for MUP as patients with known primary melanomas of the same AJCC stage. b i Conclusion: /i /b Strong heterogeneity was found between physicians dealing with MUP. Thus, a consensus document should be strongly encouraged.
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.C.6489283
Abstract: The response rates upon neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma are higher as compared with stage IV disease. Given that successful ICB depends on systemic immune response, we hypothesized that systemic immune suppression might be a mechanism responsible for lower response rates in late-stage disease, and also potentially with disease recurrence in early-stage disease. Plasma and serum s les of cohorts of patients with melanoma were analyzed for circulating proteins using mass spectrometry proteomic profiling and Olink proteomic assay. A cohort of paired s les of patients with stage III that progressed to stage IV disease ( i n /i = 64) was used to identify markers associated with higher tumor burden. Baseline patient s les from the OpACIN-neo study ( i n /i = 83) and PRADO study ( i n /i = 49 NCT02977052) were used as two independent cohorts to analyze whether the potential identified markers are also associated with disease recurrence after neoadjuvant ICB therapy. When comparing baseline proteins overlapping between patients with progressive disease and patients with recurrent disease, we found leucine-rich alpha-2-glycoprotein 1 (LRG1) to be associated with worse prognosis. Especially nonresponder patients to neoadjuvant ICB (OpACIN-neo) with high LRG1 expression had a poor outcome with an estimated 36-month event-free survival of 14% as compared with 83% for nonresponders with a low LRG1 expression ( i P /i = 0.014). This finding was validated in an independent cohort ( i P /i = 0.0021). LRG1 can be used as a biomarker to identify patients with high risk for disease progression and recurrence, and might be a target to be combined with neoadjuvant ICB. Significance: LRG1 could serve as a potential target and as a biomarker to identify patients with high risk for disease recurrence, and consequently benefit from additional therapies and intensive follow-up. /
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.22665705.V1
Abstract: Figure S2 shows a flowchart of patients PRADO study
Publisher: American Society of Clinical Oncology (ASCO)
Date: 05-2018
DOI: 10.1200/EDBK_200241
Abstract: In this article, we will focus on the practice-changing developments for stage III melanoma, from the use of the sentinel node (SN) biopsy to complete lymph node dissection (CLND) and upcoming adjuvant therapies. MSLT-1 (Multicenter Selective Lymphadenectomy Trial-1) was the first and only prospective randomized controlled trial to examine whether the SN biopsy has any notable melanoma-specific survival benefit (primary endpoint). MSLT-1 randomly assigned 2,001 patients to undergo either wide local excision (WLE) and an SN biopsy or WLE and nodal observation. Two prospective randomized controlled trials have examined the potential benefit for immediate CLND versus delayed CLND after sequential observation. Both the DECOG-SLT and MSLT-2 trials failed to demonstrate a notable benefit for immediate CLND therefore, sequential follow-up with ultrasonography and a delayed CLND in the case of relapse should be considered the new standard of care. The CheckMate 238 study demonstrated a notable benefit for adjuvant nivolumab in terms of 18-month relapse-free survival (RFS) rates compared with high-dose adjuvant ipilimumab. Single-agent adjuvant BRAF inhibition has been examined and failed to improve RFS. However, the COMBI-AD study did demonstrate a substantial benefit for combination BRAF and MEK inhibition for patients with BRAF-mutated resected stage IIIA to IIIC melanoma.
Publisher: Wiley
Date: 29-06-2020
DOI: 10.1002/JSO.26095
Publisher: Elsevier BV
Date: 02-2006
DOI: 10.1016/J.EJCA.2005.10.023
Abstract: Methods to work-up sentinel nodes (SN) vary considerably between institutes. This single institution study evaluated the positive SN-identification rate of the EORTC Melanoma Group (MG) protocol and investigated the prognostic value of the SN status regarding disease-free survival (DFS) and overall survival (OS) and evaluated the locoregional control after the SN procedure. Multivariate and univariate analyses using Cox's proportional hazard regression model was employed to assess the prognostic value of covariates regarding DFS and OS. The positive SN-identification rate was 29% at a median Breslow thickness of 2.00 mm and the false-negative rate was 9.4%. Breslow thickness and ulceration of the primary correlated with SN status. SN status, ulceration and site of the primary tumour correlated with DFS. SN status and ulceration of the primary correlated with OS. The in-transit metastasis rate correlated with SN-positivity, Breslow thickness and ulceration. Projected 3-year OS was 95% in SN-negative and 74% in SN-positive patients. Transhilar bivalving of the SN with step sections from the central planes is simple and had a high SN-positive detection rate of about 30%. The SN status is the most important predictive value for DFS and OS. In-transit metastasis rates correlated with SN-positivity, Breslow thickness and ulceration of the primary.
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.EJCA.2016.08.014
Abstract: Sentinel node biopsy (SNB) is essential for adequate melanoma staging. Most melanoma guidelines advocate to perform wide local excision and SNB as soon as possible, causing time pressure. To investigate the role of time interval between melanoma diagnosis and SNB on sentinel node (SN) positivity and survival. This is a retrospective observational study concerning a cohort of melanoma patients from four European Organization for Research and Treatment of Cancer Melanoma Group tertiary referral centres from 1997 to 2013. A total of 4124 melanoma patients underwent SNB. Patients were selected if date of diagnosis and follow-up (FU) information were available, and SNB was performed in 43 d): 19.7% versus 20.1% (p = 0.771). Median FU was 50 months (IQR 24-84 months). Sentinel node metastasis (hazard ratio [HR] 3.17, 95% confidence interval [95% CI] 2.53-3.97), ulceration (HR 1.99, 95% CI 1.58-2.51), Breslow thickness (HR 1.06, 95% CI 1.04-1.08), and male gender (HR 1.58, 95% CI 1.26-1.98) (all p < 0.00001) were independently associated with worse MSS and DFS time interval was not. No effect of time interval between melanoma diagnosis and SNB on 5-year survival or SN positivity rate was found for a time interval of up to 3 months. This information can be used to counsel patients and remove strict time limits from melanoma guidelines.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-02-2010
Abstract: We have shown that ultrasound (US) -guided fine needle aspiration cytology (FNAC) can accurately identify the sentinel node (SN). Moreover, US-guided FNAC before the surgical SN procedure could identify up to 65% of all SN metastases. Herein we analyzed in detail the different US morphologic patterns of SN metastases. From July 2001 to December 2007, a total of 650 patients with melanoma scheduled for sentinel lymph node dissection were examined. We present the first 400 with sufficient follow-up (mean 40, median 39 months). Several morphologic characteristics were scored. In case of suspicious/clearly malignant US patterns a FNAC was performed. The final histology was considered the gold standard. Median Breslow was 1.8 mm. The sensitivity and positive predictive value of the most important factors were: peripheral perfusion (PP) present (77% and 52%, respectively), loss of central echoes (LCE 60% and 65% respectively), and balloon shape (BS 30% and 96% respectively). Together these factors have a sensitivity of 82% and PPV of 52% (P .001). PP identified more patients with lower volume disease. PP and combined BS and LCE were independent prognostic factors for survival (hazard ratio, 2.19 P .015 and hazard ratio, 5.50 P .001, respectively). Preoperative US and FNAC can identify 65% of SN metastases and thus reduce the need for surgical SN procedures. Peripheral perfusion is an early sign of involvement and of crucial importance to achieve a high identification rate. Balloon shape and loss of central echoes are late signs of metastases. We recommend US evaluation to identify those patients, who can directly proceed to a complete lymph node dissection after a positive US-guided FNAC of the SN.
Publisher: Springer Science and Business Media LLC
Date: 22-06-2010
DOI: 10.1038/NRCLINONC.2010.100
Abstract: There are two hypotheses to explain melanoma dissemination: first, simultaneous lymphatic and hematogeneous spread, with regional lymph nodes as indicators of metastatic disease and second, orderly progression, with regional lymph nodes as governors of metastatic disease. The sentinel node (SN) has been defined as the first draining lymph node from a tumor and is harvested with the use of the triple technique and is processed by an extensive pathology protocol. The SN status is a strong prognostic factor for survival (83-94% for SN negative, 56-75% SN-positive patients). False-negative rates are considerable (9-21%). Preliminary results of the MSLT-1 trial did not demonstrate a survival benefit for the SN procedure, although a subgroup analysis indicates a possible benefit. A mathematical model has demonstrated 24% prognostic false positivity. SN tumor burden represents a heterogeneous patient population and is classified most frequently with the Starz, Dewar or Rotterdam Criteria. A completion lymph-node dissection might not be indicated in all SN-positive patients. Patients classified with metastases <0.1 mm by the Rotterdam Criteria have excellent survival rates. Ultrasound-guided fine-needle aspiration cytology is emerging as a staging tool for high-risk patients, but more research is necessary before this can change clinical practice.
