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Melanoma: HELP
Articles by Paola Savoia
Based on 23 articles published since 2008

Between 2008 and 2019, P. Savoia wrote the following 23 articles about Melanoma.
+ Citations + Abstracts
1 Review Ipilimumab (Anti-Ctla-4 Mab) in the treatment of metastatic melanoma: Effectiveness and toxicity management. 2016

Savoia, Paola / Astrua, Chiara / Fava, Paolo. ·a Department of Medical Sciences , University of Turin , Turin , Italy. · b Department of Health Science, "A. Avogadro" University of Eastern Piedmont , Novara , Italy. ·Hum Vaccin Immunother · Pubmed #26889818.

ABSTRACT: In the last years the onset of new therapies changed the management of malignant melanoma. Anti CTLA-4 antibody ipilimumab was the first drug to achieve a significant improvement in survival of advanced stage melanoma. This new therapeutic agent is characterized by a number of side effects that are totally different from those of traditional chemotherapy, mainly caused by the immune system activation. The purpose of this paper is to underline the central role of ipilimumab in the treatment of metastatic melanoma and to characterize related adverse events in terms of incidence, duration and severity of presentation. The early recognition of these side effects is crucial in order to ensure an appropriate management of the toxicities, thus reducing the long term clinical sequelae and the inappropriate treatment discontinuation.

2 Review Clinico-pathologic features of primary melanoma and sentinel lymph node predictive for non-sentinel lymph node involvement and overall survival in melanoma patients: a single centre observational cohort study. 2011

Quaglino, P / Ribero, S / Osella-Abate, S / Macrì, L / Grassi, M / Caliendo, V / Asioli, S / Sapino, A / Macripò, G / Savoia, P / Bernengo, M G. ·Department of Biomedical Sciences and Human Oncology, Section of Dermatology, 1st Dermatologic Division, University of Turin, Italy. pietro.quaglino@unito.it ·Surg Oncol · Pubmed #21145730.

ABSTRACT: OBJECTIVE: Completion Lymph Node Dissection (CLND) is the current standard of practice for patients with a positive Sentinel Lymph Node Biopsy (SLNB). Significant morbidity is associated to CLND, so we tried to evaluate which prognostic variables could predict NSLN invasion in SLN-positive patients and their impact on the overall survival (OS). METHODS: A retrospective chart review of 603 patients that had undergone SLNB for melanoma between 2000 and 2009 at our department was done. 100 SLN were positive at the histopathological analysis of SLN. Demographic variables, primary melanoma, SLN pathologic features and results of CLND were analysed. Multivariate logistic regression and OS analyses were carried out to test the prognostic relevance of clinico-pathologic variables on CLND results and disease course. RESULTS: Breslow thickness, ulceration and micro/macrometastatic pattern of SLN invasion carried a significantly independent higher likelihood of NSLN involvement; Starz classification did not maintain a statistical significance in multivariate analysis. Only one patient (4.3%) without adverse prognostic factors showed NSLN involvement, which was found in 33.3% of patients with one and 55.9% with two or more adverse parameters (p = 0.0001). OS analyses confirmed the prognostic significance of these factors. CONCLUSION: Waiting for the results of Multicenter Selective Lymphadenectomy Trial II, our study suggests a clinically useful and easily applicable means of identifying patients with an unfavourable disease course. The presence of one or more adverse factors identifies patients in whom CLND is mandatory to include thereafter in a more strict follow-up program. Moreover, the finding of no adverse prognostic indicators associated to the presence of significant co-morbidities and/or elderly age, could be useful in identifying patients not to treat by CLND.

3 Clinical Trial Electrochemotherapy with intravenous bleomycin in the local treatment of skin melanoma metastases. 2008

Quaglino, P / Mortera, C / Osella-Abate, S / Barberis, M / Illengo, M / Rissone, M / Savoia, P / Bernengo, M G. ·Department of Biomedical Sciences and Human Oncology, Section of Clinics and Oncological Dermatology, University of Turin, v Cherasco 23, 10126 Torino, Italy. ·Ann Surg Oncol · Pubmed #18498012.

ABSTRACT: BACKGROUND: Electrochemotherapy (ECT) combines chemotherapy and electroporation to increase drug uptake. Its role in cutaneous melanoma metastasis treatment is not well defined; indeed, few studies have been reported, without complete follow-up data. AIM: To prospectively evaluate clinical activity and tolerability of ECT with i.v. bleomycin, and to analyze the response increase associated to repeated sessions, in the largest series of cutaneous melanoma metastases reported to date (n = 233). PATIENTS AND METHODS: 14 stage III relapsed/refractory patients were enrolled according to European Standard Operating Procedures of Electrochemotherapy (ESOPE) guidelines and treated under general sedation using the Cliniporator(TM) pulse generator. RESULTS: A response was obtained in 13/14 patients (93%) after the first ECT, with a complete regression (CR) in 7 (50%). Seven patients underwent a second and three a third ECT on newly appearing and residual lesions, all achieving a response. Overall, a response was obtained in 93% metastases, with lower response rates in >1 cm(2) lesions. The CR rate was 58%; none of the CR nodules relapsed. The repeated ECT sessions gave rise to a new response in 21/29 (72%) re-treated lesions. The local tumor control rate was 74.5% at 2 years. CONCLUSION: ECT is a safe procedure, easily performed in terms of toxicities and cost-effectiveness ratios, and constitutes a therapeutic tool for relapsed/refractory cutaneous melanoma patients. The repeated ECT sessions are associated with a response increase in re-treated lesions which could allow to overcome the reduced activity in >1 cm(2) sized metastases.

