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Summary Objectives To determine the prevalence of hepatitis C virus (HCV) infection in patients with B-cell non-Hodgkin's lymphoma (NHL) in British Columbia. Design A cross-sectional analysis. Setting The British Columbia Cancer Agency (BCCA), a Canadian provincial tertiary oncology referral center. Subjects Consecutive patients with B-cell NHL registered onto the BCCA lymphoma database in 1996 and part of 1997 and a control group of patients with T-cell NHL registered on the database from 1995 through 1997. Patients with HIV infection were excluded from the analysis. A second control group (n = 1085) consisted of health-care workers tested for HCV infection following a needle-stick injury. Interventions Stored sera from patients with B-cell NHL (n = 88) and T-cell NHL (n = 37), identified from the database, were tested for the presence of HCV infection with commercially available serologic tests. Main outcome measures HCV seropositivity in the B-cell lymphoma group compared to the control groups (T-cell NHL and health-care workers). Results 2.3% of the B-cell NHL group, none of the T-cell NHL group and 1% of the health-care worker control group were positive for HCV infection. These results were not statistically significantly different. Conclusion Patients in British Columbia with B-cell NHL do not have an increased prevalence of HCV infection. These data suggest that the lymphotrophism of HCV may differ by regional, racial and genotypic variations around the world.

Background: Consolidative radiotherapy (RT) is frequently administered to patients (pts) with classical Hodgkin lymphoma (CHL) that have bulky disease at diagnosis and/or residual abnormalities on post-chemotherapy CT imaging. However, this may contribute to the development of secondary malignancies and cardiac disease. The HD15 trial demonstrated that RT can be omitted in cases with residual disease on CT imaging following BEACOPP-based chemotherapy that are PET-negative (PET-neg). It is unknown whether this can be extended to patients treated with ABVD chemotherapy including patients presenting with a bulky disease at diagnosis. Further, it is unclear whether consolidative RT can be used to salvage cases that are PET positive (PET-pos) following ABVD. Methods: The British Columbia (BC) Cancer Agency Centre for Lymphoid Cancer Database and case records were screened to identify all adult (> 16 y) pts with advanced stage CHL (stage 1 bulky (> 10cm), stage 2 with B symptoms and/or bulky disease and all stage III/IV) treated with curative intent using ABVD chemotherapy who underwent a restaging PET scan at the end of treatment. Clinical factors including mass size at diagnosis, mediastinal involvement, residual mass size post therapy and relapse site were collected. Patients that were HIV positive, had refractory disease (progression during chemotherapy or at the time of post-treatment imaging) or toxicity that precluded response evaluation, were excluded for this analysis. Since July 2005, all pts in BC with advanced stage HL, including those with bulky disease, were recommended to be treated with 6 cycles of ABVD followed by a PET scan if residual abnormalities > 2 cm were observed on CT imaging. Results: In total, 316 pts with CHL who met the above criteria were identified. Pt characteristics were: 48% females; median age 33 y (16-82 y); stage 1 1.3%; stage 2 47.2%; stage III/IV 51.5%; extranodal disease 40.5%; B symptoms 66%; 13% international prognostic score > 4 13%; bulky disease 62%. At the end of treatment, 264 (83.5%) were PET-neg (indeterminate n=4), none of whom received RT, and 52 (16.5%) were PET-pos, of which 79% (n=41) received consolidative RT (30-35 Gy). With a median follow-up for living pts of 4.6 y (range 0.6 - 13.5 y), the 5-y freedom from treatment failure (FFTF) for the whole cohort was 83% and 5-y overall survival (OS) was 94.5%. Overall, pts with a PET-neg scan post treatment had a superior 5-y FFTF compared to those with a PET-pos scan (89% vs 56%, P < 0.00001) (Figure 1a). In the PET-neg group, there was no difference in outcome comparing the bulky (n=112) and non-bulky (n=152) subgroups (5-y FFTF 89% vs 88.5%, p=0.50, respectively, Figure 1b; 5-y OS 96% vs 94%, P=0.51). Similar survival estimates were observed when the analysis is restricted to PET-neg cases with a bulky mediastinal mass at diagnosis (n=102) (5 y FFTF 89%; 5 y OS 96%). Of the PET-pos pts who were able to receive consolidative RT (PET-pos RT) (n=41), the 5-y FFTF was 60% and the 5 y OS was 94%. For those with mediastinal PET-pos disease who received RT (n=29, 72% bulky at diagnosis), the 5-y FFTF was 69.5%. For all PET-pos RT pts, 13 subsequently relapsed: 1 within the RT field only; 5 outside of the RT field only; and 7 relapsed both within and outside of the RT field. Conclusions: Advanced stageCHL pts, including those with bulky disease, that have a negative PET scan following ABVD chemotherapy have an excellent outcome without additional consolidative RT, thus potentially avoiding long-term effects. Radiotherapy may be useful in select responding patients with PET-pos residual uptake. With a PET-guided approach, we have significantly reduced the need for RT. Disclosures Savage: Seattle Genetics: Honoraria, Speakers Bureau; BMS: Honoraria; Infinity: Honoraria; Roche: Other: Institutional research funding. Connors:Seattle Genetics: Research Funding; Roche: Research Funding. Villa:Lundbeck: Honoraria. Gerrie:Janssen: Other: Advisory board; Roche: Honoraria, Other: Advisory board, Research Funding; Lundbeck: Honoraria, Other: Advisory board, Research Funding. Shenkier:Roche: Honoraria, Other: Travel funds. Scott:Celgene: Consultancy, Honoraria. Pickles:Janssen: Honoraria; Oncura: Honoraria; Sanofi: Honoraria; Abbvie: Honoraria; Amgen: Honoraria, Other: Advisory board; Astellas: Honoraria, Other: Advisory board.

Low-grade primary central nervous system lymphoma (PCNSL) is a rare variant of PCNSL. Although little is known about its precise incidence and clinical characteristics, the available data suggest that low-grade PCNSL may have a distinct clinical presentation, radiographic characteristics on magnetic resonance imaging, and prognosis as compared to classic high-grade PCNSL. Most importantly, survival data on low-grade PCNSL appear to be more favorable as compared to classic high-grade PCNSL, even with treatment strategies generally not considered efficient enough to treat classic high-grade PCNSL. T-cell PCNSL represents a small proportion of all PCNSL. The presentation and outcome seem to be similar to that of B-cell PCNSL. Good performance status and administration of methotrexate appear to be associated with improved survival. Pediatric PCNSL is extremely rare, and the optimal management is yet to be defined. Except for human immunodeficiency virus-related PCNSL, the prognosis for pediatric patients with this tumor appears to be significantly better than in adults. Most children with PCNSL can achieve long-term remissions with intensive chemotherapy alone (70% 5-year event-free survival), while cranial irradiation is usually reserved for relapsed disease. Further progress in the management of childhood PCNSL will require large prospective multinational trials.

The addition of rituximab (R) to standard CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy has altered the significance of previously recognized prognostic factors. We sought to re-examine the prognostic utility of (1) the number of extranodal sites of disease involvement, and (2) a primary extranodal presentation in patients with DLBCL treated with immunochemotherapy. We retrospectively analyzed all patients with DLBCL diagnosed between January 1979 and May 2006 who were treated with an anthracycline-based therapy with curative intent. In all, 1781 patients were identified, of whom 513 (29%) received R-CHOP. In the R-CHOP group, extranodal involvement as defined by the International Prognostic Index (>or=2 sites) was not prognostic on multivariate analysis, but the presence of any extranodal involvement (>or=1 site) was associated with decreased progression-free survival (HR 1.6, 95% CI 1.1-2.4, p = 0.024) and overall survival (HR 1.8, 95% CI 1.1-2.7, p = 0.011). A total of 133 (26%) R-CHOP treated patients presented with primary extranodal DLBCL. There was no difference in outcome between patients with primary extranodal and nodal DLBCL, and no primary site of involvement was associated with an inferior outcome. In patients with DLBCL treated with R-CHOP, the presence of extranodal disease remains prognostic, whereas a primary extranodal presentation did not affect outcome.

Background: The addition of rituximab to CHOP (R-CHOP; CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy improves outcome in patients with diffuse large B-cell lymphoma (DLBCL). We evaluated the risk of central nervous system (CNS) relapse in the R-CHOP in a population-based cohort of patients with DLBCL. Methods: Patients with DLBCL diagnosed from 1 September 1999 to 14 January 2005 at the British Columbia Cancer Agency (BCCA) were identified. Patients were included if they were ≥16 years old with advanced stage or any stage with testicular involvement and were treated with CHOP (1999–2001) or R-CHOP (2001–2005) with curative intent. Results: Four hundred and thirty-five patients were identified; 126 (29%) were treated with CHOP and 309 (71%) with R-CHOP. With a median follow-up of 5.7 years, there were 31 CNS relapses in total with a trend to a reduced likelihood of CNS relapse in R-CHOP-treated patients (3-year risk 9.7% versus 6.4, P = 0.085). In multivariate analysis, the use of rituximab significantly reduced the risk of CNS relapse [hazard ratio (HR) 0.45, P = 0.034]; this benefit was more striking in patients who achieved a complete response (HR 0.18, P = 0.005). Conclusion: The use of R-CHOP appears to reduce the overall risk of CNS relapse in patients with DLBCL particularly in patients who achieve a complete response.

Purpose To assess the incidence and predictive factors for development of transformed lymphoma in a population-based series of patients with follicular lymphoma (FL). Patients and Methods The Lymphoid Cancer Database was used to identify patients with FL diagnosed and treated in the province of British Columbia, Canada. Transformed lymphoma was defined as the development of aggressive non-Hodgkin's lymphoma (NHL) in patients with FL. Factors present at the time of initial diagnosis of indolent NHL and at transformation were analyzed for their impact on risk of transformation and subsequent outcome. Results Between 1986 and 2001, 600 patients with newly diagnosed FL met the inclusion criteria. With a median follow-up of 109 months (range, 10 to 244), 170 (28%) developed transformation, 107 (63%) based on biopsy confirmation. The annual risk of transformation was 3% continuously through 15 years. A multivariate analysis of clinical factors at diagnosis identified advanced stage as the only predictor of future transformation. The median post-transformation survival was 1.7 years. The 5-year survival was superior for patients with limited extent transformation compared with those with advanced cases (66% v 19%, P < .0001). Patients with transformation based on clinical versus histological criteria had an identical median survival of 1.8 years (P = .2). Conclusion The annual risk of transformation of FL is 3% continuing without plateau beyond 15 years. Advanced stage at diagnosis is predictive of future transformation. Clinically diagnosed transformation has an equal impact on outcome as biopsy proven transformation.

Purpose No biomarkers have been identified to predict outcome with the use of an antiangiogenesis agent for cancer. Vascular endothelial growth factor (VEGF) genetic variability has been associated with altered risk of breast cancer and variable promoter activity. Therefore, we evaluated the association of VEGF genotype with efficacy and toxicity in E2100, a phase III study comparing paclitaxel versus paclitaxel plus bevacizumab as initial chemotherapy for metastatic breast cancer. Patients and Methods DNA was extracted from tumor blocks of patients from E2100. Three hundred sixty-three samples were available to evaluate associations between genotype and outcome. Genotyping was performed for selected polymorphisms in VEGF and VEGF receptor 2. Testing for associations between each polymorphism and efficacy and toxicity was performed. Results The VEGF-2578 AA genotype was associated with a superior median overall survival (OS) in the combination arm when compared with the alternate genotypes combined (hazard ratio = 0.58; 95% CI, 0.36 to 0.93; P = .023). The VEGF-1154 A allele also demonstrated a superior median OS with an additive effect of each active allele in the combination arm but not the control arm (hazard ratio = 0.62; 95% CI, 0.46 to 0.83; P = .001). Two additional genotypes, VEGF-634 CC and VEGF-1498 TT, were associated with significantly less grade 3 or 4 hypertension in the combination arm when compared with the alternate genotypes combined (P = .005 and P = .022, respectively). Conclusion Our data support an association between VEGF genotype and median OS as well as grade 3 or 4 hypertension when using bevacizumab in metastatic breast cancer.

In an open-label, randomized, phase 3 trial, we compared the efficacy and safety of paclitaxel with that of paclitaxel plus bevacizumab, a monoclonal antibody against vascular endothelial growth factor, as initial treatment for metastatic breast cancer.We randomly assigned patients to receive 90 mg of paclitaxel per square meter of body-surface area on days 1, 8, and 15 every 4 weeks, either alone or with 10 mg of bevacizumab per kilogram of body weight on days 1 and 15. The primary end point was progression-free survival; overall survival was a secondary end point.From December 2001 through May 2004, a total of 722 patients were enrolled. Paclitaxel plus bevacizumab significantly prolonged progression-free survival as compared with paclitaxel alone (median, 11.8 vs. 5.9 months; hazard ratio for progression, 0.60; P0.001) and increased the objective response rate (36.9% vs. 21.2%, P0.001). The overall survival rate, however, was similar in the two groups (median, 26.7 vs. 25.2 months; hazard ratio, 0.88; P=0.16). Grade 3 or 4 hypertension (14.8% vs. 0.0%, P0.001), proteinuria (3.6% vs. 0.0%, P0.001), headache (2.2% vs. 0.0%, P=0.008), and cerebrovascular ischemia (1.9% vs. 0.0%, P=0.02) were more frequent in patients receiving paclitaxel plus bevacizumab. Infection was more common in patients receiving paclitaxel plus bevacizumab (9.3% vs. 2.9%, P0.001), but febrile neutropenia was uncommon (1% overall).Initial therapy of metastatic breast cancer with paclitaxel plus bevacizumab prolongs progression-free survival, but not overall survival, as compared with paclitaxel alone. (ClinicalTrials.gov number, NCT00028990 [ClinicalTrials.gov].).

