Combined therapy with dabrafenib and trametinib in BRAF-mutated metastatic melanoma in a real-life setting: the INT Milan experience.

Purpose: Combination therapy with dabrafenib and trametinib is safer and more effective than BRAF inhibitor-based monotherapy for metastatic melanoma.

Methods: We retrospectively analyzed BRAF-mutated metastatic melanoma patients treated at our institution with daily oral dabrafenib 300 mg and trametinib 2 mg from November 2013 to April 2016. This clinical record included both untreated and previously treated stage IV melanomas.

Cutaneous melanoma in children and adolescents: the Italian rare tumors in pediatric age project experience.

Objective: To describe a series of cutaneous melanoma in children collected by the Italian Rare Tumors in Pediatric Age project.

Study Design: From 2000 to 2012, 54 patients younger than 18 years of age were prospectively registered and treated at 12 Italian pediatric centers on the basis of the same diagnostic/therapeutic recommendations and with the same forms to record clinical data.

Results: Considering the estimated annual incidence in Italy, the registered cases accounted for 30% of those expected in children and 10% of adolescents.

Side effects of Bacillus Calmette-Guérin (BCG) in the treatment of intermediate- and high-risk Ta, T1 papillary carcinoma of the bladder: results of the EORTC genito-urinary cancers group randomised phase 3 study comparing one-third dose with full dose and 1 year with 3 years of maintenance BCG.

Background: Although bacillus Calmette-Guérin (BCG) has proven highly effective in non-muscle-invasive bladder cancer (NMIBC), but it can cause severe local and systemic side effects.

Objectives: The objective was to determine whether reducing the dose or duration of BCG was associated with fewer side effects. Efficacy comparisons of one-third dose versus full dose BCG given for 1 yr versus 3 yr have previously been published.

Final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Guérin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of maintenance.

Background: The optimal dose and duration of intravesical bacillus Calmette-Guérin (BCG) in the treatment of non-muscle-invasive bladder cancer (NMIBC) are controversial.

Objective: To determine if a one-third dose (1/3D) is not inferior to the full dose (FD), if 1 yr of maintenance is not inferior to 3 yr of maintenance, and if 1/3D and 1 yr of maintenance are associated with less toxicity.

Design, Setting, And Participants: After transurethral resection, intermediate- and high-risk NMIBC patients were randomized to one of four BCG groups: 1/3D-1 yr, 1/3D-3 yr, FD-1 yr, and FD-3 yr.

Can gemcitabine instillation ablate solitary low-risk non-muscle-invasive bladder cancer? Results of a phase II marker lesion study.

Purpose: The purpose of this phase II study was to evaluate whether low-risk non-muscle-invasive bladder cancer can be ablated with intravesical gemcitabine in a marker lesion study.

Patients And Methods: The study had a Simon II-stage design. Thirteen patients were to be recruited for stage I.

Immunohistochemical expression and localization of somatostatin receptor subtypes in androgen ablated prostate cancer.

Objective: The aim was to examine the expression and localization of the five somatostatin receptors (termed SSTR1 to 5) in radical prostatectomies (RPs) from patients with prostatic adenocarcinoma (PCa) under complete androgen ablation (CAA) before operation.

Material: The five SSTRs were evaluated in the epithelial, smooth muscle and endothelial cells of normal-looking epithelium (Nep), high-grade prostatic intraepithelial neoplasia (HGPIN) and PCa in 20 RPs with clinically detected PCa from patients under CAA. Twenty RPs with clinically detected PCa from hormonally untreated patients were used as control group.

Small nodular melanoma: the beginning of a life-threatening lesion. A clinical study on 11 cases.

Aims And Background: Because of its high thickness, nodular melanoma often bears a poor prognosis. Thus, an earlier diagnosis of this type of lesion while it is still thin would be an important step in secondary prevention. The principal aim of the present study was to better define the initial clinical features of nodular melanoma to allow an early diagnosis.

A prospective, randomised EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma.

Background: Nephron-sparing surgery (NSS) can safely be performed with slightly higher complication rates than radical nephrectomy (RN), but proof of oncologic effectiveness is lacking.

Objective: To compare overall survival (OS) and time to progression.

Design, Setting, And Participants: From March 1992 to January 2003, when the study was prematurely closed because of poor accrual, 541 patients with small (≤5 cm), solitary, T1-T2 N0 M0 (Union Internationale Contre le Cancer [UICC] 1978) tumours suspicious for renal cell carcinoma (RCC) and a normal contralateral kidney were randomised to NSS or RN in European Organisation for Research and Treatment of Cancer Genito-Urinary Group (EORTC-GU) noninferiority phase 3 trial 30904.

Sequential intravesical chemoimmunotherapy with mitomycin C and bacillus Calmette-Guérin and with bacillus Calmette-Guérin alone in patients with carcinoma in situ of the urinary bladder: results of an EORTC genito-urinary group randomized phase 2 trial (30993).

