Laurie H Sehn

University of British Columbia - Vancouver, Vancouver, British Columbia, Canada

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Publications (63)544.96 Total impact

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    ABSTRACT: Effective treatment of diffuse large B cell lymphoma (DLBCL) is plagued by heterogeneous responses to standard therapy, and molecular mechanisms underlying unfavorable outcomes in lymphoma patients remain elusive. Here, we profiled 148 genomes with 91 matching transcriptomes in an R-CHOP-treated DLBCL cohort to uncover molecular subgroups linked to treatment failure. Systematic integration of high-resolution genotyping arrays and RNA-seq data revealed novel deletions in RCOR1 to be associated with unfavorable progression free survival (P = 0.001). Integration of expression data from the clinical samples with data from RCOR1 knockdowns in the lymphoma cell lines KM-H2 and Raji yielded an RCOR1 loss-associated gene signature comprising of 233 genes. This signature identified a subgroup of patients with unfavorable overall survival (OS) (P = 0.023). The prognostic significance of the 233-gene signature for OS was reproduced in an independent cohort comprising 195 R-CHOP treated patients (P = 0.039). Additionally, we discovered that within the IPI low risk group, the gene signature provides additional prognostic value that was independent of the cell-of-origin phenotype. Taken together, we present a novel and reproducible molecular subgroup of DLBCL, impacting risk-stratification of R-CHOP treated DLBCL patients and revealing a possible new avenue for therapeutic intervention strategies.
    Blood 11/2014; · 9.78 Impact Factor
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    ABSTRACT: High-dose therapy and autologous stem cell transplant (HDT/ASCT) is the preferred treatment for chemosensitive relapsed/refractory Hodgkin lymphoma (HL). The role for HDT/ASCT in chemoresistant HL is less well defined. We evaluated long-term outcomes of relapsed/refractory HL patients whose disease was refractory to secondary chemotherapy preceding HDT/ASCT.
    Annals of Oncology 08/2014; · 7.38 Impact Factor
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    ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with variable therapeutic responses and alternative therapies are needed for patients with unfavourable treatment outcomes after standard treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). One promising candidate is brentuximab vedotin, an antibody-drug conjugate targeting CD30-expressing cells. However, CD30 (TNFRSF8) expression patterns in DLBCL are not well described thus far. Here, we examined CD30 expression in a population-based cohort of immunocompetent patients from British Columbia with de novo DLBCL using immunohistochemistry. 385 cases of formalin-fixed paraffin-embedded DLBCL in tissue microarrays were evaluated. 95 cases (25%) harboured CD30+ tumour cells. Using a > 0% cut-off, CD30 expression was predictive of superior 5-year progression-free survival within R-CHOP treated germinal centre B-cell-like (GCB) DLBCL (86% vs. 64%, P = 0·020), which was independent of the International Prognostic Index. Epstein-Barr virus (EBV) was identified in 11 (3%) cases, all of which were non-GCB (P = 0·001) and almost exclusively positive for CD30 expression (10/11) (P < 0·001). We conclude CD30 is expressed in a substantial proportion of DLBCL and CD30 immunohistochemistry may be a useful prognostic marker in R-CHOP treated GCB-DLBCL. The significant association of CD30 with EBV-positive non-GCB DLBCL suggests a distinct pathobiology for these cases.
    British Journal of Haematology 08/2014; · 4.94 Impact Factor
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    ABSTRACT: Vascular endothelial growth factor is involved in lymphoma growth, suggesting a potential role for anti vascular endothelial growth factor therapies in hematological malignancies. In this phase III study, patients with CD20-positive diffuse large B-cell lymphoma were randomized to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone plus either placebo (R-CHOP) or bevacizumab (RA-CHOP). Treatment was administered every 21 (8 cycles) or 14 days (6 cycles plus 2 rituximab cycles) per institutional practice. An early analysis of risk/benefit by the Data and Safety Monitoring Board showed that RA-CHOP increased cardiotoxicity without prolonging progression-free survival compared with R-CHOP, and the trial was stopped early. The study protocol was amended to allow for 12 additional months of follow-up to evaluate safety. With 787 patients enrolled, median follow up was 23.7 and 23.6 months for R-CHOP and RA-CHOP, respectively. Median progression-free survival for R-CHOP and RA CHOP was 42.9 and 40.2 months, respectively (hazard ratio=1.09; P=0.49). The proportion of deaths was identical for R-CHOP (21%, 83/387) and RA-CHOP (21%, 82/390). Relative to R-CHOP, RA-CHOP had a higher rate of left ventricular ejection fraction perturbation (18% versus 8%; odds ratio=2.51; 95% confidence interval: 1.60-3.93) and congestive heart failure (16% versus 7%; odds ratio=2.79; 95% confidence interval: 1.72-4.54). Bevacizumab added to R-CHOP increased cardiac events, without increasing efficacy, arguing against further evaluation of RA-CHOP in patients with diffuse large B-cell lymphoma. The MAIN study is registered at, NCT00486759.