Background Breast cancer is a complex disease with clinical, pathological, and molecular heterogeneity. Recent studies have identified several subtypes of breast cancers driven by specific molecular pathways that can be inhibited by targeted drugs. We studied the feasibility of using molecular data from whole genome and transcriptome sequencing of breast cancers to guide treatment. Methods Patients were consented as part of the Personalized Onco-Genomics (POG) study at the British Columbia Cancer Agency. Fresh tumor, blood for normal DNA, and archival tumor were collected. Tissue and blood samples were sequenced using the Ion Torrent AmpliSeq panel, followed by comprehensive DNA and RNA sequencing. In-depth bioinformatic analyses were performed. Somatic mutations, copy number changes, structural variants and gene expression were characterized. Results from genomic analyses were reviewed in a multi-disciplinary team. Results From August 2012 to October 2014, tissue samples from 30 patients with advanced stage breast cancer were analyzed. The median age at diagnosis was 53 years (range 32-75). The median number of lines of cytotoxic therapy prior to sequencing was 2 (range 0-10). All cases were invasive ductal carcinoma; 63% were ER+ and HER2-; 27% triple negative; 7% ER+ and HER2+; and 3% ER- and HER2+. The most frequently mutated genes were TP53 (67%), PI3KCA (23%), ESR1 (20%), ATM (10%), ARID1A (10%), and BRCA1/2 (10%). Somatic mutations in other genes of interest including HER2, PARP1, NF1, BAP1, PTEN, NOTCH1, were also identified. Molecular data were informative for patient care and/or actionable to guide treatment in 57% (17/30) of cases. Conclusion The use of whole genome sequencing technology to identify valuable molecular information to guide personalized breast cancer treatment is feasible. Further studies are warranted to evaluate the usefulness of genome-wide sequencing of breast cancers in clinical practice. Citation Format: Sophie Sun, Karen A. Gelmon, Stephen Chia, Caroline Lohrisch, Tamara Shenkier, Diego Villa, Yaoqing Shen, Martin Jones, Erin Pleasance, Katayoon Kasaian, Peter Eirew, Sreeja Leelakumari, Yusanne Ma, Tony Ng, Stephen Yip, Steven JM Jones, Marco A. Marra, Janessa J. Laskin. Personalized oncogenomics in advanced stage breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1122. doi:10.1158/1538-7445.AM2015-1122

Introduction: Outcomes of patient with primary central nervous system lymphoma (PCNSL) remain poor despite high-dose methotrexate (HDMTX)-based chemotherapy regimens. The addition of rituximab (R) to chemotherapy improves response rates and outcomes in patients with systemic B-cell non-Hodgkin lymphomas. However, R does not penetrate the blood-brain barrier, and therefore its impact in patients with PCNSL is unknown. With disappointing outcomes, in 2006, we routinely started adding R to HDMTX for the treatment of PCNSL. Herein, we evaluated the outcome of patients receiving HDMTX with or without R. Methods: Patients diagnosed with PCNSL (DLBCL histology only) between January 2000 and December 2013, and who were treated with at least one cycle of HDMTX, were identified in the Lymphoid Cancer Database. Since January 2000, patients with PCNSL in British Columbia have been treated with HDMTX 8 g/m2 every 2 weeks, pro-rated for creatinine clearance. Responding patients received a maximum of 10 cycles. Beginning in December 2006, rituximab 375 mg/m2 is given every 2 weeks with HDMTX for a total of 4 doses. Progression free survival (PFS) was defined as the time interval from date of diagnosis to first evidence of progression/relapse, death or last follow-up. Overall survival (OS) was defined as the time interval from date of diagnosis to death or last follow-up. Results: A total of 82 patients were identified. Median age at diagnosis was 61years (range 18-80), 42 (51%) were >60 years old, 48 (59%) were male, 18 (23%) had elevated LDH and 50 (61%) had performance status > 1. Median largest mass size was 4cm (range 1-9). Concurrent ocular (7 patients), leptomeningeal (3 patients), and spinal cord (1 patient) involvements were seen. For treatment, 55 (67%) received HDMTX and 27 (33%) received HDMTX+R. Patients received a median of 4 (range 1-9) HDMTX cycles, with no difference between R versus no R groups. Ten (12%) patients (6 HDMTX, 4 HDMTX+R) received whole brain radiotherapy (RT), as part of initial treatment due to chemo-intolerance. In 79 patients evaluable for response, the overall response rate to initial treatment was 55%: CR 40%, PR 15%, SD 5%, and PD 41%. There were no significant differences in the baseline characteristics or response rates between the two groups. A total of 14/32 patients (44%) relapsed after CR (all in the brain, including 1 to the contralateral eye) and 8/12 (67%) relapsed after PR (7 in brain, 1 to bilateral eyes). At 1st relapse/progression (N = 56), 39 (69%) patients received RT, 4 received repeat courses of HDMTX, 2 received high dose chemotherapy/autologous stem cell transplantation (ASCT) and 1 received temozolamide + R. 10 patients were managed supportively. Four patients had a systemic relapse without involvement of the CNS (1 Breast, 1 testis, 1 axilla and 1 scalp). They received R-CHOP (3), CHOP then R-GDP and ASCT (1). After a median follow-up of 5 years (range 0.1 to 12.7) in living patients, the 5-year OS was 38% (SE 6%), with no difference between patients treated with or without R (HR 0.81, 95% CI 0.40, 1.63; p= 0.55). The 5-year PFS was 20% (SE 5%), again with no difference between the two groups (HR 0.84, 95% CI 0.47, 1.48; p= 0.54). In the subset of 50 patients receiving > 4 cycles of chemotherapy (34 HDMTX, 16 HDMTX+R), the addition of rituximab did not impact PFS (p= 0.36) or OS (p= 0.08). In the subset of 72 patients who did not receive WBRT as part of initial therapy (49 HDMTX, 23 HDMTX + R), the addition of rituximab did not impact PFS (p= 0.48) or OS (p= 0.47). Conclusions: Our preliminary data shows no advantage to the addition of systemic R on the outcomes of PCNSL, consistent with its known poor CNS penetrance. Improved treatment modalities for PCNSL are still warranted. Disclosures Shenkier: F Hoffmann-La Roche: Other. Connors:F Hoffmann-La Roche: Other. Gerrie:F Hoffmann-La Roche: Other. Klasa:F Hoffmann-La Roche: Other. Savage:F Hoffmann-La Roche: Other. Sehn:F Hoffmann-La Roche: Other. Villa:F Hoffmann-La Roche: Other.

Introduction: While R-CHOP has improved survival for DLBCL, outcome in patients (pts) with relapsed/refractory disease remains dismal and may have worsened since the introduction of immunochemotherapy. High-dose chemotherapy and stem cell transplantation (SCT) offers the best chance of secondary cure, but the majority of patients are ineligible due to age, co-morbidities or disease refractory to salvage chemotherapy. Novel agents will address this unmet medical need; however, their impact is difficult to assess without a reliable historical comparator. Herein, we evaluate the outcome in an unselected population with relapsed/refractory DLBCL following R-CHOP in whom SCT is not feasible. Methods: The BC Cancer Agency Lymphoid Cancer Database was used to identify all pts diagnosed with de novo DLBCL between Dec 2000 to Jan 2013 who were treated with curative intent R-CHOP and subsequently progressed or relapsed. Patients were excluded if they were HIV positive, had CNS involvement at diagnosis, PMBCL, composite/discordant histology or transformed lymphoma. Clinical information at baseline and at relapse/progression was compiled. Overall survival (OS) from relapse was calculated from the date of 1st relapse/progression to death or last follow-up. Progression-free survival (PFS) from relapse was defined as interval from 1st relapse/progression to the date of 2nd relapse, initiation of next line of therapy, death or last follow-up. Results: 379 pts with relapsed/refractory DLBCL were identified. 53 underwent SCT and were excluded from analysis. The remaining 326 (274 SCT-ineligible and 52 SCT-eligible pts who did not receive SCT due to toxicity or chemo-refractoriness) were analyzed. Response to primary treatment was: 44% CR; 20% PR; 2% SD; 34% PD. 174 (53%) were primary refractory (progression during or within 3 mos of primary R-CHOP). Median time from diagnosis to first recurrence was 7.8 mos (range 0 – 116). Patient characteristics at relapse: median age 70 y (range 21-93); 55% male; 59% elevated LDH; 58% ECOG PS >1; 55% stage III/IV; 18% >1 extra-nodal site; 53% IPI score at relapse > or = 3. 14 (4%) relapsed with an indolent histology only and 74 (23%) exhibited CNS involvement at relapse (54 isolated, 20 concurrent systemic). Treatment at initial relapse: 78 supportive care; 77 radiotherapy (RT) alone; 2 single agent rituximab (for indolent relapse); 168 (R)-chemo +/- RT (79 single agent, 89 multi-agent). (R)-GDP was the most commonly used multi-agent regimen (75%). 1 pt had missing information. Median follow-up for living pts from the time of first relapse was 3 y. Median OS and PFS from relapse for the entire cohort were 3.9 and 2.1 mos, respectively. Outcome was worse for pts with primary refractory disease (median OS 2.5 mos, median PFS 1.7 mos). On multivariate analysis elevated LDH, ECOG PS >1, Stage III/IV and primary refractory status were independent predictors of OS and PFS from relapse. Pts who relapsed > 2 y from diagnosis had a better median OS and PFS from relapse (11 mos and 5.7 mos, respectively). Excluding pts with CNS involvement, pts who received chemo +/- RT (median OS 6.1, median PFS 3.1 mos) or RT alone (median OS 5.7, median PFS 3.3 mos) had a marginally better outcome. Disease control was similar between pts who received multi-agent vs single agent chemotherapy (median PFS 3.3 vs 2.9 mos). Median OS and PFS from relapse for the 74 pts with CNS involvement were 3.3 mos and 2.2 mos, respectively; this was similar compared to the entire cohort. Outcome was also similar between those with isolated CNS recurrence and concurrent systemic disease but 10 pts with isolated CNS relapse survived > 2 yrs. The 14 pts with indolent histology-only relapse had a significantly better outcome (median OS 36 mos, median PFS 12 mos). Conclusion: The outcome in pts who relapse or progress following R-CHOP is exceedingly poor with standard therapy, with median OS less than 4 mos. Pts who receive treatment at initial relapse fare slightly better, but this may reflect more favorable pt characteristics. Disease control was equivalent for multi-agent vs single agent treatment. While CNS relapse is a rare event in DLBCL, a high proportion of relapsed/refractory pts have CNS disease. The presence of CNS disease did not negatively impact outcome, as outcome was dismal in the entire cohort. Novel treatments are greatly needed and these survival estimates may serve as a comparator to assess their benefit. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Savage: F Hoffmann-La Roche: Research funding to support BCCA Lymphoid Cancer Database Other. Villa:F Hoffmann-La Roche: Other. Shenkier:F Hoffmann-La Roche: Research funding to support BCCA Lymphoid Cancer Database Other. Gerrie:F Hoffmann-La Roche: Other. Klasa:F Hoffmann-La Roche: Other. Connors:F Hoffmann-La Roche: Other. Sehn:F Hoffmann-La Roche: Research funding to support BCCA Lymphoid Cancer Database Other.

Standardized guidelines for the baseline evaluation and response assessment of primary CNS lymphoma (PCNSL) are critical to ensure comparability among clinical trials for newly diagnosed patients. The relative rarity of this tumor precludes rapid completion of large-scale phase III trials and, therefore, our reliance on the results of well-designed phase II trials is critical. To formulate this recommendation, an international group of experts representing hematologic oncology, medical oncology, neuro-oncology, neurology, radiation oncology, neurosurgery, and ophthalmology met to review current standards of reporting and to formulate a consensus opinion regarding minimum baseline evaluation and common standards for assessing response to therapy. The response guidelines were based on the results of neuroimaging, corticosteroid use, ophthalmologic examination, and CSF cytology. A critical issue that requires additional study is the optimal method to assess the neurocognitive impact of therapy and address the quality of life of PCNSL survivors. We hope that these guidelines will improve communication among investigators and comparability among clinical trials in a way that will allow us to develop better therapies for patients.

Purpose To describe the demographic and tumor related characteristics and outcomes for patients with primary T-cell CNS lymphoma (TPCNSL). Patients and Methods A retrospective series of patients with TPCNSL was compiled from twelve cancer centers in seven countries. Results We identified 45 patients with a median age of 60 years (range, 3 to 84 years). Twenty (44%) had Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. Twenty-six (58%) had involvement of a cerebral hemisphere and sixteen (36%) had lesions of deeper sites in the brain. Serum lactate dehydrogenase was elevated in 7 (32%) of 22 patients, and CSF protein was elevated in 19 of 24 patients (79%) with available data. The median disease-specific survival (DSS) was 25 months (95% CI, 11 to 38 months). The 2- and 5-year DSS were 51% (95% CI, 35% to 66%) and 17% (95% CI, 6% to 34%), respectively. Univariate and multivariate analyses were conducted for age (≤ 60 v > 60 years), PS (0 or 1 v 2, 3, or 4), involvement of deep structures of the CNS (no v yes), and methotrexate (MTX) use in the primary treatment (yes v no). Only PS and MTX use were significantly associated with better outcome with hazard ratios of 0.2 (95% CI, 0.1 to 0.4) and 0.4 (95% CI, 0.2 to 0.8), respectively. Conclusion This is the largest series ever assembled of TPCNSL. The presentation and outcome appear similar to that of B cell PCNSL. PS 0 or 1 and administration of MTX are associated with better survival.

