Prognostic value of baseline metabolic tumor volume in early-stage Hodgkin lymphoma in the standard arm of the H10 trial.

We tested baseline positron emission tomography (PET)/computed tomography (CT) as a measure of total tumor burden to better identify high-risk patients with early-stage Hodgkin lymphoma (HL). Patients with stage I-II HL enrolled in the standard arm (combined modality treatment) of the H10 trial (NCT00433433) with available baseline PET and interim PET (iPET2) after 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine were included. Total metabolic tumor volume (TMTV) was measured on baseline PET. iPET2 findings were reported negative (DS1-3) or positive (DS4-5) with the Deauville scale (DS). The prognostic value of TMTV was evaluated and compared with baseline characteristics, staging classifications, and iPET2. A total of 258 patients were eligible: 101 favorable and 157 unfavorable. The median follow-up was 55 months, with 27 progression-free survival (PFS) and 12 overall survival (OS) events. TMTV was a prognosticator of PFS (P < .0001) and OS (P = .0001), with 86% and 84% specificity, respectively. Five-year PFS and OS were 71% and 83% in the high-TMTV (>147 cm3) group (n = 46), respectively, vs 92% and 98% in the low-TMTV group (≤147 cm3). In multivariable analysis including iPET2, TMTV was the only baseline prognosticator compared with the current staging systems proposed by the European Organization for Research and Treatment of Cancer/Groupe d'Etude des Lymphomes de l'Adulte, German Hodgkin Study Group, or National Comprehensive Cancer Network. TMTV and iPET2 were independently prognostic and, combined, identified 4 risk groups: low (TMTV≤147+DS1-3; 5-year PFS, 95%), low-intermediate (TMTV>147+DS1-3; 5-year PFS, 81.6%), high-intermediate (TMTV≤147+DS4-5; 5-year PFS, 50%), and high (TMTV>147+DS4-5; 5-year PFS, 25%). TMTV improves baseline risk stratification of patients with early-stage HL compared with current staging systems and the predictive value of early PET response as well.

Interim Positron Emission Tomography Response-Adapted Therapy in Advanced-Stage Hodgkin Lymphoma: Final Results of the Phase II Part of the HD0801 Study.

PURPOSE: The clinical impact of positron emission tomography (PET) evaluation performed early during first-line therapy in patients with advanced-stage Hodgkin lymphoma, in terms of providing a rationale to shift patients who respond poorly onto a more intensive regimen (PET response-adapted therapy), remains to be confirmed. PATIENTS AND METHODS: The phase II part of the multicenter HD0801 study involved 519 patients with advanced-stage de novo Hodgkin lymphoma who received an initial treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and who underwent an early ifosfamide-containing salvage treatment followed by stem-cell transplantation if they showed a positive PET evaluation after two cycles of chemotherapy (PET2). The primary end point was 2-year progression-free survival calculated for both PET2-negative patients (who completed a full six cycles of ABVD treatment) and PET2-positive patients. Overall survival was a secondary end point. RESULTS: In all, 103 of the 512 evaluable patients were PET2 positive. Among them, 81 received the scheduled salvage regimen with transplantation, 15 remained on ABVD (physician's decision, mostly because of minimally positive PET2), five received an alternative treatment, and two were excluded because of diagnostic error. On intention-to-treat analysis, the 2-year progression-free survival was 76% for PET2-positive patients (regardless of the salvage treatment they received) and 81% for PET2-negative patients. CONCLUSION: Patients with advanced-stage Hodgkin lymphoma for whom treatment was at high risk of failing appear to benefit from early treatment intensification with autologous transplantation, as indicated by the possibility of successful salvage treatment in more than 70% of PET2-positive patients through obtaining the same 2-year progression-free survival as the PET2-negative subgroup.

The prognostic value of positron emission tomography performed after two courses (INTERIM-PET) of standard therapy on treatment outcome in early stage Hodgkin lymphoma: A multicentric study by the fondazione italiana linfomi (FIL).