    Haematologica 06/2014; · 5.94 Impact Factor
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    ABSTRACT: Due to disease rarity, there is limited information regarding the optimal therapy and outcome of patients with advanced stage nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). 42 patients with NLPHL by the REAL/WHO classification with advanced stage disease were identified and paired 1:2 with a matched control with classical Hodgkin lymphoma (CHL) with matching by age, gender, stage, decade of diagnosis, and treatment received. The median follow-up was 11.3 years (range 1.9-35.5) for NLPHL patients and 10.7 years (1.6-26.3) for CHL patients. The majority received ABVD-like chemotherapy. Although the 10 year overall survival (OS) (P=0.579) and Hodgkin lymphoma-freedom from treatment failure (HL-FFTF) were similar between NLPHL and CHL (75% vs 73%, P=0.610), the time to progression (TTP), which also includes the development of secondary aggressive lymphoma, was inferior in NLPHL (10 y 63% vs 73%, P=0.040). Splenic involvement was associated with an inferior 10 y TTP in patients treated with ABVD (48 vs 71%, P=0.049) and an increased cumulative incidence of transformed aggressive lymphoma (P=0.014) providing a rationale for further evaluation of CHOP +/- rituximab in NLPHL.
    Blood 04/2014; · 9.78 Impact Factor
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    ABSTRACT: We examined the relationship between location of residence at the time of diagnosis of diffuse large B-cell lymphoma (DLBCL) and health outcomes in a geographically large Canadian province with publicly funded, universally available medical care.Patients and Methods.The British Columbia Cancer Registry was used to identify all patients 18-80 years of age diagnosed with DLBCL between January 2003 and December 2008. Home and treatment center postal codes were used to determine urban versus rural status and driving distance to access treatment.Results.We identified 1,357 patients. The median age was 64 years (range: 18-80 years), 59% were male, 50% were stage III/IV, 84% received chemotherapy with curative intent, and 32% received radiotherapy. There were 186 (14%) who resided in rural areas, 141 (10%) in small urban areas, 183 (14%) in medium urban areas, and 847 (62%) in large urban areas. Patient and treatment characteristics were similar regardless of location. Five-year overall survival (OS) was 62% for patients in rural areas, 44% in small urban areas, 53% in medium urban areas, and 60% in large urban areas (p = .018). In multivariate analysis, there was no difference in OS between rural and large urban area patients (hazard ratio [HR]: 1.0; 95% confidence interval [CI]: 0.7-1.4), although patients in small urban areas (HR: 1.4; 95% CI: 1.0-2.0) and medium urban areas (HR: 1.4; 95% CI: 1.0-1.9) had worse OS than those in large urban areas.Conclusion.Place of residence at diagnosis is associated with survival of patients with DLBCL in British Columbia, Canada. Rural patients have similar survival to those in large urban areas, whereas patients living in small and medium urban areas experience worse outcomes.