As Sunil Verma and associates note, evidence is rapidly accumulating that aromatase inhibitors offer advantages over tamoxifen in terms of efficacy and toxicity.[1][1],[2][2],[3][3] However, none of these studies has shown an overall survival advantage. At the time our guidelines[4][4] were

Plasmablastic lymphoma (PBL) is a recently described type of non-Hodgkin's lymphoma (NHL) that occurs in up to 3% of patients with HIV infection. Although the clinical-pathological features of several patients with HIV-associated plasmablastic lymphoma are documented, detailed description of clinical outcome is limited to isolated case reports. Generally, the response to lymphoma therapy is poor and survival is short. Response to highly active anti-retroviral therapy (HAART), however, has also been described. In this report, we describe the clinical course of two patients diagnosed with HIV-associated PBL in the era of HAART. One patient had a complete response to HAART, with a response-duration of 14 months, followed by relapse in the gastrointestinal tract several months after an anti-retroviral holiday. He is currently in complete remission (CR) eight months from diagnosis of relapse after receiving a full course of combination chemotherapy with modified CHOP, and 25 months from initial diagnosis. A second patient responded to brief chemotherapy in conjunction with HAART and is in clinical CR ten months from diagnosis. These cases illustrate that immunologic and virologic control with HAART may be beneficial for treating PBL and may possibly maintain continued CR. We advocate a high index of suspicion for primary PBL or its recurrence in patients with HIV infection, a history of low CD4 counts or high viral load, and oral or gastrointestinal symptoms.

8555 Background: The outcome of peripheral T-cell lymphomas (PTCLs) treated with anthracycline-based chemotherapy (CHT) regimens is poor. Previous studies have suggested a benefit of high dose chem...

Summary Purpose To define both the natural history of and prognostic factors affecting outcome post relapse from a complete response in advanced stage diffuse large-cell lymphoma. Patients and methods A total of 468 patients aged 17–74 years received the 12-week duration chemotherapy regimens MACOP-B, VACOP-B and ACOP-12 between 1 April 1981 and 31 December 1995 for advanced stage diffuse large, mixed or immunoblastic lymphoma. Of these 402 entered a complete remission, 97 (24%) of whom subsequently relapsed. Initial staging data, follow-up, and relapse information were analyzed to define the natural history of relapse and also subjected to univariate and multivariate correlation with overall (OS) and failure free survival (FFS). Results Eleven percent of the relapses were low grade. All other relapses were of intermediate grade with 75% occurring within the first two years, the remainder up until the eleventh year. Median and five-year OS from the time of relapse for intermediate grade relapse were 12 months and 20%; for FFS they were eight months and 18% respectively. Adverse independent factors, for both OS and FFS were: less than one year to relapse, decreasing performance status at relapse, and more than three nodal sites at relapse. Conclusions Low-grade relapse is not uncommon in patients who initially presented with diffuse large cell lymphoma. As the management of low- and intermediate grade disease is so different biopsy proof of the nature of the relapse is of value. The prognostic factors identified need to be taken into consideration when analyzing results from trials of secondary treatment so as to avoid erroneous conclusions about comparative treatment efficacy.

Introduction The only known curative option for relapsed/refractory peripheral T-cell lymphoma (PTCL) is secondary chemotherapy followed by high dose chemotherapy and stem cell transplant (HDC/SCT), if chemosensitivity is demonstrated. The optimal choice of regimen in this setting, as well as in the transplant ineligible population is unknown. Gemcitabine, dexamethasone, and cisplatin (GDP) was developed as an alternative to DHAP with a favorable side effect profile and administration in the outpatient setting. Since 2002, it has been used as the preferred second-line regimen in patients (pts) with relapsed aggressive lymphoma at the BC Cancer Agency (BCCA), including those with PTCL intended for treatment with HDC/SCT, as well as for selected pts treated with palliative intent. Patients and Methods The BCCA Lymphoid Cancer database, provincial cancer pharmacy database, and the Leukemia/BMT Program of BC database were screened to identify all pts who received GDP for relapsed/refractory PTCL, excluding cutaneous ALCL. Clinical factors and whether transplant was planned at the time of relapse/progression were collected. Disease refractory to primary therapy was defined as progressive disease (PD) during primary treatment or relapse within 3 months (m) of treatment completion. All endpoints were calculated from the date of the first cycle of GDP unless stated otherwise. Results 51 pts were identified between 2002 and 2012 with either relapsed (n=31, 61%) or primary refractory (n=20, 39%) PTCL with the following histologic subtypes: PTCL-NOS, n=17 (33%); ALCL, n=16 (31%) [ALK-positive, n=4 (8%); ALK-negative, ALCL n=10 (20%); ALK status unknown, n=2 (4%)]; AILT, n=13 (25%); NK/T cell nasal type, n=4 (8%); hepatosplenic, n=1 (2%); subcutaneous panniculitis-like, n=2 (4%). First-line treatment consisted of a CHOP-like regimen in the majority of pts (n=48) and one patient with NK/TCL received SMILE. Two pts with NK/TCL received radiation alone. The median time to progression or relapse after initial diagnosis was 7.4 m (range 0.8-150.2). At relapse, the median age was 56 years (y) (range 17-86), 43% had an elevated LDH and most had advanced stage disease (stage III/IV, 88%), good performance status (PS 0-1, 69%) and a high or high-intermediate secondary IPI (sIPI >3, 57%). Pts received an average of 3 cycles of GDP (range 1-6). In total, 36 pts (71%) were planned for HDC/SCT, based on age and lack of significant comorbidities, following a response to GDP. Those planned for transplant were more likely to be younger (< 60 y) (p=.050) with a good PS (0-1) at relapse (p=0.049) but had a similar sIPI risk distribution (p=0.195). Of these, 26 ultimately underwent HDC/SCT (transplant rate 72%; auto, n=15; allo, n=11 [non-myeloablative n=2]). Pts who underwent alloSCT (vs autoSCT) were more likely to have disease that was refractory to primary therapy (p=.045). Of the 10 pts planned for SCT who did not undergo transplant, 8 were due to PD, 1 did not have a matched sibling donor, and 1 refused transplant. The overall response rate (ORR) to GDP for all 51 pts was 80% (CR 47%) and with a median follow-up of 10.4 m for living pts, the 2 y progression free survival (PFS) following GDP was 25% and the 2 y overall survival (OS) was 43% with no differences amongst the histologic subtypes. For pts planned for transplant, the ORR was 83% (CR 58%). The 2 y PFS and OS for this group intended for transplant were 30% and 50%, respectively, and those with relapsed disease (n=22) had a superior outcome to those with primary refractory disease (n=14) (2 y PFS 42.5% vs 9%, p=.0027). The 2 y post-transplant OS was 53% and there was no difference observed between the relapsed and refractory pts who were ultimately transplanted (p=.23). For all non-transplanted pts (n=25), the median PFS after GDP was 4.4 m and the median OS was 6.8 m. In responding pts, the median duration of response was 6.8 m. The small group of non-transplanted pts with a good PS (0-1) at the time of GDP, had an improved PFS (7.9 m vs 1.6 m, p=.044) and median OS (3.7 y vs 4.2 m) following GDP with 3 pts alive and without PD. Overall, GDP was well tolerated with no treatment related deaths. Conclusion Our results suggest that GDP is an effective secondary therapy for relapsed PTCL and can lead to long-term survival, especially in those pts who subsequently undergo HDC/SCT. Selected pts with good PS may have durable remissions in the palliative setting. Disclosures: Off Label Use: Off label use of gemcitabine in the treatment of PTCLs. Connors:F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding. Savage:Eli-Lilly: Consultancy.

Introduction Splenic marginal zone lymphoma (SMZL) is uncommon and accounts for less than 1% of all non-Hodgkin lymphomas. The optimal treatment for SMZL is unknown. We describe the outcome of 108 patients with SMZL treated in British Columbia. Methods All patients with SMZL diagnosed between 1985 and June 2012 were identified in the BC Cancer Agency Centre for Lymphoid Cancer and Lymphoma Pathology Databases. Overall survival (OS) was measured from time of diagnosis to death or last follow-up. Progression-free survival (PFS) was measured from the date of diagnosis to the date of lymphoma recurrence or transformation, or death. Time to transformation (TTT) was calculated from date of diagnosis to date of transformation to aggressive lymphoma. Results 108 patients were identified with a diagnosis of SMZL. Baseline patient characteristics: median age 67 years (range 30-88), male 41%, stage IV 98%, B symptoms 17%, performance status ≥2 22%, splenomegaly 93%, bone marrow involvement 93%, peripheral blood involvement 87%. Hepatitis C serology was positive in 5 of 60 patients with available data. As initial treatment, 53 underwent splenectomy (10 with chemotherapy), 38 chemotherapy alone (21 with a rituximab-containing regimen), 2 received antiviral therapy for hepatitis C, and 15 were observed. Of the 43 patients who had splenectomy alone, 9 subsequently received chemotherapy upon progression, 1 had excision for a soft tissue mass, and 4 transformed to diffuse large B cell lymphoma (DLBCL). Of the 38 who received chemotherapy first line, 6 subsequently received combined chemotherapy and splenectomy, 1 splenectomy alone, 4 chemotherapy alone, and 7 transformed to DLBCL. Neither of the 2 patients who received antivirals had further progression. With a median follow-up of 7 years (range 3 months to 18 years) for living patients, the 5 and 10 year OS were 65% and 48%, respectively. The 5 and 10 year PFS were 38% and 18%, respectively. The 5 year OS for patients who had a splenectomy as their first-line therapy compared to other treatments was 76% vs 53% (p=0.01); and the 5 year OS for patients who received chemotherapy alone as first-line compared to other treatments was 52% vs 72% (p=0.04). There was no difference in outcomes between those treated with rituximab containing chemotherapy as first line compared to other treatments (p=0.65). The 5 and 10 year PFS after first-line splenectomy were 52% and 18%, respectively. A total of 14 patients transformed to DLBCL with a median TTT of 3.2 years (range 6 months to 11.9 years). The 5, 10, 15 year rates of transformation were 9%, 21% and 35%, respectively. Conclusions Splenectomy remains a reasonable treatment option for patients with SMZL. Patients selected for splenectomy as initial management of symptomatic disease experience improved outcomes. The transformation rate in SMZL is similar to that of other indolent lymphomas. Disclosures: Connors: F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding. Skinnider:Roche Canada: Research Funding. Gascoyne:Roche Canada: Research Funding. Sehn:Roche Canada: Research Funding. Savage:Roche Canada: Research Funding. Slack:Roche Canada: Research Funding. Shenkier:Roche Canada: Research Funding. Klasa:Roche Canada: Research Funding. Gerrie:Roche Canada: Research Funding. Villa:Roche Canada: Research Funding.

Background Post-transplant lymphoproliferative disorders (PTLD) develop in the setting of immunosuppression following solid organ transplant or allogeneic stem cell transplant (alloSCT). Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (‘PTLD-like’) can occur with the use of immunosuppressive agents for autoimmune or related disorders. The optimal first-line treatment and risk stratification tool for PTLD remains unclear and rituximab (R) monotherapy is often used following a reduction of immunosuppression (RIS), reserving combination chemotherapy for those failing this initial approach. However, this approach may not be suitable in those with high risk disease. The aim of this study was to review the outcome of patients with PTLD and PTLD-like disease, Methods Using the British Columbia Cancer Agency (BCCA) Lymphoid Cancer Database, all patients diagnosed with PTLD and PTLD-like conditions from 1981-2013 were identified, excluding primary CNS lymphoma, low-grade lymphomas and HIV associated lymphomas. Results 104 patients were identified: 86 PTLD and 18 PTLD-like. PTLD: Median age 47 y (range 6-71); 64% male; 60% late onset (> 1 year from transplant); 71% extranodal (EN) disease; 14% graft involved; 49% elevated LDH (n=36, missing n=13); 59% PS > 2 (n=45, missing n=10); 60% prior renal transplant. Pathology: 57% EBV positive (n=43, missing n=11); 2% early lesions, 13% polymorphic, 79% monomorphic (83% DLBCL), 1.1% classical Hodgkin lymphoma (CHL) and 4.7% unknown. All patients underwent initial RIS, followed by: observation (n=23, 27%), single agent rituximab (n=37, 43%), anthracycline based combination chemotherapy + R (n= 9 (n=6 + R), 10%), single agent chemotherapy + R (n=8 (n=4 + R), 9%); 4 (5%) were too frail to treat. With a median follow-up for living patients of 4.0 y (range 0.8-16.2 y), the 3-y OS and 3-y TTP were 50% and 48%, respectively. Polymorphic cases had a more favorable outcome compared to monomorphic cases with a 3-y OS of 91% vs. 45% (p=0.029) and a 3-y TTP of 73% vs. 44% (p=0.037). Monomorphic PTLD prognostic factors (n=63): In univariate analysis for TTP, an elevated LDH (p=0.006), poor PS >2 (p=.0012), EN sites > 1 (p=0.005), B symptoms (p=0.0019) and GI (p=0.022), kidney (p=0.009) and hepatic (p 2 (n=7, missing n=2); 92% EBV positive (n= 12, missing n=5). Pathology: 1 polymorphic (6%); 15 monomorphic (83%) (DLBCL n=11, 73%, DLBCL/CHL grey zone lymphoma n=2, 13%), 1 CHL (6%), 1 Hodgkin-like (6%), 1 unknown (6%). The majority of patients had a history of rheumatoid arthritis (n=10, 56%) and had been on treatment with methotrexate (n=10, 56%). The median time from onset of autoimmune disorder to the development of PTLD-like disease was 11 y (0.16-50) and the median duration of drug exposure prior to the development of the PTLD-like disease was 5 y (0.16-15y). All patients underwent RIS, followed by observation (n=6, 32%); single agent rituximab (n=4, 21%); anthracycline based combination chemotherapy + R (n=6, 37%; R, n=4); or single agent chemotherapy + R (n=1, 5.3%); 1 was too frail. With a median follow-up of 4.9 y (range 0.3-17 y), the 3-y TTP and OS were 65% and 77%, respectively. Conclusion For PTLD, a select group of patients with a low IPI score appear to have high cure rates with single agent rituximab. For those with multiple IPI factors a risk-adapted strategy with earlier use of chemotherapy may be preferred. In the group with PTLD-like disease we observed Hodgkin lymphoma and Hodgkin-like proliferations but also grey zone lymphomas, the latter of which has not been previously reported. Patients with PTLD-like disorders have a more favorable outcome than those with PTLD. Disclosures: Klasa: Roche Canada: Research Funding. Sehn:Roche/ Genentech: Consultancy, Honoraria, Research Funding. Villa:Celgene: Honoraria; Lundbeck: Honoraria; Roche: Honoraria, Research Funding. Shenkier:Roche Canada: Research Funding. Connors:Roche Canada: Research Funding; F Hoffmann-La Roche: Research Funding. Savage:F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding.

