Princess Margaret Hospital Research Articles

Early Recovery Of Absolute Lymphocyte Counts ≥ 0.2x109/L At Day 21 Can Predict Reduced Risk Of Relapse In Acute Lymphoblastic Leukemia Following Allogeneic Stem Cell Transplantation

IntroductionPredicting transplant's outcome has been an important issue. Many factors have been elucidated. We evaluated impact of lymphocyte counts on transplant outcome including relapse in patients with acute lymphoblastic leukemia. MethodsA total of 117 patients with acute lymphoblastic leukemia receiving hematopoietic stem cell transplants (HSCTs) between year 1999 and 2012 at Princess Margaret Hospital, Toronto, Canada were evaluated for the occurrence of early recovery of absolute lymphocyte counts (ALC) and their impact on transplant's outcome. Patients who received T cell depletion were excluded from analysis, a total of 94 cases were finally included in the analysis. ALCs were regularly monitored on daily basis for first 28 days. ResultsSixty two patients (66%) were matched related donor and 31 (33%) were female. Seventy one patients (75%) were in 1st complete remission (CR1) versus 23 (25%) beyond CR1. Thirty four patients (64%) were Philadelphia chromosome positive. GVHD prophylaxis was CSA/MMF (n=28, 30%), CSA/MTX (n=64, 68%), other (n=2, 2%). Conditioning regimen was myeloablative in 91 patients (97%) versus reduced intensity in 3 patients (3%). Fifty eight patients received peripheral blood stem cells as a stem cell source. Different cut offs of ALCs including 0.2, 0.3, 0.5 and 1.0x109/L at day 21 and day 28 were evaluated for transplant outcomes in order to select the best cut off of ALC recovery. We selected ALC 0.2x109/L at day 21 as a cutoff of ALC recovery based on the p-value.With a median follow-up of 60 months for survivors (range 2 to 116.5 months), 71 patients (75%) showed early recovery of ALC at day 21 (i.e. patients with ALC ≥ 0.2 x109/L at day 21), while 23 patients did not reach 0.2x109/L of ALC at day 21 (i.e. patients with ALC ≤ 0.2 x109/L at day 21). The overall survival (OS) and non-relapse mortality (NRM) were not significantly different between the groups: for 3 years OS rate, 47% in early ALC recovery group vs 35% in late ALC recovery group (p=0.35 ); for 3 year NRM rate, 38% in early ALC recovery group vs 26% in late ALC recovery group (p =0.33 ). However, a lower incidence of relapse was observed in early ALC recovery group (17%) compared to late ALC recovery group (39% at 3 years; p=0.005).The cumulative incidence of acute GVHD grades 2 to 4, grades 3/4 at day 120 and overall chronic GVHD at 2 years was 62%, 32% and 45% for patients with ALC ≥ 0.2 x109/L versus 65%, 25% and 39% for those with ALC ≤ 0.2 x109/L at day 21. CMV viraemia rate was 44% versus 43% in early versus late ALC recovery groups. The median time to neutrophil and platelet engraftment was 16 and 12 days in early ALC recovery group versus 23 and 21 days in late ALC recovery group.In multivariate analysis, ALC ≥ 0.2 x109/L at day 21 was an independent favorable risk factor for relapse (p=0.017, Hazard ratio [HR] 0.183) together with chronic GVHD (p≤0.001, HR 0.058). For overall survival, acute GVHD grade 3-4 (p=0.03, HR 2.857), chronic GVHD (p=0.001, HR 0.103) and age as continuous variable (p=0.05, HR 1.04) were independent factors. For NRM acute GVHD grade 3-4 was the only independent prognostic factor (p=0.006, HR 6.896) ConclusionEarly recovery of absolute lymphocyte counts ≥0.2x109/L at day 21 can predict reduced relapse risk in ALL patients following allogeneic stem cell transplantation. The impact of lymphocyte counts on overall survival and non-relapse mortality was not statistically significant.▪ Disclosures:No relevant conflicts of interest to declare.

Lymphocyte Recovery At Day 28 Post-Transplant Is Predictive Of Relapse In Patients With Acute Myeloid Leukemia Transplanted With Peripheral Blood Stem Cell Grafts

