Antonino Mulè

Early chemotherapy intensification with BEACOPP in advanced-stage Hodgkin lymphoma patients with a interim-PET positive after two ABVD courses

Interim 2‐[18F]Fluoro‐2‐deoxy‐D‐glucose Positron Emission Tomography performed after two chemotherapy cycles (PET‐2) is the most reliable predictor of treatment outcome in ABVD‐treated Hodgkin Lymphoma (HL) patients. We retrospectively analysed the treatment outcome of a therapeutic strategy based on PET‐2 results: positive patients switched to BEACOPP, while negative patients continued with ABVD. Between January 2006 and December 2007, 219 newly diagnosed HL patients admitted to nine centres were enrolled; 54 patients, unfit to receive this treatment were excluded from the analysis. PET‐2 scans were reviewed by a central panel of nuclear medicine experts, according to the Deauville score ( Meignan, 2009 ). After a median follow up of 34 months (12–52) the 2‐year failure free survival (FFS) and overall survival for the entire cohort of 165 patients were 88% and 98%; the FFS was 65% for PET‐2 positive and 92% for PET‐2 negative patients. For 154 patients in which treatment was correctly given according to PET‐2 review, the 2‐year FFS was 91%: 62% for PET‐2 positive and 95% for PET‐2 negative patients. Conclusions: this strategy, with BEACOPP intensification only in PET‐2 positive patients, showed better results than ABVD‐treated historic controls, sparing BEACOPP toxicity to the majority of patients (Clinical Trials.gov Identifier NCT00877747).

Risk Factors for the Development of Secondary Malignancy After High-Dose Chemotherapy and Autograft, With or Without Rituximab: A 20-Year Retrospective Follow-Up Study in Patients With Lymphoma

PURPOSE High-dose chemotherapy with peripheral blood progenitor cell (PBPC) autograft is effective in high-risk lymphoma, particularly with the addition of rituximab; however, it is associated with risk of secondary malignancy. These issues have been addressed in a series of 1,347 patients with lymphoma treated with a high-dose sequential (HDS) program. PATIENTS AND METHODS A total of 1,024 patients with B-cell lymphoma, 234 patients with Hodgkins lymphoma, and 89 patients with T-cell lymphoma were treated with HDS between 1985 and 2005 at 11 Gruppo Italiano Terapie Innovative Linfomi centers. HDS was given as salvage treatment to 707 patients (52%); 655 patients (49%) received a modified HDS, with high-dose cytarabine and two consecutive PBPC harvests. Rituximab-supplemented HDS was given to 523 patients (39%). RESULTS At a median follow-up of 7 years, the median overall survival (OS) was 16.2 years; in B-cell lymphoma the OS was significantly superior with rituximab HDS compared to HDS alone. The cumulative incidence at 5 and 10 years of secondary myelodysplasia/acute leukemia (sMDS/AL) were 3.09% and 4.52%, respectively, that of solid tumors were 2.54% and 6.79%, respectively. Factors associated with sMDS/AL were male sex and use of the second harvest PBPC for the graft; factors found to be associated with solid tumor were advanced age, post-HDS radiotherapy, and rituximab addition to HDS. Despite the increased risk of solid tumors, rituximab addition to HDS was still associated with survival advantages. CONCLUSION This analysis has relevant implications for the design and use of intensive chemoimmunotherapy with autograft. In addition, it offers useful insights toward the understanding and prevention of tumor development.

Characterization of Solid Breast Masses Use of the Sonographic Breast Imaging Reporting and Data System Lexicon

Objective. The purpose of this study was to determine the reliability of sonographic American College of Radiology Breast Imaging Reporting And Data System (BI‐RADS) classification in differentiating benign from malignant breast masses. Methods. One hundred seventy‐eight breast masses studied by sonography with a known diagnosis were reviewed. All lesions were classified according to the sonographic BI‐RADS lexicon. Pathologic results were compared with sonographic features. Sensitivity, specificity, accuracy, and positive predictive value (PPV) and negative predictive value (NPV) for the sonographic BI‐RADS lexicon were calculated. Results. Twenty‐six cases were assigned to class 3, 73 to class 4, and 79 to class 5. Pathologic results revealed 105 malignant and 73 benign lesions. The sonographic BI‐RADS lexicon showed 71.3% accuracy, 98.1% sensitivity, 32.9% specificity, 67.8% PPV, and 92.3% NPV. The NPV for class 3 was 92.3%. The PPVs for classes 4 and 5 were 46.6% and 87.3%. Typical signs of malignancy were irregular shape, antiparallel orientation, noncircumscribed margin, echogenic halo, and decreased sound transmission. Typical signs of benignity were oval shape and circumscribed margin. Conclusions. The sonographic BI‐RADS lexicon is an important system for describing and classifying breast lesions.