Introduction Hodgkin lymphoma is a highly curable lymphoid malignancy when treated with multi-agent chemotherapy regimens such as doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). The optimal timing of curative intent chemotherapy and the impact of treatment delay on clinical outcomes in Hodgkin lymphoma are currently unknown. Patients and Methods Adult patients diagnosed with Hodgkin lymphoma in British Columbia (BC) between January 1999 and December 2010 were identified in the BC Cancer Agency Centre for Lymphoid Cancer Database. Patients were included if they received at least one cycle of ABVD with curative intent. Patients treated with regimens other than ABVD and those treated with palliative intent were excluded. Additional demographic data were obtained from the BC Cancer Registry. Chemotherapy administration data, including drugs, dates administered, and treatment center, were obtained from the BC Cancer Agency provincial pharmacy database. Time to treatment initiation was defined as the time between the date of definitive histological confirmation of Hodgkin lymphoma and date of the first dose of ABVD. We then evaluated the effect of time to treatment initiation on overall survival (OS) and progression-free survival (PFS) at 5 years. Results A total of 879 patients were identified: 110 (13%) received ABVD within 2 weeks of diagnosis, 260 (30%) within 3 – 4 weeks, 405 (46%) within 5 – 8 weeks, and 104 (12%) beyond 8 weeks. Inpatient chemotherapy, elevated LDH, poor performance status, advanced stage, B symptoms, and bulky disease were all associated with treatment initiation within 2 weeks (p45 and nodular lymphocyte predominant histology were significantly associated with treatment initiation >8 weeks (p8 weeks included systematic delays in the process of referral, staging, and scheduling of treatment (n=66), uncontrolled comorbidities (n=13), patient refusal of earlier treatment (n=9), pregnancy (n=5), revised pathological diagnosis (n=4), unknown cause of delay (n=4), and social or substance abuse factors (n=3). With a median follow-up of 5.6 years (range 1 month – 14 years) in living patients, the 5-year OS estimates were 90% (standard error (SE) 3%) for time to treatment8 weeks (P = 0.012). Five-year PFS estimates were 82% (SE 4%) for time to treatment8 weeks (P = 0.198). In multivariate analysis, age, gender, performance status, stage, and time to treatment were significantly associated with OS, while only age and stage were significantly associated with PFS. Conclusions In a publicly funded healthcare system with universal access to cancer treatment and standardized diagnostic review, initiation of ABVD beyond 8 weeks appears to be associated with worse OS but not PFS. Reasons for treatment delay in this group are heterogeneous and may be responsible for the detrimental effect on OS. Nonetheless, clinicians should make every effort possible to initiate curative-intent chemotherapy as soon as a diagnosis of Hodgkin lymphoma is established. Disclosures: No relevant conflicts of interest to declare.

8552 Background: DLBCL is potentially curable with combination chemotherapy such as CHOP-R. Although it is generally regarded appropriate to start chemotherapy promptly after diagnosis, the impact of the time from diagnosis to treatment initiation on treatment outcome is unknown. Methods: Patients diagnosed with DLBCL and treated with at least one cycle of CHOP-R with curative intent during 2003 – 2008 in British Columbia were identified in the Lymphoid Cancer Database. Additional demographic data were obtained from the BC Cancer Registry. The BC Cancer Agency provincial pharmacy database was used to obtain dates of chemotherapy administration. The impact of the time interval from the date of pathologic diagnosis to treatment on overall survival (OS) and progression-free survival (PFS) was evaluated. Results: A total of 793 patients were identified: 199 (25%) received CHOP-R 8 weeks. High international prognostic index, primary mediastinal DLBCL, and hospitalization at the time of CHOP-R start were associated with earlier initiation of chemotherapy (p8 weeks, p=0.006 (PFS) and p=0.024 (OS). A multivariate analysis demonstrated no significant difference between the groups. Conclusions: In a publicly funded healthcare system, earlier initiation of chemotherapy was strongly associated with poor prognostic factors, as well as inferior PFS and OS. The timing of chemotherapy initiation appears to be related to clinical factors instead of system or socioeconomic barriers. Notwithstanding the lack of detrimental outcomes in those commencing CHOP-R after 8 weeks, clinicians should endeavor to initiate curative chemotherapy as soon as possible after a diagnosis of DLBCL is established.

Malignant lymphomas (ML) with t(3;14) or variant t(2;3) and t(3;22) have recently been recognized. These translocations have been shown to associate predominantly with B-cell diffuse large cell lymphoma (DLCL) and less frequently with follicular lymphoma (FL). The molecular alterations associated with these translocations involve one of the immunoglobulin gene (Ig) loci and a recently cloned gene, bcl-6 located at 3q27 which codes for a zinc-finger protein that may function as a transcription factor. We have identified by cytogenetic analysis 22 cases of ML with a 3q27/Ig translocation. The pathologic diagnoses of these cases include DLCL, FL, small non-cleaved non-Burkitt lymphoma and chronic lymphocytic leukaemia. Molecular analysis confirmed a bcl-6 rearrangement in 10/12 cases tested. The karyotype in 5/22 cases revealed the t(3;14) or variant in association with another lymphoma-specific translocation, t(14;18) in three cases and t(8;14) in two cases. ML with dual translocations that implicate Ig genes in the deregulation of proto-oncogenes are being increasingly recognized and may represent distinct subtypes or ‘hybrid’forms of malignant lymphoma.

Abstract 303 Background: Primary mediastinal large B-cell lymphoma (PMBCL) was distinguished from DLBCL in the REAL/WHO classification by virtue of distinct clinical and pathologic features. In DLBCL, R-CHOP has demonstrated a clear benefit over CHOP chemotherapy in randomized trials, some of which have included a small subset of PMBCL pts (pts). However, large studies evaluating R-CHOP in PMBCL are lacking. Further, the role of consolidative radiotherapy (RT) to the mediastinum remains unclear particularly with the more frequent use of FDG-PET. At the BCCA, from 2001–2005, R-CHOP with consolidative RT was recommended in all pts with PMBCL. After 2005, FDG-PET scan was used to guide RT usage following 6 cycles of R-CHOP. We evaluated: 1) the outcome of pts with PMBCL in R-CHOP vsCHOP treated pts; 2) prognostic factors in R-CHOP treated pts; 3) the impact of the introduction of PET based approach to guide RT compared to the use routine RT. Methods: Using the BC Cancer Agency Centre for Lymphoid Cancer database, we identified all pts with PMBCL by the REAL/WHO classification treated with R-CHOP in addition to an earlier group treated with CHOP chemotherapy. For R-CHOP treated pts, from 2001–2005, consolidative RT to the mediastinumwas routinely administered following R-CHOP (‘RT’ era). Since 2005, a PET was planned at the end of chemotherapy to guide RT (‘PET’ era). If the PET was negative, pts were observed and if the PET was positive, consolidative RT was given, if feasible. Results: In total, 176 pts were identified: 96 received R-CHOP; 80 received CHOP. Baseline clinical features were similar between the treatment groups. Compared to those treated with CHOP, R-CHOP pts had an improved time to progression (TTP) (5 y 78% vs 65%, p=0.018) and overall survival (OS) (5 y 88% vs 70%, p=0.015). Further, refractory disease (progressive disease (PD) on chemotherapy or relapse < 3 months after treatment completion) was more frequent in CHOP treated pts (16% vs 5%, p=0.016). There was no difference in the risk of central nervous system (CNS) relapse (3.2% vs2.1%, p=0.823). For the R-CHOP treated pts, 46 were treated in the ‘RT era’; 80% received consolidative RT; 50 were treated in the ‘PET era’; 38% received RT. In the RT era, there was a greater proportion of pts with extranodal sites > 1 (p=0.007) and the presence of a pleural/pericardial effusion (p=0.009). In an era to era outcome comparison, there was no difference in the 5 y TTP (RT era 76% vs PET era 83%, p=0.626) or 5 y OS (82% vs 89%, p=0.773). In univariate analysis, the presence of B symptoms was associated with an inferior TTP (5 y 67% vs 90%, p=0.014) and OS (5 y 83% vs 94%, p=0.047). An effusion at diagnosis was associated with an inferior TTP (p=0.017) but not OS (p=0.277). Using recursive partitioning, age > 38 y was identified as the optimal cut-off and was associated with an inferior OS (p=0.003) and there was a trend to a worse TTP (p=0.096). The aaIPI was not predictive of TTP (p=0.357) or OS (p=0.386). In multivariate analysis (including variables with p value 38 y (HR 2.98, p=0.025) were associated with an inferior TTP. For OS, age > 38 y (HR 6.7, p=0.003) and B symptoms (HR 4.5, p=0.023) were associated with an inferior outcome. Treatment era (RT vsPET) did not affect TTP or OS in MVA. In total, 59 pts treated with R-CHOP had a PET scan at the end of treatment, 50 in the PET era and 9 pts in the ‘RT era’ by self-pay: 35 (59%) were PET-negative (neg) (2 received RT) and 24(41%) were PET-positive (pos) (23 received RT). With a median follow-up of 5.4 y, there was no difference in the TTP (5 y 78% vs 83%, p=0.735) or OS (5 y 88.5% vs 95%, 0.271) for PET-neg and PET-pos cases, respectively. In total, there were 6 relapses in PET-neg cases: 2 CNS and 4 mediastinal. There were 4 relapses in the PET pos cases (PD in the mediastinum at PET scan n=1; within in RT field n=1; within and outside RT field n=1; outside RT field n=1). Conclusion: We confirm the superior outcome using R-CHOP compared to CHOP chemotherapy in PMBCL, however, rituximab does not appear to impact the rare risk of CNS relapse. The introduction of a PET-guided RT approach in R-CHOP treated PMBCL pts has maintained excellent outcomes in the majority of pts while reducing the use of RT. The presence of B symptoms at diagnosis was associated with an increased risk of relapse and may reflect more aggressive underlying disease biology. Disclosures: Savage: Roche: Research Funding. Klasa:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Villa:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Slack:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Gascoyne:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Connors:Roche: Research Funding. Sehn:F. Hoffmann-La Roche (Roche Canada): Research Funding.

Abstract 1602 Introduction: MCL presents a therapeutic challenge remaining incurable with standard therapy. Most pts exhibit aggressive behaving advanced (adv) stage disease at diagnosis and require multi-agent chemotherapy, while others may have an indolent course. Improved outcomes with rituximab (R) and autologous stem cell transplant (ASCT) have been reported for select pts within the context of small clinical trials. In the province of BC, a new policy was introduced in 2003 recommending upfront ASCT for all eligible pts with adv stage MCL. This largely coincided with the availability of R which was included in the protocol: 6 cycles R-CHOP induction followed by ASCT and 2 cycles R maintenance (R weekly × 4 at 2 and 6 mo). The aim of this study was to review the clinical profile of MCL within a non-selected population of pts and to evaluate outcomes before and after this policy change. Methods: Using the BC Cancer Agency Centre for Lymphoid Cancer database, we identified all pts diagnosed with MCL between Jan 1990 and Dec 2010. Pathology was centrally reviewed and clinical data was retrieved from the database and medical records. Within this grp, we identified a SCT eligible cohort ( Results: In total 535 pts were identified, median age 67 y (range 22–94), 71% male, 88% adv stage, 8% limited (lim) stage (stage I/II, bulk 10 y), mainly diagnosed prior to SCT policy (where f/up is shorter) and were treated with various regimens. Within this grp, median age was 57 y and 28% had lim stage, but no obvious associated clinical parameters were noted. To evaluate the impact of initial SCT, we compared outcomes in SCT eligible pts (n=179), diagnosed prior to (pre-SCT, n=93) and following its introduction in 2003 (post-SCT, n=86). Clinical characteristics were comparable between the pre-SCT and post-SCT grps; median age 56 y, MIPI score 20% high, 28% intermed, 52% low. Within the pre-SCT grp, initial treatment included CHOP-like chemo (n=46), intensive chemo (n=20), non-anthracycline-based tx (n=20) and SCT (n=3, 1 allo; received prior to policy initiation), median f/up 11 y. Within the post-SCT grp, initial treatment included SCT (n=50, 2 allo), CHOP-like chemo (n=31), non-anthracycline-based tx (n=5), median f/up 4.4 y. Thirty-six post-SCT pts did not undergo SCT (13 co-morbidities, 13 progressive disease during induction, 6 unknown/not offered, 4 declined). R was received by 8/93 (9%) pre-SCT pts and 81/86 (94%) post-SCT pts. Based on era of treatment, outcomes were significantly improved in the post-SCT grp compared with the pre-SCT grp, median OS not reached v 3.4 y, p=0.001 (5-y OS 58% v 34%) and median PFS 3.5 y v 1.3 y, p Conclusion: Outcomes for MCL have significantly improved in the modern era following the introduction of upfront ASCT in BC. Availability of rituximab coincided with this policy change and likely contributed to this improvement. Similar to prior observations, a subset of pts with indolent behaving disease can be observed without impacting OS. Patients with limited stage disease have a more favorable outcome, but no survival plateau was noted. Disclosures: den Brok: F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Song:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. OLeary:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Klasa:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Savage:Roche: Research Funding. Shenkier:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Villa:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Slack:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Shepherd:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Gascoyne:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Connors:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Sehn:F. Hoffmann-La Roche (Roche Canada): Research Funding.

