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0000-0003-3685-0210
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Publisher: Wiley
Date: 19-08-2011
DOI: 10.1002/JSO.22029
Abstract: Regional relapse of melanoma may occur as satellite or in-transit metastases proximal to the primary tumor in the direction of the lymph flow. The management of in-transit metastases is challenging because the efficacy of treatment is largely dictated by the biological behavior of the patient's melanoma. This review examines local treatment modalities.
Publisher: Elsevier BV
Date: 03-2012
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: Elsevier BV
Date: 07-2018
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: 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: Springer Science and Business Media LLC
Date: 28-10-2014
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: 07-2008
Publisher: Massachusetts Medical Society
Date: 30-06-2011
Publisher: Springer Science and Business Media LLC
Date: 25-07-2015
DOI: 10.1007/S00259-015-3135-1
Abstract: Sentinel lymph node biopsy is an essential staging tool in patients with clinically localized melanoma. The harvesting of a sentinel lymph node entails a sequence of procedures with participation of specialists in nuclear medicine, radiology, surgery and pathology. The aim of this document is to provide guidelines for nuclear medicine physicians performing lymphoscintigraphy for sentinel lymph node detection in patients with melanoma. These practice guidelines were written and have been approved by the European Association of Nuclear Medicine (EANM) to promote high-quality lymphoscintigraphy. The final result has been discussed by distinguished experts from the EANM Oncology Committee, national nuclear medicine societies, the European Society of Surgical Oncology (ESSO) and the European Association for Research and Treatment of Cancer (EORTC) melanoma group. The document has been endorsed by the Society of Nuclear Medicine and Molecular Imaging (SNMMI). The present practice guidelines will help nuclear medicine practitioners play their essential role in providing high-quality lymphatic mapping for the care of melanoma patients.
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: Springer Science and Business Media LLC
Date: 10-05-2019
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: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2018
Publisher: Elsevier BV
Date: 03-2014
Publisher: Springer Science and Business Media LLC
Date: 10-10-2017
DOI: 10.1245/S10434-017-6072-3
Abstract: This phase III study was undertaken to evaluate the efficacy of an allogeneic whole-cell vaccine (Canvaxin™) plus bacillus Calmette-Guerin (BCG) after complete resection of stage IV melanoma. After complete resection of ≤5 distant metastases, patients were randomly assigned to BCG+Canvaxin (BCG/Cv) or BCG+placebo (BCG/Pl). The primary endpoint was overall survival (OS) secondary endpoints were disease-free survival (DFS), and immune response measured by skin test (ClinicalTrials.gov identifier: NCT00052156). Beginning in May 1998, 496 patients were randomized. In April 2005, the Data Safety Monitoring Board recommended stopping enrollment due to a low probability of efficacy. At that time, median OS and 5-year OS rate were 38.6 months and 44.9%, respectively, for BCG/Pl versus 31.4 months and 39.6% in the BCG/Cv group (hazard ratio (HR), 1.18 p = 0.250). Follow-up was extended at several trial sites through March 2010. Median OS and 5-year and 10-year survival was 39.1 months, 43.3 and 33.3%, respectively, for BCG/Pl versus 34.9 months, 42.5 and 36.4%, in the BCG/Cv group (HR 1.053 p = 0.696). Median DFS, 5- and 10-year DFS were 7.6 months, 23.8 and 21.7%, respectively, for BCG/Pl versus 8.5 months, 30.0%, and 30.0%, respectively, for the BCG/Cv group (HR 0.882 p = 0.260). Positive DTH skin testing correlated with increased survival. In this, the largest study of postsurgical adjuvant therapy for stage IV melanoma reported to date, BCG/Cv did not improve outcomes over BCG lacebo. Favorable long-term survival among study patients suggests that metastasectomy should be considered for selected patients with stage IV melanoma.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-03-2013
Abstract: Elesclomol, an investigational first-in-class compound, induces oxidative stress, triggers mitochondrial-induced apoptosis in cancer cells, and shows synergy with taxanes in tumor models. Following completion of a phase II trial of elesclomol in combination with paclitaxel that met its primary end point of progression-free survival (PFS), this randomized, double-blind, controlled phase III study was conducted to confirm the efficacy and tolerability of elesclomol in combination with paclitaxel versus paclitaxel alone in patients with advanced melanoma. Patients with stage IV chemotherapy-naive melanoma (n = 651) were randomly assigned 1:1 to paclitaxel 80 mg/m 2 either alone or in combination with elesclomol 213 mg/m 2 administered weekly for 3 weeks of a 4-week cycle. Patients were stratified by prior systemic treatment, M1 subclass, and baseline lactate dehydrogenase (LDH) levels. The primary end point was PFS. The study did not achieve its PFS end point (hazard ratio, 0.89 P = .23). The study was stopped when an early overall survival data analysis indicated an imbalance in total deaths favoring paclitaxel, predominantly in patients with high LDH levels. A prospectively defined subgroup analysis revealed a statistically significant improvement in median PFS for the combination in patients with normal baseline LDH. The addition of elesclomol to paclitaxel did not significantly improve PFS in unselected patients with advanced melanoma. The association between baseline LDH and clinical outcomes suggests that LDH may be a predictive factor for treatment with this combination, consistent with recent findings on the association between elesclomol anticancer activity and cellular metabolic state.
Publisher: Springer Science and Business Media LLC
Date: 21-02-2017
Publisher: Elsevier BV
Date: 11-2015
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: Wiley
Date: 19-08-2011
DOI: 10.1002/JSO.22028
Abstract: In-transit melanoma metastases are often confined to a limb. In this circumstance, treatment by isolated limb perfusion or isolated limb infusion can be a remarkably effective regional treatment option.
Publisher: Elsevier BV
Date: 10-2017
No related grants have been discovered for ALESSANDRO TESTORI.