This retrospective study included 246 patients with a new diagnosis of Hodgkin Lymphoma (HL) with a localized-stage (IA-IIA), consecutively admitted from January 2002 to December 2008, by twelve Italian hematological centers on behalf of Fondazione Italiana Linfomi (FIL). Patients were staged at baseline and after two cycles of chemotherapy with PET. All patients were treated with four cycles of ABVD followed by involved-field radiotherapy. No treatment change, based on PET-2 results was allowed. Endpoint of the study was the predictive role of PET-2 on 2-y failure-free survival (FFS). PET-2 was positive in 36 patients (15%) and negative in 210. After a mean follow-up of 46 (3-105) months 19/36 PET-2 positive patients progressed or relapsed and 17 achieved and maintained a CCR. The positive and negative predictive value of a PET2 was 53% and 95%, respectively. The sensibility, specificity and accuracy of PET2 were 65.5%, 92% and 89%, respectively. PET-2 positive scans were centrally reviewed according to the recently defined Deauville Criteria. Upon review the PPV and NPV was 73% and 96% overall. Factors with prognostic significance for progression in univariate analysis were a positive PET-2 (P = 0.000) and the presence of bulky disease (P < 0.01). In a multivariate analysis the only factor that affected negatively FFS was a positive PET-2 (P = 0.000). This study confirms that interim-PET could be considered a prognostic test also in early stage HL, but is unlikely to be a factor that will justify the change of therapeutical approach.

A systematic review and meta-analysis of total thyroidectomy versus bilateral subtotal thyroidectomy for Graves' disease.

BACKGROUND: Our aim was to perform a meta-analysis of high-quality published trials, randomized and observational, comparing total thyroidectomy (TT) and bilateral subtotal thyroidectomy (ST) for Graves' disease. METHODS: All studies published from 1970 to August 2012 were identified. All randomized controlled trials (RCTs) were included. Selection of high-quality, nonrandomized comparative studies (NRCTs) was based on a validated tool (Methodological Index for Nonrandomized Studies). Recurrent hyperthyroidism during follow-up, progression of ophthalmopathy, postoperative temporary and permanent hypoparathyroidism, and permanent recurrent laryngeal nerve (RLN) palsy were compared using odds ratios (ORs). RESULTS: Twenty-three studies were included (4 RCTs and 19 NRCTs) compromising 3,242 patients (1,665 TT, 1,577 ST). TT was associated with a decrease in recurrent hyperthyroidism (P < .00001; OR, 0.10; 95% confidence interval [CI], 0.06-0.18), but with an increase in both temporary (P < .00001; OR, 2.70; 95% CI, 2.04-3.56) and permanent hypoparathyroidism (P = .005; OR, 2.91; 95% CI, 1.59-5.32). Progression of ophthalmopathy (P = .76; OR, 0.90; 95% CI, 0.48-1.71) and permanent RLN palsy (P = .82; OR, 0.91; 95% CI, 0.41-2.02) were similar. CONCLUSION: TT offers a better chance of cure of hyperthyroidism than bilateral ST and can be accomplished safely with only a small increase in temporary and permanent hypoparathyroidism.

Early interim 18F-FDG PET in Hodgkin's lymphoma: evaluation on 304 patients.

PURPOSE: The use of early (interim) PET restaging during first-line therapy of Hodgkin's lymphoma (HL) in clinical practice has considerably increased because of its ability to provide early recognition of treatment failure allowing patients to be transferred to more intensive treatment regimens. METHODS: Between June 1997 and June 2009, 304 patients with newly diagnosed HL (147 early stage and 157 advanced stage) were treated with the ABVD regimen at two Italian institutions. Patients underwent PET staging and restaging at baseline, after two cycles of therapy and at the end of the treatment. RESULTS: Of the 304 patients, 53 showed a positive interim PET scan and of these only 13 (24.5%) achieved continuous complete remission (CCR), whereas 251 patients showed a negative PET scan and of these 231 (92%) achieved CCR. Comparison between interim PET-positive and interim PET-negative patients indicated a significant association between PET findings and 9-year progression-free survival and 9-year overall survival, with a median follow-up of 31 months. Among the early-stage patients, 19 had a positive interim PET scan and only 4 (21%) achieved CCR; among the 128 patients with a negative interim PET scan, 122 (97.6%) achieved CCR. Among the advanced-stage patients, 34 showed a persistently positive PET scan with only 9 (26.4%) achieving CCR, whereas 123 showed a negative interim PET scan with 109 (88.6%) achieving CCR. CONCLUSION: Our results demonstrate the role of an early PET scan as a significant step forward in the management of patients with early-stage or advanced-stage HL.

Positron emission tomography in the staging of patients with Hodgkin's lymphoma. A prospective multicentric study by the Intergruppo Italiano Linfomi.