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment option for patients with acute myeloid leukemia (AML). The impact of lymphocyte recovery on post- transplant outcomes has been suggested but has not been evaluated in a homogeneous population of AML patients. The present study attempted to evaluate the impact of lymphocyte recovery at 28 days post-HCT in a homogeneous population of 212 patients with AML that underwent HCT between 1999 and 2011 at the Princess Margaret Hospital, Toronto, Canada. All patients in the study group received peripheral blood stem cells as a graft source. Patients were divided into two groups: those with absolute lymphocyte count (ALC) ≥0.5x109/L (n=122, 57%) and those with ALC <0.5x109/L (n=90, 43%), at day 28 post-transplant.Median age of all patients was 49 years (range 18-70), 102 patients (48%) were female. HCT was performed in first complete remission (CR1) for 134 patients (63%) and second complete remission (CR2) for 78 patients (37%). Cytogenetics at diagnosis were available in 189 patients (89%). Donors were matched related (n=145, 68%) or matched unrelated (n=67, 32%). Myeloablative conditioning was administered to 131 (62%) patients, 81 (38%) received reduced-intensity conditioning (RIC) regimens. Median follow up duration among survivors was 49 months (range 7-120 months).Univariate analysis demonstrated overall survival (OS) was significantly different in favor of the group with ALC ≥0.5x109/L vs those with ALC <0.5x109/L (p=0.016) with a 3-year OS of 57% vs 39% respectively. The cumulative incidence of relapse (CIR) was significantly lower in the group with ALC ≥0.5x109/L vs those with the ALC <0.5x109/L (p=0.0002), with a 3-year CIR of 16% vs 37% respectively (Figure). Cumulative incidences of non-relapse mortality (NRM) were not significantly different between the two groups (p=0.22).Multivariable analysis for OS and NRM did not demonstrate ALC ≥0.5x109/L at 28 days post-transplant to be an independent prognostic factor. Multivariable analysis for CIR demonstrated that ALC ≥0.5x109/L at 28 days post-transplant is an independent prognostic factor decreasing the risk of relapse compared to ALC <0.5x109/L (p=0.015, HR=0.47, 95%CI=0.25-0.86), which implies that early lymphocyte recovery suggests lower risk of relapse post-transplant. Significant decrease in CIR was also seen with the occurrence of chronic graft-versus-host disease (GvHD) (p=0.00002, HR=0.29, 95%CI=0.16-0.51), while increased CIR was associated with the use of RIC regimens (p=0.03, HR=1.9, 95%CI=1.1-3.5).The present study concludes that lymphocyte recovery with ALC ≥0.5x109/L at day 28 post transplant is associated with decreasing risk of relapse in a homogeneous population of AML patients that underwent allogeneic peripheral blood HCT, but without overall survival benefit.▪ Disclosures:No relevant conflicts of interest to declare.

Implementing Cybord As First-Line Therapy For Transplant-Eligible Multiple Myeloma Patients : A Single-Center Preliminary Comparaison

IntroductionThe best induction regimen for first-line therapy in multiple myeloma patients who are eliglible for autologous stem cell transplant (ASCT) is still unknown. In 2009, we started to use CyBorD and gradually changed our first-line therapy from Vel-Dex to CyBorD based on published work from Princess Margaret Hospital in Toronto. Here, we describe the first 10 patients to have received CyBorD and compare them to an historical cohort from the same institution. MethodsWe conducted a retrospective review of patient's charts and transplant database from 2009/10/02 to 2013/04/19. We collected information on blood labs, cytogenetics, immunofixation, response rates, adverse events and graft collection. Patients not receiving the anticipated protocol or less than 3 cycles of treatment arm were excluded from this review. ResultsAll patients (100%) in both cohorts received an ASCT (CyBorD, n=10 and Vel-Dex, n=11). The 2 groups were comparable and there was 1 patient in each arm with unfavorable cytogenetics. The response rates pre ASCT were CR = 20%, >VGPR = 90% compared to CR = 0%, >VGPR = 81,8% in CyBorD and Vel-Dex patients respectively. Response rates at 100 days post-ASCT was CR = 60%, >VGPR = 100% compared to CR = 36.4%, >VGPR = 90.9% in CyBorD and Vel-Dex patients respectively. Patients in CyBorD had a median of 1 (1-2) day for graft collection and a median number of graft cells of 5,01 x 109(2,06-6,48) compared to 1 (1-2) and 4,46 x 109 (3-6,82) in the Vel-Dex group. The rate of grade 3/4 thrombocytopenia was 0%(n=0) vs 9%(n=1) in CyborD and Vel-Dex patients respectively. No case of neuropathy grade 3 or 4 was observed in the CyBorD arm. ConclusionCyBorD is an effective and safe induction regimen for first-line therapy in ASCT eligible multiple myeloma patients. It produces less neuropathy and has an easier schedule to administer. It is now our standard protocol for these patients but dexamethasone has been reduced to once weekly for every cycle since then. NBCyBorD (Cyclophosphamide 300 mg/m2 PO days 1,8,15,22; Bortezomib 1,5 mg/m2 SC days 1,8,15,22, Dexamethasone 20 mg PO bid days 1-4, 9-12, 17-20 for cycles 1-2, 20 mg PO bid once weekly for cycles 3-4.) Disclosures:Duquette:Janssen: Consultancy, Honoraria. Off Label Use: CyborD is a widely accepted regimen but has not been accepted by the FDA.