4 Article Characterization and implications of thyroid dysfunction induced by immune checkpoint inhibitors in real-life clinical practice: a long-term prospective study from a referral institution. 2018

Guaraldi, F / La Selva, R / Samà, M T / D'Angelo, V / Gori, D / Fava, P / Fierro, M T / Savoia, P / Arvat, E. ·Division of Oncological Endocrinology, Department of Medical Sciences, University of Turin, Turin, Italy. federica.guaraldi3@unibo.it. · Pituitary Unit, Department of Biomedical and Neuromotor Sciences (DIBINEM), IRCCS Institute of Neurological Sciences of Bologna, University of Bologna, Via Altura 3, 40139, Bologna, Italy. federica.guaraldi3@unibo.it. · Division of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy. · Division of Oncological Endocrinology, Department of Medical Sciences, University of Turin, Turin, Italy. · Hygiene, Public Health and Medical Statistics Unit, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy. · Pituitary Unit, Department of Biomedical and Neuromotor Sciences (DIBINEM), IRCCS Institute of Neurological Sciences of Bologna, University of Bologna, Via Altura 3, 40139, Bologna, Italy. · Department of Health Sciences, "A. Avogadro" University of Eastern Piedmont, Novara, Italy. ·J Endocrinol Invest · Pubmed #29043574.

ABSTRACT: PURPOSE: Autoimmune diseases are typically associated with immune checkpoints blockade. This study aims at assessing, in real-life clinical practice, the prevalence and impact of thyroid disorders induced by immune checkpoint inhibitors. METHODS: 52 patients (30 F; age 61 ± 13 years) with advanced melanoma treated with ipilimumab (3 mg/kg i.v./3 weeks; 4 doses) were included. For disease progression, 29 (16 F) of them received nivolumab (3 mg/kg i.v./2 weeks) or pembrolizumab (2 mg/kg i.v./3 weeks). Thyroid function and autoimmunity were assessed before, after 6 weeks, at the end of ipilimumab, as well as before and every 3 months during nivolumab/pembrolizumab treatment. RESULTS: During ipilimumab, 7 (4 F) patients developed thyroid dysfunction (4 thyroiditis, 1 associated with hypothyroidism; 2 thyrotoxicosis in a previously euthyroid multinodular goiter; 1 hypothyroidism worsened). During PD1 inhibitors, 7 patients (3 F) developed hypothyroidism with severe manifestations in 6 of them; 3 patients suffered from euthyroid autoimmune thyroiditis from baseline, one after ipilimumab; 2 patients developed after transient thyrotoxicosis. Mean follow-up after anti-CTLA4 inhibitors treatment was 36 ± 28 months. Thyroid disorders occurred 45.1 ± 20.8 and 151 ± 67 days after the initiation of CTLA4 and PD1 inhibitors, respectively. Autoimmune disorders and BRAF mutation were associated with a better clinical response to CTLA4 followed by PD1 treatment. CONCLUSIONS: Immune checkpoint blockade is burdened by a high incidence of autoimmune thyroid dysfunction, which is often severe. Therefore, early and careful monitoring and, eventually, treatment are crucial to prevent the negative impact of thyroid dysfunction on the clinical outcome.

5 Article Complete response to anti-PD-1 nivolumab in massive skin metastasis from melanoma: efficacy and tolerability in an elderly patient. 2017

Sponghini, Andrea / Patrucco, Federica / Giorgione, Roberto / Farinelli, Pamela / Zottarelli, Francesca / Rondonotti, David / Savoia, Paola. ·aDepartment of Oncology, Maggiore Hospital bDepartment of Health Sciences, University of Eastern Piedmont, Novara, Italy. ·Anticancer Drugs · Pubmed #28489616.

ABSTRACT: The advent of immune checkpoint inhibitors anti-PD-1/PD-L1 has delivered new and effective treatment options with proven clinical benefits for patients affected by metastatic melanoma. The 30-40% of treated patients experience an objective tumour regression, with a significantly prolonged survival and an improved quality of life. Here, we report a case of a 75-year-old Caucasian woman affected by a massive cutaneous metastasis from a BRAF wild-type melanoma who experienced multiple relapses after surgery and repeated electrochemotherapy treatments. A poor response was observed after systemic therapy with ipilimumab, whereas a marked reduction in the lesion size was obtained during the treatment with nivolumab, with an objectively complete response after 6 months. Therapy was well tolerated, without immune-related side effects. During treatment, LDH levels decreased up to the standard values. Our experience confirms the good efficacy and the safety of anti-PD-1 nivolumab for the treatment of relapsed or refractory massive skin lesions, also in elderly patients.

6 Article A study of melanoma in Eastern European migrants in Italy. 2017

Astrua, Chiara / Fava, Paolo / Brizio, Matteo / Savoia, Paola. ·Department of Medical Science, University of Turin, Turin, Italy. · Department of Medical Science, University of Turin, Turin, Italy, Department of Health Sciences, "A. Avogadro" University of Eastern Piedmont, Novara, Italy. ·Eur J Dermatol · Pubmed #28057605.