Simultaneous immunohistochemical expression of HBME-1 and galectin-3 differentiates papillary carcinomas from hyperfunctioning lesions of the thyroid

Aims : The histological diagnosis is critical for the postsurgical management and follow‐up of thyroid malignancies. The differential diagnosis between papillary carcinoma and hyperfunctioning lesions, either with papillary hyperplasia or with a follicular architecture, can create real diagnostic difficulty. The aim of this study was to evaluate the expression of several antibodies considered to be markers of malignancy in malignant and hyperfunctioning thyroid neoplasms and to include the most effective of them in a diagnostic panel.

Diagnostic efficacy of immunocytochemistry on fine needle aspiration biopsies processed by thin-layer cytology.

OBJECTIVE To evaluate the efficacy of immunocytochemistry (ICC) performed on smears processed by thin-layer cytology (TLC). STUDY DESIGN During the period January 2001-September 2003, 3,573 consecutive fine needle aspiration biopsies were processed with both conventional smears (CSs) and TLC diagnosed by a single pathologist; 113 required immunocytochemical study. CSs were fixed in ethanol whereas TLC slides were processed with the ThinPrep 2000 method (Cytyc Co., Marlborough, Massachusetts, U.S.A); both were stained with Papanicolaou stain. ICC staining was carried out on only TLC slides. RESULTS The 113 cytologic cases were grouped as follows: 32 thyroid nodules with 16 histologic controls (HCs), 24 lymph nodes (regardless of location) with 15 HCs, 18 liver and pancreatic lesions (3 HCs), 11 lung nodules (6 HCs), 5 kidney and adrenal gland lesions (1 HC), 6 abdominal (2 HCs) and 4 mediastinal masses (1 HC), 6 salivary gland tumors (3 HCs), 4 bone masses (2 HCs) and 3 subcutaneous lesions (1 HC). ICC contributed to the diagnosis in 104 cases (92%), whereas it was inconclusive in 9. The cytologic diagnoses were histologically confirmed in 46 of 50 cases (92%). CONCLUSION ICC can be successfully applied on TLC slides with better results than on CSs, and its yield can be useful in making the correct diagnosis on fine needle aspiration biopsy.

Diffusion-weighted Imaging in Evaluating the Response to Neoadjuvant Breast Cancer Treatment

Abstract:  The aim of this study was to investigate the role of diffusion imaging in the evaluation of response to neoadjuvant breast cancer treatment by correlating apparent diffusion coefficient (ADC) value changes with pathological response. From June 2007 to June 2009, all consecutive patients with histopathologically confirmed breast cancer undergoing neoadjuvant chemotherapy were enrolled. All patients underwent magnetic resonance imaging (MRI) (including diffusion sequence) before and after neoadjuvant treatment. The ADC values obtained using two different methods of region of interest (ROI) placement before and after treatment were compared with MRI response (assessed using RECIST 1.1 criteria) and pathological response (assessed using Mandard’s classification).

High Doses of Antimetabolites Followed by High-Dose Sequential Chemoimmunotherapy and Autologous Stem-Cell Transplantation in Patients With Systemic B-Cell Lymphoma and Secondary CNS Involvement: Final Results of a Multicenter Phase II Trial