Background: Bacillus Calmette-Guérin (BCG) is the intravesical treatment of choice for carcinoma in situ (CIS).

Objective: Our aim was to assess if sequential mitomycin C (MMC) plus BCG after transurethral resection (TUR) is worthy of further study in non-muscle-invasive bladder cancer patients with CIS.

Design, Setting, And Participants: In a noncomparative phase 2 study, 96 patients with primary/secondary/concurrent CIS of the urinary bladder were randomized to sequential MMC plus BCG or to BCG alone after TUR.

Somatostatin receptor subtypes in hormone-refractory (castration-resistant) prostatic carcinoma.

The aim of this study was to examine the tissue expression and localisation of the somatostatin receptors (SSTRs) in hormone-refractory (HR) prostate cancer (PCa). Five SSTRs were evaluated immunohistochemically in 20 radical prostatectomies (RPs) with Gleason score (GS) 3+3=6 PCa, in 20 RPs with GS 4+4=8 and 4+5=9 PCa, and 20 transurethral resection of the prostate specimens with HR PCa. The mean values in the cytoplasm (all five SSTRs were expressed), membrane (only SSTR3 and SSTR4 were expressed) and nuclei (only SSTR4 and SSTR5 were expressed) of the glands in HR PCa were 20-70% lower than in the other two groups, the differences being statistically significant.

Immunohistochemical expression and localization of somatostatin receptor subtypes in androgen ablated prostate cancer.

Objective: The aim was to examine the expression and localization of the five somatostatin receptors (termed SSTR1-5) in radical prostatectomies (RPs) from patients with prostatic adenocarcinoma (PCa) under complete androgen ablation (CAA) before operation.

Material: The five SSTRs were evaluated in the epithelial, smooth muscle and endothelial cells of normal-looking epithelium (Nep), high-grade prostatic intraepithelial neoplasia (HGPIN) and PCa in 20 RPs with clinically detected PCa from patients under CAA. 20 RPs with clinically detected PCa from hormonally untreated patients were used as control group.

Sorafenib's inhibition of prostate cancer growth in transgenic adenocarcinoma mouse prostate mice and its differential effects on endothelial and pericyte growth during tumor angiogenesis.

Objective: To evaluate Sorafenib's efficacy (60 mg/kg/d per os) in preventing the transformation of high grade prostate intraepithelial neoplasia (HGPIN) into adenocarcinoma (ADC) and in inhibiting the onset and progression of poorly differentiated carcinoma (PDC) in transgenic adenocarcinoma mouse prostate (TRAMP) mice.

Study Design: Forty-four TRAMP mice were randomly divided into 2 groups of 22 and assigned to daily treatment by gavage with vehicle only or Sorafenib from the 10th to the 26th week of age. At 26 weeks of age the mice were killed, and their genitourinary apparatus was removed and examined by histology, immunohistochemistry and confocal microscopy.

Immunohistochemical expression of somatostatin receptor subtypes in prostate tissue from cystoprostatectomies with incidental prostate cancer.

Objective: To examine immunohistochemically the expression of the five somatostatin receptors (SSTRs) in cystoprostatectomies (CyPs) with incidental prostate cancer.

Materials And Methods: The five SSTRs (SSTR1-5) were evaluated in 'normal-looking' epithelium (NEp), high-grade prostatic intraepithelial neoplasia (HGPIN) and pT2a Gleason score 6 adenocarcinoma in 20 CyP specimens with incidental prostate cancer and 20 radical prostatectomy (RP) specimens with clinically detected prostate cancer.

Results: For cytoplasm expression, the mean percentage of positive secretory cells with strong cytoplasmic staining increased from NEp to HGPIN and prostate cancer, being slightly lower in the CyP than in the RP specimens.

GnRH receptor expression in human prostate cancer cells is affected by hormones and growth factors.

GnRH receptors (GnRH-R) have been found in various malignancies, including prostate cancer (PCa). They mediate the direct antitumor effects of GnRH analogs. Nevertheless, few reports concern drug-induced modulation of GnRH-R levels.

In vivo characterization of melanin in melanocytic lesions: spectroscopic study on 1671 pigmented skin lesions.

The purpose of this study is to determine the role of melanin in the various steps of progression of melanocytic neoplasia. To this aim, we perform a retrospective analysis on 1671 multispectral images of in vivo pigmented skin lesions previously recruited in the framework of a study focused on the computer-assisted diagnosis of melanoma. The series included 288 melanomas in different phases of progression, i.

Intermittent androgen deprivation for locally advanced and metastatic prostate cancer: results from a randomised phase 3 study of the South European Uroncological Group.

