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.

Intensity-modulated radiotherapy in the treatment of breast cancer.

Intensity-modulated radiotherapy (IMRT) is a newer method of radiotherapy that uses beams with multiple intensity levels for any single beam, allowing concave dose distributions and tighter margins than those possible using conventional radiotherapy. IMRT is ideal for treating complex treatment volumes and avoiding close proximity organs at risk that may be dose limiting and provides increased tumour control through an escalated dose and reduces normal tissue complications through organ at risk sparing. Given the potential advantages of IMRT and the availability of IMRT-enabled treatment planning systems and linear accelerators, IMRT has been introduced in a number of disease sites. This systematic review examined the evidence for IMRT in the treatment of breast cancer to quantify the potential benefits of this new technology and to make recommendations for radiation treatment programmes considering adopting this technique. Providing that avoidance of acute adverse effects associated with radiation is an outcome of interest, then IMRT is recommended over tangential radiotherapy after breast-conserving surgery, based on a review of six published reports including 2012 patients. There were insufficient data to recommend IMRT over standard tangential radiotherapy for reasons of oncological outcomes or late toxicity. Future research should focus on studies with longer follow-up and provide data on late toxicity and disease recurrence rates.

Intensity-modulated radiotherapy in the treatment of head and neck cancer.

Intensity-modulated radiotherapy (IMRT) is a newer method of radiotherapy that uses intensity-modulated beams that can provide multiple intensity levels for any single-beam direction and any single-source position, allowing concave dose distributions and dose gradients with narrower margins than those possible using conventional methods. IMRT is ideal for treating complex treatment volumes and avoiding close proximity organs at risk that may be dose limiting and provides increased tumour control through an escalated dose and reduces normal tissue complications through organ at risk sparing. Given the potential advantages of IMRT and the availability of IMRT-enabled treatment planning systems and linear accelerators, IMRT has been introduced in a number of disease sites, including head and neck cancer. This systematic review examined the evidence for IMRT compared with two-dimensional external beam radiotherapy (EBRT) in the treatment of head and neck cancer in order to quantify the potential benefits of this new technology and made recommendations for radiation treatment programmes considering adopting this technique. Findings were in favour of IMRT compared with two-dimensional EBRT where avoidance of the adverse outcomes xerostomia, osteoradionecrosis and blindness are the main outcomes of interest, based on a review of 15 papers including 1555 patients. There are insufficient data to recommend IMRT over two-dimensional EBRT if treatment-related outcomes are the main outcomes of interest. Future research should focus on additional normal tissue preservation, and the role of IMRT in the treatment of recurrent head and neck cancer, as well as its use in combination with surgery, chemotherapy and/or brachytherapy.

Intensity-modulated radiotherapy in the treatment of lung cancer.

Intensity-modulated radiotherapy (IMRT) is an advancement in radiotherapy that uses intensity-modulated beams, which can provide multiple intensity levels for any single beam direction and any single source position, allowing shaped distributions and dose gradients with narrower margins than previously possible. IMRT is ideal for treating complex treatment volumes and avoiding close proximity organs at risk that may be dose limiting, allowing dose escalation (to improve tumour control) and/or reducing normal tissue complications (through organ at risk sparing). Given these potential advantages of IMRT and the availability of IMRT planning systems and linear accelerators, IMRT has been introduced in a number of disease sites. This systematic review examined the evidence for IMRT in the treatment of lung cancer in order to quantify the potential benefits and to make recommendations for radiation treatment programmes considering adopting IMRT. This review revealed two retrospective cohort studies reporting on cancer outcomes, which was considered insufficient on which to make evidence-based recommendations. However, due to the known dosimetric properties of IMRT and extrapolating from clinical outcomes from other disease sites, IMRT should be considered for lung cancer patients where the tumour is in close proximity to an organ at risk, where the target volume includes a large volume of an organ at risk, or in scenarios where dose escalation would be potentially beneficial while minimising normal tissue toxicity. Until randomised data are available, future research in IMRT for lung cancer should include a comprehensive prospective assessment of the relevant outcomes, including tumour control and normal tissue toxicity.

Intensity-modulated radiotherapy in the treatment of prostate cancer.

