First-line therapy, autologous stem-cell transplantation, and post-transplantation maintenance in the management of newly diagnosed mantle cell lymphoma.

Background: In Ontario, no clearly defined standard of care for the management of mantle cell lymphoma (mcl) has been developed, and substantial variability from centre to centre is evident. This guidance document was prompted by the need to harmonize practice in Ontario with respect to first-line, conditioning, and post-transplantation maintenance therapy for patients newly diagnosed with transplantation-eligible mcl. Methods: The medline and embase databases were systematically searched from January 2013 to January 2020 for evidence, and the best available evidence was used to draft recommendations relevant to first-line therapy, autologous stem-cell transplantation, and post-transplantation maintenance in the management of transplantation-eligible newly diagnosed mcl. Final approval of this guidance document was obtained from the Stem Cell Transplant Advisory Committee. Recommendations: These recommendations apply to all cases of transplantation-eligible newly diagnosed mcl:■ Alternating cycles of r-chop (rituximab plus cyclophosphamide-doxorubicin-vincristine-prednisolone) and r-dhap [rituximab plus dexamethasone-high-dose cytarabine-cisplatin] is the recommended first-line treatment for symptomatic patients newly diagnosed with mcl before autologous stem-cell transplantation (asct).■ Rituximab plus hyperfractionated cyclophosphamide-vincristine-doxorubicin-dexamethasone (r-hypercvad), alternating with methotrexate and cytarabine, is not recommended for the treatment of patients with newly diagnosed mcl.■ beam (carmustine-etoposide-cytarabine-melphalan), beac (carmustine-etoposide-cytarabine-cyclophosphamide), and total-body irradiation-based regimens are reasonable conditioning options for patients with mcl who have responded to first-line therapy and who are undergoing asct.■ Maintenance therapy with rituximab is recommended for patients with newly diagnosed mcl who have undergone asct.

Baseline staging imaging for distant metastasis in women with stages I, II, and III breast cancer.

Background: In Ontario, there is no clearly defined standard of care for staging for distant metastasis in women with newly diagnosed and biopsy-confirmed breast cancer whose clinical presentation is suggestive of early-stage disease. This guideline addresses baseline imaging investigations for women with newly diagnosed primary breast cancer who are otherwise asymptomatic for distant metastasis. Methods: The medline and embase databases were systematically searched for evidence from January 2000 to April 2019, and the best available evidence was used to draft recommendations relevant to the use of baseline imaging investigation in women with newly diagnosed primary breast cancer who are otherwise asymptomatic. Final approval of this practice guideline was obtained from both the Staging in Early Stage Breast Cancer Advisory Committee and the Report Approval Panel of the Program in Evidence-Based Care. Recommendations: These recommendations apply to all women with newly diagnosed primary breast cancer (originating in the breast) who have no symptoms of distant metastasis Staging tests using conventional anatomic imaging [chest radiography, liver ultrasonography, chest-abdomen-pelvis computed tomography (ct)] or metabolic imaging modalities [integrated positron-emission tomography (pet)/ct, integrated pet/magnetic resonance imaging (mri), bone scintigraphy] should not be routinely ordered for women newly diagnosed with clinical stage i or stage ii breast cancer who have no symptoms of distant metastasis, regardless of biomarker status. In women newly diagnosed with stage iii breast cancer, baseline staging tests using either anatomic imaging (chest radiography, liver ultrasonography, chest-abdomen-pelvis ct) or metabolic imaging modalities (pet/ct, pet/mri, bone scintigraphy) should be considered regardless of whether the patient is symptomatic for distant metastasis and regardless of biomarker profile.

Follow-up care for survivors of lymphoma who have received curative-intent treatment.

OBJECTIVE: This evidence summary set out to assess the available evidence about the follow-up of asymptomatic survivors of lymphoma who have received curative-intent treatment. METHODS: The medline and embase databases and the Cochrane Database of Systematic Reviews were searched for evidence published between 2000 and August 2015 relating to lymphoma survivorship follow-up. The evidence summary was developed by a Working Group at the request of the Cancer Care Ontario Survivorship and Cancer Imaging programs because of the absence of evidence-based practice documents in Ontario for the follow-up and surveillance of asymptomatic patients with lymphoma in complete remission. RESULTS: Eleven retrospective studies met the inclusion criteria. The proportion of relapses initially detected by clinical manifestations ranged from 13% to 78%; for relapses initially detected by imaging, the proportion ranged from 8% to 46%. Median time for relapse detection ranged from 8.6 to 19 months for patients initially suspected because of imaging and from 8.6 to 33 months for those initially suspected because of clinical manifestations. Only one study reported significantly earlier relapse detection for patients initially suspected because of clinical manifestations (mean: 4.5 months vs. 6.0 months, p = 0.042). No benefit in terms of overall survival was observed for patients depending on whether their relapse was initially detected because of clinical manifestations or surveillance imaging. SUMMARY: Findings in the present study support the importance of improving awareness on the part of survivors and clinicians about the symptoms that might be associated with recurrence. The evidence does not support routine imaging for improving outcomes in this patient population.

