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Background:Preoperative treatment of resectable liver metastases from colorectal cancer (CRC) is a matter of debate. The aim of this study was to assess the feasibility and activity of bevacizumab plus FOLFIRI in this setting.Methods:Patients aged 18-75 years, PS 0-1, with resectable liver-confined metastases from CRC were eligible. They received bevacizumab 5 mg kg−1 followed by irinotecan 180 mg m−2, leucovorin 200 mg m−2, 5-fluorouracil 400 mg m−2 bolus and 5-fluorouracil 2400 mg m−2 46-h infusion, biweekly, for 7 cycles. Bevacizumab was stopped at cycle 6. A single-stage, single-arm phase 2 study design was applied with 1-year progression-free rate as the primary end point, and 39 patients required.Results:From October 2007 to December 2009, 39 patients were enrolled in a single institution. Objective response rate was 66.7% (95% exact CI: 49.8-80.9). Of these, 37 patients (94.9%) underwent surgery, with a R0 rate of 84.6%. Five patients had a pathological complete remission (14%). Out of 37 patients, 16 (43.2%) had at least one surgical complication (most frequently biloma). At 1 year of follow-up, 24 patients were alive and free from disease progression (61.6%, 95% CI: 44.6-76.6). Median PFS and OS were 14 (95% CI: 11-24) and 38 (95% CI: 28-NA) months, respectively.Conclusion:Preoperative treatment of patients with resectable liver metastases from CRC with bevacizumab plus FOLFIRI is feasible, but further studies are needed to define its clinical relevance. [ABSTRACT FROM AUTHOR]

Purpose: Radioimmunotherapy with Y-ibritumomab tiuxetan has been used successfully used in the treatment of CD20-positive non-Hodgkin's lymphoma (NHL). Pretherapy imaging with In-ibritumomab tiuxetan has been used in provisional dosimetry studies. Posttherapy imaging of Y-ibritumomab tiuxetan for clinical use is appealing as it would simplify the data acquisition process and allow measurements of actual doses absorbed during treatment. Methods: The study included 29 patients with non-Hodgkin's lymphoma, of whom 16 (group I) received a pretherapy In-ibritumomab tiuxetan diagnostic study and Y-ibritumomab tiuxetan treatment 1 week later, and 13 (group II) received only Y-ibritumomab tiuxetan treatment. Planar imaging and blood sampling were performed in all patients. The doses absorbed by organs at risk were calculated using a whole-body average attenuation correction factor (relative dosimetry approach) and, in the case of the In-ibritumomab tiuxetan image sets, also using organ-specific attenuation correction factors (absolute dosimetry method). Red marrow absorbed doses were based on gamma counting of blood samples. Results: The estimated red marrow absorbed doses from In and Y data were equivalent. In all cases, the doses absorbed by organs at risk were found to be within prescribed limits. The relative dosimetry approach applied to both the Y and In data significantly underestimated the doses relative to those obtained with the In absolute dosimetry method which is generally accepted as the reference method (MIRD 16). In the case of In, the relative dosimetry approach values were highly correlated ( R = 0.61) with the reference method values. Relative dosimetry estimates may be adjusted multiplying by a correction factor of 2.8. The Y-ibritumomab tiuxetan relative dosimetry data correlated poorly with the reference method values ( R = 0.02). Conclusion: Based on patient-specific dosimetry, the administered activity may be increased by an average factor of 2.4, indicating that most patients could be undertreated. The relative dosimetry approach based on planar imaging largely underestimates doses relative to reference values. Dosimetry based on planar bremsstrahlung imaging is not a dependable alternative to In dosimetry. [ABSTRACT FROM AUTHOR]