ABSTRACT: Cancer survival rates are lower in Eastern Europe. To describe, based on a single-centre database in northern Italy, clinical, histopathological, and prognostic features of melanoma in a migrant population from Eastern Europe. MATERIALS & METHODS: We retrospectively analysed data from 18,190 consecutive foreign patients who visited our institution, with 49 cases of melanoma from Eastern Europe. The control group was represented by 1,003 Italian melanoma patients diagnosed and followed at our centre during the same time period. Patients from Eastern Europe were mainly females with lower median age, without significant differences regarding primary melanoma site, relative to the control group. Diagnosis was made at the place of birth in 30.6% and in our centre for the remainder. Median Breslow thickness was greater (p = 0.0178), and aggressive histotypes (p = 0.0017) and ulcerated melanomas (p = 0.002) were significantly over-represented, particularly when diagnosed in the patients' native country. Disease was more advanced at diagnosis (p = 0.0001), regardless of the place of initial diagnosis (51% had a progressive disease within one year which rose to 80% if diagnosed before admission to our centre), and the percentage of patients who died within one year was significantly higher (p = 0.022), relative to the control group. Our study shows a poor prognosis for melanoma patients diagnosed in Eastern Europe. Moreover, for migrant populations moving from Eastern to Western European countries, financial difficulties, poor social integration, and language barriers, with consequent late access to healthcare facilities, may account for a worse prognosis.

7 Article Baseline neutrophils and derived neutrophil-to-lymphocyte ratio: prognostic relevance in metastatic melanoma patients receiving ipilimumab. 2016

Ferrucci, P F / Ascierto, P A / Pigozzo, J / Del Vecchio, M / Maio, M / Antonini Cappellini, G C / Guidoboni, M / Queirolo, P / Savoia, P / Mandalà, M / Simeone, E / Valpione, S / Altomonte, M / Spagnolo, F / Cocorocchio, E / Gandini, S / Giannarelli, D / Martinoli, C. ·Oncology of Melanoma Unit, European Institute of Oncology, Milan. · Medical Oncology and Immunotherapy, Istituto Nazionale Tumori Fondazione 'G. Pascale', Naples. · Melanoma Oncology Unit, Veneto Region Oncology Research Institute, Padua. · Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan. · Istituto Toscano Tumori, University Hospital of Siena, Siena. · IV Oncology Division, Istituto Dermopatico dell'Immacolata IRCCS, Rome. · Immunotherapy and Somatic Cell Therapy Unit, Scientific Institute of Romagna, Meldola. · Department of Medical Oncology, National Institute for Cancer Research, IRCCS San Martino, Genoa. · Dermatologic Clinic, Department of Medical Sciences, University of Turin, Turin. · Unit of Medical Oncology, Department of Oncology and Hematology, Papa Giovanni XXIII Hospital, Bergamo. · Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan. · Statistical Unit, Regina Elena National Cancer Institute, Rome, Italy. · Oncology of Melanoma Unit, European Institute of Oncology, Milan chiara.martinoli@ieo.eu. ·Ann Oncol · Pubmed #26802161.

ABSTRACT: BACKGROUND: Clinical responses to ipilimumab are variable in terms of onset, magnitude and duration. Upfront identification of patients who are more likely or unlikely to benefit from treatment is a major need. PATIENTS AND METHODS: Prospectively collected data from 720 advanced melanoma patients treated with ipilimumab 3 mg/kg within the Italian expanded access program were analyzed. The derived neutrophil-to-lymphocyte ratio (dNLR) was calculated from baseline peripheral blood cell counts, and receiver operating characteristic curve was used to evaluate the best cutoff for this marker. Patients were stratified according to dichotomized baseline absolute neutrophil counts (ANC), dNLR and their combination. The prognostic values of ANC and dNLR for survival were assessed using multivariate Cox proportional hazard models. A subgroup analysis including LDH in the models was also carried out. RESULTS: The median follow-up was 16.5 months. The optimal cutoff for dNLR was 3. Baseline ANC and dNLR were significantly associated with the outcome of ipilimumab-treated melanoma patients, in terms of disease progression and death (P < 0.0001 for all). Furthermore, for each elevated variable, prognosis worsened. Patients with both ANC ≥ 7500 and dNLR ≥ 3 had a significantly and independently increased risk of death [hazard ratio(HR) = 5.76; 95% confidence interval (CI) 4.29-7.75] and of progression (HR = 4.10; 95% CI 3.08-5.46) compared with patients with both lower ANC and dNLR. Patients with one of the two factors elevated displayed an intermediate risk of progression and death. The 1- and 2-year survival rates were 2% and 0%, respectively, for patients with ANC ≥ 7500 and dNLR ≥ 3, and 43% and 24%, respectively, for patients with both lower ANC and dNLR. CONCLUSIONS: Although these findings need to be confirmed and validated, we suggest that a neutrophil-based index may help risk-group stratification and assist disease-management strategies. Furthermore, the potential predictive value of this index for response to ipilimumab should be investigated in randomized clinical trials.

8 Article Multiple primary melanomas (MPMs) and criteria for genetic assessment: MultiMEL, a multicenter study of the Italian Melanoma Intergroup. 2016