Three-dimensional conformal radiotherapy (3DCRT) as the primary treatment for prostate cancer has improved outcomes compared with conventional radiotherapy, but with an associated increase in toxicity due to radiation effects on the bladder and rectum. Intensity-modulated radiotherapy (IMRT) is a newer method of radiotherapy that uses intensity-modulated beams that can provide multiple intensity levels for any single beam direction and any single source position allowing concave dose distributions and dose gradients with narrower margins than those possible using conventional methods. IMRT is ideal for treating complex treatment volumes and avoiding close proximity organs at risk that may be dose limiting and provides increased tumour control through an escalated dose and reduces normal tissue complications through organ at risk sparing. Given the potential advantages of IMRT and the availability of IMRT-enabled treatment planning systems and linear accelerators, IMRT has been introduced in a number of disease sites, including prostate cancer. This systematic review examined the evidence for IMRT in the treatment of prostate cancer in order to quantify the potential benefits of this new technology and to make recommendations for radiation treatment programmes considering adopting this technique. The findings were in favour of recommending IMRT over 3DCRT in the radical treatment of localised prostate cancer where doses greater than 70 Gy are required, based on a review of 11 published reports including 4559 patients. There were insufficient data to recommend IMRT over 3DCRT in the postoperative setting. Future research should examine image-guided IMRT in the post-prostatectomy setting, with altered fractionation, and in combination with hormone and chemotherapy.

Intensity-modulated radiotherapy in the treatment of gynaecological cancers.

Intensity-modulated radiotherapy (IMRT) is a newer method of radiotherapy that uses intensity-modulated beams that can provide multiple intensity levels for any single beam direction and any single source position allowing concave dose distributions and dose gradients with narrower margins than those possible using conventional methods. IMRT is ideal for treating complex treatment volumes and avoiding close proximity organs at risk that may be dose limiting and provides increased tumour control through an escalated dose and reduces normal tissue complications through organ at risk sparing. Given the potential advantages of IMRT and the availability of IMRT-enabled treatment planning systems and linear accelerators, IMRT has been introduced in a number of disease sites. This systematic review examined the evidence for IMRT in the treatment of gynaecological cancers to quantify the potential benefits of this new technology and to make recommendations for radiation treatment programmes considering adopting this technique. Findings were based on a review of four cohort studies, one of which was prospective, including a total of 619 patients. If reducing acute and chronic toxicity are the main outcomes of interest, then IMRT may be considered over three-dimensional conformal radiotherapy for women with gynaecological cancers; if disease-related outcomes are the main outcomes of interest, there are insufficient data to recommend IMRT over three-dimensional conformal radiotherapy. Future research should focus on prospective multicentre studies reporting on both acute and chronic toxicity as well as survival and recurrence. Dose escalation studies should be carried out to investigate the effect of higher doses on disease.

Bevacizumab combined with chemotherapy for patients with advanced colorectal cancer: a systematic review.

BACKGROUND: Fluoropyrimidine-based chemotherapy is considered standard treatment of advanced colorectal cancer. Recent studies indicate benefit to the addition of bevacizumab, a recombinant monoclonal antibody targeting vascular endothelial growth factor. METHODS: Medline, EMBASE, Cochrane Library, and conference proceedings were searched to identify randomized trials in advanced colorectal cancer comparing chemotherapy plus bevacizumab with chemotherapy alone. A meta-analysis of published data was carried out. RESULTS: Five trials comparing chemotherapy plus bevacizumab with chemotherapy alone as first- or second-line treatment were identified. Our meta-analysis indicates an advantage in favor of the addition of bevacizumab to chemotherapy in terms of overall survival (OS) [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.69-0.90; P = 0.0005], progression-free survival (PFS) (HR 0.63; 95% CI 0.49-0.81, P = 0.0004), and response rate (RR 1.50; 95% CI 1.06-2.10, P = 0.02). The most commonly observed adverse effects related to bevacizumab included hypertension, proteinuria, bleeding, and thrombosis. Gastrointestinal perforation and poor wound healing were also observed; however, their incidence was rare. CONCLUSIONS: For patients with advanced colorectal cancer receiving first- or second-line fluoropyrimidine-based chemotherapy, the addition of bevacizumab improves PFS and OS at the expense of increased incidence of toxicity. The magnitude of benefit may differ based on the chemotherapy regimen with which bevacizumab is partnered.

Cancer Care Ontario Colonoscopy Standards: standards and evidentiary base.