Publisher: MDPI AG
Date: 18-04-2020
Abstract: Immunotherapeutic and targeted drugs improved survival of patients with metastatic melanoma. There is, however, a lack of evidence regarding their healthcare costs in clinical practice. The aim of our study was to provide insight into real-world healthcare costs of patients with metastatic cutaneous melanoma. Data were obtained from the Dutch Melanoma Treatment Registry for patients who were registered between July 2012 and December 2018. Mean total/monthly costs per patient were reported for all patients, patients who did not receive systemic therapy, and patients who received systemic therapy. Furthermore, mean episode/monthly costs per line of therapy and drug were reported for patients who received systemic therapy. Mean total/monthly costs were € 89,240/€ 6809: € 7988/€ 2483 for patients who did not receive systemic therapy (n = 784) and € 105,078/€ 7652 for patients who received systemic therapy (n = 4022). Mean episode/monthly costs were the highest for nivolumab plus ipilimumab (€ 79,675/€ 16,976), ipilimumab monotherapy (€ 79,110/€ 17,252), and dabrafenib plus trametinib (€ 77,053/€ 12,015). Dacarbazine yielded the lowest mean episode/monthly costs (€ 6564/€ 2027). Our study showed that immunotherapeutic and targeted drugs had a large impact on real-world healthcare costs. As new drugs continue entering the treatment landscape for (metastatic) melanoma, it remains crucial to monitor whether the benefits of these drugs outweigh their costs.
Publisher: Elsevier BV
Date: 04-2016
Publisher: Oxford University Press (OUP)
Date: 28-02-2013
DOI: 10.1111/BJD.12238
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.EJCA.2021.08.044
Abstract: Little is known about outcomes of adjuvant-treated melanoma patients beyond the clinical trial setting. Since 2019, adjuvant-treated melanoma patients have been registered in the DMTR, a population-based registry to monitor the quality and safety of melanoma care in the Netherlands. This study aims to describe treatment patterns, relapse, and toxicity rates of adjuvant-treated melanoma patients beyond the clinical trial setting. Analyses were performed on adjuvant-treated melanoma patients included in the DMTR. Descriptive statistics were used to analyse patient-, and treatment characteristics. A baseline registration completeness analysis was performed, and an analysis on trial eligibility in clinical practice patients. Recurrence-free survival (RFS) at 12-months was estimated with the Kaplan-Meier method. A total of 641 patients were treated with adjuvant anti-PD-1 therapy. RFS at 12-months was 70.6% (95% CI, 66.9-74.6) with a median follow-up of 12.8 months. Sex, stage of disease and Breslow thickness were associated with a higher hazard for RFS. Eighteen per cent of the anti-PD-1-treated patients developed grade ≥3 toxicity. Sixty-one per cent of patients prematurely discontinued anti-PD-1 therapy. Adjuvant anti-PD-1 treatment of resected stage III/IV melanoma in daily practice showed slightly higher toxicity rates and more frequent premature discontinuation but similar RFS rates compared to trials.
Publisher: Elsevier BV
Date: 12-2017
Publisher: American Society of Clinical Oncology (ASCO)
Date: 06-2011
Abstract: Prognosis in patients with sentinel node (SN) –positive melanoma correlates with several characteristics of the metastases in the SN such as size and site. These factors reflect biologic behavior and may separate out patients who may or may not need additional locoregional and/or systemic therapy. Between 1993 and 2008, 1,080 patients (509 women and 571 men) were diagnosed with tumor burden in the SN in nine European Organisation for Research and Treatment of Cancer (EORTC) melanoma group centers. In total, 1,009 patients (93%) underwent completion lymph node dissection (CLND). Median Breslow thickness was 3.00 mm. The median follow-up time was 37 months. Tumor load and tumor site were reclassified in all nodes by the Rotterdam criteria for size and in 88% by the Dewar criteria for topography. Patients with submicrometastases ( 0.1 mm in diameter) were shown to have an estimated 5-year overall survival rate of 91% and a low nonsentinel node (NSN) positivity rate of 9%. This is comparable to the rate in SN-negative patients. The strongest predictive parameter for NSN positivity and prognostic parameter for survival was the Rotterdam-Dewar Combined (RDC) criteria. Patients with submicrometastases that were present in the subcapsular area only, had an NSN positivity rate of 2% and an estimated 5- and 10-year melanoma-specific survival (MSS) of 95%. Patients with metastases 0.1 mm, especially when present in the subcapsular area only, may be overtreated by a routine CLND and have an MSS that is indistinguishable from that of SN-negative patients. Thus the RDC criteria provide a rational basis for decision making in the absence of conclusions provided by randomized controlled trials.
Publisher: Elsevier BV
Date: 12-2017
Publisher: Informa UK Limited
Date: 11-2011
DOI: 10.1586/ERA.11.115
Abstract: Melanoma incidence is still increasing, but the mortality rate has remained unchanged. Lymph node metastases are the single most important prognostic factor for stage I/II melanoma patients. Currently, the standard of care with regard to the staging of these patients is the surgical sentinel node procedure. Ultrasound is not routine for the diagnostic work-up of primary melanomas. Some may use ultrasound for the preoperative assessment of the tumor thickness and lymphatic drainage, but this has not found wide application. For the follow-up of melanoma patients, ultrasound has been proven to be superior to physical examination for the detection of lymph node metastases. A meta-analysis has shown that ultrasound is superior to computed tomography (CT) and/or positron emission tomography (PET)-CT for the detection of lymph node metastases, whereas PET-CT was superior for the detection of distant visceral metastases. Ultrasound of regional lymph nodes has been incorporated into many national guidelines across Europe and in Australia for the follow-up of melanoma patients. A new avenue for ultrasound (US)-guided fine-needle aspiration cytology (FNAC) is the pre-sentinel node modality. Like the situation in breast and thyroid cancer, US-FNAC, a minimally invasive procedure, may decrease the need for surgical sentinel node staging. New ultrasound morphology criteria have significantly increased the sensitivity of this technique. Peripheral perfusion is an early sign of metastases (77% sensitivity, 52% positive-predictive value), whereas balloon-shaped lymph node was a late sign of metastases (30% sensitivity, 96% positive-predictive value). Together, these new ultrasound morphology criteria were able to accurately demonstrate metastases in 65% of sentinel node-positive patients. Future perspectives of ultrasound in melanoma include the start of a large multicenter, multicountry validation study - USE-FNAC - by the European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group. In light of new and promising adjuvant therapies, the need for ultrasound staging might increase rapidly.
Publisher: Springer Science and Business Media LLC
Date: 18-10-2013
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.22665696.V1
Abstract: Figure S5 shows that complement factor B (CFB), component 7 (C7) and alpha-1B-glycoportein (A1BG) expression are increased upon melanoma progression and recurrence.
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.EJCA.2013.08.023
Abstract: Sentinel node (SN) biopsy (SNB) and completion lymph node dissection (CLND) when SN-positive have become standard of care in most cancer centres for melanoma. Various SN tumour burden parameters are assessed to determine the heterogeneity of SN-positivity. The aim of the present study was to validate the prognostic significance of various SN tumour burden micromorphometric features and classification schemes in a large cohort of SN-positive melanoma patients. In 1539 SN-positive patients treated between 1993 and 2008 at 11 melanoma treatment centres in Europe and Australia, indices of SN tumour burden (intranodal location, tumour penetrative depth (TPD) and maximum size of SN tumour deposits) were evaluated. Non-subcapsular location, increasing TPD and increasing maximum size were all predictive factors for non-SN (NSN) status and were independently associated with poorer melanoma-specific survival (MSS). Patients with subcapsular micrometastases 1mm was the most reliable and consistent parameter independently associated with higher non-SN-positivity, poorer disease-free survival (DFS) and poorer MSS. In this large retrospective, multicenter cohort study, several parameters of SN tumour burden including intranodal location, TPD and maximum size provided prognostic information, but their prognostic significance varied considerably between the different centres. This could be due to s le size limitations or to differences in SN detection, removal and examination techniques.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2014
Publisher: Springer Science and Business Media LLC
Date: 27-05-2015
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22546879.V1
Abstract: Figure S5 shows that complement factor B (CFB), component 7 (C7) and alpha-1B-glycoportein (A1BG) expression are increased upon melanoma progression and recurrence.
