Program In Evidence-Based Care Research Articles

Randomized controlled trials (RCTs) examining continuous (CS) versus intermittent strategies (IS) of delivering systemic treatment (Tx) for untreated metastatic colorectal cancer (mCRC): A meta-analysis from the Cancer Care Ontario program in evidence-based care.

3534 Background: Given the varying impact on efficacy demonstrated in individual RCTs of CS vs IS of delivering systemic Tx for mCRC, a meta-analysis of the available RCTs was performed. Methods: RCTs that compared a CS versus IS of delivering systemic Tx were identified by a systematic search (MEDLINE, EMBASE and ASCO and ESMO proceedings) and review. The results of identified trials were clinically homogeneous (Table) so the data was pooled using Review Manager software (RevMan 5.2). Overall survival (OS) hazard ratios were extracted directly from the most recently reported trial results. A random effects model was used for all pooling. Results: 10 RCTs were identified (n= 4,296). After an induction period, the maintenance Tx patients received during the IS was: none (5 trials, n=2,562), fluoropyrimidine (F) (2 trials, n=759), biologic (B) (2 trials, n=852), F+B (1 trial, n=123). Results of the meta-analysis are summarized in the Table (HR>1 favors CS). Sensitivity analyses performed demonstrate results are robust independent of the induction or maintenance Tx used. QOL (data from 2 trials) was either the same in both arms (single Tx induction trial with no maintenance Tx, n=354) or improved in the IS arm (combination tx induction trial with no maintenance Tx, n=1,630). Conclusions: IS of delivering systemic Tx for mCRC do not result in a statistically significant reduction in OS compared to a CS of delivery whether or not maintenance therapy is included. QOL is the same or better with an IS. [Table: see text]

High-intensity focused ultrasound for prostate cancer: a practice guideline

The aim of this practice guideline was to develop evidence-based recommendations for clinicians on the use of high-intensity focused ultrasound (HIFU) in patients with localized prostate cancer. The guideline was developed using the methods of Cancer Care Ontario's Program in Evidence-Based Care (PEBC). The core methodology of the PEBC's guideline development process is systematic review. A comprehensive literature search was undertaken to identify high-quality studies, reviews and other practice guidelines on the use of HIFU in prostate cancer. The evidence formed the basis of the recommendations, which were reviewed and amended where necessary, by clinical experts in medical and radiation oncology and urology. The literature review yielded limited evidence. No randomized controlled trials or meta-analyses comparing HIFU with currently accepted management approaches were identified. The body of evidence is primarily based on data from case series. Internal feedback was provided by the PEBC Genitourinary Disease Site Group membership and the Report Approval Panel. External peer review included targeted review by clinical experts specifically requested to comment on the guideline, and professional consultation through an online survey of health care professionals. HIFU is currently not recommended as an alternative to accepted curative treatment approaches for localized prostate cancer.

Alignment of Practice Guidelines with Targeted-therapy Drug Funding Policies in Ontario

We evaluated clinical practice guideline (cpg) recommendations from Cancer Care Ontario's Program in Evidence-Based Care (pebc) for molecularly targeted systemic treatments (tts) and subsequent funding decisions from the Ontario Ministry of Health and Long-Term Care. We identified pebc cpgs on tt published before June 1, 2010, and extracted information regarding the key evidence cited in support of cpg recommendations and the effect size associated with each tt. Those variables were compared with mohltc funding decisions as of June 2011. From 23 guidelines related to 17 tts, we identified 43 recommendations, among which 38 (88%) endorsed tt use. Among all the recommendations, 38 (88%) were based on published key evidence, with 82% (31 of 38) being supported by meta-analyses or phase iii trials. For the 38 recommendations endorsing tts, funding was approved in 28 (74%; odds ratio related to cpg recommendation: 29.9; p = 0.003). We were unable to demonstrate that recommendations associated with statistically significant improvements in overall survival [os: 14 of 16 (88%) vs. 8 of 14 (57%); p = 0.10] or disease- (dfs) or progression-free survival [pfs: 16 of 21 (76%) vs. 3 of 5 (60%); p = 0.59] were more likely to be funded than those with no significant difference. Moreover, we did not observe significant associations between funding approvals and absolute improvements of 3 months or more in os [6 of 6 (100%) vs. 3 of 6 (50%), p = 0.18] or pfs [6 of 8 (75%) vs. 10 of 12 (83%), p = 1.00]. For use of tts, most recommendations in pebc cpgs are based on meta-analyses or phase iii data, and funding decisions were strongly associated with those recommendations. Our data suggest a trend toward increased rates of funding for therapies with statistically significant improvements in os.

Management of a suspicious adnexal mass: a clinical practice guideline.