    The Oncologist 02/2014; · 4.10 Impact Factor
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    ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease and "double-hit" DLBCL, with both MYC and BCL2 translocations has a poor prognosis. In this study, we investigated whether MYC and BCL2 protein expression in tissue would predict survival in DLBCL. The study included 106 cases of de novo DLBCL treated with rituximab and cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or CHOP-like regimens. The results were validated on an independent cohort of 205 DLBCL patients. Patients with low expression of BCL2 (≤30%) and MYC (≤50%) had the best prognosis, whereas those with high BCL2 (>30%) and MYC (>50%) had the worst outcome. In multivariate analysis, the combination of the BCL2 and MYC was an independent predictor of overall survival (OS) and event-free survival (EFS) (P = 0·015 and P = 0·005, respectively). The risk of death was nine times greater for patients with high BCL2 and MYC compared to those with low expression. High BCL2 and MYC was a strong predictor of poor OS (P < 0·001) and EFS (P = 0·0017) in patients with the germinal centre B-cell (GCB) type, but not in the non-GCB type. In DLBCL, high co-expression of MYC and BCL2 was an independent predictor of poor survival, and could be used to stratify patients for risk-adapted therapies.
    British Journal of Haematology 02/2014; · 4.94 Impact Factor
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    ABSTRACT: The cellular microenvironment in follicular lymphoma is of biological and clinical importance. Studies on the clinical significance of non-malignant cell populations have generated conflicting results, which may partly be influenced by poor reproducibility in immunohistochemical marker quantification. In this study, the reproducibility of manual scoring and automated microscopy based on a tissue microarray of 25 follicular lymphomas as compared to flow cytometry is evaluated. The agreement between manual scoring and flow cytometry was moderate for CD3, low for CD4 and moderate to high for CD8 with some labs scoring closer to the flow cytometry results. Agreement in manual quantification across the 7 laboratories was low to moderate for CD3, CD4, CD8 and FOXP3 frequencies, moderate for CD21, low for MIB1 and CD68 and high for CD10. Manual scoring of the architectural distribution resulted in moderate agreement for CD3, CD4 and CD8 and low agreement for FOXP3 and CD68. Comparing manual scoring to automated microscopy demonstrated that manual scoring increased the variability in the low and high frequency interval with some labs showing a better agreement with automated scores. Manual scoring reliably identified rare architectural patterns of T-cell infiltrates. Automated microscopy analyses for T-cell markers by two different instruments were highly reproducible and provided acceptable agreement with flow cytometry. These validation results provide explanations for the heterogeneous results on the prognostic value of the microenvironment in follicular lymphoma. We recommend a more objective measurement such as computer-assisted scoring in future studies of the prognostic impact of microenvironment in follicular lymphoma patients.
    Haematologica 02/2014; · 5.94 Impact Factor
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    ABSTRACT: The International Prognostic Index (IPI) has been the basis for determining prognosis in patients with aggressive non-Hodgkin lymphoma (NHL) for the past 20 years. Using raw clinical data from the National Comprehensive Cancer Network (NCCN) database collected during the rituximab era, we built an enhanced IPI with the goal of improving risk stratification. Adults (n=1,650) with de novo diffuse large B-cell lymphoma (DLBCL) diagnosed over a 10-year period at 7 NCCN cancer centers were included. Clinical features were assessed for their prognostic significance, with statistical efforts to further refine the categorization of age and normalized LDH. This new NCCN-IPI identified 5 predictors (age, LDH, sites of involvement, Ann Arbor stage, ECOG performance status) and assigned a maximum of 8 points. Four risk groups were formed: low (0-1), low-intermediate (2-3), high-intermediate (4-5) and high (6-8). Compared to the IPI, the NCCN-IPI better discriminated low and high risk subgroups (5-year overall survival [OS]: 96% vs 33%) than the IPI (5 year OS: 90% vs 54%), respectively. When validated using an independent cohort from the British Columbia Cancer Agency (n=1,138), it also demonstrated enhanced discrimination for both low and high risk patients. The NCCN-IPI is easy to apply and more powerful than the IPI for predicting survival in the rituximab era.