PURPOSE Treatment of secondary CNS dissemination in patients with aggressive lymphomas remains an important, unmet clinical need. Herein, we report the final results of a multicenter phase II trial addressing a new treatment for secondary CNS lymphoma based on encouraging experiences with high doses of antimetabolites in primary CNS lymphoma and with rituximab plus high-dose sequential chemoimmunotherapy (R-HDS) in relapsed aggressive lymphoma. PATIENTS AND METHODS HIV-negative patients with aggressive B-cell lymphoma and secondary CNS involvement at diagnosis or relapse, age 18 to 70 years, and Eastern Cooperative Oncology Group performance status ≤ 3 were enrolled and treated with high-doses of methotrexate and cytarabine, followed by R-HDS (cyclophosphamide, cytarabine, and etoposide) supported by autologous stem-cell transplantation (ASCT). Treatment included eight doses of rituximab and four doses of intrathecal liposomal cytarabine. The primary end point was 2-year event-free survival; the planned accrual was 38 patients. RESULTS Thirty-eight patients were enrolled; CNS disease was detected at presentation in 16 patients. Toxicity was usually hematologic and manageable, with grade 4 febrile neutropenia in 3% of delivered courses and grade 4 nonhematologic toxicity in 2% of delivered courses. Four patients died because of toxicity. Autologous stem cells were successfully collected in 24 (89%) of 27 patients (median, 10 × 10(6)/kg); 20 patients underwent ASCT. Complete response was achieved in 24 patients (complete response rate, 63%; 95% CI, 48% to 78%). At a median follow-up of 48 months, 17 patients remained relapse free, with a 2-year event-free survival rate of 50% ± 8%. At 5 years, 16 patients were alive, with a 5-year overall survival rate of 41% ± 8% for the whole series and 68% ± 11% for patients who received transplantation. Systemic (extra-CNS) and/or meningeal disease did not affect outcome. CONCLUSION The combination of high doses of antimetabolites, R-HDS, and ASCT is feasible and effective in patients age 18 to 70 years old with secondary CNS lymphoma, and we propose it as a new standard therapeutic option.

Diagnostic efficacy of conventional as compared to liquid-based cytology in thyroid lesions. Evaluation of 10,360 fine needle aspiration cytology cases

OBJECTIVE To evaluate the efficacy of thyroid fine needle aspiration cytology (FNAC) processed by liquid-based cytology (LBC) as compared to conventional smears (CS) in 10,360 consecutive cases in 3 reference periods. STUDY DESIGN In 1997-1998, 2,394 FNACs had CS; in 2001-2002, 3,463 had both CS and LBC; and in 2004-2005, 4,503 had only LBC. Three arbitrary parameters of efficacy were chosen to compare the two different methods: rate of inadequacy (IR), rate of indeterminacy (INDR) and rate of malignancy (MR). In the same biennia 6,184 thyroidectomy specimens were examined. RESULTS IR was, respectively, 8.4% in 1997-1998, 18.4% in 2001-2002 and 13.3% in 2004-2005. MR was respectively 2.2%, 2.5% and 2.2%. INDR was 16.6% in 1997-1998, 23.3% in 2001-2002 and 15.9% in 2004-2005. In each biennium, respectively, 16.9%, 27.6% and 28% of malignant neoplasms were histologically diagnosed. CONCLUSION LBC was used as an alternative method in the cytologic diagnosis for the preoperative selection of thyroid neoplasms, decreasing indeterminate diagnoses without MR changes.

Helicobacter pylori eradication as exclusive treatment for limited-stage gastric diffuse large B-cell lymphoma: results of a multicenter phase 2 trial.

To the editor: We read with great interest the article by Kuo et al on a retrospective study of Helicobacter pylori ( Hp ) eradication as exclusive treatment in Taiwanese patients with early-stage gastric diffuse large B-cell lymphoma (DLBCL).[1][1] Interestingly, a substantial portion of these

Comparison between whole-body MRI with diffusion-weighted imaging and PET/CT in staging newly diagnosed FDG-avid lymphomas.

OBJECTIVES To compare whole body-MRI (WB-MRI) with diffusion-weighted imaging and FDG-PET/CT in staging newly diagnosed FDG-avid lymphomas. METHODS 68 patients (37 males, 31 females; median age 42 years; range 15-86 years) with histologically confirmed lymphoma (37 Classical Hodgkin, 16 Diffuse large B-cell, 10 Follicular, 5 Mantle cell) underwent both MRI and FDG-PET/CT before treatment. Ann Arbor stages obtained with WB-MRI and FDG-PET/CT were compared using Cohens k statistics. Moreover WB-MRI and FDG-PET/CT stages were compared with the pathological stages obtained after the diagnostic iter using also bone marrow and available biopsies if clinically indicated. RESULTS The agreement between WB-MRI and FDG-PET/CT was excellent. WB-MRI stage was equal to those of FDG-PET/CT in 62/68 patients (91.2%). There was an excellent agreement between WB-MRI stage and pathological stage (63/68 patients; 92.6%), and between FDG-PET/CT and pathological stage (64/68 patients; 94.1%). The differences between the stages were more frequent in the patients with Mantle cell lymphoma. CONCLUSIONS WB-MRI can be considered as a promising technique for FDG-avid lymphoma staging.