Publisher: British Editorial Society of Bone & Joint Surgery
Date: 09-2006
DOI: 10.1302/0301-620X.88B9.17873
Abstract: A chordoma which occurs as a primary tumour outside the axial skeleton is known as an extra-axial chordoma, parachordoma or chordoma periphericum. It is extremely rare and therefore survival, recurrence and the rates of metastasis are not known. Whilst few recurrences have been described, the extra-axial chordoma has the potential for late recurrence at up to 12 years. Metastases are even less frequent. We report the case of a 56-year-old woman who developed an extra-axial chordoma of the right thoracic wall in close relationship with the tenth rib. The tumour was completely removed and the prognosis is excellent.
Publisher: Oxford University Press (OUP)
Date: 08-2006
DOI: 10.1016/J.EJCTS.2006.04.020
Abstract: Isolated limb perfusion (ILP) is a treatment option for irresectable melanoma lesions, because with ILP 20-fold higher concentrations of chemotherapy can be achieved locally than is systemically possible and high response rates are subsequently achieved. Jehovah's witnesses do not accept any form of blood transfusion, either autologous or homologous blood or only blood products. The use of an extracorporeal circuit, without the use of any blood products is acceptable for Jehovah's witnesses. The case of a 59-year-old Jehovah's witness with an irresectable melanoma recurrence for which an ILP. Because of adequate blood flow through the perfused limb, the limb did not become acidotic, even though there was a significant drop in the Hb concentration in the limb during the ILP. Isolated limb perfusions without the use of any blood transfusion products are technically possible, but an adequate preoperative hemoglobin concentration is a prerequisite.
Publisher: Wiley
Date: 21-02-2019
DOI: 10.1002/IJC.32172
Abstract: Talimogene laherparepvec (T-VEC) is a modified herpes simplex virus, type 1 (HSV-1), which can be administered intralesionally in patients with stage IIIB/C-IVM1a unresectable melanoma (EMA label). The phase 3 OPTiM registration study showed an overall response rate (ORR) of 26%. Since December 2016, 48 eligible patients started treatment at the Netherlands Cancer Institute. We included 26 patients in this study with a follow up time ≥6 months, reporting Overall Response Rate (ORR), Disease Control Rate (DCR), Adverse Events (AE), prior treatment for melanoma and baseline characteristics, documented in a prospectively maintained database. In house developed treatment protocol consists of clinical evaluation, periodic PET-CT and histological biopsies for response evaluation. Median follow-up was 12.5 months. Of 26 patients, 16 (61.5%) had a Complete Response (CR) as their best response. Seven (26.9%) patients had a Partial Response (PR) as their best response, 1 (3.8%) patient Stable Disease (SD) and 2 (7.7%) patients Progressive Disease (PD). Best ORR was 88.5%. DCR was 92.3%. Grade 1-2 AEs occurred in all patients. Mostly, these consisted of fatigue, influenza-like symptoms and injection site erythema. All patients underwent prior treatment. Prior treatment did not influence response or toxicity of T-VEC. Best ORR for T-VEC monotherapy at our institute was 88.5% with 61.5% achieving a CR. This prospective study for T-VEC in early metastatic (stage IIIB/C-IVM1a) melanoma demonstrated superior results to the phase 3 OPTiM study and confirms the role of oncolytic immunotherapy for melanoma.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2010
Publisher: Georg Thieme Verlag KG
Date: 04-04-2011
Publisher: Elsevier BV
Date: 09-2010
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.EJCA.2019.05.020
Abstract: The American Joint Committee on Cancer-8 (AJCC) classification of melanoma was implemented in January 2018. It was based on data gathered when checkpoint inhibitors were not used as adjuvant therapy in stage III melanoma. The European Organization for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 double-blind phase III trial evaluated pembrolizumab vs placebo in AJCC-7 stage IIIA (excluding lymph node metastasis ≤1 mm), IIIB or IIIC (without in-transit metastasis) patients after complete lymphadenectomy. Patients (n = 1019) were randomised 1:1 to pembrolizumab 200 mg or placebo every 3 weeks (total of 18 doses, ∼1 year). At 1.25-year median follow-up, pembrolizumab prolonged relapse-free survival (RFS) in the total population (1-year RFS rate: 75.4% vs 61.0% hazard ratio [HR] 0.57 logrank P < 0.0001) and consistently in the AJCC-7 subgroups. Prognostic and predictive values of AJCC-8 for RFS were evaluated in this study. Patient distribution according to the AJCC-8 stage subgroups was 8% (IIIA), 34.7% (IIIB), 49.7% (IIIC), 3.7% (IIID) and 3.8% (unknown). AJCC-8 classification was strongly associated with RFS (HRs for stage IIIB, IIIC and IIID vs IIIA were 4.0, 5.7 and 12.2, respectively) but showed no predictive importance for the treatment comparison regarding RFS (test for interaction: P = 0.68). The 1-year RFS rate for pembrolizumab vs placebo and the HRs (99% confidence interval) within each AJCC-8 subgroup were as follows: stage IIIA (92.7% vs 92.5% 0.76 [0.11-5.43]), IIIB (79.0% vs 65.5% 0.59 [0.35-0.99]), IIIC (73.6% vs 53.9% 0.48 [0.33-0.70]) and IIID (50.0% vs 33.3% 0.69 [0.24-2.00]). AJCC-8 staging had a strong prognostic importance for RFS but no predictive importance: the RFS benefit of pembrolizumab was observed across AJCC-8 subgroups in resected high-risk stage III melanoma patients.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22546885.V1
Abstract: Figure S3 shows that SAA1, CRP and LDHB are associated with melanoma disease progression.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22546891.V1
Abstract: Figure S1 shows a flowchart of patients OpACIN-neo study
Publisher: Oxford University Press (OUP)
Date: 02-11-2017
DOI: 10.1002/BJS.10644
Abstract: The optimal extent of groin completion lymph node dissection (CLND) (inguinal or ilioinguinal dissection) in patients with melanoma is controversial. The aim of this study was to evaluate whether the extent of groin CLND after a positive sentinel node biopsy (SNB) is associated with improved outcome. Data from all sentinel node-positive patients who underwent groin CLND at four tertiary melanoma referral centres were retrieved retrospectively. Baseline patient and tumour characteristics were collected for descriptive statistics, survival analyses and Cox proportional hazards regression analyses. In total, 255 patients were included, of whom 137 (53·7 per cent) underwent inguinal dissection and 118 (46·3 per cent) ilioinguinal dissection. The overall CLND positivity rate was 18·8 per cent the inguinal positivity rate was 15·5 per cent and the pelvic positivity rate was 9·3 per cent. The pattern of recurrence, and 5-year melanoma-specific survival, disease-free survival and distant-metastasis free survival rates were similar for both dissection types, even for patients with a positive CLND result. Cox regression analysis showed that type of CLND was not associated with disease-free or melanoma-specific survival. There was no significant difference in recurrence pattern and survival rates between patients undergoing inguinal or ilioinguinal dissection after a positive SNB, even after stratification for a positive CLND result. An inguinal dissection is a safe first approach as CLND in patients with a positive SNB.
