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Purpose Studies in classical Hodgkin lymphoma (cHL) typically measure the time to events from diagnosis. We evaluated the risk of relapse at event-free survival time points in cHL and compared the risk of death to expected mortality rates in British Columbia (BC). Methods The BC Cancer Agency Lymphoid Cancer Database was screened to identify all patients age 16 to 69 years diagnosed with cHL between 1989 and 2012 treated with the chemotherapy regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (or equivalent). We compared the observed mortality to the general population using age-, sex-, and calendar period–generated expected mortality rates from BC life-tables. Relative survival was calculated using a conditional approach and expressed as a standardized mortality ratio of observed-to-expected deaths. Results One thousand four hundred two patients were identified; 749 patients were male (53%), the median age was 32 years, and 68% had advanced-stage disease. The median follow-up time was 8.4 years. Seventy-two percent of relapses occurred within the first 2 years of diagnosis. For all patients, the 5-year risk of relapse from diagnosis was 18.1% but diminished to 5.6% for patients remaining event free at 2 years. For advanced-stage patients who were event free at 2 years, the 5-year risk of relapse was only 7.6%, and for those who were event free at 3 years, it was comparable to that of limited-stage patients (4.1% v 2.5%, respectively; P = .07). Furthermore, international prognostic score ≥ 4 and bulky disease were no longer prognostic in patients who were event free at 1 year. Although the relative survival improved as patients remained in remission, it did not normalize compared with the general population. Conclusion Patients with cHL who are event free at 2 years have an excellent outcome regardless of baseline prognostic factors. All patients with cHL had an enduring increased risk of death compared with the general population.

Introduction A number of novel therapies are under investigation in relapsed or refractory peripheral T-cell lymphoma (PTCL); however, their relative impact on outcome is unknown. We examined the survival of patients with PTCL after relapse or progression in the absence of hematopoietic stem-cell transplantation and explored factors influencing survival. The three most common subtypes encountered in North America were evaluated: PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large-cell lymphoma (ALCL; anaplastic lymphoma kinase [ALK] positive and ALK negative. Patients and Methods After exclusions, 153 patients were analyzed (PTCL-NOS, n = 79 [52%]; AITL, n = 38 [25%]; ALK-positive ALCL, n = 11 [7%]; ALK-negative ALCL, n = 27 [16%; including ALK status unknown, n = 1]). Results Median time from initial diagnosis to relapse or progression after primary therapy was 6.7 months, and median age at relapse was 66 years (ALK-positive ALCL, 39 years). Median overall survival (OS) and median progression-free survival (PFS) after relapse or progression (second PFS) were 5.5 and 3.1 months, respectively, and were only marginally better in patients who received chemotherapy at relapse (n = 89 [58%]; 6.5 and 3.7 months, respectively). Patients with good performance status (PS) of 0 or 1 (n = 47) at relapse who received chemotherapy had a more favorable OS (P < .001; median OS, 13.7 months) and PFS (P = .006; median second PFS, 5.0 months), which remained significant in multivariate analysis (OS: hazard ratio [HR], 2.09; P = .002; second PFS: HR, 1.66; P = .030). Conclusion Most patients with relapsed or refractory PTCL have poor outcomes with short survival. Select patients with good PS have more favorable outcomes with standard chemotherapy.

Purpose The International Prognostic Score (IPS) is the most widely used risk stratification index for Hodgkin's lymphoma (HL). It is based on patients treated before 1992 and predicts 5-year freedom from progression (FFP) and overall survival (OS) ranging from 42% to 84% and 56% to 89%, respectively. The IPS has not been validated in a recently treated population in which outcomes have improved compared with historic results. Patients and Methods By using the British Columbia Cancer Agency Lymphoid Cancer Database, we identified all patients age ≥ 16 years newly diagnosed with advanced-stage HL (stage III to IV, or stage I to II with “B” symptoms or bulky disease ≥ 10 cm) from 1980 to 2010, treated with curative intent with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or an ABVD-equivalent regimen with complete clinical information. Results In all, 740 patients were identified. Five-year FFP and OS were 78% and 90%, respectively. The IPS was prognostic for both FFP (P < .001) and OS (P < .001), with 5-year FFP ranging from 62% to 88% and 5-year OS ranging from 67% to 98%. Analysis limited to patients age 16 to 65 years (n = 686) demonstrated a narrower range of outcomes, with 5-year FFP ranging from 70% to 88% and 5-year OS ranging from 73% to 98%. Conclusion The IPS remains prognostic for advanced-stage HL, but the range of outcomes has narrowed considerably. This improvement in outcome with ABVD should be acknowledged before consideration of alternate initial therapies and when comparing results from current trials with those of historic controls.

Purpose To determine if mastectomy (Mx) use, chemotherapy (CT) intensity, or treatment sequence of CT, radiation therapy (RT), and Mx have improved outcome for inflammatory breast cancer (IBC). Patients and Methods A retrospective analysis of 485 patients with IBC diagnosed in British Columbia between 1980 and 2000 analyzed locoregional relapse-free survival (LRFS) and breast cancer–specific survival (BCSS) by treatment intent and treatment received. Curative intent was defined as delivery of more than four cycles of anthracycline-based CT plus locoregional RT in patients without distant metastases. Results Median follow-up among survivors was 6.5 years. Median BCSS was 1.0 and 3.2 years for patients with distant metastases at diagnosis or those who were curatively treated, respectively. Among patients treated curatively (n = 308), there were no significant differences in LRFS or BCSS with timing of Mx before or after CT/RT, time between diagnosis and RT, or the sequence of RT and CT. Patients receiving more intensive CT had improved 10-year BCSS compared with standard CT (43.7% v 26.3%; P = .04). Ten-year LRFS for patients having Mx after CT, Mx before CT, and without Mx was 62.8%, 58.6%, and 34.4%, respectively (P = .0001); the corresponding 10-year BCSS was 36.9%, 19.9%, and 22.5%, respectively (P = .005). On multivariate analysis, Mx was associated with improved LRFS (P = .04). Independent prognostic factors for BCSS were menopausal status (P = .02), estrogen receptor status (P = .02), and CT type (P = .05). Conclusion This retrospective analysis suggested that mastectomy, in conjunction with CT and RT, seemed to enhance locoregional control, whereas modern CT regimens seemed to improve BCSS.

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...

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.

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.

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...

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]

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.

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...

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.

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.