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Paola Queirolo

Publications and source records attributed to Paola Queirolo.

10 recordsLinked to original sources
PubMed2006

Targeted therapies in melanoma.

In the last decade the incidence of melanoma has been rising. Despite this, survival remains substantially constant because early diagnosis of thin lesions has increased. By contrast, metastatic melanoma continues to have a poor prognosis and it still represents a challenge for oncologists. Response rates with single agent dacarbazine range from 10% to 25% with median survival of 8 months. The advent of new drugs with specific mechanisms of action could help to improve the poor results of traditional therapies. In this review, we focused on the novel agents that entered clinical trials in melanoma patients. We show the results of some clinical trials with target-oriented drugs in melanoma patients. Moreover pre-clinical data and rationale for use in melanoma was explained. Trials with protein-kinase inhibitors, anti-CTLA-4 agents, pro-apoptotic oligonucleotides and anti-angiogenic agents were reviewed. Combinations with chemotherapeutic agents, immunotherapy and vaccine therapy were also analyzed.

Adjuvants, Immunologic↗
PubMed2006

Impact of E27X, a novel CDKN2A germ line mutation, on p16 and p14ARF expression in Italian melanoma families displaying pancreatic cancer and neuroblastoma.

Mutations in the CDKN2A gene underlie melanoma susceptibility in as many as 50% of melanoma kindreds in selected populations, and several CDKN2A founder mutations have been described. Inherited mutations in CDKN2A have been found to be associated with other, non-melanoma cancers including pancreatic cancer (PC) and neural system tumors (NST). Here we report a novel germline mutation in exon 1 of the CDKN2A gene, E27X, which we first detected in melanoma patients living in or originally from a small geographic area bordering Liguria in north-western Italy. A subset of melanoma kindreds positive for this mutation displayed PC and neuroblastoma. E27X generates a premature stop codon, leading to dramatically reduced protein levels of p16 and leaving p14ARF unaltered. As PC and NSTs have been postulated to be preferentially associated with CDKN2A mutations located in exon 2 and/or affecting p14ARF alone, the position of E27X in exon 1alpha provides interesting insights towards clarifying the mechanisms by which the CDKN2A/ARF locus is involved in cancer predisposition.

Adult↗
PubMed2005

Update: current management issues in malignant melanoma.

The incidence of melanoma has increased continuously during the last decade. Surgery is the mainstay of therapy but, for patients with thick lesions or regional metastatic lymph nodes, there is a high risk of relapse. For this group of patients, there is no standard therapy or general agreement amongst oncologists. In this article, we review the current management of melanoma with regard to past completed adjuvant trials and open trials. Moreover, we discuss the role of chemotherapy in metastatic melanoma, in particular with attention to the use of fotemustine.

Chemotherapy, Adjuvant↗
PubMed2004

Sentinel lymph node biopsy in patients with Stage I/II melanoma: Clinical experience and literature review.

BACKGROUND: The sentinel lymph node (sN) represents one of the most powerful predictors of the outcome of patients with Stages I and II cutaneous melanoma, and may be relevant for the therapeutic planning of early-stage melanoma patients. Since adopting the technique of lymphatic mapping with vital blue dye (Patent Blue-V) in July 1993, we have periodically up-dated the methodology and revised our results in order to define the contribution of radio-guided surgery (RGS) to the detection of the sN as well as the role of intraoperative frozen section examination of the sN. MATERIALS AND METHODS: Between July 1993 and December 1997, 180 patients with clinically node-negative primary cutaneous melanoma (Stages I-II) underwent sN biopsy followed by "selective lymph node dissection" (SLND) whenever sN metastasis was detected. Presently, complete data are available in 165 patients who were divided into two consecutive subsets of 39 and 126 patients, based on the technique for the identification of the sN: Patent Blue-V only or Patent Blue-V associated to RGS. Moreover, in this second subset of patients intraoperative frozen section findings were compared with definitive pathologic examination. RESULTS: As regards the first subset of 39 patients (17 males and 22 females; mean age 51.3 years), the sN was identified in 35 patients (89.7%); 8 patients (22.8%) were found to have metastatic melanoma cells in their sN, and they all underwent SLND of the affected basin. As regards the second set of 126 patients (54 males and 72 females; mean age 53.5 years), the sN was detected in every case by means of the combined technique (Patent Blue-V and RGS): in 4 of 126 patients (3.2%), the sN was detected by means of RGS only whereas in no patient was the sN detected by Patent Blue-V only. Frozen section examination was performed in 123 of 126 patients who had sN detection by Patent Blue-V and RGS, and the intraoperative examination had a sensitivity of 66.6% (22 of 33), specificity of 100% (90 of 90), negative predictive value of 89.1% (90 of 101), and accuracy of 91% (112 of 123). The benefit of frozen section examination in avoiding a two-stage procedure was 17.9% (22 of 123 patients). In patients with thicker lesions (pT(3)-pT(4)), the sensitivity and the benefit of intraoperative examination were 76% (19 of 25) and 32% (19 of 59 patients), respectively. CONCLUSIONS: Sentinel node lymphadenectomy can be better accomplished when both procedures (lymphatic mapping with Patent Blue-V and RGS) are used because the two methods look quite complementary. In fact, the use of the radiocolloid mapping allows to detect a hot spot in the regional basin prior to making the skin incision in order to perform a minimal invasive access, and it may also more accurately differentiate the true sN from a secondary echelon node (non-sN). The use of frozen section examination should be restricted to patients with pT(3)-pT(4) primary melanoma, due to the higher sensitivity and benefit in terms of avoiding a two-stage operative procedure.