The changing incidence of human papillomavirus-associated oropharyngeal cancer using multiple imputation from 2000 to 2010 at a Comprehensive Cancer Centre

Introduction Human papillomavirus (HPV) is a risk and prognostic factor for oropharyngeal cancer (OPC). Determining whether the incidence of HPV-associated OPC is rising informs health policy. Methods HPV status was ascribed using p16 immunohistochemistry in 683/1474 OPC patients identified from the Princess Margaret Hospital's Cancer Registry (from 2000 to 2010). Missing p16 data was estimated using multiple (n=100) imputation (MI) and validated using an independent OPC cohort (n=214). Non-OPC head and neck squamous cell carcinoma (HNSCC) (n=3262) were also used for time-trend comparison. Regression was used to compare HNSCC subsets and time-trends. The c-index was used to measure the predictive ability of MI. Results The incidence of OPC rose from 23.3% of all HNSCC in 2000 to 31.2% in 2010 (p=0.002). In the subset of OPC tested for p16, there was no change in p16 positivity over time (p=0.9). However, p16 testing became more frequent over time (p<0.0001), but was nonetheless biased, favouring never-smokers [OR 1.87 (95% CI 1.29–2.70)] and tumors of the tonsil [OR 2.30 (1.52–3.47)] or base-of-tongue [OR 1.72 (1.10–2.70)]. These same factors were also associated with p16-positivity [ORs 3.22 (1.27–8.16), 7.26 (3.50–15.1), 5.83 (2.70–12.7), respectively]. Following MI and normalization, the proportion of OPC that was p16-associated rose from 39.8% in 2000 to 65.0% in 2010, p=0.002, fully explaining the rise in OPC in our patient population. Conclusion The rise in HNSCC referrals seen from 2000 to 2010 at our institution was driven primarily by p16-associated OPC. MI was necessary to derive reliable conclusions when cases with missing data are considerable.

EOutcomes-H&amp;N: Development of an electronic point-of-care outcomes collection system for head and neck cancer.

247 Background: Outcomes data increases the ability to understand the impact of cancer treatment and helps ensure that we direct appropriate investments to achieve improvements in quality of care. Cancer Care Ontario (CCO) has developed an outcomes data collection system for patients with head and neck cancer treated with radiotherapy. Methods: Clinicians involved in the care of these patients agreed on 5 key clinical outcomes to collect as a part of this initiative: local failure, regional failure, distant metastasis, second primaries, and treatment toxicity. Based on the Princess Margaret Hospital Head and Neck Cancer Anthology of Outcomes process, CCO has developed a similar system to collect outcomes data at the point-of-care on a provincial scale. The population-based provincial system aims to provide practice efficiencies and allow for evolution of the system in response to user feedback and expansion to other clinical areas. Results: The system includes a secure web application and iPad mobile application to facilitate the collection and management of outcomes data for head and neck cancer patients treated with radiotherapy in Ontario. Cancer centres upload patient clinic schedule details (including patient identifiers and appointment dates) prior to clinics. A list of patient summaries, including corresponding diagnosis, radiotherapy information and previously recorded outcomes is then generated. In clinic, physicians use these lists to capture outcomes noted at the point-of-care. Data captured are then transferred in real time to a secure central database. Following initial testing, the application was piloted to assess usability, system reliability, and overall satisfaction. Initial results show high physician satisfaction and no documented issues with system availability. Feedback has identified potential improvements and will inform future modifications. Conclusions: The identification of potential variation in recurrence, toxicity and survival data will inform the areas in which quality improvement initiatives or additional investments may be needed. The intent is to leverage project learnings for future outcomes initiatives in other diseases and treatment modalities.

A Phase II Trial of Saracatinib, an Inhibitor of src Kinases, in Previously-Treated Advanced Non–Small-Cell Lung Cancer: The Princess Margaret Hospital Phase II Consortium

BackgroundThe src family of kinases may play a role in the malignant phenotype through effects on migration, motility, adhesion and proliferation. The activity of saracatinib, an orally available inhibitor of src kinases, was evaluated in patients with advanced, platinum-pretreated NSCLC. Patients and MethodsEligible patients with advanced NSCLC of any histologic subtype and who had obtained a best response to prior platinum-based chemotherapy of at least stable disease received saracatanib 175 mg orally daily in a 28 day cycle. The primary end point was the proportion of patients progression-free after 4 cycles (16 weeks) of therapy; 8 such patients of 32 evaluable were required to deem the therapy active. Immunohistochemistry for src expression was performed on archival tissue from enrolled patients. ResultsThirty-seven patients received a median of 2 cycles (range, 1–14) each. Six of 31 evaluable patients were progression-free at 16 weeks. Two partial responses were observed, lasting 3.7 and 14.6 months; 1 responder had an EGFR exon 19 deletion. An additional 4 patients had stable disease for at least 4 cycles. The median progression-free and overall survival times were 1.8 and 7.6 months. No correlation between src protein expression and outcome was observed. ConclusionsThere may be a subset of saracatinib-responsive NSCLC that is currently molecularly undefined. Further studies of this agent in a population preselected for target mutations that potentially relevant to src pathways, such as EGFR, should be considered.