Sentinel lymph node biopsy is widely accepted as standard care in melanoma despite lack of pertinent randomized trials results. A possible pitfall of this procedure is the inaccurate identification of the sentinel lymph node leading to biopsy and analysis of a nonsentinel node. Such a technical failure may yield a different prognosis. The purpose of this study is to analyze the incidence of false negativity and its impact on clinical outcome and to try to understand its causes. The Melanoma Data Base at National Cancer Institute of Naples was analyzed comparing results between false-negative and tumor-positive sentinel node patients focusing on overall survival and prognostic factors influencing the clinical outcome. One hundred fifty-one cases were diagnosed to be tumor-positive after sentinel lymph node biopsy and were subjected to complete lymph node dissection. Thirty-four (18.4%)patients with tumor-negative sentinel node subsequently developed lymph node metastases in the basin site of the sentinel procedure. With a median follow-up of 42.8 months the 5-year overall survival was 48.4% and 66.3% for false-negative and tumor-positive group respectively with significant statistical differences ( P < .03). The sensitivity of sentinel lymph node biopsy was 81.6%, and a regional nodal basin recurrence after negative-sentinel node biopsy means a worse prognosis, compared with patients submitted to complete lymph node dissection after a positive sentinel biopsy. The evidence of higher number of tumor-positive nodes after delayed lymphadenectomy in false-negative group compared with tumor-positive sentinel node cases, confirmed the importance of an early staging of lymph nodal involvement. Further data will better clarify the role of prognostic factors to identify cases with a more aggressive biological behavior of the disease. [ABSTRACT FROM AUTHOR]

The current study focuses the analysis on the possible relationship between HLA allele frequency and clinical outcome of melanoma in a population of 382 Italian patients, as compared with 203 ethnically matched controls. In a 3-year follow-up study, results showed significant differences between groups of patients selected according to clinical stage, histology, and progression of the disease. A*01 seems to be correlated with a less aggressive variant of the disease, whereas DRB1*01-DQB1*0501 seems to be associated with metastatic progression of melanoma. Moreover, a negative association with B*13, B*44, as well as with DRB1*04-DQB1*0302 was found. A multivariate logistic regression model showed HLA-DRB1*04 to behave as an independent favorable prognostic marker of melanoma in our population (OR = 2.34, CI = 1.15–4.74). [ABSTRACT FROM AUTHOR]

To evaluate the role of epiluminescence microscopy (ELM) in the differential diagnosis of cutaneous pigmented lesions, and to improve the early diagnosis of cutaneous malignant melanoma (CMM), 15,719 pigmented lesions from 8782 consecutive patients were evaluated using ELM with a hand-held video microscope imaging system (MS 500B Micro-Scopeman, Moritex). Comparison between risk levels as inferred from ELM screening and histology was performed on 2731 surgically excised lesions. ELM sensitivity, specificity, positive and negative predictive values, as well as agreement with histological results for the different subgroups of lesions, were determined. Overall agreement was 87·3% (ranging from 85·1% to 92·2% for melanocytic and non-melanocytic lesions, respectively); sensitivity and specificity were high (values ranging from 87·3% to 96·3% among different subsets of ELM-analysed lesions) and statistically significant (P < 0·0001). ELM screening identified 165 new cases of CMM with a high proportion of lesions (115; 70%) in an early phase of tumour growth (Breslow thickness ≤ 1·5 mm). Thus, ELM is helpful to the clinician in deciding which pigmented lesions need surgical excision, as well as in diagnosing early CMM lesions. [ABSTRACT FROM AUTHOR]

Iodine-131 metaiodobenzylguanidine (MIBG) scintigraphy, computed tomography (CT) and ultrasonography (US) were used to localize tumour lesions in 28 children with histologically proven neuroblastoma. Overall, a total of 73 lesions were detected on imaging studies. MIBG scintigraphy, CT and US localized 63 (86%), 49 (67%) and 36 (49%) of these lesions, respectively. The findings of the three imaging techniques were concordant in respect of only 31 (42%) of the lesions. The best agreement among MIBG scintigraphy, CT and US was observed for abdominal lesions (the techniques were concordant for 22 of 23 lesions, i.e. 96%). MIBG scintigraphy detected nine out of ten (90%) liver metastases, but agreement with CT and US was observed in only six instances (60%). The imaging findings were concordant in respect of only two (33%) out of six lymph node metastases; the MIBG scan was normal in the other four cases. Imaging agreement was observed for a lesion located in the pelvis. MIBG and CT findings were concordant in four lesions located in the chest, but US was not performed. MIBG scintigraphy depicted the majority (96%) of the skeletal lesions (23/24); CT showed five of these, but, again, US was not performed. The imaging findings were not concordant as regards the remaining five lesions located in different anatomical sites. The results indicated that MIBG imaging is more sensitive that CT and US in localizing the majority of neuroblastoma lesions. Since the metastatic spread of neuroblastoma is unpredictable, we recommend MIBG scintigraphy as the initial imaging modality for staging of these patients. US and, particularly, CT should be performed thereafter to clarify the anatomical detail of the lesions detected on MIBG scans, or when MIBG findings are normal or equivocal. [ABSTRACT FROM AUTHOR]