Publisher: Oxford University Press (OUP)
Date: 2019
DOI: 10.1111/BJD.17143
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2014
Publisher: Springer Science and Business Media LLC
Date: 08-10-2018
DOI: 10.1038/S41591-018-0198-0
Abstract: Adjuvant ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) both improve relapse-free survival of stage III melanoma patients
Publisher: Wiley
Date: 09-2016
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22546888.V1
Abstract: Figure S2 shows a flowchart of patients PRADO study
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-12-2015
Publisher: Springer Science and Business Media LLC
Date: 10-05-2019
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.EJCA.2013.10.019
Abstract: Cutaneous malignant melanoma causes the majority of skin cancer related deaths and features increasing incidence and mortality rates in the Netherlands. Conditional survival analysis is performed on patients who survived the preceding year(s). Patients with invasive melanoma, as recorded in the population-based Netherlands Cancer Registry, were included. To assess prognosis of melanoma survivors according to gender and Breslow thickness, conditional five-year relative survival was calculated for lymph node negative melanoma patients and conditional one-year relative survival was analysed for melanoma patients with and without nodal involvement. Between 1994 and 2008, 40,050 patients developed a melanoma (stage I-III, of whom 6% with nodal involvement). Six to 8years after diagnosis, survival of patients with a 1-2mm (T2) thick melanoma equalised the general population. Conditional five-year relative survival for patients with >4mm thick (T4) melanomas increased from about 60% at diagnosis to 90% at 7years after diagnosis. Largest improvements were found in patients with thick melanomas and female patients with nodal involvement. The prognosis for melanoma survivors improved with each additional year of survival after diagnosis, except for patients with a ⩽1mm thick melanoma, who never had any excess mortality during follow-up. Conditional survival of melanoma was better amongst females, amongst those with lower Breslow thickness and nodal stage.
Publisher: Elsevier BV
Date: 11-2006
DOI: 10.1016/J.EJSO.2006.03.044
Abstract: Clear cell sarcoma (CCS), also known as clear cell sarcoma of tendons and aponeuroses or malignant melanoma of soft tissue, is a rare malignant tumor and is histogenitically related to melanoma. The aim of this study was to describe our experience with the sentinel node (SN) procedure for CCS patients and to discuss the potential value of this technique for CCS patients. Five patients with a subcutaneous CCS, who underwent an SN procedure, are described. Two patients had positive SNs, with additional tumor positive nodes in both lymph node dissection specimens. Only the patients with tumor positive SNs developed recurrent disease during an average follow-up of 33 months. None of the negative SN patients developed recurrent disease and all were alive after an average follow-up of 39 months. SN status seems to predict additional nodal involvement and recurrent disease as well as survival. The SN procedure might be a useful and accurate staging procedure in CCS patients, comparable to the situation in melanoma.
Publisher: American Association for Cancer Research (AACR)
Date: 28-03-2023
DOI: 10.1158/2767-9764.22348747.V1
Abstract: Figure S1 shows a flowchart of patients OpACIN-neo study
Publisher: Oxford University Press (OUP)
Date: 20-02-2017
DOI: 10.1002/BJS.10475
Abstract: Nodal staging with sentinel node biopsy (SNB) and completion lymph node dissection (CLND) provides prognostic information to patients with melanoma and their physicians. It is not known whether the timing of CLND is associated with survival outcome and/or CLND tumour load. This study investigated whether CLND timing is associated with CLND tumour load, disease-free survival (DFS) and/or melanoma-specific survival (MSS). A retrospective cohort of patients with SNB-positive melanoma from nine European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group centres undergoing surgery between 1993 and 2009 were examined. Patients were selected based on availability of CLND and follow-up data. The CLND interval was defined as the number of days between diagnosis and CLND. Patient and tumour characteristics were collected. Five-year DFS and MSS rates were calculated. Cox and logistic regression analysis were performed, adjusting for known prognostic redictive indicators. A total of 784 patients were included in the study. Their median age was 51 (i.q.r. 40–62) years, and 418 patients (53·3 per cent) were men. Median Breslow thickness was 3·0 (i.q.r. 2·0–5·0) mm, and 148 patients (18·9 per cent) had a residual tumour load. Median CLND interval was 84 (i.q.r. 65–105) days. Five-year DFS and MSS rates were not significantly different for patients operated on with a median CLND interval of less than 84 days and those with an interval of at least 84 days (DFS: 54·2 versus 53·3 per cent respectively MSS: 66·9 versus 65·1 per cent). In a multivariable Cox model, CLND interval was not a significant prognostic indicator. CLND interval was negatively correlated with identification of positive non-sentinel nodes, but following adjustment for known risk factors this effect was no longer found. The time interval between diagnosis of melanoma and CLND did not influence CLND tumour load, DFS or MSS.
Publisher: Springer Science and Business Media LLC
Date: 26-02-2016
DOI: 10.1245/S10434-016-5142-2
Abstract: Combined superficial (inguinal) and deep (iliac and obturator) groin dissection (CGD) is the standard treatment of patients with stage IIIB and IIIC melanoma groin metastases however, the additional value of iliac lymphadenectomy is debated. In our institute, imaging with positron emission tomography/computed tomography (PET/CT) is part of the regular preoperative work-up. The aim of this study was to evaluate the diagnostic value of PET/CT in detecting iliac lymph node metastases. This retrospective study included 70 melanoma patients with stage IIIB or IIIC melanoma and an indication for therapeutic CGD, who were treated at our institution between 2003 and 2013. Median disease-free survival (DFS) was 9 months and median follow-up time was 16 months. The results of PET/CT were compared with the results of pathological analysis after CGD. Additional quantitative analysis of PET/CT imaging was performed. For superficial melanoma groin metastases, sensitivity of PET/CT was 97 %, specificity was 50 %, positive predictive value (PPV) was 90 %, and negative predictive value (NPV) was 71 %. For iliac lymph node metastases, sensitivity of PET/CT was 67 %, specificity was 91 %, PPV was 73 %, NPV was 81 %, and false negative rate was 33 %. The results of this retrospective study indicate that PET/CT imaging could be a valuable method in preoperative work-up in this patient category however, PET/CT alone should not be used as a tool to determine the extent of surgery, since one-third of patients with iliac lymph node involvement will be missed on PET/CT.
Publisher: American Association for Cancer Research (AACR)
Date: 28-03-2023
DOI: 10.1158/2767-9764.22348741.V1
Abstract: Figure S3 shows that SAA1, CRP and LDHB are associated with melanoma disease progression.
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.22665687.V1
Abstract: Table S2 shows the patient characteristics OpACIN-neo
Publisher: MDPI AG
Date: 21-07-2020
Abstract: This review describes the progress that the concept of adjuvant therapies has undergone in the last 50 years and focuses on the most recent development where an adjuvant approach has been scientifically evaluated in melanoma clinical trials. Over the past decade the development of immunotherapies and targeted therapies has drastically changed the treatment of stage IV melanoma patients. These successes led to trials studying the same therapies in the adjuvant setting, in high risk resected stage III and IV melanoma patients. Adjuvant immune checkpoint blockade with anti-CTLA-4 antibody ipilimumab was the first drug to show an improvement in recurrence-free and overall survival but this was accompanied by high severe toxicity rates. Therefore, these results were bypassed by adjuvant treatment with anti-PD-1 agents nivolumab and pembrolizumab and BRAF-directed target therapy, which showed even better recurrence-free survival rates with more favorable toxicity rates. The whole concept of adjuvant therapy may be integrated with the new neoadjuvant approaches that are under investigation through several clinical trials. However, there is still no data available on whether the effective adjuvant therapy that patients finally have at their disposal could be offered to them while waiting for recurrence, sparing at least 50% of them a potentially long-term toxic side effect but with the same rate of overall survival (OS). Adjuvant therapy for melanoma has radically changed over the past few years—anti-PD-1 or BRAF-directed therapy is the new standard of care.
Publisher: Springer Science and Business Media LLC
Date: 14-10-2014
Publisher: Springer Science and Business Media LLC
Date: 15-01-2008
Publisher: Wiley
Date: 22-05-2018
DOI: 10.1002/JSO.25090
Abstract: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine carcinoma of the skin. To describe clinical outcome and prognostic factors of MCC patients in two expert-centers. Patients with histologically confirmed MCC in 1990-2014 were included. Data on patient, tumor characteristics and treatment were retrospectively collected. A total of 351 Patients were evaluated, 153 (44%) males, median age 74 years (range 28-94). Median follow-up time was 28 months (IQR 13-58). Median primary tumor size was 17 mm (range 2-135). At time of diagnosis 112 (32%) patients had lymph node metastases. The cohorts' 5-year overall survival (OS) was 58%. Using a competing risk analysis the 5-year relapse and MCC related death was 42% and 22%. Adjuvant radiation therapy (XRT) was associated with reduced recurrence (SDH 0.54 CI 0.3-0.9). Nodal involvement (SDH 2.7 CI 1.1-6.6) and the male gender were associated with higher MCC related death (SDH 3.1 CI 1.2-7.9) CONCLUSION: In a large cohort a low MCC related death, in the presence of a low OS was seen. This indicates that a significant number of MCC patients die due to other causes than MCC. Adjuvant XRT was associated with relapse. Male gender and nodal metastasis were associated with MCC related death.