Uterine adenosarcomas: A dual-institution update on staging, prognosis and survival

ObjectiveUterine adenosarcomas (AS) are rare tumors thought to have a favorable prognosis. The aim of this study was to evaluate clinicopathological characteristics and treatment outcome in women with uterine AS. MethodsPatients with uterine AS were identified from the institutional databases at two regional cancer centers, Princess Margaret Hospital, Toronto and Vancouver General Hospital. All cases underwent specialist pathological review and were re-staged according to FIGO criteria (2009). Patient demographics, treatment data and outcomes were evaluated. ResultsBetween 1984 and 2010, 64 patients with confirmed AS were identified: 30 exhibited sarcomatous overgrowth (AS+SO). 47 patients presented with stage I disease: 27 IA and 18 IB. 57 of the 58 patients with known surgical management underwent hysterectomy: 55 having bilateral salpingo-oophorectomy, 12 having lymph node dissection. 14 patients received adjuvant treatment: 10 radiotherapy, 3 chemotherapy and 1 both. Sixteen of the 45 patients (35.6%) with follow-up recurred; median time to recurrence 21.2months, range 2.1–87.8months. Recurrence was associated with myometrial invasion (p=0.05). Two of the 10 women (20%) with AS+SO receiving adjuvant treatment recurred compared to 9 of the 14 (64%) who did not. One of the 5 women (20%) with stage IB disease who received adjuvant treatment recurred (20%) compared to 6 of the 7 (85.6%) who did not. ConclusionsLong term surveillance is required given the variable time to recurrence. For those with AS+SO and myometrial invasion adjuvant treatment should be considered and further investigation of adjuvant strategies is warranted.

Efficacy and biomarker findings from AVaglio, a phase III trial of bevacizumab plus temozolomide and radiotherapy in newly diagnosed glioblastoma

WCN 2013 No: 1207 Topic: 36 — Other topic Efficacy and biomarker findings from AVaglio, a phase III trial of bevacizumab plus temozolomide and radiotherapy in newly diagnosed glioblastoma W. Wick, T. Cloughesy, W. Mason, R. Henriksson, F. Saran, R. Nishikawa, M. Hilton, J. Garcia, C. Pallaud, O. Chinot. University Medical Centre, Heidelberg, Germany; University of California, Los Angeles, CA, USA; Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada; Regional Cancer Center Stockholm, Stockholm, Sweden; Umea University, Umea, Sweden; The Royal Marsden NHS Foundation Trust, Surrey, UK; International Medical Center, Saitama Medical University, Saitama, Japan; F. Hoffmann-La Roche, Basel, Switzerland; Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France Background: Glioblastoma has a high disease burden and poor prognosis. AVAgliowas the first double-blind, placebo-controlled phase III study evaluating bevacizumab in newly diagnosed glioblastoma. Objectives: To evaluate efficacy, safety and potential biomarkers (plasma VEGF-A/VEGFR-2 prioritised). Patients and methods: Patients received single-agent bevacizumab or placebo plus standard-of-care treatment (radiotherapy plus temozolomide) until progression/unacceptable toxicity. Co-primary endpoints were investigator-assessed PFS and OS. Secondary endpoints included health-related quality of life (HRQoL). Exploratory endpoints included correlative biomarker analysis, KPS, corticosteroid use. Results: Baseline characteristics were balanced for intent-to-treat (n = 921) and biomarker-evaluable (n = 571) populations. Bevacizumab significantly prolonged PFS (HR = 0.64, 95% CI 0.55– 0.74, p b 0.0001; median 10.6 vs 6.2 months) and delayed HRQoL time to definitive deterioration (p b 0.0001). Interim OS did not cross the threshold for significance (HR = 0.89, 95% CI 0.75–1.07, p = 0.2135). Functional independence (KPS ≥ 70%) was maintained during PFS in both arms (median bevacizumab vs placebo: 9 vs 6 months). Patients treated with bevacizumab had a diminished corticosteroid requirement. Patients with low and high baseline plasma VEGF-A concentrations derived similar PFS benefit with bevacizumab (p = 0.610): low VEGF-A (HR = 0.64, 95% CI 0.48– 0.84) versus high (HR = 0.59, 95% CI 0.45–0.78). Similarly, PFS benefit in patients with low and high baseline VEGFR-2 levels was comparable (p = 0.736): low VEGFR-2 (HR = 0.54, 95% CI 0.41– 0.71) versus high (HR = 0.66, 95% CI 0.50–0.87). Conclusion: Addition of bevacizumab to standard-of-care therapy provided a significant clinically meaningful PFS improvement with stable/improved HRQoL/KPS and reduced corticosteroid requirement. NoVEGF-A/VEGFR-2 predictive/prognostic effectwas observed. Interim OS analysis did not cross the threshold for significance. doi:10.1016/j.jns.2013.07.2268 Abstract — WCN 2013 No: 2103 Topic: 36 — Other topic Flow cytometric analysis of cerebrospinal fluid is low diagnostic yield without atypical morphology or prior history of hematologic malignancy WCN 2013 No: 2103 Topic: 36 — Other topic Flow cytometric analysis of cerebrospinal fluid is low diagnostic yield without atypical morphology or prior history of hematologic malignancy G.H.J. Stevens, A.M.B. Collie, B.T. Hill, K. Fenner, E. Gazdick, L.A. Rybicki, E.H. Hsi. Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH, USA; Pathology, Cleveland Clinic, Cleveland, OH, USA; Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA; Quality Health Science, Cleveland Clinic, Cleveland, OH, USA Background: Flow cytometric analysis (FCA) of cerebrospinal fluid (CSF) has utility in detecting central nervous system (CNS) involvement by hematologic malignancies. Yet, the majority of samples are negative by FCA. Objective: Identify pre-test characteristics of CSF specimens that will allow the rational use of FCA in the diagnosis of hematologic malignancy in CSF. Design: Retrospective data was collected from the medical record and flow cytometric reports for all CSF samples submitted for FCA between 2007 and 2009. Patients: 423 patients for whom 501 CSF samples were submitted for FCA. Results: A positive diagnosis of a hematologic malignancy was made in 41 specimens (8.2%). The FCA-positive specimens showed atypical morphology, either blasts or atypical lymphocytes, in 98% of Abstracts / Journal of the Neurological Sciences e629 (2013) e629–e678 e654