Introduction: Octreoscan (OS) is currently the gold standard for diagnosis of somatostatin receptor positive NET but it is limited by a lower spatial resolution and physiological uptake noises. DOTATATE is a somatostatin analogue, radiolabelled with 68Ga and adapted for PET imaging. Aim(s): To evaluate diagnostic performance and prognostic role of 68Ga-DOTATATE PET (DP) in NET. Materials and methods: Fifty-one patients with NET (40 sporadic, 17 MEN-I) of different origin were enrolled. DP was performed in all cases by acquiring whole body studies 40-60 min after the radioligand i.v. injection (74-111 MBq). OS was also performed in 27/51 patients using injection of Indium-111-DTPA-Phel-OSreotide (120-200 MBq). Examination results were rated considering histology, CT/MR examination and clinical follow-up. Results: DP had a patient based sensitivity and specificity of 77% and 100% and a lesion-based sensitivity and specificity of 64% and 85%, respectively. Positive and negative predictive values were 100% and 65%. The sensitivity was 100% in pancreas and gut, 75% in lung and thyroid, <50% in stomach. In the subgroup undergone both DP and OS, there was concordance in 21 and discordance in six cases (five DP positive/OS negative and one DP negative/OS positive). DP SUVmax was significantly higher in patients with stable than with progressive disease. Conclusion: In patients with NETs, DP shows higher diagnostic performance than OS and is believed to predict clinical behavior of the tumor. [ABSTRACT FROM AUTHOR]

Background: High-dose interferon-alpha 2b (IFN-alpha 2b) is the only approved systemic therapy in the United States for the adjuvant treatment of melanoma. The study objective was to explore the immunomodulatory mechanism of action for IFN-alpha 2b by measuring serum regulatory T cell (Treg), serum transforming growth factor-beta (TGF-beta), interleukin (IL)-10, and autoantibody levels in patients with melanoma treated with the induction phase of the high-dose IFN-alpha 2b regimen.Methods: Patients with melanoma received IFN-alpha 2b administered intravenously (20 MU/m2 each day from day 1 to day 5 for 4 consecutive weeks). Serum Treg levels were measured as whole lymphocytes in CD4+ cells using flow cytometry while TGF-beta, IL-10, and autoantibody levels were measured using enzyme-linked immunosorbent assays.Results: Twenty-two patients with melanoma received IFN-alpha 2b treatment and were evaluated for Treg levels. Before treatment, Treg levels were significantly higher in patients with melanoma when compared with data from 20 healthy subjects (P = 0.001; Mann-Whitney test). Although a trend for reduction of Treg levels following IFN-α 2b treatment was observed (average decrease 0.29% per week), statistical significance was not achieved. Subgroup analyses indicated higher baseline Treg levels for stage III versus IV disease (P = 0.082), early recurrence versus no recurrence (P = 0.017), deceased versus surviving patients (P = 0.021), and preoperative neoadjuvant versus postoperative adjuvant treatment groups (not significant). No significant effects were observed on the levels of TGF-beta, IL-10, and autoantibodies in patients with melanoma treated with IFN-alpha 2b.Conclusions: Patients with melanoma in this study showed increased basal levels of Treg that may be relevant to their disease and its progression. Treg levels shifted in patients with melanoma treated with IFN-alpha 2b, although no firm conclusions regarding the role of Tregs as a marker of treatment response or outcome can be made at present. [ABSTRACT FROM AUTHOR]