Adolescent↗
PubMed2004

Sentinel lymph node biopsy in melanoma patients: the medical oncologist's perspective.

With the advent of sentinel node (sN) biopsy in melanoma patients, elective lymph node dissection (ELND) can be considered an exceeded procedure. Regardless of the possible therapeutic benefits, sN biopsy efficiently predicts prognosis avoiding the morbidity rate of ELND. The importance of the sN is underlined by multivariate analyses, which show that the sN status represents the most important prognostic factor influencing disease-free and distant disease-free survival in patients with stage I and II melanoma. Moreover, sN biopsy provides a minimally invasive method for identifying those patients with subclinical nodal metastasis who actually have stage III disease, with a very high risk of occult distant metastases and who may benefit by adjuvant therapy.

Analysis of Variance↗
PubMed2004

Early onset may predict G101W CDKN2A founder mutation carrier status in Ligurian melanoma patients.

Although the presence of multiple cases of melanoma on the same side of a family is the best predictor of germline CDKN2A mutation, other features (i.e. early age at onset) may be useful to identify carriers. We analysed the records of 682 hospital-based Ligurian melanoma patients. Of these, 238 cases (34 familial, 14 non-familial multiple primary and 190 non-familial single primary melanomas) were consecutively enrolled for screening of the CDKN2A and CDK4 genes. Screening of the 34 familial patients revealed that nine were carriers of the CDKN2A G101W founder mutation. Of the 14 non-familial multiple primary melanoma patients, three carried the G101W founder mutation and one the P48T mutation. For the non-familial patients with a single melanoma, 17 of 190 carried germline CDKN2A mutations, with most (16/17) carrying the G101W Ligurian founder mutation and one a novel single base pair substitution, D74Y. The effect of mutation on age at diagnosis was significant (P=0.012) after correcting for melanoma type (familial or non-familial), number of primaries (single or multiple), gender and disease occurrence (incident or prevalent). Early age at onset may be a good predictor of CDKN2A mutation in Liguria, where the G101W founder mutation is prevalent among melanoma patients, independent of family history.

Adolescent↗
PubMed2002

Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: clinical and immunologic findings.