Stroke and Cancer: Misfortunes Never Come Singularly

Cancer patients exhibit an elevated stroke risk (1–5). In a case-control study examining the epidemiology of cancer in stroke patients and their clinical course, we identified 72 active cancer and 72 control patients from the 1493 stroke admissions to Princess Margaret Hospital, Hong Kong in 2009. The prevalence of cancer among stroke patients was 4·8% (Table 1), and stroke was the first symptom of their cancer in nine patients. The proportions of ischemic stroke (IS) (79·2%) and haemorrhagic stroke (HS) (20·8%) in cancer group were comparable with noncancer group, and vascular risk factors (hypertension, diabetes mellitus, and hyperlipidemia) were less prevalent. The cancers we identified followed the local cancer epidemiology, with lung and colorectal cancer being the two most common types. In HS, both groups had similar proportions of deep parenchymal and lobar haemorrhages, but multiple haemorrhages were only seen in the three cancer patients. Except for the two acute promyelocytic leukaemia patients who bled, the distributions of other cancers among HS patients were similar to those with IS. Among IS, the proportions of patients in the four Oxfordshire-classified syndromes were comparable in the two groups. The etiology of IS was undetermined in half of the cancer patients compared with only 28·3% of the noncancer patients. There was no difference in the severity of neurological impairment [National Institutes of Health Stroke Scale (NIHSS) 10·7 (cancer) and 11·8 (noncancer)], but cancer patients had a higher hospital-acquired pneumonia (11·1% vs. 4·2%) and hospital mortality (31·9% vs. 12·5%) rates. At three-months poststroke, cancer remained the most important independent predictor of mortality [odds ratio 12·4 (3·0–51·4)], and more cancer patients were disabled. We concluded that stroke and cancer, when coinciding, carried a high morbidity and mortality rate. Often, the occurrence of stroke in cancer patients could not be sufficiently explained by conventional etiology, implicating the role of cancer-related factors in their stroke pathophysiology.

Comparative Review of Consensus-Based Clinical Target Volume Definitions For Prostate Radiotherapy

Background: A major obstacle in the delivery of postoperative radiation therapy (RT) for prostate cancer is accurate delineation of the tumor targets and organs at risk. Although postoperative prostate cancer contouring atlases are quite common, there is still no widely accepted contouring guideline. The purpose of this study is to critically review the various postoperative prostate RT treatment planning consensus guidelines or atlases currently available. Methods: A literature search was conducted using various electronic databases with the key terms: prostate, contour, planning tumour volume, clinical target volume, delineation or definition, guidelines or atlas, and radiation oncology. The search was limited to English publications from the years 1985 to 2011. Results: A total of seven publications relating to contouring guidelines for postoperative prostate radiotherapy were identified. There are four distinct consensus guidelines developed by major institutions: Princess Margaret Hospital, the Australian and New Zealand Radiation Oncology Genito-Urinary Group, the European Organization for Research and Treatment of Cancer, and the Radiation Therapy Oncology Group. Conclusions: After reviewing the consensus contouring guidelines for postoperative prostate cancer radiation therapy that were available in the literature, it is clear that there disagreement with regards to what anatomical borders should be used for delineating an appropriate prostate bed CTV. Additional studies comparing the reproducibility of the various guidelines as well as the performance of these guidelines on clinically important outcomes are needed.

