ALBERT

Description: Abstract 1562 Background: PET-CT is of central importance in the staging of patients with Hodgkin (HL) and non-Hodgkin aggressive lymphoma and in the assessment of their response to therapy. Repeated imaging of patients is associated with cumulative exposure to substantial doses of radiation that have been linked to an increased life attributed risk of cancer. Reduction of the PET CT imaging region will decrease significantly the cumulative radiation dose. Objectives: This study aims to evaluate whether a limited PET-CT focused to the initially involved field of view (FOV) at diagnosis, above or below the diaphragm, is sufficient for effective follow up and decision making in patients with early stage curable lymphoma. Methods: We retrospectively reviewed all patients treated in our center for HD and non-Hodgkin aggressive lymphoma that were diagnosed with stage I or II disease according to the Ann-Arbor staging system during September 2006 to December 2010. Included were patients that had a PET-CT preformed as part of their initial staging and that were followed by interim PET-CT and/or a PET CT at the completion of therapy. Clinical and epidemiologic data were extracted from the patients' medical charts. All PET-CT were reviewed by a nuclear medicine specialist. We then analyzed whether limiting the PET-CT imaging to the initially involved FOV at diagnosis, above or below the diaphragm, would miss findings obtained by standard PET CT. Results: Out of 668 patients 44 were eligible for full analysis. Patient median age at diagnosis was 37.5 years (range 19–84) and 59% of patients were females. Twenty seven patients had HD and 17 had diffuse large B cell lymphoma (DLBCL). Two cases of primary mediastinal DLBCL were included in the DLBCL group. Forty two patients had stage II disease while 2 patients were diagnosed at stage I. Thirty five patients (79%) had their lymphoma located above the diaphragm while 9 patients (21%) had disease involvement below the diaphragm. One hundred twenty seven PET-CT examinations were analyzed. Of these, 44 were preformed at diagnosis. Of the 43 interim exams preformed 32 were compatible with complete response (CR) and 11 were compatible with partial response (PR). Of the 40 PET-CT preformed at the end of treatment 34 were compatible with CR, 4 were compatible with PR and 2 showed a stable or progressive disease. There was no single case in which disease progressed outside the initially involved FOV. Thus, elements of response to therapy were contained and available for analysis within the preliminary filed of involvement in all cases. Conclusion: Our findings suggest that limiting PET-CT analysis of the initially involved FOV, above or below the diaphragm, in patients with early stage curable lymphoma may be satisfactory for response assessment and the associated clinical decision making. The use of limited PET-CT will significantly reduce patient exposure to cumulative radiation. The time required to complete limited PET-CT is reduced by 50% and the cost by more than 15%. To our best of knowledge this is the first analysis demonstrating the potential utility of reduction of PET CT FOV in curable lymphoma in adults. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 2820 Introduction: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma (NHL), yet there are no standard guidelines regarding the best chemotherapeutic regimens for its management. The most prevalent regimens, especially in advanced disease, incorporate anthracyclines. There is no proof, however, that they are superior to non-anthracycline containing regimens, or even to single agent therapy. Methods: Systematic review and meta-analysis of randomized controlled trials comparing anthracycline-containing regimens (ACR) to non-anthracycline containing chemotherapy (non-ACR) for adult patients with FL. Trials assessing rituximab or other immunotherapy were included only if the anthracycline was the only difference between study arms. A comprehensive search was conducted with no restrictions, until July 2010. Two reviewers appraised the quality of trials and extracted data. The primary outcome was overall survival. Time to event data was extracted and pooled hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Secondary outcomes included survival at 5 years, disease control defined as progression free survival (PFS) or response duration (RD), transformation rate to aggressive lymphoma, complete remission (CR), overall response (OR), and adverse events. Risk ratios (RR) for dichotomous outcomes were pooled using random effects model. Heterogeneity was assessed using the I2 measure of inconsistency. Results: We identified ten trials, conducted between the years 1974–2006 and randomizing 2422 adult patients. Nine trials included naïve patients; one included relapsed and refractory FL patients. Six trials compared between the same chemotherapeutic regimens, with the addition of anthracyclines in the intervention arm as the only difference. There was no statistically significant difference between ACR and non-ACR arms, regarding overall survival at the end of follow up or all cause mortality at five years (HR 0.97; 95% CI 0.76 – 1.23 and RR 0.94; 95% CI 0.76 – 1.17, respectively, I2=0% for both analyses). PFS and RD favored the ACR arm, with a HR of 0.69, 95% CI 0.51–0.91 for disease control, 3 studies, I2=11%. There was no significant difference with regard to CR and OR, but analyses were heterogeneous. In four out of the ten trials, different chemotherapeutic regimens were compared, and only one study-arm contained anthracyclines. Similar to the results obtained with the same regimens comparison, there was no benefit for ACR with regard to OS (HR 0.94; 95% CI 0.77 – 1.15) and mortality at five years (RR 0.98; 95% CI 0.84 – 1.16). Disease control was improved with ACR (HR 0.74; 95% CI 0.60–0.93). In all studies, there were no data regarding transformation rate to aggressive lymphoma. Toxicity data reported was insufficient for appropriate meta-analysis. Overall, ACR were more often associated with cytopenias, especially neutropenia, although the frequency of serious infections or death related to chemotherapy was similar to non-ACR. Also, alopecia and gastrointestinal side-effects, including nausea and vomiting, were more common with ACR. Cardiotoxicity was reported in five trials, and albeit rare, was associated with anthracycline use (RR 8.62; 95% CI 1.58 to 47.05). Conclusion: The use of anthracyclines in patients with FL has no demonstrable benefit on overall survival. However, ACR improve disease control, as measured by progression free survival and response duration with an increased risk for side effects, notably cardiotoxicity. Disclosures: Shpilberg: Roche: Consultancy, Honoraria.