Plerixafor for autologous stem-cell mobilization and transplantation for patients in Ontario.

BACKGROUND: High-dose chemotherapy with autologous stem-cell transplantation (asct) is an accepted part of standard therapy for patients with hematologic malignancies. Usually, stem-cell mobilization uses granulocyte colony-stimulating factor (g-csf); however, some patients are not able to be mobilized with chemotherapy and g-csf, and such patients could be at higher risk of failing mobilization. Plerixafor is a novel mobilization agent that is absorbed quickly after subcutaneous injection and, at the recommended dose of 0.24 mg/kg, provides a sustained increase in circulating CD34+ cells for 10-18 hours. The main purpose of the present report was to evaluate the most current evidence on the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct for patients in Ontario so as to make recommendations for clinical practice and to assist Cancer Care Ontario in decision-making with respect to this intervention. METHODS: The medline and embase databases were systematically searched for evidence from January 1996 to March 2015, and the best available evidence was used to draft recommendations relevant to the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct. Final approval of this practice guideline report was obtained from both the Stem Cell Transplant Steering Committee and the Report Approval Panel of the Program in Evidence-Based Care. RECOMMENDATIONS: These recommendations apply to adult patients considered for asct: ■ Adding plerixafor to g-csf is an option for initial mobilization in patients with non-Hodgkin lymphoma or multiple myeloma who are eligible for asct when chemotherapy cannot be used and only g-csf mobilization is available.■ For patients with a low peripheral blood CD34+ cell count (for example, <10/µL) at the time of anticipated stem-cell harvesting, or with an inadequate first-day apheresis collection, it is recommended that plerixafor be added to the mobilization regimen to maximize stem-cell collection and to prevent the need for remobilization.■ It is recommended that patients who have failed a previous mobilization attempt undergo remobilization with g-csf and plerixafor, with or without chemotherapy.

The organization of colposcopy services in Ontario: recommended framework.

OBJECTIVE: The purpose of this guideline is to help ensure the provision of high-quality colposcopy practices in the province of Ontario, including those conducted as diagnostic procedures in follow-up to an abnormal cervical screening test. METHODS: This document updates the recommendations published in the 2008 colposcopy guideline from Cancer Care Ontario, The Optimum Organization for the Delivery of Colposcopy Service in Ontario. A systematic review of guidelines was conducted to evaluate the existing evidence and recommendations concerning these key aspects of colposcopy: □ Training, qualification, accreditation, and maintenance of competence□ Practice setting requirements□ Operational practice□ Quality indicators and outcomes. RESULTS: This guideline provides recommendations on training and maintenance of competence for colposcopists in the practice settings in which colposcopic evaluation and treatments are conducted. It also provides recommendations on operational issues and quality indicators for colposcopy. CONCLUSIONS: This updated guideline is intended to support quality improvement for colposcopy for all indications, including the follow-up of an abnormal cervical screening test and work-up for lower genital tract lesions that are not clearly malignant. The recommendations contained in this document are intended for clinicians and institutions performing colposcopy in Ontario, and for policymakers and program planners involved in the delivery of colposcopy services.

Extracorporeal photopheresis in the management of graft-versus-host disease.