WE‐G‐WAB‐02: BEST IN PHYSICS (JOINT IMAGING‐THERAPY)‐MR and Linac Magnetic Field Mutual Decoupling for An MRI‐Guided Radiation Therapy System

Purpose: An MR‐guided RT system, including a 6X TrueBeam Varian linac and a 1.5T IMRIS MRI scanner‐on‐rails, is under installation at our institution. Numerical simulations and experiments were performed to quantify and test the magnetic field mutual decoupling between the MR and linac/couch ensemble. Methods: Linear programming and finite element methods were used to perform numerical simulations for the MR‐linac/couch system. First, the 1.5 T MR field was reconstructed and matched to data from manufacturer. The next step was to perform magnetic force simulations and measurements for a simplified assembly, replicating all key ferromagnetic sub‐structures of the couch (wrists, breaks, etc.). To guide the experiment, CAD data of the couch/linac (Varian) was used for various simulation scenarios, i.e. MR distance‐to‐couch/linac and gantry rotation. Measurements were performed for a) magnetic forces acting on various couch components, b)magnetic fringe field mapping (gauss probe) in the vicinity of linac and couch (e.g. wrists, breaks), c)MR imaging field homogeneity. The final set of simulations was for the entire MR‐linac vault, including ferromagnetic structural components obtained from architectural drawings of the facility (e.g. doors, beams, r‐bar). Results: The simulated MR fringe field was in good agreement with the measurements (within 1 gauss). The magnetic pull forces on the couch components were computed for arbitrary directions to match the experimental setups. For all scenarios the simulated and measured data was in good agreement. The couch operated optimally in the MR field. The fringe field at the linac head was less than 20 gauss. For all intended imaging locations, the MR full shimming was achieved, compensating for the presence of the linac/couch. Conclusion: The MR, linac, and couch ensemble was modeled via numerical simulations. The independent and optimal operation of all components was experimentally validated. The MR‐linac system can be integrated and operate with no special modifications. J. Winter and L. Petropoulos are employees of IMRIS. J. Marle and M. Sweitzer are employees of Varian Medical Systems. IMRIS and Varian are companies co‐developing the MRgRT system. Funding for the MRgRT project at Princess Margaret Hospital was provided by the Canadian Foundation for Innovation.

Editorial introductions

Editorial introductions

SU‐C‐103‐06: Isocenter Calibration Concept and Feasibility for MR‐Guided Radiation Therapy (MRgRT)

Purpose: To describe and assess feasibility of a novel MR‐to‐Linac isocenter calibration tool for magnetic resonance guided radiotherapy (MRgRT™). Methods: The MRgRT system co‐developed by IMRIS and Varian employs a movable MR system, which travels into a Linac vault. To support MR‐based couch corrections based on MR‐to‐MR registration, we developed a software tool to calibrate the MR‐to‐Linac coordinate system transformation and apply it to MR images acquired for treatment guidance. To assess feasibility, we quantified repeatability of the movable MRI system at MR isocenter by securing an ACR phantom to a fixed IMRIS interventional table, and moving the MR system between the two adjacent rooms simulate normal function. We performed 18 cycles over two days in which we acquired 3D MRI datasets with 1 mm isotropic resolution. We assessed position variability by registering the MR volume for each cycle to the first volume, and tabulating transform parameters. Separately, we investigated if a calibrated position encoder on the magnet mover could minimize the z‐direction shift variability. Results: Greatest isocenter variability was observed in the z direction, with mean shift of 0.21 +/− 0.12 mm over both days. The greatest rotational variability was observed about the z‐axis, with mean rotation of 0.8 +/− 0.8 mrad over both days. Maximum shift was 0.51 mm in the z direction, and maximum rotation was 1.7 mrad about the z‐axis. In the separate repeatability experiment we found that the calibrated position encoder reduced the mean z‐shift variability from 0.59 +/− 0.35 mm to 0.17 +/− 0.13 mm. Conclusion: We showed that the movable MRI system provides a consistent within‐day and between‐day isocenter location, and z‐shift variability can be minimized with a position encoder. This work demonstrates the feasibility of using an MR‐to‐Linac isocenter calibration tool for the MRgRT system. Jeff Winter, Michael Westmore and Meir Dahan are all employees of IMRIS, the company co‐developing the MRgRT system. Funding for the MRgRT project at Princess Margaret Hospital was provided by the Canadian Foundation for Innovation.