Publisher: Rockefeller University Press
Date: 15-03-2023
DOI: 10.1084/JEM.20221952
Abstract: Neoadjuvant ipilimumab + nivolumab has demonstrated high pathologic response rates in stage III melanoma. Patients with low intra-tumoral interferon-γ (IFN-γ) signatures are less likely to benefit. We show that domatinostat (a class I histone deacetylase inhibitor) addition to anti-PD-1 + anti-CTLA-4 increased the IFN-γ response and reduced tumor growth in our murine melanoma model, rationalizing evaluation in patients. To stratify patients into IFN-γ high and low cohorts, we developed a baseline IFN-γ signature expression algorithm, which was prospectively tested in the DONIMI trial. Patients with stage III melanoma and high intra-tumoral IFN-γ scores were randomized to neoadjuvant nivolumab or nivolumab + domatinostat, while patients with low IFN-γ scores received nivolumab + domatinostat or ipilimumab + nivolumab + domatinostat. Domatinostat addition to neoadjuvant nivolumab ± ipilimumab did not delay surgery but induced unexpected severe skin toxicity, h ering domatinostat dose escalation. At studied dose levels, domatinostat addition did not increase treatment efficacy. The baseline IFN-γ score adequately differentiated patients who were likely to benefit from nivolumab alone versus patients who require other therapies.
Publisher: Springer Science and Business Media LLC
Date: 30-05-2017
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.EJSO.2012.12.014
Abstract: We assessed clinical-pathological features and outcomes of cutaneous melanoma patients after ilio-inguinal lymph node dissection (LND) in relation to the presence of metastases in iliac-obturator nodes. We analyzed 390 consecutive patients who underwent ilio-inguinal therapeutic LND [TLND] (237) due to clinical/cytologically detected metastases or after completion LND [CLND] (153) due to positive SLN biopsy (in one cancer centre 1994-2009). Median follow-up time was 60 months. The 5-year overall survival (OS) rate was 49% and median OS - 52 months in the entire group of patients. According to univariate analysis following factors had significant negative influence on OS: presence of metastases to iliac-obturator nodes (5-year OS for positive versus negative: 54.5% and 32%, respectively), macrometastases, higher Breslow thickness, ulceration, higher Clark level, male gender, number of metastatic lymph nodes, extracapsular extension, and, additionally in the CLND group - micrometastases size ≥ 0.1 mm according to the Rotterdam criteria and non-subcapsular location of micrometastases. Iliac-obturator involvement was also negative factor for OS in multivariate analysis. The presence of iliac-obturator nodal metastases correlated with the following factors: type of LND-CLND versus TLND (15% versus 27.5%) of iliac-obturator involvement, respectively), higher Breslow thickness, extracapsular extension of nodal metastases, male gender. We have not identified any metastases in iliac-obturator nodes in group of patients with micrometastases size ≤1.0 mm and primary tumour Breslow thickness <4.0 mm or no ulcerated primary tumours. Metastases to iliac-obturator nodes have additional negative prognostic value for melanoma patients with inguinal basin involvement. We are able to identify the subgroup of patients after positive SLN biopsy without metastases to iliac-obturator nodes, probably requiring only inguinal LND.
Publisher: Springer Science and Business Media LLC
Date: 28-01-2021
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.22665693.V1
Abstract: Figure S6 shows that neutrophil count and neutrophil-to-lymphocyte ratio (NLR) are not associated with recurrence in non-responding patients
Publisher: Elsevier BV
Date: 06-2019
Publisher: Elsevier BV
Date: 11-2009
DOI: 10.1016/J.EJCA.2009.08.015
Abstract: The sentinel node (SN) status has been recognised to be the most important prognostic factor in melanoma. Many studies have investigated additional factors to further predict survival/lymph node involvement. The EORTC Melanoma Group (MG) has formulated the following question: How should we report the microanatomic location and SN tumour burden? The EORTC MG recommends the following: the EORTC MG SN pathology protocol or a similarly extensive protocol, which has also been proven to be accurate, should be used. Only measure what you can see not what you presume. Cumulative measurements decrease the accuracy and reproducibility of measuring. The most reproducible measure is a single measurement of the maximum diameter of the largest lesion in any direction (1-D). If there is any infiltration into the parenchyma, this lesion can no longer be considered solely subcapsular. Reporting of the microanatomic location of metastases should be an assessment of the entire sentinel node, not only of the largest lesion. Multifocality reflects a scattered metastatic pattern, not to be confused with multiple cohesive foci, which fall under the regular location system. A subcapsular metastasis should have a smooth usually curved outline, not ragged or irregular. We recommend all pathologists to report the following items per positive SN for melanoma patients: the microanatomic location of the metastases according to Dewar et al. for the entire node, the SN Tumour Burden according to the Rotterdam Criteria for the maximum diameter of the largest metastasis expressed as an absolute number, and the SN Tumour Burden stratified per category 1.0mm.
Publisher: Elsevier BV
Date: 03-2019
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.EJSO.2017.02.009
Abstract: US-FNAC is a common diagnostic tool in the work-up of many cancers. Results in melanoma were initially poor (sensitivity 20-40%). Introduction of the Berlin Morphology criteria has shown potential improvement up to 65-80% in selected patients. This cohort study evaluates the long-term survival outcome of melanoma patients undergoing Ultrasound (US) guided Fine Needle Aspiration Cytology (FNAC) prior to sentinel node biopsy (SNB) or direct lymphadenectomy. Between 2001 and 2010 over 1000 consecutive melanoma patients prospectively underwent targeted US-FNAC prior to SNB. The Berlin US morphology criteria: peripheral perfusion (PP), loss of central echoes (LCE) and balloon shape (BS) were registered. FNAC was performed if any factor was present. All patients underwent SNB or lymphadenectomy in case of positive FNAC. Median follow-up was 61 months (IQR 40-95). SN positivity rate was 21%. Survival analyses demonstrated that patients with positive US-FNAC had poor survival. After adjustment for SN status and other known prognostic features, patients with positive US-FNAC (hazard ratio (HR) 1.80, 95% CI 1.10-2.96) had worse survival than patients with normal US (reference). Patients with suspicious US and negative FNAC (HR 1.13, 95% CI 0.71-1.78) had survival comparable to patients with normal US. The long-term US-FNAC results support this step-wise approach to melanoma patients. Patients with positive US-FNAC have a poor survival and can be spared a SNB. Patients with suspicious US and negative FNAC should undergo SNB to detect microscopic occult disease. Completely US-FNAC negative patients might only require follow-up and no SN staging at all.
Publisher: Future Medicine Ltd
Date: 09-2023
Publisher: American Association for Cancer Research (AACR)
Date: 28-03-2023
DOI: 10.1158/2767-9764.22348723.V1
Abstract: Table S3 shows the patient characteristics PRADO
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.CRC-23-0015
Abstract: The response rates upon neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma are higher as compared with stage IV disease. Given that successful ICB depends on systemic immune response, we hypothesized that systemic immune suppression might be a mechanism responsible for lower response rates in late-stage disease, and also potentially with disease recurrence in early-stage disease. Plasma and serum s les of cohorts of patients with melanoma were analyzed for circulating proteins using mass spectrometry proteomic profiling and Olink proteomic assay. A cohort of paired s les of patients with stage III that progressed to stage IV disease (n = 64) was used to identify markers associated with higher tumor burden. Baseline patient s les from the OpACIN-neo study (n = 83) and PRADO study (n = 49 NCT02977052) were used as two independent cohorts to analyze whether the potential identified markers are also associated with disease recurrence after neoadjuvant ICB therapy. When comparing baseline proteins overlapping between patients with progressive disease and patients with recurrent disease, we found leucine-rich alpha-2-glycoprotein 1 (LRG1) to be associated with worse prognosis. Especially nonresponder patients to neoadjuvant ICB (OpACIN-neo) with high LRG1 expression had a poor outcome with an estimated 36-month event-free survival of 14% as compared with 83% for nonresponders with a low LRG1 expression (P = 0.014). This finding was validated in an independent cohort (P = 0.0021). LRG1 can be used as a biomarker to identify patients with high risk for disease progression and recurrence, and might be a target to be combined with neoadjuvant ICB. LRG1 could serve as a potential target and as a biomarker to identify patients with high risk for disease recurrence, and consequently benefit from additional therapies and intensive follow-up.
