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Melanoma: HELP
Articles by Paola Savoia
Based on 21 articles published since 2010
(Why 21 articles?)
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Between 2010 and 2020, P. Savoia wrote the following 21 articles about Melanoma.
 
+ Citations + Abstracts
1 Review Targeting the ERK Signaling Pathway in Melanoma. 2019

Savoia, Paola / Fava, Paolo / Casoni, Filippo / Cremona, Ottavio. ·Department of Health Science, University of Eastern Piedmont, via Solaroli 17, 28100 Novara, Italy. paola.savoia@med.uniupo.it. · Section of Dermatology, Department of Medical Science, University of Turin, 10124 Turin, Italy. fava_paolo@yahoo.it. · San Raffaele Scientific Institute, Division of Neuroscience, via Olgettina 58, 20132 Milano, Italy. casoni.filippo@hsr.it. · Università Vita Salute San Raffaele, via Olgettina 58, 20132 Milano, Italy. casoni.filippo@hsr.it. · San Raffaele Scientific Institute, Division of Neuroscience, via Olgettina 58, 20132 Milano, Italy. cremona.ottavio@hsr.it. · Università Vita Salute San Raffaele, via Olgettina 58, 20132 Milano, Italy. cremona.ottavio@hsr.it. ·Int J Mol Sci · Pubmed #30934534.

ABSTRACT: The discovery of the role of the RAS/RAF/MEK/ERK pathway in melanomagenesis and its progression have opened a new era in the treatment of this tumor. Vemurafenib was the first specific kinase inhibitor approved for therapy of advanced melanomas harboring BRAF-activating mutations, followed by dabrafenib and encorafenib. However, despite the excellent results of first-generation kinase inhibitors in terms of response rate, the average duration of the response was short, due to the onset of genetic and epigenetic resistance mechanisms. The combination therapy with MEK inhibitors is an excellent strategy to circumvent drug resistance, with the additional advantage of reducing side effects due to the paradoxical reactivation of the MAPK pathway. The recent development of RAS and extracellular signal-related kinases (ERK) inhibitors promises to add new players for the ultimate suppression of this signaling pathway and the control of pathway-related drug resistance. In this review, we analyze the pharmacological, preclinical, and clinical trial data of the various MAPK pathway inhibitors, with a keen interest for their clinical applicability in the management of advanced melanoma.

2 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.

3 Review Usefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the Treatment of Basal Cell Carcinoma. 2015

Savoia, Paola / Deboli, Tommaso / Previgliano, Alberto / Broganelli, Paolo. ·Department of Medical Sciences, University of Turin, Torino 10126, Italy. paola.savoia@unito.it. · Department of Medical Sciences, University of Turin, Torino 10126, Italy. tommaso.deboli@alice.it. · Department of Medical Sciences, University of Turin, Torino 10126, Italy. alberto.previgliano@unito.it. · Città della Salute e della Scienza, Turin 10126, Italy. paolobroganelli@inwind.it. ·Int J Mol Sci · Pubmed #26426005.

ABSTRACT: Basal cell carcinoma (BCC) is the most common cancer in individuals with fair skin type (I-II) and steadily increasing in incidence (70% of skin malignancy). It is locally invasive but metastasis is usually very rare, with an estimated incidence of 0.0028%-0.55%. Conventional therapy is surgery, especially for the H region of the face and infiltrative lesions; in case of inoperable tumors, radiotherapy is a valid option. Recently, topical photodynamic therapy (PDT) has become an effective treatment in the management of superficial and small nodular BCC. PDT is a minimally invasive procedure that involves the administration of a photo-sensibilizing agent followed by irradiation at a pre-defined wavelength; this determines the creation of reactive oxygen species that specifically destroy target cells. The only major side effect is pain, reported by some patients during the irradiation. The high cure rate and excellent cosmetic outcome requires considering this possibility for the management of patients with both sporadic and hereditary BCC. In this article, an extensive review of the recent literature was made, in order to clarify the role of PDT as a possible alternative therapeutic option in the treatment of BCC.

4 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.