Bruno, William / Pastorino, Lorenza / Ghiorzo, Paola / Andreotti, Virginia / Martinuzzi, Claudia / Menin, Chiara / Elefanti, Lisa / Stagni, Camilla / Vecchiato, Antonella / Rodolfo, Monica / Maurichi, Andrea / Manoukian, Siranoush / De Giorgi, Vincenzo / Savarese, Imma / Gensini, Francesca / Borgognoni, Lorenzo / Testori, Alessandro / Spadola, Giuseppe / Mandalà, Mario / Imberti, Gianlorenzo / Savoia, Paola / Astrua, Chiara / Ronco, Anna Maria / Farnetti, Alessandra / Tibiletti, Maria Grazia / Lombardo, Maurizio / Palmieri, Giuseppe / Ayala, Fabrizio / Ascierto, Paolo / Ghigliotti, Giovanni / Muggianu, Marisa / Spagnolo, Francesco / Picasso, Virginia / Tanda, Enrica Teresa / Queirolo, Paola / Bianchi-Scarrà, Giovanna. ·Department of Internal Medicine, Medical Specialties and Surgical Science and Integrated Diagnostics, University of Genoa, Genoa, Italy; Genetics of Rare Cancers, IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. · Department of Internal Medicine, Medical Specialties and Surgical Science and Integrated Diagnostics, University of Genoa, Genoa, Italy; Genetics of Rare Cancers, IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. Electronic address: l.pastorino@unige.it. · Department of Internal Medicine, Medical Specialties and Surgical Science and Integrated Diagnostics, University of Genoa, Genoa, Italy. · Department of Internal Medicine, Medical Specialties and Surgical Science and Integrated Diagnostics, University of Genoa, Genoa, Italy; Department of Internal Medicine, Medical Specialties and Surgical Science and Integrated Diagnostics, University of Genoa, Genoa, Italy. · Immunology and Molecular Oncology Unit, Veneto Institute of Oncology, Istituto Oncologico Veneto (IOV)-IRCCS, Padua, Italy. · Section of Oncology and Immunology, Department of Surgery, Oncology, and Gastroenterology, University of Padua, Padua, Italy. · Melanoma and Soft Tissue Sarcoma Unit, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy. · Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. · Melanoma and Sarcoma Surgery Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. · Medical Genetics Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. · Department of Dermatology, University of Florence, Florence, Italy. · Unit of Medical Genetics, Department of Biomedical Experimental and Clinical Sciences, University of Florence, Florence, Italy. · Plastic Surgery Unit, Regional Melanoma Referral Center, Santa Maria Annunziata Hospital, Florence, Italy. · Division of Dermatoncological Surgery, European Institute of Oncology, Milan, Italy. · Medical Oncology Unit, Ospedale Papa Giovanni XXIII, Bergamo, Italy. · Dermatology Unit, Ospedale Papa Giovanni XXIII, Bergamo, Italy. · Department of Medical Sciences, Dermatology Section, University of Turin, Turin, Italy. · Dermatoncological Surgery Unit, Presidio Sanitario Gradenigo, Turin, Italy. · Anatomopathology Unit, Università dell'Insubria, Ospedale di Circolo, Varese, Italy. · Dermatology Unit, Ospedale di Circolo, Varese, Italy. · Cancer Genetics Unit, Institute of Biomolecular Chemistry, National Research Council, Sassari, Italy. · Department of Melanoma, National Cancer Institute Pascale Foundation, Naples, Italy. · Dermatology Unit, IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. · Department of Plastic and Reconstructive Surgery, IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. · Department of Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliera Universitaria (AOU) San Martino-Istituto Nazionale dei Tumori (IST) Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. ·J Am Acad Dermatol · Pubmed #26775776.

ABSTRACT: BACKGROUND: Multiple primary melanoma (MPM), in concert with a positive family history, is a predictor of cyclin-dependent kinase (CDK) inhibitor 2A (CDKN2A) germline mutations. A rule regarding the presence of either 2 or 3 or more cancer events (melanoma and pancreatic cancer) in low or high melanoma incidence populations, respectively, has been established to select patients for genetic referral. OBJECTIVE: We sought to determine the CDKN2A/CDK4/microphthalmia-associated transcription factor mutation rate among Italian patients with MPM to appropriately direct genetic counseling regardless of family history. METHODS: In all, 587 patients with MPM and an equal number with single primary melanomas and control subjects were consecutively enrolled at the participating centers and tested for CDKN2A, CDK4, and microphthalmia-associated transcription factor. RESULTS: CDKN2A germline mutations were found in 19% of patients with MPM versus 4.4% of patients with single primary melanoma. In familial MPM cases the mutation rate varied from 36.6% to 58.8%, whereas in sporadic MPM cases it varied from 8.2% to 17.6% in patients with 2 and 3 or more melanomas, respectively. The microphthalmia-associated transcription factor E318K mutation accounted for 3% of MPM cases altogether. LIMITATIONS: The study was hospital based, not population based. Rare novel susceptibility genes were not tested. CONCLUSION: Italian patients who developed 2 melanomas, even in situ, should be referred for genetic counseling even in the absence of family history.

9 Article Dermatological approach to vemurafenib skin toxicity: a single centre experience. 2016

Fava, Paolo / Marra, Elena / Astrua, Chiara / Brizio, Matteo / Cavaliere, Giovanni / Quaglino, Pietro / Fierro, Maria T / Savoia, Paola. ·Department of Medical Science, University of Turin, Turin, Italy - paola.savoia@unito.it. ·G Ital Dermatol Venereol · Pubmed #25296968.

ABSTRACT: BACKGROUND: Targeted therapies have recently changed the approach to advanced melanoma. RAF inhibitors represent the emerging standard of care for metastatic BRAF mutated melanomas. Cutaneous reactions are the most common side effects during vemurafenib treatment, and affect the quality of life. The aim of this study was to provide some practical advices to manage the drug related cutaneous reactions. METHODS: A cohort of BRAF-mutated metastatic melanoma patients treated at our institution included 20 female and 21 male patients; median age was 56 years (32-87 years). All patients were treated at a dose of 960 mg b.i.d. orally. RESULTS: After a median treatment duration of 7 months (range 0.5-25.2), 29/39 patients (74.4%) developed cutaneous toxicities. We identified 22 cases of maculo-papular rash (56%) and 18 of warts (46%); in a total of 10 cases we observed alterations of keratinization (25.6%), while 6 of our patients presented photosensitivity (15 %). Six patients developed keratoacanthomas; no second melanomas were observed. CONCLUSIONS: Skin involvement during vemurafenib treatment is frequent but in the majority of cases cutaneous side effects are self-limiting and easy to manage. Moreover, sun protection is mandatory in vemurafenib treated patients, and should be started together with BRAF inhibitor in order to minimize the impact of photosensitivity on quality of life.