Description: Background High dose chemo/radiotherapy with autologous hematopoietic cell transplantation (HCT) has been shown to be an effective therapy for a variety of malignancies. However, as more patients survive both the disease and the early post HCT period, it has become apparent that other potential long term complications, mainly secondary malignancies may hamper patients' prospects. Objectives We analyzed the incidence of different secondary malignancies occurring after consolidation with autologous HCT compared to other modalities for the treatment of various hematological and non-hematological malignancies. Methods Systematic review and meta-analysis of randomized controlled trials comparing high dose therapy with autologous HCT to other treatment modalities (observation, immunotherapy or chemotherapy). We searched the Cochrane Library, MEDLINE and conference proceedings. Outcomes assessed were rates of AML/MDS, solid tumors and overall secondary malignancies. Relative risks (RR) with 95% confidence intervals (CIs) were estimated and pooled. Heterogeneity is given when approporiate. Results Our search yielded 74 trials fulfilling inclusion criteria; among them 38 trials recruiting 10131 patients reporting secondary malignancies were included. Baseline diseases were lymphoproliferative diseases (n=17), plasma cell dyscrasias [PCD] (n=5) and solid tumors (n=16). The studies were conducted between the years 1987 and 2007. Median follow up was 55 (range 12-144) months. High dose therapy consisted of variety of regimens. Comparative arm regimens were either observation (n= 6), intensive chemotherapy [〉6 gr/m2 of cyclophosphamide or high doses of etoposide] (n= 6), or standard chemotherapy (n= 24). Overall, the RR for secondary malignancies was 1.25 (95% CI 0.99-1.57) (38 studies, 10131 pts). Among all patients, there was a higher rate of MDS/AML in patients given HCT compared to other treatments [RR=1.71 (95% CI 1.18-2.48)], (33 studies, 8778 patients), Figure. Subgroup analysis showed similar results in patients with lymphoproliferative diseases [RR=2.35 (95% CI 1.36-4.05), (16 studies, 3090 patients)]. However, the rate of AML/MDS was not increased in patients treated for PCD or solid malignancies [RR=1.41 (95% CI 0.28-7.08), 3 studies, 304 patients and RR=1.24 (95% CI 0.72-2.15), 14 studies, 5384 pts, respectively], Figure. Subgroup analysis based on the comparator's intensity- showed a higher rate of MDS/AML merely in patients given HCT compared to observation and to low intensity [RR=4.86 (95% CI 1.43-16.47), (5 studies, 732 patients) and RR=2.09 (95% CI 1.30-3.35), (19 studies, 6036 patients)]. Overall, there was no difference in the rate of secondary solid malignancies between patients given HCT and patients given other treatments [RR=0.95 (95% CI 0.67-1.32), (19 studies, 5925 patients)], with similar results in subgroup analysis according to the baseline diseases. Conclusions The rate of secondary MDS/AML is higher in patients given high dose therapy and autologous HCT compared to other treatment options, with statistically significant higher rates only in the subgroup of patients with lymphoproliferative diseases. The rate of secondary solid malignancies is similar among all patients given either high dose therapy or alternative therapy. Disclosures: No relevant conflicts of interest to declare.