In this prospective multicentric study, we investigated the contribution of positron emission tomography (PET) scanning to the staging of Hodgkin's lymphoma (HL) by computed tomography (CT) and attempted to determine whether it has any impact on therapeutic approach. One hundred eighty six consecutive patients with HL from six Italian centers were enrolled in this study. They were staged with conventional methods; 2-[fluorine-18]fluoro-2-deoxy-D: -glucose PET scanning were prospectively compared to CT. CT and FDG-PET stages were concordant in 156 patients (84%) and discordant in 30 patients (16%). PET stage in comparison to CT stage was higher in 27 patients (14%) and lower in 3 patients (1%). The programmed treatment strategy was modified in 11 out of 30 patients (37%) after the definition of final stage. If we considered the 123 CT staged patients with localized stage, ten patients (8%) with a change of stage from localized to advanced after PET evaluation were treated with different strategy. FDG-PET was shown to be a relevant, non-invasive method that supplements conventional procedures and should therefore be used routinely to stage HL, particularly in early stage patients, where a change in stage may modify disease management.

The predictive value of positron emission tomography scanning performed after two courses of standard therapy on treatment outcome in advanced stage Hodgkin's disease.

BACKGROUND AND OBJECTIVES: We explored the predictive value on therapy outcome of an early evaluation of treatment response by 18F-fluorodeoxyglucose position emission tomography (18F-FDG-PET) scan performed after two courses of conventional standard-dose chemotherapy in advanced-stage Hodgkin's disease. DESIGN AND METHODS: One hundred and eight patients with newly-diagnosed Hodgkin's disease in stage IIA with adverse prognostic factors, or in stage IIB through IVB, were re-staged with FDG-PET after two cycles of ABVD (PET-2). The end-point of the study was the predictive value of PET-2 on 2-year progression-free survival and 2-year failure-free survival. No treatment variation based only on PET-2 results was allowed. RESULTS: Eighty-eight patients attained complete remission (CR) while 20 showed disease progression during therapy or within 6 months after having reached CR; one patient relapsed. PET-2 was positive in 20 patients: 17 progressed during therapy, one relapsed and two remained in CR. By contrast, 85/88 (97%) patients with a negative PET-2 remained in CR; three progressed or relapsed early after the end of the chemotherapy. Thus, the positive predictive value of a PET-2 was 90% and the negative predictive value was 97%. The sensitivity, specificity and overall accuracy of PET-2 were 86%, 98% and 95%, respectively. The 2-year probability of failure-free survival for PET-2 negative and for PET-2 positive patients was 96% and 6%, respectively (log rank test = 116.7, p < 0.01). INTERPRETATION AND CONCLUSIONS: 18F-FDG-PET scan performed after two courses of conventional standard-dose chemotherapy in advanced-stage Hodgkin's disease was able to predict treatment outcome in 103/108 (95%) of the patients.

18FDG-positron emission tomography in post treatment evaluation of residual mass in Hodgkin's lymphoma: long-term results.

In patients with Hodgkin's lymphoma (HL) at the end of first line therapy an accurate imaging technique with high prognostic value is needed to assess response to treatment and predict those patients who will suffer disease relapse. This technique and its results permit the quick initiation of a second line therapy in patients suffering from a progressive disease or those unresponsive to treatment avoid over-treatment of patients in complete remission or those having a non-active residual disease. We included a (18)FDG-positron emission tomography (PET) scan to the diagnostic set-up to investigate 28 patients following the end of their treatment. Fifteen patients out of the 28 (54%) had positive CT scans while 13 (46%) had negative ones. Eleven patients out of the 15 CT positive (73%) had negative PET scans and no relapse. The remaining four patients (27%) had positive PET scans with only one relapse (25%). With respect to the 13 patients who had negative CT scans, 9 patients (69%) had negative PET scans and no relapse. The remaining 4 patients (31%) had positive PET scans with 3 relapse cases (75%). In our final assessment after a median follow-up period of 45 months, starting from PET execution to the last follow-up, overall sensitivity of the CT and the PET were 25 and 100% respectively, specificity 42 and 83% respectively, positive predictive value (PPV) 7 and 50% respectively, negative predictive value (NPV) 77 and 100% respectively, and accuracy 39 and 86% respectively. In our experience, FDG-PET performed in patients after induction therapy appears to offer important additional information: FDG-PET results are predictors of prognosis giving 100% DFS in PET negative patients and 54% DSF in PET positive patients.

PET scan evaluation of thymic mass after autologous peripheral blood stem-cell transplantation in an adult with non-Hodgkin's lymphoma.

We report the case of a 31-year-old man with anaplastic large-cell lymphoma successfully treated with chemotherapy who showed mediastinal widening 5 months after autologous stem-cell transplantation. CT scan and PET evaluations were consistent with the diagnosis of benign thymic hyperplasia. Because of the rapid and aggressive course of this type of lymphoma, and the progressive widening of the mass at CT scan, we performed a mediastinal biopsy that confirmed these findings, showing normal thymic tissue. This is the first case of benign thymic hyperplasia defined with FDG-PET and confirmed by histologic evaluation.