Publisher: Elsevier BV
Date: 02-2019
Publisher: Springer Science and Business Media LLC
Date: 03-05-2011
Publisher: Springer Science and Business Media LLC
Date: 04-2008
DOI: 10.1038/NCPONC1111
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2016
DOI: 10.1097/CMR.0000000000000271
Abstract: Sentinel node biopsy is a widely used staging procedure in melanoma. It is usually performed using the triple technique: lymphatic mapping after injection of a radiopharmaceutical, blue dye injection, and the use of a gamma probe. Blue dye offers visual confirmation of the location of the sentinel lymph node (SN). There are some disadvantages such as blurring of the surgical field, skin coloring, and possible anaphylactic reactions. We aimed to answer the question whether patent blue is truly necessary for correct intraoperative identification of the SN. One day preoperatively, lymphoscintigraphy (with or without single-photon emission computed tomography with integrated computed tomography) is performed and the location of the SN is marked on the skin. Perioperatively, patent blue is injected around the tumor. A handheld gamma-ray detection probe is used to determine the location of the incision and detect the SN during the operation. SNs are pursued in all regions indicated by imaging. In only six of the 681 patients (0.9%) a blue, not radioactive, sentinel node was removed. In one of them (0.15%), this was the only node excised. None of these lymph nodes harbored metastases. This study suggests that blue dye has no additional value in finding the sentinel node and is of low significance in detecting metastases. Therefore, blue dye can be safely omitted from the standardized triple technique. It may be useful in selected cases according to the surgeon’s discretion.
Publisher: Elsevier BV
Date: 03-2012
Publisher: Springer Science and Business Media LLC
Date: 26-04-2018
Publisher: Springer Science and Business Media LLC
Date: 28-03-2016
Publisher: American Association for Cancer Research (AACR)
Date: 28-03-2023
DOI: 10.1158/2767-9764.22348735.V1
Abstract: Figure S5 shows that complement factor B (CFB), component 7 (C7) and alpha-1B-glycoportein (A1BG) expression are increased upon melanoma progression and recurrence.
Publisher: Elsevier BV
Date: 12-2017
Publisher: Elsevier BV
Date: 2023
DOI: 10.1016/J.EJCA.2022.10.028
Abstract: Is there nowadays any benefit of continuing the practice of routine wide local excision (WLE) for primary stage I/II cutaneous melanoma? WLE aims to eradicate potential microsatellites around melanomas and thereby reduce local recurrence rates and improve overall survival. Six large prospective randomised trials investigated WLE versus wider WLE, they all failed to show any effect on overall survival (OS). A literature search was performed to identify data on outcome after omitting WLE. Additionally circumstantial evidence was gathered from pathology studies and outcomes of modified surgical techniques, as well as publications on morbidity. No prospective and one retrospective study was found. The retrospective study showed no difference in OS after correction for confounding factors. Pathology studies showed a low incidence of residual melanoma in WLE specimen (0-4.2%). Mohs surgery does not show a difference in recurrence rates or OS. WLE is associated with considerable postoperative morbidity, which increases with wider excision margins. There is no solid prospective evidence to support the classic dogma of a 2-step approach with the use of WLE for primary cutaneous melanoma that has been completely excised on diagnostic excision biopsy. We recommend to setup and conduct a prospective randomised trial to compare the classical 2-step approach with WLE to a complete diagnostic excision only to abolish the routine practice of WLE in the future.
Publisher: Elsevier BV
Date: 10-2012
Publisher: Wiley
Date: 11-08-2020
DOI: 10.1002/JSO.26155
Publisher: American Association for Cancer Research (AACR)
Date: 28-03-2023
DOI: 10.1158/2767-9764.22348729.V1
Abstract: Table S1 shows an overview evaluated immuno-oncology markers by Olink proteomic assay
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22546870.V1
Abstract: Table S2 shows the patient characteristics OpACIN-neo
Publisher: Springer Science and Business Media LLC
Date: 25-05-2011
Publisher: Elsevier BV
Date: 03-2018
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22546867
Abstract: Table S3 shows the patient characteristics PRADO
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.22665702.V1
Abstract: Figure S3 shows that SAA1, CRP and LDHB are associated with melanoma disease progression.
Publisher: American Association for Cancer Research (AACR)
Date: 28-03-2023
DOI: 10.1158/2767-9764.22348744
Abstract: Figure S2 shows a flowchart of patients PRADO study
Publisher: American Association for Cancer Research (AACR)
Date: 28-03-2023
DOI: 10.1158/2767-9764.22348747
Abstract: Figure S1 shows a flowchart of patients OpACIN-neo study
Publisher: Elsevier BV
Date: 09-2008
DOI: 10.1016/J.SURONC.2008.06.004
Abstract: The sentinel node (SN) procedure in melanoma patients is important for prognostic information, but has no impact on survival. Micrometastases are identified in approximately 20% of the SNs. When a Completion Lymph Node Dissection (CLND) is performed for positive SN, additional non-SN lymph node involvement is also approximately 20%. Several classification criteria have been proposed to identify patients with SNs without a risk for additional nodes or a good prognosis. Micro anatomic analyses of metastatic SNs suggest that patients with sub-micrometastases (<0.1mm) in the SN may be judged as SN negative. Patients with this limited tumor burden in their SN have an excellent prognosis and are highly unlikely to benefit from CLND. New techniques such as ultrasound of the lymph nodal basin can be promising as an alternative for SN biopsy.
Publisher: MDPI AG
Date: 11-05-2010
Publisher: American Association for Cancer Research (AACR)
Date: 28-03-2023
DOI: 10.1158/2767-9764.22348741
Abstract: Figure S3 shows that SAA1, CRP and LDHB are associated with melanoma disease progression.
Publisher: Oxford University Press (OUP)
Date: 14-08-2007
DOI: 10.1002/BJS.5814
Abstract: Sentinel node (SN) status is the most important prognostic factor for overall survival in stage I or II melanoma. Yet SN-positive tumours with submicroscopic involvement of the SN (clusters of cells smaller than 0·1 mm) have shown a distant recurrence rate of only 9 per cent at 5 years, as good as that in SN-negative patients. This study compared the outcome after completion lymph node dissection (CLND) in SN-positive tumours with elective total lymph node dissection (TLND) in patients with palpable nodes. A total of 188 patients were identified 124 had TLND and 64 had CLND. Median follow-up was 56 and 37 months respectively. There were no significant differences between the groups regarding tumour Breslow thickness, ulceration and site of the primary tumour. Survival rates were calculated from date of primary excision. All patients with primary melanomas on extremities or trunk were included. On univariable analysis, the site of the primary tumour (extremity versus trunk) (P & 0·001), Breslow thickness (P = 0·005) and ulceration (P & 0·001) were prognostic for overall survival. There was a non-significant 13 per cent difference in overall survival at 5 years between CLND and TLND (P = 0·115). Excluding 15 patients who had SN disease with submicrometastases reduced the difference to 6 per cent (P = 0·415). This study showed no significant survival benefit for SN-positive CLND compared with TLND, especially when patients with nodes containing submicrometastases were excluded.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2013
Publisher: American Association for Cancer Research (AACR)
Date: 28-03-2023
DOI: 10.1158/2767-9764.22348738
Abstract: Figure S4 shows the serum analysis using Olink proteomic assay
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.EJCA.2019.03.010
Abstract: The sentinel lymph node (SLN) biopsy is a highly accurate staging procedure and the most important prognostic factor in melanoma patients. The European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group aimed to design an updated evolved SLN protocol for the histopathological workup and reporting. We herein recommend extending the distance between steps according to the short axis dimension of the lymph node and optimise both conventional sectioning and staining procedures including immunohistochemistry. We also provide guidance on the description of the spatial localisation of melanoma deposits in a SLN. The histopathological features to be reported include the following: presence or absence of the metastasis, the intranodal location of the metastasis (subcapsular, parenchymal, combined, extensive confluent and extensive multifocal), the number of the metastatic deposits (1, 2-5, 6-10, 11-20 and >20), the maximum dimension of the largest metastasis (indicating its site) and the presence of extracapsular extension and of naevus cells. This updated EORTC protocol is expected to clarify and simplify the existing procedures, ensuring a reasonable workload for the laboratory and for the pathologists resulting in cost saving with no loss, and possible increase, in accuracy.