582 Background: Inferior stage-adjusted survival for BC among obese (O) women has been reported. This may reflect differences in treatment planned for O women, in treatment received (due to toxicity), or in tumor biology arising in different cellular environments, such as high serum insulin levels, which are associated with a higher risk of recurrence. Methods: We examined whether overweight (BMI 25-30) or obese (BMI >30) women had a higher Oncotype Dx Recurrence Score (RS) after ER+, node negative (NN) or N0i+ BC than normal weight women. Included were all participants at the BC Cancer Agency in a RS clinical utility study in consecutive ER+ NN, N0i+ BC (n=156) at the BC Cancer Agency and in the TAILORx trial (n=56). Sixteen were excluded (n=5 withdrew consent; 1 triple negative; 3 test failed; 2 her2+; 1 neoadjuvant treatment, n=4 height and weight missing). Results: A similar proportion of O patients had low, intermediate, and high RS tumors. Cancers with a high RS were more likely to be grade 3 (55% of grade 3 tumours had high RS, 33% intermediate RS, 12% low RS) and fewer were strongly ER positive (69% of high RS versus 97% of intermediate and low RS). Conclusions: While this data does not support differences in tumor risk arising in O versus non obese environments in ER+, NN BC, examination of a larger data set may be more informative. [Table: see text]

549^ Background: The Oncotype DX 21-gene Recurrence Score assay (RS) can potentially predict the magnitude of chemotherapy benefit in patients with stage I-II, node-negative, ER+ disease who will be treated with tamoxifen for 5 years. While use in the United States has grown significantly since its introduction, it is not yet routinely ordered by oncologists in most parts of Canada. The primary purpose of this study was to measure the impact of the Oncotype DX test on the physician’s treatment recommendation in ER+ pN0 breast cancer in British Columbia. Methods: After providing informed consent, patients and medical oncologists completed respective pre-RS questionnaires indicating their treatment preferences and level of confidence and a decisional conflict scale (patients only). At a subsequent visit, after the RS result was known and discussed, the patient and oncologist completed a second set of questionnaires. The proportion of physician treatment recommendations that changed from baseline to follow-up (post RS) were calculated with 95% confidence interval (CI). A prospective health economic (HE) analysis was also performed. Results: From May 2010 to July 2011, two participating BCCA centres enrolled 156 patients. Of the 150 for whom successful RS assay results were obtained, physicians changed their chemotherapy recommendation in 45 cases (30%; 95% CI 22.8-38.0%); either to add (10%; 95% CI 5.7-16.0%) or omit (20%; 95% CI 13.9-27.3%) adjuvant chemotherapy. As a secondary end-point, in 84 cases (56%; 95% CI 47.7-64.1%) there was a change in either the planned chemo and/or endocrine therapy recommendation. There was an overall significant improvement in physician confidence post RS (p < 0.001). Patient decisional conflict also significantly decreased following the RS assay (p < 0.001). The HE analysis is ongoing and will be presented separately. Conclusions: Within the context of a publicly funded health care system, the RS assay significantly affects adjuvant treatment recommendations in ER+ node negative breast cancer, in addition to reducing patient decisional conflict.

Abstract 780FN2 Background: Testicular involvement of diffuse large B-cell lymphoma (Te-DLBCL) is associated with a poor outcome and a high risk of central nervous system (CNS) relapse. Rituximab is now routinely used into the treatment of both limited (LIM) and advanced (ADV) stage disease but it is unclear if this can reduce the rate of CNS relapse given it's limited penetration of the blood brain barrier and frequent parenchymal relapses in Te-DLBCL. A recent phase II study by the IELSG using R-CHOP, contralateral testicular radiation (RT) and IT prophylaxis in LIM stage patients demonstrated improved survival rates and a lower rate of CNS relapse compared with historical series. Herein, we evaluated the impact of R-CHOP on the natural history in all patients with Te-DLBCL Methods: The Centre for Lymphoid Cancer Database was used to identify patients with Te-DLBCL who were treated with curative intent. LIM stage was defined as stage I/II without bulk (< 10 cm) or B symptoms and also included patients with discordant involvement of the bone marrow with a low grade lymphoma whose stage was otherwise limited stage, and ADV stage included all others. Results: 109 patients with Te-DLBCL treated between 1985–2011 were identified including 10 patients (11%) with discordant non-follicular low grade lymphoma in the bone marrow (9) or lymph node (1). Twenty-one patients were excluded: chemotherapy refusal (7), palliative (n=9), HIV + (2), peritesticular and not testicular involvement (2), clinical information N/A (1). Of the remaining 88 patients, 40 received CHOP-like chemotherapy and 48 received R-CHOP. The median age at diagnosis was 68 y (range 26–83 y) and half the patients had LIM stage disease. Most patients received either prophylactic contralateral testicular RT (59) or had bilateral orchiectomy (11) with few exceptions: refusal (3), PD or death on therapy (12), unknown (3). Five patients with CNS disease at presentation (R-CHOP n=4; CHOP n=1) also received HD methotrexate (HDMtx) and IT CHT. Only nine patients (7 ADV) received CNS prophylaxis (R-CHOP n=4; CHOP n=5) either IT (8) or IT + HDMtx (1) R-CHOP treated patients were more likely to have > 1 extranodal (EN) sites involved (p=0.030), and there was a trend to a greater proportion of patients with ADV disease (p=.087). With a median follow up of 60 mos, the 5 year TTP and OS for the CHOP and R-CHOP treated patients was similar (TTP 52% vs 67.5%, p=.181; OS 52.5% and 57%, p=0.262). However, an improved TTP (p=.025) and a trend to improved OS (p=.085) was observed in ADV stage patients but not LIM stage patients (TTP p=.617, OS p=.407) treated with R-CHOP. In univariate analysis, stage, EN sites > 1, IPI (0-2 v 3–5) and urinary tract (UT) involvement (kidney, adrenal or ureter) were prognostic for both TTP and OS. In multivariate analysis treatment with rituximab, > 1 EN sites and UT disease were prognostic for both TTP (rituximab p=.006, > 1 EN sites, p=.014, and a trend for UT disease p=.067) and OS (rituximab, p=.009, > 1 EN sites p=.025, UT disease p=.016) Excluding patients with CNS disease at diagnosis, there was no difference in the time to CNS relapse (TTCNS) in R-CHOP (5 y 27%) compared to CHOP treated patients (5 y 23%) (p=.789) in both LIM (5 y 16.5% vs 23.5%, p=.901) and ADV disease (5 y 27% vs 23%, p=0.386). In univariate analysis, the IPI, EN sites, PS and UT disease were associated with an increased risk of CNS relapse. In multivariate analysis, only UT disease (HR 9.18, p Conclusion: Although survival has improved in Te-DLBCL patients since the introduction of rituximab, the benefit is likely primarily through systemic disease control as there remains an inherently high risk of CNS relapse. Patients with ADV stage disease and particularly with UT tract involvement, have frequent early leptomeningeal relapse and should be considered for up-front CNS treatment. Given the propensity for late parenchymal relapses in LIM stage patients, strategies to test agents with CNS penetration need further investigation. Disclosures: Villa: Roche: Research Funding. Shenkier:Roche: Research Funding. Sehn:Roche: Honoraria, Research Funding. Klasa:Roche: Research Funding. Gascoyne:Roche: Research Funding. Connors:Roche: Research Funding. Savage:Roche: Honoraria, Research Funding.

Abstract 96 Introduction: Recently, a number of novel therapies have been under investigation in PTCLs, however, it remains a challenge to compare these agents and determine the impact on outcome. The purpose of this population-based study was to determine the spectrum of survival in PTCL patients (pts) following relapse and to explore factors influencing survival. The three most common subtypes encountered in North America were evaluated: PTCL-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AILT), anaplastic large cell lymphoma, ALK positive (ALK-pos) and ALK-negative (ALK-neg). Material and Methods: The Centre for Lymphoid Cancer Database was screened to identify all pts ≥ 16 y with the above histologies that relapsed or had progressive disease (PD) following primary therapy. In addition to the timing of relapse (very early < 9 mos from diagnosis; early 9–24 mos and late > 24 mos), clinical information at the time of relapse was collected where possible. Responses were determined by the treating physician: Response = any clinical and/or radiographic response; PD = no change or disease progression. Results: In total, 276 pts diagnosed between 1976 and 2010 were identified with primary progressive or relapsed PTCL with initial diagnoses by the WHO classification. 68 were excluded: unconfirmed pathology (6), CNS disease (5), complications during primary CHT (17), no primary chemotherapy (CHT) (27), incomplete chart or lost follow-up (13). 208 pts were analyzed (PTCL-NOS = 109 (52%), ALCL = 54 (26%) (ALK-pos = 18; ALK-neg = 33; ALK status unknown = 3), AILT = 45 (22%). The majority of pts received anthracyclines as part of their primary CHT (89%). The median age at the time of relapse was 62.5 y (range 20 to 86 y) (PTCL-NOS 62 y, ALK-neg 62 y, ALK-pos 40.5 y, AILT 68 y). 129 (62%) pts were refractory to initial CHT. 53 pts were planned for HDC/SCT, however, only 38 (72%) ultimately received it (allo 17, auto 21). 37 pts (18%) were either too ill for any therapy (34) or refused therapy (3). The remaining pts received some type of treatment for their relapsed PTCL: systemic CHT (gemcitabine, CHOP(like), alkylators alone) (103) radiation alone (19) or steroids (11). The median follow-up for surviving pts after relapse/progression was ∼ 4 y. The median overall survival (OS) following relapse for the whole cohort was 7.0 mos (HDC/SCT 47.1 mos; no HDC/SCT 5.4 mos). The median progression free survival (PFS) following relapse was 4.6 mos (HDC/SCT 27.7 mos, no HDC/SCT 2.8 mos). The 3 y OS and PFS following relapse were 55% and 48%, respectively in the HDC/SCT group and similar whether an autologous or allogeneic SCT was performed. The corresponding 3 y OS and PFS estimates in the no HDC/SCT group were19% and 13.5 %, respectively. There was no difference in OS and PFS amongst the histologic subtypes. Considering the no HDC/SCT pts who received CHT (n=103), 55% were determined to have to have had a response to chemotherapy, and the median OS and PFS was 7.0 mos and 4.0 mos, respectively (responders vs non-responders/PD OS 16.7 mos vs 3.0 mos, p In multivariate analysis, the secondary IPI (sIPI), PS ≥ 2, late relapse and HDC/SCT were all prognostic for both PFS (sIPI ≥3 (HR 1.8, p=.009), PS ≥2 (HR 2, p =.002), HDC/SCT(HR.28, p 24 mos (HR=.64, p 24 mos from the date of diagnosis (PTCL-NOS 12 (43%); ALK-neg ALCL 6 (21%); ALK-pos ALCL 3 (11%); AILT 6 (21%)) and only 8 (31%) subsequently received HDC/SCT but the median PFS and OS was very favourable in this group, 25.4 mos and 41.4 mos, respectively (no HDC/SCT PFS 14 mos and OS 32.3 mos). Conclusions: The outcome of the majority of pts with relapsed/progressive PTCL is poor and with brief remissions to systemic therapy, highlighting the urgent need for novel agents specifically active in PTCL. Outcomes were far superior in pts who were able to be transplanted and efforts need to focus on expanding the number of pts eligible for this curative therapy. Standard clinical factors were prognostic at relapse and are critical when comparing the efficacy of new agents. PTCL pts with rare, very late relapses have a much more favourable prognosis and further highlight the diverse disease biology of PTCLs. Disclosures: Sehn: Roche/Genentech: Consultancy, Honoraria, Research Funding. Villa:Roche: Research Funding. Shenkier:Roche: Research Funding. Savage:Celgene: Consultancy; Allos Therapeutics: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria.

8034 Background: Consolidative radiotherapy (RT) is frequently administered following chemotherapy (CHT) for advanced stage Hodgkin lymphoma (HL) patients who have bulky disease at diagnosis and/or residual abnormalities on post-CHT CT imaging. The GHSG HD15 trial has recently shown that RT can be omitted in cases that have residual disease on CT imaging following BEACOPP-based CHT but are FDG-PET-negative (PET-neg). However, it is unknown whether this also applies to patients treated with ABVD CHT and to those with initial bulky disease. Further, the effectiveness of RT for cases that are PET positive (PET-pos) following ABVD CHT remains unclear. Methods: Since July 2005, adult (> 16 y) patients in British Columbia (BC) with advanced stage HL (stage III /IV and/or the presence B symptoms and/or bulky disease [> 10cm]) have been recommended to undergo FDG-PET imaging if residual abnormalities > 2 cm are seen on the post CHT CT scan. If the PET scan was negative, patients were observed, regardless of initi...