    Blood 11/2013; · 9.78 Impact Factor
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    ABSTRACT: PURPOSEMantle-cell lymphoma (MCL) has a variable natural history but is incurable with current therapies. MicroRNAs (miRs) are useful in prognostic assessment of cancer. We determined an miR signature defining aggressiveness in B-cell non-Hodgkin lymphomas (NHL) and assessed whether this signature aids in MCL prognosis. METHODS We assessed miR expression in a training set of 43 NHL cases. The miR signature was validated in 44 additional cases and examined on a training set of 119 MCL cases from four institutions in Canada. miRs significantly associated with overall survival were examined in an independent cohort of 114 MCL cases to determine association with patient outcome. miR expression was combined with current clinical prognostic factors to develop an enhanced prognostic model in patients with MCL.ResultsFourteen miRs were differentially expressed between aggressive and indolent NHL; 11 of 14 were validated in an independent set of NHL (excluding MCL). miR-127-3p and miR-615-3p were significantly associated with overall survival in the MCL training set. Their expression was validated in an independent MCL patient set. In comparison with Ki-67, expression of these miRs was more significantly associated with overall survival among patients with MCL. miR-127-3p was combined with Ki-67 to create a new prognostic model for MCL. A similar model was created with miR-615-3p and Mantle Cell Lymphoma International Prognostic Index scores. CONCLUSION Eleven miRs are differentially expressed between aggressive and indolent NHL. Two novel miRs were associated with overall survival in MCL and were combined with clinical prognostic models to generate novel prognostic data for patients with MCL.
    Journal of Clinical Oncology 07/2013; · 18.04 Impact Factor
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    ABSTRACT: IntroductionA 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: 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.
    Journal of Clinical Oncology 04/2013; · 18.04 Impact Factor
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    ABSTRACT: The hallmark t(14;18)(q32;q21) in follicular lymphoma (FL) results in constitutive overexpression of the BCL2 protein, allowing B cells to abrogate the default germinal center apoptotic program. Most tumors are characterized by recurrent secondary genetic alterations including genomic gains, losses, and mutations, some providing a growth advantage, including alterations in MLL2, EPHA7, TNFRSF14, and EZH2. The sequence in which these events occur and how they contribute to progression and ultimately to transformation is unclear. Lastly, crosstalk between neoplastic B cells and non-neoplastic immune and stromal cells in the microenvironment plays an important role in sustaining tumor cell growth, cultivating immune privilege, and promoting transformation.
    The Journal of clinical investigation 10/2012; 122(10):3424-31. · 15.39 Impact Factor
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    ABSTRACT: PURPOSE: To evaluate treatment and outcomes in a population-based cohort of patients diagnosed with primary breast lymphoma. METHODS AND MATERIALS: Prognostic factors, management, and outcomes (local control, lymphoma-specific survival, and overall survival) were analyzed for all patients diagnosed with limited-stage, primary breast non-Hodgkin lymphoma (n = 50) diagnosed in British Columbia between 1981 and 2009. RESULTS: The median follow-up was 3.5 years; 64% presented with a breast mass. Histologic subtypes were indolent (n = 16 [32%]) or aggressive (n = 34 [68%]). Of those with indolent lymphoma, 81% had stage I, and 19% had stage II disease; 13% received no initial treatment; 75% received radiotherapy (RT) alone. One (6%) patient received surgical resection alone, and 1 (6%) patient received surgical resection in addition to RT. Of those with aggressive lymphoma, 62% had stage I and 38% had stage II disease; 3% received no initial treatment; 6%, RT alone; 38%, chemotherapy only; 41%, chemotherapy and RT; 9%, surgical resection alone; and 3%, surgical resection in addition to chemotherapy and RT. In patients with indolent and aggressive disease, 5-year local control estimates were 92% and 96%, lymphoma-specific survivals were 91% and 71%, and overall survivals were 75% and 54%, respectively. On univariate analysis, stage (I vs. II) (P = .006) and RT use (P = .032) were statistically significant predictors of improved overall survival in patients with indolent breast lymphoma. Combined chemoradiation was associated with a trend for improved overall survival (P = .061) in patients with aggressive disease. There were 4 cases of central nervous system relapse, all occurred in subjects with aggressive primary breast lymphoma. CONCLUSIONS: Patients with indolent breast lymphoma were most frequently treated with RT alone and achieved high rates of local control and survival. Patients with aggressive histology most often treated with chemotherapy, alone or combined with RT, had excellent local control but lower survival compared with indolent disease. Improved systemic therapies are needed to improve outcomes for patients with aggressive breast lymphoma.
    Clinical Breast Cancer 09/2012; · 2.42 Impact Factor
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    ABSTRACT: 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.