Publisher: Oxford University Press (OUP)
Date: 07-09-2012
DOI: 10.1002/BJS.8878
Abstract: The therapeutic value of immediate completion lymph node dissection (CLND) for sentinel node (SN)-positive melanoma is unknown. The aim of this study was to evaluate the impact of immediate CLND on the outcome of patients with SN-positive melanoma. Patients with SN metastases treated between 1993 and 2008 at ten cancer centres from the European Organization for Research and Treatment of Cancer Melanoma Group were included in this retrospective study. Maximum tumour size, intranodal location and penetrative depth of SN metastases were measured. Outcome in those who had CLND was compared with that in patients who did not undergo completion lymphadenectomy. Of 1174 patients with SN-positive melanoma, 1113 (94·8 per cent) underwent CLND and 61 (5·2 per cent) did not. Median follow-up for the two groups was 34 and 48 months respectively. In univariable survival analysis, CLND did not significantly influence disease-specific survival (hazard ratio (HR) 0·89, 95 per cent confidence interval 0·58 to 1·37 P = 0·600). However, patients who did not undergo CLND had more favourable prognostic factors. Matched-pair analysis, with matching for age, Breslow thickness, tumour ulceration and SN tumour burden, showed that CLND had no influence on survival (HR 0·86, 0·46 to 1·61 P = 0·640). After adjusting for prognostic factors in multivariable survival analyses, no difference in survival was found. In these two cohorts of patients with SN-positive melanoma and prognostic heterogeneity, outcome was not influenced by CLND.
Publisher: American Association for Cancer Research (AACR)
Date: 28-03-2023
DOI: 10.1158/2767-9764.22348735
Abstract: Figure S5 shows that complement factor B (CFB), component 7 (C7) and alpha-1B-glycoportein (A1BG) expression are increased upon melanoma progression and recurrence.
Publisher: American Association for Cancer Research (AACR)
Date: 28-03-2023
DOI: 10.1158/2767-9764.22348732
Abstract: Figure S6 shows that neutrophil count and neutrophil-to-lymphocyte ratio (NLR) are not associated with recurrence in non-responding patients
Publisher: Wiley
Date: 15-04-2017
DOI: 10.1002/JSO.24635
Abstract: Although the EORTC 18071-trial has shown a clear survival benefit for adjuvant ipilimumab, accurately selecting patients for this toxic adjuvant therapy is important. We aimed to identify prognostic factors for death and disease recurrence in AJCC stage IIIC melanoma patients. Retrospective analysis of patients who underwent lymph node dissection (LND) for stage IIIC melanoma in our institution between 2000 and 2016. Baseline characteristics, melanoma-specific survival (MSS), and disease-free survival (DFS) were assessed, and prognostic factors for recurrence and survival were analyzed using uni- and multivariable analysis. A total of 205 patients were included. Median follow-up was 20 months (interquartile range 11-43 months), median MSS was 28 months, and median DFS was 11 months. Five-year MSS was 33% and 5-year DFS was 23%. N3 (≥4 involved lymph nodes) and extracapsular extension (ECE) carried an increased risk of disease recurrence after LND and death by melanoma. Patients with both N3 and ECE had virtually no long-term survival. Although survival for patients with stage IIIC is poor in general, patients with both N3 disease and ECE constitute the group with the worst prognosis and should be considered for adjuvant therapy with ipilimumab or any other future effective adjuvant therapy (study).
Publisher: Massachusetts Medical Society
Date: 10-05-2018
Publisher: Elsevier BV
Date: 2016
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-12-2011
Publisher: Springer Science and Business Media LLC
Date: 12-04-2017
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-12-2008
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22546876.V1
Abstract: Figure S6 shows that neutrophil count and neutrophil-to-lymphocyte ratio (NLR) are not associated with recurrence in non-responding patients
Publisher: Elsevier BV
Date: 07-2019
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.EJSO.2018.06.020
Abstract: A significant disparity regarding survival outcome for melanoma among European regions is well recognized and access to high quality care for European melanoma patients needs to be improved. There is an unmet need for the implementation of minimal standard of care within defined clinical pathways and Quality Assurance (QA) indicators. The EU-MELACARE study aims to identify shared variables for cutaneous melanoma cases recorded in melanoma registries across Europe. Opinion leaders involved in melanoma data registration and care quality analysis in 34 European countries were invited to respond to an expert survey covering questions regarding the melanoma registration practice in their countries and the characteristics, coverage and variables collected by the relevant melanoma registries. Data regarding 13 melanoma registries from 11 European countries contributed to the study. The majority (61,5%) were population based registries and more than half (62%) had national coverage. The included registries collected a median of 38 variables (Interquartile Range, IRQ 21-76). We identified 24 shared variables available in >70% of registries. This study provides valuable specific information on information recorded for melanoma cases are registered within Europe. A core of shared variables has been identified, which will constitute the basis for a standardized set of QA indicators for assessing and monitoring melanoma care across European countries.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22546882.V1
Abstract: Figure S4 shows the serum analysis using Olink proteomic assay
Publisher: Springer International Publishing
Date: 25-07-2017
Publisher: Springer Science and Business Media LLC
Date: 07-07-2010
Publisher: John Libbey Eurotext
Date: 03-2011
Abstract: Ultrasound-guided fine needle aspiration cytology (US-guided FNAC) of regional nodal basins is increasingly incorporated into the national follow-up schemes of high risk melanoma patients. In this paper we describe an additional added value of US-guided FNAC in the detection and verification of subcutaneous/in-transit metastases. A patient presented with a long lasting, smooth, movable node, close to the scar of the primary melanoma, mimicking a lipoma in every clinical follow-up. Ultrasound at once suspected a metastasis. FNAC was performed within one day of s ling in an outpatient setting, without side effects. A hypothesis of an auto-vaccination in this case could not be proven by examining the T-cell response. Despite the clinically benign aspect of this metastasis, US-guided FNAC can provide diagnosis within 1 day. FNAC is a rapid, cost-effective method, free of complications, of great value in the diagnosis of putative metastases.
Publisher: American Association for Cancer Research (AACR)
Date: 28-03-2023
DOI: 10.1158/2767-9764.22348726
Abstract: Table S2 shows the patient characteristics OpACIN-neo
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.22665684
Abstract: Table S3 shows the patient characteristics PRADO
Publisher: American Association for Cancer Research (AACR)
Date: 28-03-2023
DOI: 10.1158/2767-9764.22348729
Abstract: Table S1 shows an overview evaluated immuno-oncology markers by Olink proteomic assay
Publisher: American Association for Cancer Research (AACR)
Date: 28-03-2023
DOI: 10.1158/2767-9764.22348723
Abstract: Table S3 shows the patient characteristics PRADO
Publisher: Springer Science and Business Media LLC
Date: 10-02-2017
DOI: 10.1245/S10434-017-5803-9
Abstract: Data on isolated limb perfusion (ILP) in elderly melanoma patients are scarce. We aimed to evaluate the efficacy and safety of ILP in our institutional cohort of melanoma patients. We performed retrospective analysis of stage IIIB/C melanoma patients who underwent ILP for melanoma in-transit metastases (ITMs) in our institution between 2000 and 2016. Normothermic ILP was performed with either melphalan or melphalan and tumor necrosis factor. Baseline and treatment characteristics, locoregional progression-free survival (LPFS) and melanoma-specific survival (MSS) were assessed and prognostic factors for response, recurrence, and survival were analyzed using univariable and multivariable analysis. Overall, 91 patients were included in this study. Based on the median age of 70 years, we split patients into younger and elderly groups. No differences in response rates were observed between age groups, with an overall response rate of 81% and complete response (CR) rate of 47%. LPFS did not differ between age groups, and median LPFS was 16 months for patients with a CR. Median MSS was 38 months and differed between younger (45 months) and elderly patients (18 months). Toxicity was generally mild and did not differ between age groups. Two patients (2.2%) suffered Wieberdink IV toxicity, while no patients required utation because of severe toxicity. CR was prognostic for improved LPFS and MSS, while patients >70 years of age and patients with stage IIIC disease had a higher risk of melanoma-specific death. Because of its safety profile and high CR rates, ILP is a viable option for patients with bulky or multiple melanoma ITMs, including elderly (>70 years of age) patients.