Abstract 854 Background: Residual abnormalities of uncertain significance are frequently seen on post-therapy CT scans in patients (pts) with advanced-stage diffuse large B-cell lymphoma (DLBCL) following treatment with R-CHOP. However, the value of consolidative radiation therapy (XRT) to these sites is unknown. FDG-PET scanning may allow for the discriminate use of XRT to eradicate sites of residual disease. Method: Since 2005, pts with advanced-stage DLBCL in British Columbia (BC) have been treated with a systematic policy recommending a post-chemotherapy PET scan for pts with residual abnormalities ≥2cm on CT scan, followed by XRT to PET-positive sites that are amenable to radiation. Pts with a negative PET scan are observed (regardless of initial or residual bulk), while pts with a PET scan that is widely positive and not suitable for XRT are treated at the discretion of individual physicians. All PET scans are performed in a central location using a combined PET/CT scanner; staging PET scans are not routinely performed. Using the databases of the BC Cancer Agency Centre for Lymphoid Cancer and Department of Functional Imaging, we identified all pts with newly diagnosed advanced-stage DLBCL between January 2005 and June 2009 treated with R-CHOP who underwent a post-treatment PET scan based on this management algorithm. This analysis does not include pts with primary progressive disease; pts with a complete remission on post-treatment CT scan; pts who were HIV positive; or those with transformed lymphoma. Results: 196 pts were identified with the following baseline characteristics: median age 64 y (range 18–89 y); 61% male; 62% stage III/IV; 41% PS>1; 21% >1 extranodal site; 57% elevated LDH; 46% bulky site ≥10cm; 56% IPI 0–2, 44% IPI 3–5. All pts received 3-weekly R-CHOP (6-8 cycles) with curative intent. Median follow-up for living pts is 32 mos (range 5–65 mos). 121/196 (62%) had a negative post-therapy PET (PET-Neg), 66/196 (34%) had a positive PET (PET-Pos), and 9 (4%) were indeterminate. Median SUV of PET-Pos scans was 3.4 (range 1.8–25). None of the PET-Neg pts received XRT. 51/66 (77%) of PET-Pos pts received XRT (3000-4000 cGy) to sites of PET positivity (46 single field, 5 multiple fields), with only 7 relapses to date. 15/66 (23%) PET-Pos pts did not receive XRT due to: multiple sites not amenable to XRT 11; physician choice 3; biopsy negative 1. Only 3/9 pts (33%) with an indeterminate PET received XRT. There was no difference in the 3-y PFS (80% v 75%, p=0.41) and 3-y OS (84% v 77%, p=0.10) between the PET-Neg and PET-Pos pts, respectively. The 3-y PFS was similar for PET-Pos pts who received XRT (84%) and PET-Neg pts (80%) and was superior to PET-Pos pts who did not receive XRT (42%). Pts with an indeterminate scan had a favorable outcome with a 3-y PFS of 89%. Conclusion: Pts with advanced-stage DLBCL who have residual abnormalities on CT scan following R-CHOP and receive consolidative radiation to sites of PET positivity have an outcome similar to pts with a negative post-therapy PET. The favorable outcome observed in the PET-positive cohort treated with XRT is higher than expected from historical reports, suggesting a benefit for the rational use of PET-guided XRT following chemotherapy for DLBCL. Pts who have residual abnormalities on CT scan that are PET-negative should be spared indiscriminate exposure to radiation as the majority have been cured with systemic therapy. Disclosures: No relevant conflicts of interest to declare.

Abstract 1803 Introduction: The recently reported PRIMA trial was the first to evaluate the benefit of rituximab maintenance (R-maintenance) following first-line immunochemotherapy in FL (Salles G, ASCO 2010). In that trial, the majority of patients (pts) received R-CHOP induction and R-maintenance was administered bi-monthly for 2 years, yielding a substantial benefit in PFS. We assessed outcomes in an unselected population of chemotherapy-naïve pts with FL treated in British Columbia (BC) with R-CVP followed by observation or 2 years of R-maintenance. Patients and Methods: Since 2004, the standard treatment policy in BC has recommended 8 cycles of R-CVP as first-line systemic therapy for symptomatic advanced stage FL. Since 2006, R-maintenance (rituximab 375 mg/m2 IV every 3 months for 2 years) has been recommended for pts achieving a complete (CR/CRu) or partial (PR) remission following induction therapy. Asymptomatic pts generally undergo a period of watchful waiting, with systemic therapy initiated only when clinically indicated. We performed a retrospective population-based analysis using the BC Cancer Agency Lymphoid Cancer Database and included all pts with FL who received first-line R-CVP between March 2004 and January 2010. Outcome of pts who received R-maintenance was compared to the group of pts who responded to R-CVP but did not receive maintenance (i.e. prior to routine maintenance policy). Primary endpoint was PFS, defined as the interval from the beginning of R-CVP to first progression, relapse or death from any cause. Pts who progressed while on R-CVP or did not achieve at least a PR were considered to have refractory lymphoma. Results: 251 pts were identified. Clinical characteristics at diagnosis were: median age 60 y (range 31–86 y), 58% male, 83% stage III/IV, 30% bulky disease ≥10cm, 20% B symptoms, 16% elevated LDH. FLIPI variables were retrievable on 95% pts: 27% low-risk, 29% intermediate-risk, 45% high-risk. Histology: 56% FL grade 1, 29% FL grade 2, 14% FL grade 3, 1% FL NOS. 48 pts (19%) were on observation before systemic treatment was initiated with a median time between diagnosis and first cycle of R-CVP of 19 m (range 4–130 m). At a median f/u of 36 m (range 0–74 m), 33 pts (13%) have died (24 from lymphoma, 3 from treatment toxicity, 6 from unrelated causes while in sustained remission). 27 pts (11%) had lymphoma refractory to R-CVP and an additional 8 pts (3%) failed to complete therapy (3 due to poor tolerance, 3 died from treatment toxicity, 2 died from unrelated causes). Pts with refractory disease were treated as follows: 6 purine analog-based regimens, 13 R-CHOP, 3 radiation therapy, 3 palliative care and 2 other chemotherapy regimens. Outcome of refractory pts was extremely poor, with a 3-year OS of 48%. 216/251 pts responded to R-CVP (ORR 86%: CR/CRu 44%, PR 37%, 5% detailed radiologic response not available). Following response to R-CVP, 59 pts were observed and 167 pts received R-maintenance. These 2 groups had similar baseline characteristics in terms of age, stage, gender and FLIPI score; however, median f/u was longer for observation pts compared to R-maintenance pts, 59m vs 34m. Eighteen pts (11%) developed progressive disease while receiving R-maintenance and within the subset of pts with available imaging studies for review, 23% pts in PR after R-CVP converted to CR/CRu while on R-maintenance. The 3-y PFS was significantly improved for pts receiving R-maintenance compared to pts on observation alone after having responded to R-CVP, 83% vs 62%, p=0.002 (see figure). The 3-y OS was similar in the 2 cohorts (93% vs. 93%, p=0.985). Conclusions: This population-based analysis confirms the benefit of R-maintenance following immunochemotherapy in pts with untreated FL. R-CVP followed by 2 years of R-maintenance is a well-tolerated and effective therapy with outcomes that compare favorably with more intensive combinations. Patients with lymphoma refractory to R-CVP have a dire prognosis; improved therapeutic approaches are needed for this high-risk subgroup. Disclosures: Connors: Hoffmann-La Roche: Research Funding. Sehn:Hoffmann-La Roche: Consultancy, Research Funding; Genentech: Consultancy.

Abstract 113 Introduction: DLBCL and HL represent highly curable lymphoid malignancies. Patients (pts) whose lymphoma is refractory to or relapses following initial therapy pose a significant therapeutic challenge. The goal of therapy is to proceed to a non-cross-resistant salvage regimen followed by high dose chemotherapy (HDC) and stem cell transplantation (SCT) for transplant eligible pts. The optimal choice of salvage therapy remains unknown. The combination of gemcitabine, dexamethasone and cisplatin (GDP) has been shown in phase II studies to induce high response rates with minimal toxicity (Baetz T, Ann Oncol, 2003; Crump M, Cancer, 2004). Based on these promising results, British Columbia Cancer Agency (BCCA) policy has recommended GDP as the preferred salvage regimen for pts with relapsed/refractory DLBCL and HL since 2002. Patients and Methods: We conducted a retrospective analysis using the BCCA Lymphoid Cancer Database and included all pts with relapsed/refractory DLBCL and HL who received GDP as salvage therapy between September 2002 and June 2010. Pts were treated with gemcitabine 1000 mg/m2 IV day 1,8; dexamethasone 40 mg PO days 1–4 and cisplatin 75 mg/m2 IV day 1, administered at 3 week intervals (2-3 cycles for transplant eligible patients and up to 6 cycles for non-transplant candidates). Primary endpoints were response rate, PFS (defined as the interval from the beginning of GDP to first progression, relapse or death from any cause) and OS. Results: 235 pts treated with GDP were identified; 152 and 83 pts with relapsed/refractory DLBCL and HL, respectively. Clinical characteristics at time of diagnosis for patients with DLBCL were: 68% male, 65% stage III/IV, 42% bulky disease ≥ 10 cm, 43% B-symptoms, 59% IPI 0–2, 41% IPI 3–5. Median age at time of GDP was 57 y (range 20–79 y). 57 pts (37%) had primary refractory disease to first-line R-CHOP; 144 (95%) were treated with GDP at first relapse/progression; median time from diagnosis to relapse after R-CHOP (excluding primary refractory pts) was 21 m (range 7–139 m). 30 pts (20%) received rituximab with GDP. Detailed radiologic response assessment following GDP(+/−R) was available for 82% pts with response rates as follows: 16% CR/CRu, 33% PR, 17% SD, 34% PD. 9 pts (6%) underwent HDC followed by allogeneic SCT and 57 pts (38%) underwent HDC followed by autologous SCT. With median follow-up of 24 m from start of GDP (range 0–84 m), 51 pts (34%) were alive and 101 pts (66%) have died (99 from lymphoma, 1 treatment toxicity during allogeneic SCT, 1 unrelated cause). 2-y PFS and OS were 21% and 28%, respectively. The 2-y PFS and OS for the subset of patients who underwent HDC/SCT were 36% and 47%, respectively. Clinical characteristics at diagnosis for the 83 pts with relapsed/refractory HL were: 55% male, 59% stage III/IV, 39% bulky disease ≥ 10 cm, 55% B-symptoms, 80% nodular sclerosis, 4% mixed cellularity, 2% nodular lymphocyte predominant, 2% lymphocyte depleted and 12% HL NOS. IPS variables were retrievable on 66% patients: 82% IPS ≤ 3 and 18% IPS ≥ 4. Median age at time of GDP was 31 y (range 17–73 y). 30 pts (36%) had primary refractory HL and 73 (88%) received GDP at first relapse/progression. Median time from diagnosis to relapse following ABVD-like therapy (excluding primary refractory pts) was 20 m (range 9–186 m). Detailed radiologic response assessment following GDP was available in 67% pts with response rates as follows: 7% CR/CRu, 64% PR, 13% SD, 16% PD. In total, 1 pt underwent HDC followed by allogeneic SCT and 69 pts (83%) proceeded to HDC and autologous SCT. With a median follow-up of 30 m from start of GDP (range 0–86 m), 70 pts (84%) were alive and 13 (16%) have died (all from HL). 2-y PFS and OS were 58% and 85%, respectively, and for the subset of pts who underwent HDC/SCT were 57% and 86%, respectively. Hospitalization rates due to complications during GDP were higher in patients with DLBCL than HL (20% vs 7%), likely reflecting differences in age and co-morbidities between the 2 cohorts. No failures of stem cell mobilization were recorded and the only toxic death was a consequence of HDC and allogeneic SCT. Conclusions: GDP is an effective and well-tolerated out-patient salvage regimen for relapsed/refractory DLBCL and HL. Outcomes appear to be comparable to those reported with more aggressive regimens. Results from an ongoing Canadian prospective trial comparing R-GDP to R-DHAP will help clarify the role of GDP in the treatment of relapsed/refractory DLBCL. Disclosures: Connors: Hoffmann-La Roche: Research Funding.

Abstract 1751 Background: The addition of rituximab to CHOP (R-CHOP) has markedly improved the progression-free and overall survival of patients (pts) with diffuse large B cell lymphoma (DLBCL). Nevertheless, 9.5% of pts harbor lymphoma that is refractory to R-CHOP (Feugier et al) and 18–27% experience relapse after initial response (GELA and MINT trial). Aim: Assess outcome of pts with primary refractory and early relapsing DLBCL (within 3 months of CR/PR post completion of R-CHOP treatment). Patients and Methods: The BCCA Lymphoid Cancer Database identified 1126 pts diagnosed with DLBCL between December 2000 and September 2009. All ages and stages were included and primary treatment was R-CHOP in all pts. Results: 166 pts(15%) had primary refractory or early relapsing disease, of which 93 were age >70 y and too frail to have received > 2 cycles of R-CHOP. Of the remaining 73 pts, 33 (45%) had primary refractory lymphoma and 40 (55 %) relapsed within 3 months of achieving a CR/PR. Pt characteristics (n=73): median age 57 y; 68% male; stage I (4 %), II (16 %), III (19 %), IV (60 %); PS 0,1 (41 %) PS 2–4 (59 %); LDH elevated (58 %); IPI 0 (1 %), 1 (15 %), 2 (15 %), 3 (30 %), 4 (35 %), 5 (2 %). There were no differences in the clinical characteristics of pts with primary refractory versus early relapsing disease. Of the 73 pts, 37 (50%) were without serious co-morbidity and were able to be treated with a curative intent that included multi-agent salvage chemotherapy with a plan to proceed to high-dose tx and autologous stem cell transplantation (ASCT), whereas 36 pts had palliative tx or comfort care only. 10 pts did undergo ASCT (3 primary refractory, 7 early relapsers). The median overall survival for the 73 pts was 10 months with only 6 pts alive without evidence of disease (range 14–106 months). 5 of these 6 pts had relapsed early after initial CR/PR, while only 1 patient had primary refractory disease. 3 of these 6 pts had salvage treatment without ASCT and 3 with ASCT. Conclusion: Chemotherapy-refractory or early relapsed disease after R-CHOP has a very poor outcome with only anecdotal survivors independent of the intended treatment approach. Biologic workup of this group of patients is urgently needed with the intention of defining the molecular underpinnings of treatment resistance. Disclosures: Savage: Roche: Honoraria. Sehn:Roche: Honoraria, Research Funding.