A Pilot Study Examining the Unmet Needs of Cancer Survivors Living with Polypathology

With improved average longevity, the issue of polypathology in the cancer population is of growing importance, because it will increasingly affect more people. The present study piloted two self-report surveys aiming to provide preliminary data on the nature of polypathology and supportive care needs (met and unmet) of cancer survivors. Survivors were recruited from outpatient clinics at the Princess Margaret Hospital in Toronto and were asked to complete and give feedback on the surveys. Of a convenience sample of 88 survivors, almost three quarters (73%) reported having polypathology, and 64% had at least 1 unmet need. Results also suggest that those with the highest number of needs were more likely to have polypathology. Our study invites further assessments with self-report surveys of the complex picture that arises when cancer is not the only disease affecting a person. It also highlights the need for innovative supportive services to address patient needs.

WE‐G‐WAB‐07: Commissioning of a Novel Integrated Platform for Online MRIgRT

Purpose: An integrated system for online MRIgRT comprising an MR scanner‐on‐rails proximal to a Varian TrueBeam linac is currently under installation at our institution. This study presents the development of a procedure to commission this platform along with the synthesis, testing, and validation of several unique tools/methods central to this challenging frontier. Methods: The commissioning procedure is organized into three phases: 1) the linac and a modified patient couch are commissioned in the absence of magnetic fields; 2) the MR magnet is energized, followed by experimental field mapping and verification of linac/couch performance proximal to the magnet; 3) MR imaging is evaluated and integrated guidance functionalities are tested. Novel methods/technologies embedded in these steps include: magnetic field finite element simulations to confirm magnetic decoupling of the MR scanner, linac, and couch; development of a novel harmonic distortion analysis/shim evaluation technique and associated phantom design incorporating comprehensive imaging QA; simulation of patient‐induced susceptibility distortions and pulse sequence optimization; development of a phantom/method to evaluate the accuracy/stability of MR scanner/couch travel. Results: The finite element simulations of the MRIgRT platform indicated acceptable magnetic forces on critical couch/linac components, undisturbed x‐ray beam production, and acceptable field uniformity within the MRI active volume (via active shimming). Validation of the harmonic distortion analysis demonstrated that complete volumetric mapping of the geometric distortion could be performed with an error bound by the imaging voxel size. Susceptibility‐induced distortions were simulated for various anatomical sites and can be reduced to within 1–2 mm by increasing the frequency encoding gradient strength with acceptable SNR losses. Lastly, the accuracy of translation and rotation measurements was established for evaluating MR scanner/couch travel. Conclusion: A comprehensive procedure has been established for the commissioning of an integrated MRIgRT platform, and various key tools/methods for assessing system performance have been developed and tested. J. Winter and L. Petropoulos are employees of IMRIS. J. Marle and M. Sweitzer are employees of Varian Medical Systems. IMRIS and Varian are companies co‐developing the MRgRT system. Funding for the MRgRT project at Princess Margaret Hospital was provided by the Canadian Foundation for Innovation.

P374: Enhanced hospital hygienic monitoring program 2011-2012 in a acute regional hospital in Hong Kong

There is increasing evidence to show that contaminated environment does play a role in transmission of healthcare associated infection. Improvement in the effectiveness of daily and terminal cleansing of high touch surfaces is identified as one of the crucial element in hospital infection prevention. In view of the growing challenge of infections caused by multi-drugs resistant organisms, an infection prevention program for cleansing staff was initiated by infection control team (ICT) in Princess Margaret Hospital.

Outcome of patients with transformed indolent non-Hodgkin lymphoma referred for autologous stem-cell transplantation

BackgroundThe proportion of potentially eligible patients with transformed indolent non-Hodgkin lymphoma who undergo autologous stem-cell transplantation (ASCT) is unknown. There are limited data describing their outcome in the rituximab era. Patients and methodsWe reviewed 105 consecutive patients with biopsy-proven transformation referred to Princess Margaret Hospital for consideration of ASCT during 1996–2009. Patients received anthracycline or platinum-based chemotherapy with or without rituximab. Responders proceeded to stem-cell mobilization and ASCT. ResultsThe median age at transformation was 54 (range 30–65) years. Patients received a median of two chemotherapy regimens for transformation, including rituximab in 39%. Fifty patients (48%) proceeded with ASCT and 55 (52%) did not, mainly due to progressive disease (n = 42). Three-year overall (OS) and progression-free survival (PFS) post-ASCT were 54% and 42%, respectively. Patients receiving rituximab with chemotherapy before transplant had a 3-year post-ASCT OS of 71% versus 47% in those who received chemotherapy alone (P = 0.046). Patients transplanted after 2004 had a 3-year post-ASCT OS of 69% versus 39% in those receiving ASCT earlier (P = 0.009). ConclusionsAbout half of transplant-eligible patients with transformation are able to undergo ASCT. Outcomes following ASCT appear to have improved over recent years, although the role of rituximab in this patient population requires further evaluation.