    Journal of Clinical Oncology 08/2012; 30(27):3383-8. · 18.04 Impact Factor
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    ABSTRACT: PURPOSE Diffuse large B-cell lymphoma (DLBCL) is curable in 60% of patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MYC translocations, with or without BCL2 translocations, have been associated with inferior survival in DLBCL. We investigated whether expression of MYC protein, with or without BCL2 protein expression, could risk-stratify patients at diagnosis. PATIENTS AND METHODS We determined the correlation between presence of MYC and BCL2 proteins by immunohistochemistry (IHC) with survival in two independent cohorts of patients with DLBCL treated with R-CHOP. We further determined if MYC protein expression correlated with high MYC mRNA and/or presence of MYC translocation. Results In the training cohort (n = 167), MYC and BCL2 proteins were detected in 29% and 44% of patients, respectively. Concurrent expression (MYC positive/BCL2 positive) was present in 21% of patients. MYC protein correlated with presence of high MYC mRNA and MYC translocation (both P < .001), but the latter was less frequent (both 11%). MYC protein expression was only associated with inferior overall and progression-free survival when BCL2 protein was coexpressed (P < .001). Importantly, the poor prognostic effect of MYC positive/BCL2 positive was validated in an independent cohort of 140 patients with DLBCL and remained significant (P < .05) after adjusting for presence of high-risk features in a multivariable model that included elevated international prognostic index score, activated B-cell molecular subtype, and presence of concurrent MYC and BCL2 translocations. CONCLUSION Assessment of MYC and BCL2 expression by IHC represents a robust, rapid, and inexpensive approach to risk-stratify patients with DLBCL at diagnosis.
    Journal of Clinical Oncology 07/2012; 30(28):3452-9. · 18.04 Impact Factor
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    ABSTRACT: Biologic factors that predict the survival of patients with a diffuse large B-cell lymphoma, such as cell of origin and stromal signatures, have been discovered by gene expression profiling. We attempted to simulate these gene expression profiling findings and create a new biologic prognostic model based on immunohistochemistry. We studied 199 patients (125 in the training set, 74 in the validation set) with de novo diffuse large B-cell lymphoma treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like therapies, and immunohistochemical stains were performed on paraffin-embedded tissue microarrays. In the model, 1 point was awarded for each adverse prognostic factor: nongerminal center B cell-like subtype, SPARC (secreted protein, acidic, and rich in cysteine) < 5%, and microvascular density quartile 4. The model using these 3 biologic markers was highly predictive of overall survival and event-free survival in multivariate analysis after adjusting for the International Prognostic Index in both the training and validation sets. This new model delineates 2 groups of patients, 1 with a low biologic score (0-1) and good survival and the other with a high score (2-3) and poor survival. This new biologic prognostic model could be used with the International Prognostic Index to stratify patients for novel or risk-adapted therapies.
    Blood 06/2012; 120(11):2290-6. · 9.78 Impact Factor
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    ABSTRACT: This phase 1 study evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of obinutuzumab (GA101), a glycoengineered type II anti-CD20 monoclonal antibody administered as induction followed by 2 years of maintenance. Cohorts of 3 to 6 patients received obinutuzumab (200-2000 mg) intravenously weekly for 4 weeks. Patients with a complete or partial response (or stable disease and clinical benefit) continued to receive obinutuzumab every 3 months, for a maximum of 8 doses. Twenty-two patients with relapsed CD20-positive non-Hodgkin lymphoma or chronic lymphocytic leukemia with an indication for treatment and no therapy of higher priority were enrolled. Patients received a median of 4 prior regimens; 86% had received at least 1 rituximab-containing regimen. No dose-limiting or unexpected AEs were observed. Infusion-related reactions were most common (all grades, 73%; grade 3/4, 18%), followed by infection (32%), pyrexia (23%), neutropenia (23%), headache (18%), and nausea (18%). At end of induction, 5 (23%) patients achieved partial responses and 12 (54%) had stable disease. Eight patients received maintenance; best overall response was 32% (6 partial responses/1 complete response). Obinutuzumab induction and maintenance therapy was well tolerated with promising efficacy in this heterogeneous, highly pretreated population and warrants further investigation. This study was registered at (identifier NCT00576758).