5 Article Identification of Risk Factors for Multiple Non-Melanoma Skin Cancers in Italian Kidney Transplant Recipients. 2019

Zavattaro, Elisa / Fava, Paolo / Veronese, Federica / Cavaliere, Giovanni / Ferrante, Daniela / Cantaluppi, Vincenzo / Ranghino, Andrea / Biancone, Luigi / Fierro, Maria Teresa / Savoia, Paola. ·Department of Translational Medicine, University of Eastern Piedmont, Via Solaroli, 17-28100 Novara, Italy. elisa.zavattaro@med.uniupo.it. · Department of Medical Sciences, University of Turin, 10126 Turin, Italy. fava_paolo@yahoo.it. · Department of Health Science, University of Eastern Piedmont, 28100 Novara, Italy. federica.veronese@med.uniupo.it. · Department of Medical Sciences, University of Turin, 10126 Turin, Italy. g.cavali_dr@yahoo.it. · Department of Translational Medicine, University of Eastern Piedmont, Via Solaroli, 17-28100 Novara, Italy. daniela.ferrante@med.uniupo.it. · Department of Translational Medicine, University of Eastern Piedmont, Via Solaroli, 17-28100 Novara, Italy. vincenzo.cantaluppi@med.uniupo.it. · Department of Medical Sciences, University of Turin, 10126 Turin, Italy. andrea.ranghino@unito.it. · Department of Medical Sciences, University of Turin, 10126 Turin, Italy. luigi.biancone@unito.it. · Department of Medical Sciences, University of Turin, 10126 Turin, Italy. mariateresa.fierro@unito.it. · Department of Health Science, University of Eastern Piedmont, 28100 Novara, Italy. paola.savoia@med.uniupo.it. ·Medicina (Kaunas) · Pubmed #31208110.

ABSTRACT:

6 Article Melanoma-prone families: new evidence of distinctive clinical and histological features of melanomas in CDKN2A mutation carriers. 2018

Gironi, Laura Cristina / Colombo, Enrico / Pasini, Barbara / Giorgione, Roberto / Farinelli, Pamela / Zottarelli, Francesca / Esposto, Elia / Zavattaro, Elisa / Allara, Elias / Ogliara, Paola / Betti, Marta / Dianzani, Irma / Savoia, Paola. ·Department of Health Sciences, A. Avogadro University of Eastern Piedmont, Corso Mazzini 18, 28100, Novara, Italy. gironi.laura@gmail.com. · Department of Translational Medicine, A. Avogadro University of Eastern Piedmont, Novara, Italy. · Department of Medical Sciences, University of Turin, Turin, Italy. · Department of Health Sciences, A. Avogadro University of Eastern Piedmont, Corso Mazzini 18, 28100, Novara, Italy. · NIHR Blood and Transplant Research Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. ·Arch Dermatol Res · Pubmed #30218143.

ABSTRACT: Germline mutations on the CDKN2A gene, the most important known genetic factors associated with cutaneous melanomas (CMs), predispose carriers to multiple primary CMs (MPMs) with higher frequency and younger onset compared to non-carriers. Most of the largest published studies concerning clinical and histological characteristics of CMs with CDKN2A mutation carriers did not specify if the described CMs are first or subsequent to the first, and they used sporadic CMs from non-genotyped patients as controls. We conducted a single-centre observational study to compare clinical and histological CM features of 32 unrelated carriers (MUT) of 5 germline CDKN2A mutations (one of which was never previously described) compared to 100 genotyped wild-type (WT) patients. We stratified the data based on time of diagnosis, anatomical site and histological subtype of CMs, demonstrating several significant unreported differences between the two groups. MUT developed a higher number of dysplastic nevi and MPMs. We proved for the first time that anatomical distribution of CMs in MUT was independent of gender, unlike WTs. MUTs developed in situ and superficial spreading melanomas (SSMs) more frequently, with significantly higher number of SSMs on the head/neck. In MUTs, Breslow thickness was significantly lower for all invasive CMs. When CMs were stratified on the basis of the time of occurrence, statistical significance was maintained only for SSMs subsequent to the first. In WTs, Clark level was significantly higher, and ulceration was more prevalent than in MUTs. Significant differences in ulceration were observed only in SSMs. In nodular CMs, we did not find differences in terms of Breslow thickness or ulceration between WTs and MUTs. In situ CMs developed 10 years earlier in MUTs with respect to WTs, whereas no significant differences were observed in invasive CMs. In contrast to those reported previously by other authors, we did not find a difference in skin phototype.

7 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.

8 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.

9 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.

10 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.

11 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.

12 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.

13 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.

14 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.

15 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.

16 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.

17 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%).

18 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.

19 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 --

20 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 --

21 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 --