Abstract 417 Background: Trials enrolling patients with limited stage Hodgkin lymphoma conducted by European cooperative groups including EORTC, GELA and the GHSG frequently include patients with stage II B or stage II bulky (≥ 10 cm) disease in either “favorable” or “unfavorable” subgroups. Similar patients are usually excluded from North American trials of limited stage disease and rather are included in trials of advanced stage lymphoma. We sought to clarify the appropriateness of these approaches. Methods: All adult (age > 15 but < 66 y) HIV antibody negative patients with stage II A bulky, II B non-bulky or II B bulky Hodgkin lymphoma treated in British Columbia since 1981, when ABVD-type chemotherapy became standard, were identified using the BC Cancer Agency Lymphoid Cancer Database. Characteristics: n=416; male 54%; age range 16–64 y (median = 30); histologic subtype nodular sclerosis 86%, mixed cellularity 5%, not subclassifiable 6%, other 3%; subdiaphragmatic 3%; stage II A bulky 32%, II B non-bulky 32%, II B bulky 36%; localized extranodal extension (E lesion) 35%; largest mass diameter non-bulky range 1–9 cm (median 6 cm), bulky range 10–25 cm (median 12 cm); IPFP prognostic score 0, 9%; 1, 33%; 2, 32%; 3, 19%; 4, 6%; 5, 1% (data missing 36%). Results: Planned treatment consisted of 6–8 cycles of ABVD-type chemotherapy followed by radiation for a persistent residual mass (only if PET positive since 2005). 50% of patients received radiation (extended field 24%, involved field 76%). Thus, patients were treated with the same approach that is used for stage III or IV. Patients with bulky disease were much more likely to receive radiation: II A bulky 72%; II B non-bulky 11%; II B bulky 65%. For all 416 patients, with a median follow-up of 8 y, 5 and 10 y progression free survivals (PFS) were 81% and 76%; time-to-progression (TTP) estimates 83% and 81% (Fig. 1); and overall survivals (OS) were 94% and 90%. Although there is some variation, survivals were very similar across the three stage groups. This experience is instructive and indicates that when patients with stage II B bulky or non-bulky or stage II A bulky Hodgkin lymphoma are treated with the same approach as is used for advanced stage disease at least 20% of patients relapse. Conclusion: It is inappropriate to include patients with stage II B or stage II A bulky Hodgkin lymphoma on trials designed for limited stage disease. With an estimated relapse rate of at least 20% inclusion of these patients can grossly distort outcomes and compromise interpretation of the results of the trial since the expectation for the rest of the patients (stage I A and II A, low bulk) is that no more than 5% of patients will relapse. Patients with stage II B or stage II A bulky Hodgkin lymphoma should be included in trials for patients with advanced stage disease. Disclosures: Klasa: Seattle Genetics, Inc.: Research Funding.

Abstract 1554 Poster Board I-577 Introduction The International Prognostic Factor Project Score (IPS) is the most widely utilized risk stratification index for Hodgkin lymphoma (HL) (Hasenclever, N Engl J Med, 1998). Based on patients treated before 1992, it incorporates 7 adverse risk features (male gender, age ≥45 y, stage IV, hemoglobin Methods This retrospective population-based analysis used the British Columbia Cancer Agency Lymphoid Cancer Database to identify all patients ages 15-65 y diagnosed from January 1st,1990 to June 30th, 2008 with advanced stage HL (stage III/IV, or stage I/II with B symptoms or bulky disease ≥10 cm), who were treated with curative intent with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) or an ABVD-equivalent regimen and had complete information including all IPS variables. Primary endpoint was FFP, defined as the interval from diagnosis to first progression or relapse or death due to treatment toxicity; deaths from unrelated causes were censored. Results 579 patients were identified. Median age was 29 y (range 15-65); 11 (2%) stage I, 239 (41%) stage II, 202 (35%) stage III and 127 (22%) stage IV; 245 (42.3%) had bulky disease; and 359 (62%) had B symptoms. Histologies included: 455 (79%) nodular sclerosing, 35 (6%) mixed cellularity, 7 (1%) lymphocyte-rich, 11 (2%) lymphocyte depleted, 13 (2%) nodular lymphocyte predominant, 58 (10%) HL NOS. 161 (28%) patients received IFRT with primary treatment. Adverse prognostic factors were present as follows: 119 (21%) age≥45, 375 (65%) albumin Conclusion The IPS remains prognostic for patients with advanced stage HL treated in a more modern era. However, it does not identify risk groups with sufficiently good or poor outcome to justify deviation from standard therapy. Identification of truly low or high risk populations will require supplementation with molecular markers and/or the use of early PET scanning. Caution should be used when comparing results from current clinical trials to historic controls, since more recent outcomes with standard therapy are clearly superior to those previously reported. Disclosures No relevant conflicts of interest to declare.

Abstract 408 Introduction: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) is the current standard of care for the treatment of diffuse large B cell lymphoma (DLBCL). Doxorubicin has an integral role but is associated with significant toxicity. The omission of doxorubicin in patients who are frail, have poor baseline cardiac function or who have previously received anthracycline therapy may compromise outcome. However, the recent introduction of rituximab may allow for improved outcomes without the use of doxorubicin. We assessed the efficacy of substituting etoposide for doxorubicin for patients with a contraindication to anthracyclines. Patients and Methods: Treatment guidelines in British Columbia (BC) recommend the substitution of etoposide for doxorubicin in standard dose R-CHOP for patients with DLBCL who have a contraindication to anthracyclines (R-CEOP). Etoposide is administered at a dose of 50 mg/m2 IV on day 1 and 100 mg/m2 PO on days 2 and 3 of each cycle. Patients with limited stage disease receive 3-4 cycles of chemotherapy with or without radiation therapy; patients with advanced stage disease receive 6 cycles of chemotherapy. We performed a retrospective population-based analysis using the BC Cancer Agency Lymphoid Cancer and pharmacy databases and included all patients with newly diagnosed DLBCL who were treated with curative intent with R-CEOP from December 2000 to March 2009. Patients who began treatment with R-CHOP but then switched to R-CEOP (due to intolerance or because a maximum threshold of anthracycline dosing was reached) were also included in the analysis if R-CEOP was administered for more than 50% of cycles delivered. Outcome of this population was compared with a 2:1 control group treated with R-CHOP in the same time period and matched for age, clinical stage and International Prognostic Index (IPI). End points were time to progression (TTP) and overall survival (OS). Results: We identified 81 patients treated with R-CEOP who met the stated inclusion criteria. Clinical characteristics were as follows: median age 73 y (range 34-93), 55 (68%) male, 15 (18%) limited stage and 66 (82%) advanced stage. Adverse prognostic factors according to the IPI were as follows: 85% age > 60 y, 58% stage III/IV, 31% PS > 1, 43% elevated LDH, and 12% > 1 extranodal site. IPI score: 19 (23%) low risk, 33 (41%) low-intermediate, 18 (22%) high-intermediate, and 11 (14%) high risk. Reasons for etoposide substitution were: 71 (88%) cardiac contraindication, 7 (9%) prior exposure to anthracyclines and 3 (4%) other co-morbidities. 72 (89%) patients received rituximab as part of the treatment, 25 (31%) received partial treatment with R-CHOP and then switched to R-CEOP and 56 (69%) received no anthracycline therapy. The control group included 162 randomly chosen patients matched for age, stage and IPI score and treated with R-CHOP. At a median follow-up of 28 months (range 3-86), 33/81 (41%) R-CEOP patients had died (23 with lymphoma, 3 treatment toxicity, 7 unrelated causes). The 5-year TTP was similar for patients treated with R-CEOP compared to patients in the R-CHOP control group, 57% versus 62%, respectively (p=0.21). (Fig. 1) The 5-y OS was lower for patients receiving R-CEOP compared with the R-CHOP control group (49% versus 64%, p=0.02), reflecting the underlying co-morbidities and frailty of this population. Interestingly, the 5-y TTP and 5-y OS rates were similar for patients in the R-CEOP cohort who had received partial treatment with an anthracycline and those who had received no anthracycline treatment (p=0.49 and p=0.77, respectively). Conclusions: A significant proportion of patients with DLBCL who are unable to receive anthracycline-based therapy can be cured with the etoposide-substituted regimen R-CEOP. R-CEOP is well tolerated even by patients with numerous co-morbidities. Moreover, the outcome of these patients does not appear to be significantly different compared to a similar population treated with standard R-CHOP. Disclosures: No relevant conflicts of interest to declare.

e11510 Background: To determine the response, tolerability, and long-term outcome of a neoadjuvant platinum-containing regimen for locally advanced breast cancer (LABC). To search for correlation between pathologic complete response (pCR) and predefined biomarkers in this cohort. Patients and Methods: Patients with LABC received eight cycles of either sequence A or B. Sequence A was doxorubicin 60 mg/m2 and paclitaxel 175 mg/m2 (AT) q3w X 4 followed by cisplatin (C) 60 mg/m2 and paclitaxel 90 mg/m2 (CT) q2w X 4. Sequence B was CT x 4 followed by AT x 4. In addition to estrogen receptor and HER2, immunohistochemistry (IHC) for MDR-1, MRP-1, topoisomerase IIα(topoIIα) and p53 was performed. Results: 88 patients were evaluable for response and toxicity. Median follow-up was 97 months. The overall pCR rate was 21.5%. For subgroups ER+/HER2-, HER2 +, and double negative (ER-/ HER2-) disease the pCR was 5.9%,23.3% and 35% respectively, p=0.006. Five year(y) overall survival for the entire cohort was 71.1%. Five y overall survival was 88.1% (CI 77.1%, 99.1%) for the ER positive HER2 negative group compared to 68.5% (CI 51.3%, 85.7%) and 49.5 (CI 27.4%, 71.6%) in the HER2 positive and “double negative” group respectively (p=0.0077). Over-expression of topo IIα was correlated with pCR (p No significant financial relationships to disclose.

598 Background: Anthracyclines and taxanes are now standard of care for LABC. Phase III trials have demonstrated pathological complete responses of the breast (pCR) of 20–34% in studies of primary operable and LABC. Recent trials in the HER-2 negative population reported pCR rates of 20–29%.We have completed a multi-centre phase II trial of a neoadjuvant sequential anthracycline and taxane combination regimen in a HER-2 negative LABC population. Methods: Women with HER-2 negative stage IIB-IIIC breast cancer were enrolled. Treatment consisted of 4 cycles of FEC100 (5-FU 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2) followed by 4 cycles of XT (docetaxel 75 mg/m2 and capecitabine 1,000 mg/m2 PO BID x 14 days q3 weekly). Hormone receptor positive cases were prescribed standard endocrine therapy. A correlative translational component with baseline and interval biopsies and serum collection was also performed. Results: A total of 51 patients (27% stage IIB; 43% IIIA; 20% IIIB; and 10% IIIC) were accrued across 4 BCCA centres from November 2004-December 2007. Median age was 54 years (33–67 years). 59% of tumours were ER positive. There were no primary progressors on FEC100, though 2 patients had significant toxicities requiring early discontinuation. 3 patients (6%) developed clinical progression on XT. The majority of patients (79%) on XT required a dose reduction or delay. There were 5 episodes (10%) of febrile neutropenia. 15 patients (29%) underwent adjuvant radiotherapy prior to surgery. The pCR rate (breast and axilla) for the entire study population was 22% (11/51). In the ER+ and triple negative subtypes the pCR (breast and axilla) was 13% and 42%, respectively. Conclusions: This multi-centre phase II trial demonstrates activity for neoadjuvant anthracyclines followed by combination docetaxel/capecitabine in a HER-2 negative LABC population. Though the pCR rate was greater in the triple negative cohort, significant improvements are still required across the biological subtypes in HER-2 negative LABC. [Table: see text]

8583 Background: Previous studies in the pre-rituximab era have identified important clinical differences between nodal and primary extranodal DLBCL. We have examined the prognostic significance of primary extranodal DLBCL in the post-rituximab era. Methods: Using the Lymphoid Cancer Database of the British Columbia Cancer Agency, all patients ≥18 years of age diagnosed with DLBCL between January 1999 and May 2006 and treated with an R-CHOP regimen were included for analysis. Patients were excluded if they were HIV positive, presented with disease in the testicular or central nervous system, or had known coincident indolent lymphoma. Primary extranodal DLBCL was defined as disease confined to one or more localized extranodal sites, with no or minimal nearby nodal involvement. Results: 513 patients were identified with the following characteristics: median age 62 y (range 19–93), male 59.1%, stage III/IV 53.8%, elevated LDH 49.5%, and performance status ≥2 38.2%. While 350 (68.2%) had at least some degree ...

1036 Background: E2100 was an open-label, multi-center, randomized, Phase III trial comparing P to P+B as initial chemotherapy for MBC. The original analysis based on investigator-assessed progress...