10 Article Differences in clinicopathological features and distribution of risk factors in Italian melanoma patients. 2015

Fava, P / Astrua, C / Chiarugi, A / Crocetti, E / Pimpinelli, N / Fargnoli, M C / Maurichi, A / Rubegni, P / Manganoni, A M / Bottoni, U / Catricalà, C / Cavicchini, S / Santinami, M / Alaibac, M / Annetta, A / Borghi, A / Calzavara Pinton, P / Capizzi, R / Clerico, R / Colombo, E / Corradin, M T / De Simone, P / Fantini, F / Ferreli, C / Filosa, G / Girgenti, V / Giulioni, E / Guarneri, C / Lamberti, A / Lisi, P / Nardini, P / Papini, M / Peris, K / Pizzichetta, M A / Salvini, C / Savoia, P / Strippoli, D / Tolomio, E / Tomassini, M A / Vena, G A / Zichichi, L / Patrizi, A / Argenziano, G / Simonacci, M / Quaglino, P. ·Dermatologic Clinic, Department of Medical Sciences, University of Turin, Turin, Italy. ·Dermatology · Pubmed #25659983.

ABSTRACT: BACKGROUND: No studies are available in the literature on the distribution of different melanoma features and risk factors in the Italian geographical areas. OBJECTIVE: To identify the differences in clinical-pathological features of melanoma, the distribution of risk factors and sun exposure in various Italian macro-areas. METHODS: Multicentric-observational study involving 1,472 melanoma cases (713 north, 345 centre, 414 south) from 26 referral centres belonging to the Italian Multidisciplinary Group for Melanoma. RESULTS: Melanoma patients in northern regions are younger, with thinner melanoma, multiple primaries, lower-intermediate phototype and higher counts of naevi with respect to southern patients; detection of a primary was mostly connected with a physician examination, while relatives were more involved in the south. Northern patients reported a more frequent use of sunbeds and occurrence of sunburns before melanoma despite sunscreen use and a lower sun exposure during the central hours of the day. CONCLUSIONS: The understanding of differences in risk factors distribution could represent the basis for tailored prevention programmes.

11 Article Favourable prognostic role of regression of primary melanoma in AJCC stage I-II patients. 2013

Ribero, S / Osella-Abate, S / Sanlorenzo, M / Savoia, P / Astrua, C / Cavaliere, G / Tomasini, C / Senetta, R / Macripò, G / Bernengo, M G / Quaglino, P. ·Section of Dermatology, Department of Medical Sciences, University of Turin, via Cherasco 23, 10126, Turin, Italy; Section of Dermatologic Surgery, Department of Oncology and Haematology via Cherasco 23, AOU Città della Salute e della Scienza di Torino, 10126, Turin, Italy. ·Br J Dermatol · Pubmed #23952011.

ABSTRACT: BACKGROUND: The prognostic significance of regression in primary melanoma has been debated over the past few years. Once it was considered to be a negative prognostic factor, as it may have prevented proper melanoma thickness measurement, therefore affecting the staging of the tumours. For this reason, it was considered to be an indication for sentinel lymph node biopsy (SLNB) in melanoma < 1 mm. OBJECTIVES: To ascertain the utility of SLNB in thin melanoma and to clarify the role of regression in disease-free survival (DFS) and overall survival (OS) in our series. METHODS: We analysed data collected from 1693 consecutive patients with AJCC (American Joint Committee on Cancer) stage I-II melanoma. RESULTS: Globally, SLNB was performed in 656 out of 1693 patients. Regression was present in 349 patients and 223 of them were characterized by thin lesions. SLNB was performed in 104 cases of thin melanoma with regression. The majority of regional lymph node metastases were observed in patients who did not undergo SLNB (89 out of 132). Among the remaining 43 'false negative' patients only three showed regression in the primary. Using the Cox multivariate model, histological regression maintained a significant protective role [hazard ratio (HR) 0·62, P = 0·012 for DFS; HR 0·43, P = 0·008 for OS] when corrected for the principal histopathological and clinical features, despite SLNB. CONCLUSIONS: We confirmed that regression alone should not be a reason to perform SLNB in thin melanoma and, on the contrary, it can be considered a favourable prognostic factor in patients with AJCC stage I-II melanoma.

12 Article Relevance of multiple basin drainage and primary histologic regression in prognosis of trunk melanoma patients with negative sentinel lymph nodes. 2013

Ribero, S / Quaglino, P / Osella-Abate, S / Sanlorenzo, M / Senetta, R / Macrì, L / Savoia, P / Macripò, G / Sapino, A / Bernengo, M G. ·Department of Biomedical Sciences and Human Oncology, Section of Dermatology, 1st Dermatologic Division, University of Turin, Turin, Italy. ·J Eur Acad Dermatol Venereol · Pubmed #22998598.