PURPOSE: To determine the immunogenicity and antitumor activity of a vaccine consisting of autologous, tumor-derived heat shock protein gp96-peptide complexes (HSPPC-96, Oncophage; Antigenics, Inc, Woburn, MA) in metastatic (American Joint Committee on Cancer stage IV) melanoma patients. PATIENTS AND METHODS: Sixty-four patients had surgical resection of metastatic tissue required for vaccine production, 42 patients were able to receive the vaccine, and 39 were assessable after one cycle of vaccination (four weekly injections). In 21 patients, a second cycle (four biweekly injections) was given because no progression occurred. Antigen-specific antimelanoma T-cell response was assessed by enzyme-linked immunospot (ELISPOT) assay on peripheral blood mononuclear cells (PBMCs) obtained before and after vaccination. Immunohistochemical analyses of tumor tissues were also performed. RESULTS: No treatment-related toxicity was observed. Of 28 patients with measurable disease, two had a complete response (CR) and three had stable disease (SD) at the end of follow-up. Duration of CR was 559+ and 703+ days, whereas SD lasted for 153, 191, and 272 days, respectively. ELISPOT assay with PBMCs of 23 subjects showed a significantly increased number of postvaccination melanoma-specific T-cell spots in 11 patients, with clinical responders displaying a high frequency of increased T-cell activity. Immunohistochemical staining of melanoma tissues from which vaccine was produced revealed high expression of both HLA class I and melanoma antigens in seven of eight clinical responders (two with CR, three with SD, and the three with long-term disease-free survival) and in four of 12 nonresponders. CONCLUSION: Vaccination of metastatic melanoma patients with autologous HSPPC-96 is feasible and devoid of significant toxicity. This vaccine induced clinical and tumor-specific T-cell responses in a significant minority of patients.

Adult↗
PubMed2002

High prevalence of the G101W germline mutation in the CDKN2A (P16(ink4a)) gene in 62 Italian malignant melanoma families.

CDKN2A germline mutation frequency estimates are commonly based on families with several melanoma cases. When we started counseling in a research setting on gene susceptibility analysis in northern and central Italy, however, we mostly found small families with few cases. Here we briefly characterize those kindred, estimate CDKN2A/CDK4 mutation test yields, and provide indications on the possibility of implementing formal DNA testing for melanoma-prone families in Italy. In September 1995 we started genetic counseling in a research setting at our Medical Genetics Center. Screening for CDKN2A/CDK4 mutations was performed on families with two melanoma patients, one of whom was younger than 50 years at onset, the other complying with one of the following: 1) being a first-degree relative, 2) having an additional relative with pancreatic cancer, or 3) having multiple primary melanomas. Sixty-two of 67 (80%) melanoma cases met our criteria. Four previously described CDKN2A mutations (G101W, R24P, V126D, and N71S) were found in 21 of the 62 families (34%) with a high prevalence of G101W (18/21). The percentage of families with two melanoma cases/family harboring a mutation was low (7%, 2/27), but rose to 45% (9/20) if one of the melanoma patients carried multiple melanomas or if pancreatic cancer was present in that family. In the 15 families with three melanoma cases the presence of a mutation was higher (67%, 10/15) and reached 100% in the 4 families with four or more melanoma cases. Our results suggest that CDKN2A/CDK4 counseling-based mutational analysis may be reasonably efficient also for families with two melanoma cases, if one patient carries multiple melanomas or if pancreatic cancer is present in the family.

Adolescent↗
PubMedDate not supplied

Cryosurgery for advanced malignant melanoma of the facial skin. A case report.

BACKGROUND: Cryosurgery is safely employed for the treatment of skin precancerous and malignant lesions of the head and neck in selected patients. The case of a 101-year-old female patient with advanced malignant melanoma of the facial skin, undergoing cryosurgery, is reported in order to assess the feasibility and tolerability of the technique, as well as the biological implications of cryosurgical treatment in this specific neoplasm. CASE REPORT: A 101-year-old woman, with a large (pT4b N0 M0) cutaneous melanoma of the facial skin on the right cheek, was treated at the Division of Surgical Oncology of the National Cancer Research Institute, Italy, from June to August 2003. The treatment was accomplished by means of serial cryosurgical applications which were performed within three months; the bulk of the lesion was cryotreated with a liquid nitrogen cryoprobe, while the residual disease was treated with a nitrous protoxide cryoprobe, by means of the insertion technique. The treatment was well tolerated, with a good aesthetic result, and the patient is recurrence- and distant-disease-free two years after the initial cryosurgical application. CONCLUSION: Cryosurgery is feasible in the treatment of head and neck melanoma, mostly for mucosal melanomas and cutaneous lesions in anatomically critical sites, as well as in high-risk surgical patients. Here, a good aesthetic result was obtained in a very elderly patient with a large cutaneous melanoma of the facial skin, avoiding skin flap transposition for tissue repair and postoperative complications (e.g., serious bleeding or postoperative pain), with a satisfactory functional and oncological outcome at two years.

Aged, 80 and over↗