QUESTION: Is there a benefit associated with the use of extracorporeal photopheresis (ecp) compared with other treatment options for patients who have received allogeneic stem-cell transplantation (sct) and are experiencing graft-versus-host disease (gvhd), if response rate, survival, or improvement in symptoms are the outcomes of interest? PERSPECTIVES: After allogeneic sct, gvhd is a common complication historically categorized as either acute (agvhd: onset ≤100 days post-transplantation) or chronic (cgvhd: >100 days post-transplantation). Graft-versus-host disease occurs when the donor's immune cells recognize the host patient's tissues and organs as foreign and attack them, causing a multitude of problems, often in liver, gastrointestinal system, and skin. Photopheresis is one therapy that has emerged since the early 2000s for the management of steroid-refractory gvhd because of its steroid-sparing ability, low associated toxicity, and efficacy in some clinical settings. The present recommendation report summarizes the available data about photopheresis for the treatment of gvhd and provides recommendations on its use. METHODOLOGY: The medline (Ovid) database was systematically searched for January 1995 to August 2013, and the best available evidence was used to draft recommendations relevant to adult and pediatric patients in Ontario who have received allogeneic sct and are experiencing gvhd. Draft recommendations were first reviewed by clinical and methodology experts before undergoing internal review. Final approval of this practice guideline report was obtained from both the Stem Cell Transplant Steering Committee and the Report Approval Panel of the Program in Evidence-Based Care. RECOMMENDATIONS: These recommendations apply to adult and pediatric patients who have received an allogeneic sct and are experiencing gvhd: ecp is an acceptable therapy for the treatment of steroid-dependent or refractory agvhd in adult and pediatric patients.ecp is an effective therapy for the treatment of steroid-dependent or refractory cgvhd in adult and pediatric patients. QUALIFYING STATEMENT: In Ontario, ecp is currently a covered therapy for patients with steroid-refractory gvhd who meet certain eligibility criteria.

Verotoxigenic Escherichia coli: costs of illness in Canada, including long-term health outcomes.

The main objective of this study was to provide cost estimates of human Escherichia coli O157 infection to facilitate future assessment of the benefits and costs of alternative preventive strategies to reduce illness. We investigated the costs of illness to Canadians from primary human infection by verotoxigenic E. coli O157 (also called Shiga toxin-producing E. coli O157) using data from the National Notifiable Diseases Registry. We used relative risk information from peer-reviewed publications to estimate the burden of illness and associated costs for eight long-term health outcomes. National estimates of the number of cases (mean and 5th and 95th percentiles), associated costs, and a rank correlation test to identify which outcomes were associated with the highest per capita costs were calculated. An estimated 22,344 cases of primary infections occur in Canada annually, costing $26.7 million. There are 37,867 additional on-going long-term health outcomes costing $377.2 million each year. Our analysis indicated that the annual cost for primary and long-term illness is $403.9 million. The analysis supports evaluation of alternative control and prevention measures and the development and implementation of policy and practices aimed at safe food production.

Assessing the existing information on the efficacy of bovine vaccination against Escherichia coli O157:H7--a systematic review and meta-analysis.

The objective of this study was to conduct a systematic review and meta-analysis to evaluate the existing information on the efficacy of commercial vaccination to reduce the prevalence of Escherichia coli O157:H7 in weaned cattle in beef feedlot finishing systems under commercial conditions. Currently, only two commercial vaccines exist, and thus, only publications reporting the use of vaccines targeting type III secreted proteins and/or siderophore receptor and porin proteins (SRP) were considered relevant. A total of 18 studies reporting 45 comparisons were included in this review. Meta-analyses were conducted variously on (i) pre-harvest outcomes, (ii) at-harvest outcomes and (iii) both pre-harvest and at-harvest outcomes combined. Overall, efficacy of vaccination was consistently observed. Efficacy and homogeneity of the results was demonstrated for the two-dose regimen, allowing us to conclude with confidence that the two-dose approach is efficacious. For pre-harvest outcomes and two-dose regimens, the odds ratios (OR) were 0.53 (95% CI = 0.45-0.62) for the two vaccines combined and 0.49 (95% CI = 0.40-0.60) for vaccine targeting type III secreted proteins. The test for heterogeneity among studies yielded a Q test P = 0.354 for the two vaccines combined and Q test P = 0.269 for the vaccine targeting type III secreted proteins, indicating homogeneity in both cases. For pre- and at-harvest outcomes combined and two-dose regimens, the odds ratios (OR) were 0.52 (95% CI = 0.44-0.61) for the two vaccines combined and 0.45 (95% CI = 0.34-0.60) for vaccine targeting type III secreted proteins. The test for heterogeneity among studies yielded a Q test P = 0.134 for the two vaccines combined indicating homogeneity and Q test P = 0.089 for the vaccine targeting type III secreted proteins indicating heterogeneity. Based on this meta-analysis, bovine vaccination appears to be an effective approach to the pre-harvest control of E. coli O157:H7.