WS2.2 What do parents experience and how do they cope with the AREST CF early surveillance program for infants and children with cystic fibrosis?

WS2.1 “Feeling my way”: Information needs for parents whose child has been diagnosed with CF following newborn screening M. Jessup1, L. Shields2, S. Grogan3, C.A. Branch-Smith3, T.A. Douglas, on behalf of AREST CF4. 1Australian Catholic University/The Prince Charles Hospital, Research Centre, Brisbane, Australia; 2James Cook University/Townsville Hospital and Health District, Tropical Health Research Unit, Townsville, Australia; 3Telethon Institute for Child Health Research, Perth, Australia; 4Curtin University/ Princess Margaret Hospital for Children, Perth, Australia

Keeping it simple: Genetics referrals for all invasive serous ovarian cancers

ObjectiveIn the province of Ontario, all women diagnosed with invasive serous ovarian cancer are eligible for genetic testing for mutations in the BRCA1 and BRCA2 genes. This study aimed to determine the proportion of these women who are seen for genetic counseling and to identify potential predictors and barriers to having genetic counseling. MethodsAll women who were diagnosed with invasive serous ovarian cancer and had genetic counseling at Princess Margaret Hospital (PMH) between 2002 and 2009 were identified. Logistic regressions and trend analyses explored age at diagnosis, year at diagnosis, and the time between diagnosis and genetic counseling. Genetic counseling outcomes were also examined. ResultsOf 623 women diagnosed with invasive serous ovarian cancer, 144 (23%) were seen for genetic counseling. As age at diagnosis increased, the likelihood of genetic counseling decreased (p=0.005). With a more recent date of diagnosis, the probability of having genetic counseling increased (p=0.032) while the time to genetic counseling decreased (p=0.001). Of women who pursued genetic testing, 31% were found to have a BRCA1 or BRCA2 mutation, 16% of whom had no family history of breast or ovarian cancer. ConclusionsDespite the availability of genetic testing, only a small proportion of women with invasive serous ovarian cancer were seen for genetic counseling. Over time, an improvement in the proportion of women being seen for genetic counseling was noted; however barriers to seeing women with a later age at diagnosis or those with no family history of breast or ovarian cancer clearly exist.

Outcomes of oxaliplatin-based adjuvant chemotherapy in pathologically lymph node positive (ypN+) rectal cancer.

e14664 Background: Standard therapy for locally advanced rectal cancer( LARC) with pre-operative chemoradiation(CRT) followed by curative surgery and adjuvant 5-flourouracil (5-FU) has resulted in a 5-year local relapse (LR) rate of less than 10% and incidence of distant metastases of about 36%. Accumulating data suggests that pathological lymph node status post CRT (ypN) is a major prognostic factor for long term outcomes in LARC .The role of adjuvant oxaliplatin-based therapy has not yet been well defined in ypN+ patients and is the focus of this study. Methods: Patients with ypN+ rectal cancer who underwent fluoropyrimidine-based preoperative CRT followed by curative surgery and received adjuvant oxaliplatin- (group 1) or fluoropyrimidine-based (group 2) chemotherapy at Princess Margaret Hospital were retrospectively reviewed.The study end point was comparison of three year disease free survival(DFS) and freedom from distant metastasis (FDM) in group 1 vs 2 using log-rank test. Results: Between 2003 and 2010, 25 pts in group 1 (adjuvant FOLFOX, n=23 and FOLFOX/bevacizumab, n=2) and 38 pts in group 2 ( adjuvant 5-FU/LV, n =37; capecitabine, n=1) were reviewed. Baseline characteristics were similar in both groups except more pts in group 2 had &lt; 12 lymph nodes (LNs) retrieved (p=0.02), whereas more pts in group 1 were female (p=0.03)and had ypN2 vs ypN1 (p=0.01). Median follow-up was 33 months in group 1 and 38 months in group 2 (range: 3-86). Median age: 58 years. Male: 51, 80%. Five pts (8%) in the entire cohort experienced LR and 20 pts (31.7%) had distant metastasis. A trend toward better three-year DFS was observed in favour of oxaliplatin-based therapy (76% in group 1 vs. 51% in group 2; HR=0.4, 95%CI = 0.1-1.0; P=0.05). Corresponding three-year FDM rates were 83% and 58%, respectively (HR=0.23; 95% CI = 0.6-0.8; p= 0.01). In multivariate analysis, number of LNs retrieved of ≥12 and adjuvant oxaliplatin-based therapy were independent prognostic factors for improved DFS and FDM, respectively. Conclusions: Our analysis suggests that in ypN+ rectal cancer, addition of oxaliplatin to adjuvant therapy is associated with better outcomes. A prospective confirmatory randomized trial would be informative.