Background: Few randomised studies have compared intermittent hormonal therapy (IHT) with continuous therapy for the treatment of advanced prostate cancer (PCa).

Objective: To determine whether intermittent therapy is associated with a shorter time to progression.

Design, Setting, And Participants: 766 patients with locally advanced or metastatic PCa received a 3-mo induction treatment.

Cutaneous melanoma in childhood and adolescence shows frequent loss of INK4A and gain of KIT.

Childhood cutaneous melanoma is a rare disease with increasing incidence. It is not clear whether it differs from adult melanoma in etiology and clinical evolution. To genetically characterize childhood melanoma, 21 pediatric patients were studied by germ-line analysis of CDKN2A, CDK4, and MC1R genes.

Immunohistochemical detection and localization of somatostatin receptor subtypes in prostate tissue from patients with bladder outlet obstruction.

Background And Aim Of The Study: Scant information on the cellular distribution of the five somatostatin receptor (SSTR) subtypes in the normal prostate and in neoplasms of the prostate has been reported in very few studies in which techniques, such as in situ hybridization histochemistry, autoradiography, and more recently immunohistochemistry, have been applied. The aim of the study was to examine immunohistochemically the distribution and localization of these 5 subtypes in the various tissue components in normal prostate.

Materials: The study was conducted in 14 surgical specimens of normal prostate tissue from adenomectomy specimens from patients with bladder outlet obstruction.

Metamorphosis of melanoma. Trends in size and thickness of cutaneous melanoma over one decade at the Istituto Nazionale Tumori, Milan.

Aims And Background: Messages about the description of the clinical features of cutaneous melanoma (CM) have remained unchanged since 1985, when the ABCD (Asymmetry, Border irregularity, Color variegation, Diameter >6 mm) rule for melanoma detection was formulated. Given the significant shift to the diagnosis of earlier-stage CMs over the past decades, it is reasonable to think that also the clinical aspects of the disease might have changed. The aim of this study was to examine trends in the presentation of CM over the last decade at our Institution, focusing on two characteristics of the disease: size and thickness.

In vivo evaluation of melanoma thickness by multispectral imaging and an artificial neural network. A retrospective study on 250 cases of cutaneous melanoma.

Aims And Background: Noninvasive diagnostic methods such as dermoscopy, sonography, palpation or combined approaches have been developed in an attempt to preoperatively estimate melanoma thickness. However, the clinical presentation is often complex and the evaluation subjective. Multispectral image analysis of melanomas allows selection of features related to the content and distribution of absorbers, mainly melanin and hemoglobin, present within the lesion.

Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial.

Objectives: This phase 2 randomized study compared the toxicity and assessed the efficacy of gemcitabine-cisplatin (GP) and gemcitabine-carboplatin (GC) in patients with advanced transitional cell carcinoma of the urothelium (TCC), with the main objective to demonstrate a reduction in toxicity of at least 25% in the GC arm.

Methods: A total of 110 chemonaive patients (55 per arm) with locally advanced or metastatic TCC received gemcitabine 1250 mg/m(2) on days 1 and 8 plus cisplatin 70 mg/m(2) on day 2 (GP) every 3 wk or gemcitabine 1250 mg/m(2) on days 1 and 8 plus carboplatin AUC 5 on day 2 (GC) every 3 wk for a maximum of six cycles.

Results: No differences between arms were noted in the overall toxicity profiles and any parameter of toxicity.

A prospective randomized EORTC intergroup phase 3 study comparing the complications of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma.

Objectives: This study compared the complications and the cancer control of elective nephron-sparing surgery (NSS) and radical nephrectomy (RN) in patients with a small (
Methods: 541 patients were randomised in a prospective, multicentre, phase 3 trial to undergo NSS (n=268) or RN (n=273) together with a limited lymph node dissection.

Results: This publication reports only on the complications reported for both surgical methods.

Gene expression profiling of renal cell carcinoma: a DNA macroarray analysis.

Objective: To examine differences in gene expression levels between renal cell carcinoma (RCC) tissue and 'normal' appearing renal tissue using a commercially available DNA macroarray.

Materials And Methods: Tissue was obtained from 47 consecutive radical nephrectomies, 29 of which were eligible. DNA macroarrays were analysed on the tumour and normal-appearing control tissue to measure the expression of 1185 cancer-related genes.

Bicalutamide 50 mg monotherapy in patients with isolated high-grade PIN: findings in repeat biopsies at 6 months.

Objectives: To evaluate morphological findings in repeat biopsies in patients with isolated high-grade prostatic intraepithelial neoplasia (HGPIN) after a 6-month course of bicalutamide (Casodex) 50 mg/day.

Methods: 20 consecutive patients with isolated HGPIN in prostate biopsies were treated for 6 months with bicalutamide 50 mg/day. After treatment, the patients were resubmitted to prostate biopsy mapping.