ABSTRACT: BACKGROUND: Lymphatic drainage to multiple basins (MLBD) is frequently observed in patients with primary melanoma located in the trunk. Conflicting data regarding the prognostic impact of MLBD are reported. OBJECTIVE AND METHODS: We reviewed our case series of 352 patients with trunk melanoma to evaluate the pattern of basin drainage and to analyse whether different basin drainages may have different significance in negative sentinel lymph node (SLN) patients. The presence of single/multiple basin drainage, the status of SLN, the presence of melanoma regression, Breslow thickness, ulceration and type of melanoma were recorded for each patients and correlated to Disease Free Survival (DFS) and Overall Survival (OS). RESULTS: MLBD occurred in 77 patients (21.9%) and single basin lymphatic drainage (SLBD) occurred in 275 patients (79.1%). The presence of metastases in SLN was not significantly different in patients with MLBD compared to those with SLBD (26% vs. 19.6%). No differences in OS and DFS were found in SLBD/MLBD independently from SLN status. However DFS was higher in patients with MLBD and negative SLN (P = 0.0001), in addition, in patients with negative SLN and SLBD disease recurrence was 19% while was only 7% in patients with negative SLN obtained from MLBD (P = 0.03). Multivariate analysis showed that Breslow thickness <2 mm, MLBD pattern and regression of melanoma were favourable variables for DFS of patients with negative SLN. CONCLUSIONS: An accurate study of the drainage basin and of all the SLNs obtained from MLBD is recommended because of the impact in prognosis of melanoma of the trunk.

13 Article Clinical and prognostic reports from 270 patients with multiple primary melanomas: a 34-year single-institution study. 2012

Savoia, P / Osella-Abate, S / Deboli, T / Marenco, F / Stroppiana, E / Novelli, M / Fierro, M T / Bernengo, M G. ·Section of Clinics and Oncological Dermatology, Department of Biomedical Sciences and Human Oncology, University of Turin, Italy. paola.savoia@unito.it ·J Eur Acad Dermatol Venereol · Pubmed #21819449.

ABSTRACT: BACKGROUND: Development of more than one primary melanoma in a sole patient is frequent, accounting for 1.2-8.2% of melanoma patients in most recent series. OBJECTIVE AND METHODS: Clinical, histological and epidemiological characteristics of 270 multiple primary melanomas patients were reviewed. RESULTS: Two-hundred and seven patients (76.7%) had two melanomas, whereas in the remaining 63 the number of primary ranged from three to eight; on the whole, 639 multiple primary melanomas were identified. Synchronous melanomas developed more frequently in patients with three or more lesions; median age was significantly lower in the group of patients with more than three melanomas than in the others. Mean Breslow's thickness significantly decreases (P<0.001) from the first (1.77±1.76 mm) to subsequent primaries (0.85±1.25 mm for the second and 0.66±0.48 mm for the third melanoma). Percentage of 'in situ' melanomas was 5.6% as first diagnosis, but increased to 24.8% for the second melanoma; number of nodular melanomas was significantly lower for succeeding diagnosis. AJCC stage at diagnosis showed a statistical prognostic significance, whereas outcome and survival did not depend on the number of primary lesions. Multivariate analysis confirmed the prognostic role of Breslow's thickness, ulceration, gender and patient age, and the better prognosis of patients with multiple melanomas, respect to those with single primary melanoma. CONCLUSIONS: Skin examination and long-term follow-up are mandatory for patients affected by melanoma, with the intent to promptly diagnose not only a disease progression but also possible new primary melanomas.

14 Article Disease progression in melanoma patients with negative sentinel lymph node: does false-negative specimens entirely account for this phenomenon? 2012

Savoia, P / Fava, P / Caliendo, V / Osella-Abate, S / Ribero, S / Quaglino, P / Macripò, G / Bernengo, M G. ·Department of Biomedical Sciences and Human Oncology, Section of Clinics and Oncological Dermatology, University of Turin, Turin, Italy. paola.savoia@unito.it ·J Eur Acad Dermatol Venereol · Pubmed #21466591.

ABSTRACT: BACKGROUND: Sentinel lymph node (SLN) status is the most important prognostic factor for subjects with primary melanoma thicker than 1 mm. OBJECTIVE: We focused our study on patients with disease progression after negative SLN biopsy (SLNB), with the aim of elucidating their clinical and histopathological characteristics, outcome and real incidence of false negative. METHODS: A total of 688 melanoma patients who underwent SLNB (1 May 1998-31 December 2008) were analysed; all patients had Breslow >1 mm or Breslow <1 mm and at least one of the following features: regression, ulceration and/or Clark level IV-V. RESULTS: Progression developed in 114 of 503 negative SLN patients (22.7%); the first metastatic site was regional in 64% and distant in 36% of these cases. Thirty-nine patients had nodal metastases in the SLN basin as first site of progression. High-risk melanomas (P = 0.001) and elderly patients (P = 0.0005) had an increased probability of progression. Women with a higher median age and lower limbs primary melanoma developed mainly regional skin metastases, while an increased probability of distant metastases was demonstrated in patients with primary on the trunk and axillary SLN (P = 0.003, P = 0.001 respectively). Age at diagnosis, Breslow thickness and regression showed a prognostic relevance in univariate and multivariate analyses on disease-free survival and overall survival. CONCLUSIONS: Even if SLN status remains the most important prognostic factor for melanoma patients, progressive disease after a negative SLNB is a relatively frequent event. However, in our opinion, only a part of negative SLNB patients with metastatic spreading should be considered as false negative (7.75%).