Background: Extranodal status is one of the five key factors in the International Prognostic Index (IPI) for diffuse large B-cell lymphoma (DLBCL). We have re-examined the prognostic utility of extranodal involvement in DLBCL patients by determining whether the number and location of extranodal sites correlate with survival, particularly in the post-rituximab era. Methods: Using the Lymphoid Cancer Database of the British Columbia Cancer Agency, all patients with a diagnosis of DLBCL were included between January 1979 and May 2006 except those who were less than age 18 at diagnosis, HIV positive, presented with disease in the testicular or central nervous system, had discordant indolent lymphoma at or before diagnosis, or did not receive any chemotherapy. Any degree of extranodal involvement was recorded as positive for extranodal disease and all sites of involvement were documented. Results: 1803 patients were identified with the following characteristics: median age 62 (range 19–93), male 58%, stage III/IV 49%, elevated LDH 51% and performance status ≥2 34%. Of the 1268 patients treated without rituximab, 358 (28%) had only nodal disease, 532 (42%) had 1 extranodal site and 378 (30%) had ≥2 extranodal sites. Among 535 patients who received rituximab, 163 (30%), 217 (41%) and 155 (29%) had 0, 1 and ≥2 extranodal sites, respectively. Of the 37 coded extranodal sites, the most commonly involved sites included soft tissue (16.2%), bone (11.3%), bone marrow (9.1%), pleura (9.1%), head and neck soft tissue (8.2%), stomach (8.7%), intestine (8.2%), lung (7.8%) and liver (5.8%). In multivariate analysis that included other IPI variables, extranodal involvement as defined in the IPI (≥2 sites) was not a significant prognostic factor in our cohort (with or without rituximab, see Table 1). However, the presence of any extranodal disease was found to correlate with a poorer overall survival in patients treated with rituximab (p=0.03). When specific extranodal sites were examined in the rituximab group, bone marrow (p Conclusions: In the post-rituximab era, extranodal involvement remains a significant prognostic factor, although not as traditionally defined in the IPI, but rather refined as the presence of any extranodal disease involvement. Furthermore, bone marrow involvement represents the only extranodal site associated with a poorer overall survival independent of the IPI. Table 1: Prognostic Significance of Extranodal Disease Involvement for Overall Survival

Consolidative radiotherapy (RT) is often administered following chemotherapy for advanced stage Hodgkin lymphoma (HL) with bulky disease at diagnosis or for residual abnormalities on post-chemotherapy CT imaging. It is unknown whether RT is necessary for such patients if the residual mass is FDG-PET-negative (PET-neg) following chemotherapy (CHT). Further, it has been previously shown that a post-therapy PET-positive (PET-pos) scan is highly predictive of future relapse; however, it is unclear whether consolidative RT can be used to salvage these cases. Methods Since July 2005, adult (> 16 y) patients in British Columbia (BC) with advanced stage HL (stage III /IV and/or the presence B symptoms and/or bulky disease (> 10cm)) have been treated with 6 cycles with ABVD followed by a PET scan for further treatment planning if residual abnormalities ≥2 cm were observed on CT imaging. Prior to this, post-treatment PET scans were obtained in some individuals by self-pay. If the PET scan was positive, RT was administered if feasible, otherwise, patients were observed. There were 68 eligible patients, including 7 self-pay patients, that were identified in the BC Lymphoid Cancer Database. 16 patients were excluded (PET not performed (5); palliative tx or refusal (3); composite lymphoma (1); progressive disease during CHT or at the time of PET scan (4); HIV + (1); PET mid-therapy (1); death due to unrelated cause prior to PET scan (n=1).), leaving a total of 52 patients who had a PET scan post-chemotherapy for a residual mass and who had adequate follow-up (median 19 m, 10–59 m). Patient characteristics include: M:F 1.1:1, Median age 29 (17–81); 55% stage II, 46% stage III/IV 44%; 49% bulky disease; 69% B symptoms; IPFP Prognostic score 0 8%; 1 39%; 2 26%; >3 26%. Results In total, 40/52 (77%) were PET-neg and 12/52 (23%) were PET-pos (SUV mean 4.4, 2.2–6.8). PET-pos patients had an inferior 2 y PFS compared to PET-neg patients (26% vs 91%, p=.001). In the PET-pos group, 10/12 received the planned RT and 5 have relapsed. In the PET-neg group, there was no difference in the 2 y PFS in patients with bulky (n=17) vs non-bulky disease (n=20) (86% vs 94%, p=.35). Conclusions Advanced stage HL patients who achieve a post-CHT PET-neg status are at a low risk of relapse and do not require additional consolidative RT thus avoiding potential long-term side effects. The majority of patients with bulky disease who have a PET-neg scan following CHT also remain in remission, however, longer follow-up is still needed. Although some patients with a positive PET-scan may be salvaged by consolidative RT, a high proportion ultimately relapse. Figure Figure Figure Figure

Background: Transformation of indolent lymphoma into diffuse large B-cell lymphoma (DLBCL) has been associated with poor survival and the optimal therapy is unknown. The addition of rituximab to CHOP chemotherapy (CHOP-R) has been shown to significantly improve the survival of patients (pts) with de novo DLBCL. However, the impact of rituximab on the survival of patients with transformed DLBCL remains unknown. Methods: As part of a large retrospective analysis examining the long term natural history of pts initially diagnosed with indolent lymphoma in British Columbia (B.C.) (n=690; follicular 600, small lymphocytic 49, lymphoplasmacytic 41), we have identified those pts who developed transformed lymphoma. The definition of transformation was based on either histological confirmation or clinical features, defined as one or more of the following: rapid discordant nodal or extranodal growth; sudden rise in LDH to > 2 x previous baseline; involvement of unusual extranodal sites; or hypercalcemia. Pts were excluded from this analysis if they received high-dose chemotherapy and stem cell transplant as part of the treatment for their transformed lymphoma (n= 9). Pts who were too frail to be treated with multi-agent chemotherapy were also excluded. The extent of disease at transformation was considered limited in pts with single nodal region involvement, no B symptoms, non-bulky disease ( Results: 108 pts with transformed lymphoma were identified in the B.C. lymphoid database, the majority of whom had a prior history of follicular lymphoma (n=103, 95%). Median age at transformation was 60 y (22–71). Transformation was histologically confirmed in 74 (69%) pts. The outcome of 23 pts who were treated with CHOP-R was compared to 85 pts who were treated with CHOP-like chemotherapy. None of the 108 pts had received rituximab as part the management of their indolent lymphoma. The median follow-up for all living pts in the CHOP-like cohort was 7 y (3–14) and 3 y (0.5–5) in the CHOP-R cohort. The post-transformation 5 y overall survival following CHOP-like chemotherapy was 33% vs 61% after CHOP-R (P= 0.01). This difference in survival remained significant when pts with clinically diagnosed transformation were excluded from the analysis (P= 0.02). For the 78 pts with advanced disease extent (59, CHOP-like; 19, CHOP-R) there was a significant difference in PT-5yOS (21% vs 57%, respectively; P= 0.005). For pts with limited disease extent (CHOP-like, 26; CHOP-R, 4) no significant difference in PT-5yOS was observed (P= 0.2). Conclusions: In rituximab-naive patients with indolent lymphoma, the addition of rituximab to CHOP chemotherapy significantly improves overall survival after transformation.

Background: DLBCL is a heterogeneous entity with patients exhibiting a wide range of clinical outcomes. A reliable prediction tool is vital for optimizing patient care. We have previously demonstrated that a revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI following treatment with rituximab and CHOP (CHOP-R). (Sehn, ASH 2005). Further exploration of clinical prognostic factors in an expanded cohort of patients yields a simplified prediction model based on stage and LDH alone. Methods: We performed a retrospective analysis to assess the predictive value of recognized clinical prognostic factors in an unselected population of patients with DLBCL treated with CHOP-R. Patients were identified using the Lymphoid Cancer Database of the British Columbia (BC) Cancer Agency and included all patients >16 y of age who were newly diagnosed with DLBCL prior to Jan 15, 2006, treated in BC with a CHOP-R protocol. Patients were excluded if they were HIV positive, had evidence of an active second malignancy or an underlying indolent NHL. Results: 523 patients were identified with the following characteristics: median age 61 y (16–93); male, 60%; stage III/IV, 55%; elevated LDH, 53%; performance status (PS) ≥2, 41%; ≥2 extranodal sites, 29%. Patients with advanced stage lymphoma (stage III/IV, B symptoms or bulky disease) or patients who were not candidates for radiation therapy were treated with 6–8 cycles of CHOP-R (91%) while those with limited stage were treated with CHOP-Rx3 and involved field radiation therapy (9%). Median follow-up for living patients is 24 months. On univariate analysis, stage, PS and LDH remain predictive for both PFS and OS. Number of extranodal sites is a borderline predictor of PFS (p=0.05) and no longer predictive of OS (p=0.276). Although age no longer predicts for PFS (p=0.17), it remains predictive of OS (p=0.001) since elderly patients are less likely to be treated successfully with secondary therapy and more likely to die from unrelated causes. On multivariate analysis, only stage (p Conclusions: A prediction model based on stage of disease and serum LDH level at presentation provides an accurate estimate of outcome following primary therapy with CHOP-R for patients with DLBCL.

Background: Isolated brain parenchyma relapse as initial site of relapse is a rare complication of NHL and carries a poor prognosis. Few large series focus on treatment characteristics and outcomes of isolated brain parenchyma relapse of NHL. Methods: The IPCG conducted a retrospective review of patient and treatment characteristics and outcomes of this complication. Following initial diagnosis and treatment of NHL (1980–2004), cases with brain parenchyma relapse as initial relapse site, with no evidence of lymphoma elsewhere in the body at the time of brain relapse, were eligible. Cases with brain, spine or leptomeningeal involvement at NHL diagnosis were not eligible. Results: 113 cases were assembled from 13 investigators in 8 countries. Preliminary data summaries are: 94 (83%) cases had diffuse large B-cell NHL, 5 (4%) follicular lymphoma, 3 (3%) Burkitt’s lymphoma, other NHL subtypes (11) . Median age at NHL diagnosis was 61yrs (16–85 yrs). 55% were male. Median ECOG at NHL diagnosis was 1. Median time from NHL diagnosis to isolated brain relapse was 1.8 yrs (3 months–15.9 yrs). 76 (67%) relapsed in brain less than 3 yrs after NHL diagnosis. Symptoms at brain relapse included mental status changes in 37%, gait/balance disturbance (27%), motor/sensory symptoms (23%). Median ECOG at brain relapse was 2. Parenchyma relapse was documented by brain imaging plus biopsy in 54 (48%), or imaging without biopsy in 58 (52%); not reported (1). 53 (48%) cases had one brain lesion; 56 (50%) had two or more lesions; not reported (4). Site of relapse was cerebral hemispheres in 53 (48%) cases, deep brain structures (brain stem/cerebellum) in 30 (27%), cerebral hemispheres and deep brain structures in 23 (21%); not reported (7). At brain relapse, CSF was positive in 11 (10%) cases, negative in 56 (50%); not reported (46[40%]). Treatment for brain relapse was chemotherapy alone in 52 (46%) cases, WBRT alone in 34 (30%), chemotherapy followed by RT in 26 (23%), and brain surgery alone (1). 78 (69%) cases are deceased. Median survival from brain parenchyma relapse to death was 1.6 yrs (95% CI: 11 months–2.6 yrs). Effect of treatment type at brain relapse on survival, will be reported. Brain lymphoma was the cause of death in 49 (63%) cases; CNS toxicity was the cause in 6 (8%) cases. Conclusion: Though a rare relapse site, prospective studies are needed to improve understanding and outcomes of isolated brain parenchyma relapse of NHL.

1534 Background: PIOL is a hemopoietic tumor that arises in the retina, vitreous or optic nerve head, and carries a high risk of ocular and CNS relapse. The natural history and optimal management are unknown. Methods: A retrospective series of 81 patients with PIOL was assembled from 15 centers in 7 countries. Only patients with isolated ocular lymphoma were included; none had brain, spinal cord, or systemic lymphoma at diagnosis. Results: The median age at diagnosis was 65 (24–85). 58% were women. The median ECOG performance status was 0, and only three had a score > 1. The median latency from symptom onset to diagnosis was 6 months (0– 36). Slit lamp exam was positive in 51, negative in 6, and not reported in 24. Vitrectomy was positive in 72 and negative in 2. 6 had a positive choroidal or retinal biopsy and 1 had no ocular surgery. CSF cytology was positive in 10 (17%), negative in 48, and unknown in 23. 21 received local therapy at diagnosis: 6 intra-ocular methotrexate (400 ug), 14 ocular radiation (median 3600 cGy), and 1 both modalities. 52 received more extensive therapy including systemic chemotherapy alone in 20 and a combination of chemotherapy and radiotherapy in 32. 5 received no treatment and details are unknown in 3. 47 patients (58%) relapsed a median of 19 months (0.5–180) after initial therapy. Sites of relapse included brain 47%, eyes 30%, brain and eyes 15%, and systemic 8%. Patients treated with ocular therapy alone did not have an increased risk of failing in the brain (p = 0.6). Progression free survival (PFS) and overall survival (OS) were 29.6 and 57 months respectively and were unaffected by the choice of therapy. CNS disease was the cause of death in 19/33 (58%). Conclusions: In this series, treatment type did not affect sites of relapse, PFS or OS in patients with PIOL. To minimize toxicity, the best initial therapy should be limited to intraocular chemotherapy or focal radiotherapy. Prospective clinical trials are needed to improve our understanding and treatment of this disease. No significant financial relationships to disclose.

7510 Background: The impact of initial treatment of indolent non-Hodgkin’s lymphoma (NHL) on the risk of transformation (TR) to aggressive NHL is unknown. High LDH and advanced stage at diagnosis have been shown to be predictive for TR; however, the effect of initial treatment is difficult to estimate as most series included heterogenous patient (pts) populations. Methods: As part of a large retrospective analysis examining TR (n = 698), we identified pts from 2 consecutive phase II studies conducted at the British Columbia Cancer Agency. Both studies had identical inclusion criteria: diagnosis of indolent NHL, no prior treatment, age16–60 y and advanced stage disease (III/ IV or I/ II with B symptoms or bulky disease ≥10cm). The first study included use of BPVACOP (bleomycin, cisplatin, etoposide, doxorubicin, cyclophosphamide,vincristine and prednisone, followed by involved field irradiation (RT) to original nodal sites of lymphoma. The second used combination alkylator-purine analogue (cyclophosphamide- cladrabine or fludaribine and prednisone). The definition of TR was based on either histological confirmation (HIST) or clinical features (CLIN), defined as one or more of the following: rapid discordant nodal or extranodal growth; sudden rise in LDH to > 2 x previous baseline; involvement of unusual extranodal sites; or hypercalcemia. Results: 260 pts were identified. BPVACOP+RT (n = 140), alkylator-purine analogue (n = 120). Median age 46 y (19–60). Follicular histology in 133 (94%) and 105 (87%), respectively. The majority were stage III/IV (89%) with equal proportions in each cohort. With a median follow-up (FU) for living pts of 90 months (1–225), 26 (18%) pts treated with BPVACOP+RT developed TR, 16 of which were confirmed with biopsy, versus 32 (27%) in the alkylator-purine group, of which 18 had biopsy confirmation. The 5 y risk of TR for BPVACOP+RT was 9% compared to 24% for the alkylator-purine analogue group (p < 0.0095). The annual risk of TR through 10 y of FU was 1.5% and 3.0%, respectively. The post-TR 5 y OS of all 58 pts with TR was 19%. Pts with TR based on CLIN vs HIST criteria did not differ in their outcome. Conclusions: The use of an anthracycline-based regimen as initial treatment for advanced stage indolent NHL is associated with a marked reduction in the risk of future TR. No significant financial relationships to disclose.