    Blood 03/2012; 119(22):5118-25. · 9.78 Impact Factor
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    ABSTRACT: For limited-stage diffuse large B-cell lymphoma (DLBCL), treatment decisions are often influenced by toxicity profiles. One strategy that minimizes chemotherapy-induced toxicities is abbreviated chemotherapy plus consolidation involved-field radiotherapy (IFRT). Involved-node radiotherapy (INRT) is a new concept to DLBCL, aimed to reduce radiotherapy-induced toxicities. We retrospectively review the long-term outcomes of limited-stage DLBCL treated with abbreviated systemic therapy and radiotherapy focusing on field size: IFRT versus INRT. The British Columbia Cancer Agency Lymphoid Cancer Database was used to identify patients diagnosed with limited-stage DLBCL (stage I/II, without B-symptoms; bulk < 10 cm) from 1981 to 2007. Patients were prescribed 3 cycles of chemotherapy plus IFRT (1981-1996) or INRT≤5 cm (1996-2007), defined as INRT to the prechemotherapy involved nodes with margins ≤ 5 cm. A total of 288 patients were identified: 56% were aged >60 years, 34% had stage II disease, 55% had extranodal disease, 19% had elevated lactate dehydrogenase levels, and 15% received rituximab. The two radiotherapy groups were IFRT (138 patients; 48%) and INRT≤5cm (150 patients; 52%); median follow-up was 117 and 89 months, respectively. Distant relapse was the most common site of failure in both groups. After INRT≤5 cm, marginal recurrence was infrequent (2%). Time to progression (P = .823), progression-free survival (P = .575), and overall survival (P = .417) were not significantly different between the radiotherapy cohorts. Radiotherapy field size was not a significant prognostic factor on multivariate analyses. This research is the first known body of work to apply the concept of INRT to limited-stage DLBCL. Reducing the field size from IFRT to INRT≤5 cm maintains a low marginal recurrence risk with no impact on overall outcome.
    Cancer 01/2012; 118(17):4156-65. · 5.20 Impact Factor
  • Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2012; 18(1 Suppl):S82-91. · 3.15 Impact Factor
  • Laurie H Sehn
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    ABSTRACT: Outcome in diffuse large B-cell lymphoma (DLBCL) has improved over the last decade and will likely improve further with the introduction of novel agents. At the present time, clinical prognostic factors are limited in their ability to identify patients with sufficiently poor outcome to justify deviation of therapy away from R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) outside of a clinical trial. Similarly, with the exception of the concurrent translocation of MYC and BCL2, there are no validated biologic markers that can be used to guide initial therapy in routine practice. Recognition of the molecular heterogeneity of DLBCL is of paramount importance and must be taken into consideration when investigating new therapies. It will be vital for novel targeted agents to be evaluated in patient populations enriched for those who are most likely to benefit. The identification of prognostic and predictive biomarkers should be initiated during the early phase of drug development so that these tests can be validated within phase 3 trials. Although currently available techniques such as immunohistochemistry may still be used, gene-expression profiling and whole genomic analytic techniques will likely play a major role in the evaluation of patients in the future to determine optimal personalized treatment for DLBCL.
    Hematology 01/2012; 2012:402-9. · 1.49 Impact Factor

Publication Stats

2k Citations
544.96 Total Impact Points


  • 2004–2014
    • University of British Columbia - Vancouver
      • Division of Medical Oncology
      Vancouver, British Columbia, Canada
  • 2013
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
  • 2012
    • BC Cancer Research Centre
      Vancouver, British Columbia, Canada
    • Peter MacCallum Cancer Centre
      • Division of Radiation Oncology and Cancer Imaging
      Melbourne, Victoria, Australia
  • 2008–2011
    • University of Miami
      • Department of Medicine
      Coral Gables, FL, United States
    • The University of Arizona
      • Department of Pathology
      Tucson, AZ, United States
    • Stanford University
      • Division of Oncology
      Stanford, CA, United States
  • 2005–2011
    • BC Cancer Agency
      • • Centre for Lymphoid Cancer
      • • Radiation Therapy Program
      Vancouver, British Columbia, Canada
  • 2008–2010
    • Vancouver Prostate Centre
      Vancouver, British Columbia, Canada