15 Article Melanoma of unknown primary site: a 33-year experience at the Turin Melanoma Centre. 2010

Savoia, Paola / Fava, Paolo / Osella-Abate, Simona / Nardò, Tiziana / Comessatti, Alessandra / Quaglino, Pietro / Bernengo, Maria Grazia. ·Department of Biomedical Sciences and Human Oncology, Section of Clinics and Oncological Dermatology, University of Turin, Italy. paola.savoia@unito.it ·Melanoma Res · Pubmed #20449885.

ABSTRACT: Unknown melanoma occurs as metastasis to skin, nodes or viscera, without a detectable cutaneous primary tumour. We reviewed our database of 4881 melanoma patients, diagnosed and followed up prospectively for a 33-year period. We identified 93 cases of metastatic melanoma without evidence of primary; however, five of these patients had a history of a previous excision of a presumed benign lesion without histological examination and were excluded from analyses. At diagnosis, metastases were cutaneous in 35.3% of cases, nodal in 43.2% and visceral in 17% of cases; in 4.5% of patients, both skin and nodes were involved. In all cases, clinical inspection and staging procedures performed at diagnosis of metastatic disease failed to identify a primary melanoma. In 11 cases (11.8%), extensively regressed pigmented lesions (without evidence of melanoma cells at the histological examination) were documented; moreover, we identified in our series five patients with unknown primary affected by vitiligo. The 5-year and 10-year overall survival rates were 49.6 and 41.4%, respectively, with a median of 4.9 years. The 5-year and 10-year time to progression rates were 39.4 and 32.3%, respectively, with a median of 2.3 years. Survival was longer in females and showed significant differences among patients with skin, lymph node or visceral involvement at diagnosis. In melanoma patients, unknown primary represents a not so rare event, with an uncertain origin. We confirmed the relatively good prognosis of unknown primary melanoma patients, a fact that has to be taken into consideration for their management.

16 Article Vitiligo is an independent favourable prognostic factor in stage III and IV metastatic melanoma patients: results from a single-institution hospital-based observational cohort study. 2010

Quaglino, P / Marenco, F / Osella-Abate, S / Cappello, N / Ortoncelli, M / Salomone, B / Fierro, M T / Savoia, P / Bernengo, M G. ·Department of Biomedical Sciences and Human Oncology, Section of Dermatology, First Dermatologic Division, University of Turin, Turin, Italy. pietro.quaglino@unito.it ·Ann Oncol · Pubmed #19622589.

ABSTRACT: BACKGROUND: The clinical features and the prognostic relevance of vitiligo lesions in melanoma patients are still controversial. This prospective observational study was designed to characterise the clinical features of melanoma-associated vitiligo, to analyse the association with other autoimmune manifestations and to ascertain whether the development of vitiligo lesions carries a prognostic relevance on the clinical course of melanoma. MATERIALS AND METHODS: A total of 2954 consecutive patients have been included; multivariate analyses of distant metastasis-free survival (DMFS) and overall survival (OS) were carried out to ascertain the independent prognostic role of vitiligo as a time-dependent covariate. RESULTS: Vitiligo was demonstrated in 83 of 2954 melanoma patients (2.8%). A significantly higher percentage of autoimmune diseases was demonstrated in vitiligo patients (7 of 83) with respect to patients without vitiligo (80 of 2871) (P = 0.004). Multivariate analyses selected the time-dependent covariate vitiligo as the favourable independent prognostic variable associated to a longer DMFS in stage III and a higher OS in both stage III and stage IV. CONCLUSION: Melanoma-associated vitiligo should be considered as a distinct clinical entity, separate from vitiligo vulgaris, and identifies a subgroup of patients characterised by a high prevalence of immune-mediated diseases and by a favourable prognosis.

17 Article Skin metastases of malignant melanoma: a clinical and prognostic survey. 2009

Savoia, Paola / Fava, Paolo / Nardò, Tiziana / Osella-Abate, Simona / Quaglino, Pietro / Bernengo, Maria Grazia. ·Department of Biomedical Sciences and Human Oncology, Section of Clinics and Oncological Dermatology, University of Turin, Italy. paola.savoia@unito.it ·Melanoma Res · Pubmed #19641475.

ABSTRACT: Skin metastases are a frequent event in the natural history of malignant melanoma, both in the early and late phases of disease progression. In this study, we reviewed our database of 4865 melanoma patients, who were diagnosed and followed up prospectively over a 30-year period at our institution. Statistical analyses were focused on patients with secondary involvement of the skin. Seven hundred and thirty-three of the 4030 patients that met the inclusion criteria (18.2%) developed cutaneous metastases; the skin was involved as first site in 413 patients (56.3%) and after regional lymph node spreading in 208 (28.4%) patients. In a lower number of patients, cutaneous metastases developed only in advanced stages of the disease. Skin metastases were mainly locoregional, when arising as the first site of relapse (89.3%) and/or in patients with a primary melanoma of the lower limbs; in contrast, disseminated metastases are more often observed after a visceral involvement and for primary melanomas of the trunk. Moreover, despite a lower disease-free survival rate (1.3 vs. 2.9 years), we showed a significantly longer time to progression to visceral involvement for the group of patients with cutaneous locoregional metastases (62.5 vs. 17.8 months). The site of primary melanoma is strictly related to the pattern of cutaneous recurrence. The disparity in clinical outcome between patients with locoregional or disseminated skin metastases should therefore be taken into consideration in their management.

18 Article Zosteriform cutaneous metastases: a literature meta-analysis and a clinical report of three melanoma cases. 2009

Savoia, Paola / Fava, Paolo / Deboli, Tommaso / Quaglino, Pietro / Bernengo, Maria Grazia. ·Department of Biomedical Sciences and Human Oncology, Section of Clinics and Oncological Dermatology, University of Turin, Turin, Italy. paola.savoia@unito.it ·Dermatol Surg · Pubmed #19508408.