Publisher: Springer Science and Business Media LLC
Date: 05-07-2016
DOI: 10.1245/S10434-016-5396-8
Abstract: Locoregional treatment is often insufficient to guarantee long-term disease-free survival (DFS) in American Joint Committee on Cancer stage IIIB melanoma, and, in order to improve survival, effective neoadjuvant and adjuvant strategies are needed . Selecting patients for these strategies requires risk stratification, for which clinical and molecular biomarkers can be used. We aimed to detect clinical biomarkers to identify high-risk stage IIIB melanoma patients. We performed retrospective analysis of stage IIIB melanoma patients who underwent lymph node dissection (LND) in our institution between 2000 and 2015. Sentinel node-positive patients with ulcerated primary tumors, as well as patients with clinically detectable nodal metastasis with non-ulcerated tumors, were included. Baseline characteristics, melanoma-specific survival (MSS), and DFS were assessed, and prognostic factors for recurrence and survival were analyzed, using univariate and multivariate analysis. Overall, 250 patients were included. Median follow-up was 52 months (interquartile range 29-108 months), median MSS was 141 months, and median DFS was 36 months. Five- and 10-year MSS was 59 and 52 %, respectively, and 5- and 10-year DFS was 47 and 41 %, respectively. Age >50 years, Breslow thickness >2 versus ≤2 mm, and N2 versus N1 disease all carried an increased risk of death by melanoma. Age >50 years and extracapsular extension carried an increased risk of disease recurrence after LND. Age >50 years, Breslow thickness >2 mm and N2 versus N1 disease are prognostic factors for poor survival in stage IIIB melanoma. These characteristics can be used to further stratify risk of death by melanoma in this already high-risk patient population and to help select the appropriate population for adjuvant therapy (trials).
Publisher: Elsevier BV
Date: 08-2018
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.22665708.V1
Abstract: Figure S1 shows a flowchart of patients OpACIN-neo study
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.22665687
Abstract: Table S2 shows the patient characteristics OpACIN-neo
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.EJCA.2017.10.031
Abstract: The 8th American Joint Committee on Cancer (AJCC) staging edition includes revisions regarding pT1 melanomas. We aimed to evaluate the expected impact of this edition on staging and survival in the Dutch pT1 melanoma population. In total, 32,935 pT1 melanoma patients, whose data were retrieved from the Netherlands Cancer Registry between 2003 and 2015, were included in the study. Patients were stratified by the 6th AJCC edition (cohort 1: 2003-2009) and 7th edition (cohort 2: 2010-2015) and all reclassified according to the 8th edition. Stage migration, sentinel lymph node biopsy (SLNB) positivity rates and relative survival were analysed. Agreement between staging systems was calculated by Cohen's kappa coefficient. In cohort 2, restaging according to the 8th edition led to an increase of 7% in the total number of patients staged pT1b. The kappa score for agreement between the 6th and 8th edition was 0.15 and 0.25 for agreement between 7th and 8th edition. Restaging according to the 8th edition resulted in a higher SLNB positivity rate for pT1b patients than pT1a patients (8% versus 5%, p = 0.08). Relative survival curves were predominantly similar between the staging editions. Implementation of the 8th AJCC staging edition will presumably not have major impact on the total number of Dutch pT1b patients. Consequently, the number of patients eligible for SLNB would roughly remain similar. In terms of SLNB positivity, the selection of high-risk pT1 melanoma patients is likely to improve. In addition, the 8th edition criteria for pT1 melanoma seem more workable for pathologists.
Publisher: Elsevier BV
Date: 02-2007
DOI: 10.1016/J.EJSO.2006.10.032
Abstract: Melanoma patients with clinically evident regional lymph node metastases are treated with therapeutic lymph node dissections (TLNDs). The aim of this study was to evaluate morbidity and mortality following TLND in our institution. Moreover, disease-free (DFS) and overall (OS) survival were evaluated and factors that influence prognosis after TLND were assessed. Between 1982 and 2005, 236 patients underwent a TLND. Patients, who received a palliative LND or a sentinel node procedure, were not included. The median Breslow thickness was 2.4mm. Ulceration was present in 23% of patients and unknown in 66%. 37 patients had unknown primary tumors. There were 129 ilio-inguinal, 50 axillary and 61 cervical dissections performed. 37% of the patients experienced at least one operation related complication. The most frequently seen complications were wound infections/necrosis and chronic lymph edema. Ilio-inguinal dissection patients experienced significantly more complications and a longer duration of hospitalization compared to axillary or cervical patients. The duration of hospitalization has been reduced in recent years from 12 to 5days. The mean follow-up was 29months. Kaplan-Meier estimated 5-year regional control was 79%, 5-year DFS was 19% and 5-year OS was 26%. The number of positive lymph nodes, the site of the primary tumor and extra capsular extension (ECE) were independent prognostic factors for DFS and only site and ECE for OS. In conclusion, TLND for stage III melanoma is accompanied with considerable short-term complications, and can achieve regional control and potential curation in approximately one in every four patients.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2016
DOI: 10.1097/CMR.0000000000000223
Abstract: Unlike breast and thyroid cancer, the use of ultrasound (US)-guided fine needle aspiration cytology (FNAC) for preoperative staging is limited in melanoma. New US morphology criteria have shown that US-FNAC can correctly identify 50% of all involved sentinel nodes (SN) in melanoma patients before surgical excision. The aim of this study was to examine a new criterion: the echo-free island (EFI). A total of 1000 consecutively staged melanoma patients (Breslow thickness or mm, but ulcerated, Clark IV/V or regressed) scheduled for SN staging underwent preoperative US. US morphology items were assessed: peripheral perfusion, loss of central echoes, balloon shape, and EFI. FNAC was performed in case of suspicious and malignant US patterns. All patients proceeded to undergo an SN biopsy or direct completion lymph node dissection (CLND) (in the case of positive FNAC). In all, 57% of the patients were men. The mean/median Breslow thickness was 2.58/1.57 mm. The mean/median follow-up was 56/53 months. SN was positive in 21%. EFI information was available in 95.3%. EFI was seen in 40 patients (4%). EFI sensitivity was 10.8%, specificity was 97.6%, positive predictive value was 50%, and negative predictive value was 80.2%. EFI was significantly correlated to peripheral perfusion (67.5%). There was no correlation to balloon shape or loss of central echoes. Five-year melanoma-specific survival of patients with EFI was significantly worse: 80% versus 92% when absent. The EFI can be useful in the early detection of SN melanoma metastasis. It is an early sign of involvement and thus associated with a decreased survival.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-10-2023
DOI: 10.1200/JCO.23.01136
Abstract: The ASCO Special Article by Seth et al entitled, "Systemic Therapy for Melanoma: ASCO Guideline Update," ( J Clin Oncol 10.1200/JCO.23.01136) published in Journal of Clinical Oncology ahead of print on August 14, 2023, is under further review. Until the authors and their institutions can fully provide additional information, readers should interpret the findings presented with caution. An update will be provided when our investigation is complete.
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2023
DOI: 10.1158/2767-9764.22665699.V1
Abstract: Figure S4 shows the serum analysis using Olink proteomic assay
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2017
Publisher: Oxford University Press (OUP)
Date: 03-02-2020
DOI: 10.1111/BJD.18873
Publisher: Springer Science and Business Media LLC
Date: 07-11-2017
Location: Netherlands
No related grants have been discovered for Alexander Christopher Jonathan van Akkooi.