Colorectal cancer (CRC) is the most common cause of non-tobacco-related cancer deaths in Canadian men and women, accounting for 10% of all cancer deaths. An estimated 7800 men and women will be diagnosed with CRC, and 3250 will die from the disease in Ontario in 2007. Given that CRC incidence and mortality rates in Ontario are among the highest in the world, the best opportunity to reduce this burden of disease would be through screening. The present report describes the findings and recommendations of Cancer Care Ontario's Colonoscopy Standards Expert Panel, which was convened in March 2006 by the Program in Evidence-Based Care. The recommendations will form the basis of the quality assurance program for colonoscopy delivered in support of Ontario's CRC screening program.

Role of oxaliplatin combined with 5-fluorouracil and folinic acid in the first- and second-line treatment of advanced colorectal cancer.

QUESTION: What is the role of oxaliplatin combined with 5-fluorouracil (5-fu) and folinic acid (fa) in the first- and second-line treatment of advanced (unresectable locally advanced or metastatic) colorectal cancer? PERSPECTIVES: Evidence was selected and reviewed by two members of the Gastrointestinal Cancer Disease Site Group (gi dsg) of Cancer Care Ontario's Program in Evidence-Based Care (pebc) and by a methodologist. The resulting practice guideline report has been reviewed and approved by the gi dsg, which comprises medical and radiation oncologists, surgeons, a pathologist, and patient representatives. External review by Ontario practitioners was obtained through a mailed survey. Final approval of the original guideline report was obtained from the Practice Guidelines Coordinating Committee. OUTCOMES: Outcomes of interest were 1-year survival, response rates, and quality of life. METHODOLOGY: The medline, cancerlit, embase, Guidelines International Network, and Cochrane Library databases were systematically searched for relevant studies. Recommendations were formed based on the evidence reviewed. Through a survey, these recommendations were appraised by Ontario clinicians; the recommendations were then revised by the gi dsg. The systematic review and modified recommendations were approved by a review body within pebc. RESULTS: The literature review found twenty-one randomized controlled trials and two meta-analyses. Evidence on first-line treatment found infusional 5-fu/fa/oxaliplatin (folfox) to be superior to bolus 5-fu/fa/irinotecan (ifl) for rates of median survival and tumour response, with lower incidences of most adverse effects except peripheral neuropathy. For second-line treatment after fluoropyrimidine monotherapy, folfox is a reasonable alternative for patients with contraindications to second-line irinotecan. After progression on infusional 5-fu/fa/irinotecan (folfiri), folfox is the preferred therapy. Evidence from a single randomized trial suggests that additional benefits can be expected with the addition of bevacizumab to the folfox regimen in second-line treatment. PRACTICE GUIDELINE: These recommendations apply to adult patients with advanced colorectal cancer who have high performance status (Eastern Cooperative Oncology Group score 0-2). Refer to Appendix A for available treatment options and to Appendix b for recommended dosages and schedules. The folfox regimen is an important component of therapy for advanced colorectal cancer. FIRST-LINE THERAPY: In one trial, folfox was shown to be superior to ifl. The folfox regimen has superior rates of median survival and tumour response. Compared with ifl, folfox has lower incidences of severe nausea, vomiting, diarrhea, and febrile neutropenia, but a higher incidence of peripheral neuropathy. Short-term infusional 5-fu/fa in combination with either oxaliplatin (folfox) or irinotecan (folfiri) are both acceptable alternatives for fit patients when combination therapy is the preferred treatment. Choice of first-line therapy may rely on patient factors and preferences-for example, less neuropathy with irinotecan versus less alopecia with oxaliplatin. SECOND-LINE THERAPY: After progression on first-line anti-thymidylate synthase monotherapy (for example, 5-fu/fa, capecitabine), irinotecan is standard second-line therapy. The folfox regimen is a reasonable alternative for patients with contraindications to the use of second-line irinotecan. After progression on both irinotecan and an anti-thymidylate synthase agent, folfox is the preferred therapy. Recent trials suggest that, as compared with folfox alone, folfox combined with bevacizumab provides additional survival benefits. QUALIFYING STATEMENTS: The role of radiation therapy, either alone or in combination with chemotherapy, for locally advanced unresectable colorectal cancer is not addressed in this guideline. Use of chronomodulated regimens is a topic that intersects with the use of oxaliplatin/5-fu combinations, particularly chronomodulation of 5-fu in these combinations. Chronomodulation of oxaliplatin has not been extensively studied, and the topic of chronomodulation is beyond the scope of this guideline and is not addressed. Although data exist to support the use of bevacizumab in combination with folfox in second-line treatment, no first-line treatment data are available on which to make a recommendation.