ABSTRACT: BACKGROUND: Despite frequent skin involvement with solid tumors, zosteriform metastases are a rare, not well-defined entity, with only few cases published in literature. The unifying characteristic is merely topographic: cutaneous lesions were distributed along dermatomes, despite the variety of clinical features, including vesicobullous, papular, and nodular lesions. Several theories have been proposed to explain the pathogenetic mechanism of zosteriform dissemination, even if none was adequately proved. OBJECTIVE: In this article, we report three new cases of patients with melanoma with skin zosteriform metastases and present a meta-analysis of literature data. METHODS AND MATERIALS: We collected all Entrez-PubMed articles about zosteriform skin metastasis since 1970 and reviewed 56 cases, including our own taken from a 4,774-patient series. RESULTS: The histotypes mainly implicated were melanoma (18%); lymphoma (14%); breast cancer (12%); squamous cell carcinoma (12%); and digestive (10.7%), respiratory (10.7%), and urinary tumors (7%), with other histotypes accounting for 14%. In only one case in our series did we describe a typical herpetiform pattern, whereas in the others we found papulonodular lesions with a dermatomeric distribution. CONCLUSION: Cutaneous metastases with zosteriform pattern are rare and show a wide clinicopathologic spectrum that could affect the disease course. The authors have indicated no significant interest with commercial supporters.

19 Article Cutaneous melanoma metastases arising on a split-skin graft donor site. 2009

Marenco, Federica / Fava, Paolo / Macripò, Giuseppe / Quaglino, Pietro / Savoia, Paola / Bernengo, Maria Grazia. ·Department of Biomedical Sciences and Human Oncology, Section of Clinical and Oncological Dermatology, University of Turin, Turin, Italy. ·Dermatol Surg · Pubmed #19438662.

ABSTRACT: -- No abstract --

20 Article CDKN2A mutations and MC1R variants in Italian patients with single or multiple primary melanoma. 2008

Pastorino, L / Bonelli, L / Ghiorzo, P / Queirolo, P / Battistuzzi, L / Balleari, E / Nasti, S / Gargiulo, S / Gliori, S / Savoia, P / Abate Osella, S / Bernengo, M G / Bianchi Scarrà, G. ·Department of Oncology, Biology and Genetics/Medical Genetics Service, University of Genoa, Genoa, Italy. l.pastorino@unige.it ·Pigment Cell Melanoma Res · Pubmed #18983535.

ABSTRACT: We evaluated the contribution of germline CDKN2A mutations and MC1R variants to the development of melanoma in a hospital-based study of single (SPM, n = 398) and multiple primary melanoma (MPM, n = 95). The overall frequency of CDKN2A mutations was 15.2%, and four-fold higher in MPM than in SPM cases (OR = 4.27; 95% CI 2.43-7.53). The likelihood of identifying a CDKN2A mutation increased with family history of melanoma and younger age at diagnosis in MPM cases. Compared to SPM patients, the risk of harboring a CDKN2A mutation rose as the number of primary melanomas increased and was not influenced by family history. The G101W and E27X founder mutations were the most common. Several other mutations (W15X, Q50X, R58X, A68L, A127P and H142R) were detected for the first time in Italian patients. One novel mutation, T77A, was identified. Several non-coding variants with unknown functional significance were also found (5'UTR -25C > T, -21C > T, -67G > C, IVS1 +37G > C); the novel 5'UTR -21C > T variant was not detected in controls. The CDKN2A A148T polymorphism was more frequent in MPM patients than in the control population (15.7% versus 6.6%). Compared to the SPM patients, MPM cases had a 2-fold increased probability of being MC1R variant carriers and a higher probability of carrying two or more variants. No specific association was observed between the type of variant and the number of melanomas, suggesting that the number rather than the type of MC1R variant increases the risk of MPM. We observed no interaction between CDKN2A status and the presence of MC1R variants. The high frequency of CDKN2A mutations in our MPM cases, independent of their family history, is of relevance to genetic counseling and testing in our population.

21 Minor Complete regression of melanoma skin metastases after electrochemotherapy plus ipilimumab treatment: an unusual clinical presentation. 2015

Brizio, Matteo / Fava, Paolo / Astrua, Chiara / Cavaliere, Giovanni / Savoia, Paola. ·Department of Medical Sciences, University of Turin v. Cherasco 23, 10126, Torino, Italy. ·Eur J Dermatol · Pubmed #26055291.

ABSTRACT: -- No abstract --

22 Minor Improvement of sensitivity in sentinel lymph node procedure in melanoma patients. 2015

Ribero, S / Osella-Abate, S / Quaglino, P / Savoia, P / Fava, P / Caliendo, V / Bernengo, M G / Macripò, G. ·Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy - simoneribero@gmail.com. ·G Ital Dermatol Venereol · Pubmed #24747956.

ABSTRACT: -- No abstract --

23 Minor FoxP3 expression on melanoma cells is related to early visceral spreading in melanoma patients treated by electrochemotherapy. 2011

Quaglino, Pietro / Osella-Abate, Simona / Marenco, Federica / Nardò, Tiziana / Gado, Chiara / Novelli, Mauro / Savoia, Paola / Bernengo, Maria Grazia. · ·Pigment Cell Melanoma Res · Pubmed #21696572.

ABSTRACT: -- No abstract --