What is the optimal strategy for preoperative identification of the adnexal mass suspicious for ovarian cancer? What is the most appropriate surgical procedure for a woman who presents with an adnexal mass suspicious for malignancy? In Canada in 2010, 2600 new cases of ovarian cancer were estimated to have been diagnosed, and of those patients, 1750 were estimated to have died, making ovarian cancer the 7th most prevalent form of cancer and the 5th leading cause of cancer death in Canadian women. Women with ovarian cancer typically have subtle, nonspecific symptoms such as abdominal pain, bloating, changes in bowel frequency, and urinary or pelvic symptoms, making early detection difficult. Thus, most ovarian cancer cases are diagnosed at an advanced stage, when the cancer has spread outside the pelvis. Because of late diagnosis, the 5-year relative survival ratio for ovarian cancer in Canada is only 40%. Unfortunately, because of the low positive predictive value of potential screening tests (cancer antigen 125 and ultrasonography), there is currently no screening strategy for ovarian cancer. The purpose of this document is to identify evidence that would inform optimal recommended protocols for the identification and surgical management of adnexal masses suspicious for malignancy. Outcomes of interest for the identification question included sensitivity and specificity. Outcomes of interest for the surgical question included optimal surgery, overall survival, progression-free or disease-free survival, reduction in the number of surgeries, morbidity, adverse events, and quality of life. After a systematic review, a practice guideline containing clinical recommendations relevant to patients in Ontario was drafted. The practice guideline was reviewed and approved by the Gynecology Disease Site Group and the Report Approval Panel of the Program in Evidence-based Care. External review by Ontario practitioners was obtained through a survey, the results of which were incorporated into the practice guideline. These recommendations apply to adult women presenting with a suspicious adnexal mass, either symptomatic or asymptomatic. IDENTIFICATION OF AN ADNEXAL MASS SUSPICIOUS FOR OVARIAN CANCER: Sonography (particularly 3-dimensional sonography), magnetic resonance imaging (mri), and computed tomography (ct) imaging are each recommended for differentiating malignant from benign ovarian masses. However, the working group offers the following further recommendations, based on their expert consensus opinion and a consideration of availability, access, and harm: Where technically feasible, transvaginal sonography should be the modality of first choice in patients with a suspicious isolated ovarian mass.To help clarify malignant potential in patients in whom ultrasonography may be unreliable, mri is the most appropriate test.In cases in which extra-ovarian disease is suspected or needs to be ruled out, ct is the most useful technique.Evaluation of an adnexal mass by Doppler technology alone is not recommended. Doppler technology should be combined with a morphology assessment.Ultrasonography-based morphology scoring systems can be used to differentiate benign from malignant adnexal masses. These scoring systems are based on specific ultrasound parameters, each with several scores base on determined features. All evaluated scoring systems were found to have an acceptable level of sensitivity and specificity; the choice of scoring system may therefore be made based on clinician preference.As a standalone modality, serum cancer antigen 125 is not recommended for distinguishing between benign and malignant adnexal masses.Frozen sections for the intraoperative diagnosis of a suspicious adnexal mass is recommended in settings in which availability and patient preference allow. SURGICAL PROCEDURES FOR AN ADNEXAL MASS SUSPICIOUS FOR MALIGNANCY: To improve survival, comprehensive surgical staging with lymphadenectomy is recommended for the surgical management of patients with early-stage ovarian cancer. Laparoscopy is a reasonable alternative to laparotomy, provided that appropriate surgery and staging can be done. The choice between laparoscopy and laparotomy should be based on patient and clinician preference. Discussion with a gynecologic oncologist is recommended. Fertility-preserving surgery is an acceptable alternative to more extensive surgery in patients with low-malignant-potential tumours and those with well-differentiated surgical stage i ovarian cancer. Discussion with a gynecologic oncologist is recommended.

Cancer Care Ontario Guideline Recommendations for Hormone Receptor Testing in Breast Cancer

Hormone receptor testing (oestrogen and progesterone) in breast cancer at the time of primary diagnosis is used to guide treatment decisions. Accurate and standardised testing methods are critical to ensure the proper classification of the patient's hormone receptor status. Recommendations were developed to improve the quality and accuracy of hormone receptor testing based on a systematic review conducted jointly by the American Society of Clinical Oncology/College of American Pathologists and Cancer Care Ontario's Program in Evidence-Based Care. Evidence-based recommendations were formulated to set standards for optimising immunohistochemistry in assessing hormone receptor status, as well as assuring quality and proficiency between and within laboratories. A formal external review was conducted to validate the relevance of these recommendations. It is anticipated that widespread adoption of these guidelines will further improve the accuracy of hormone receptor testing in Canada.

Challenges in knowledge translation: the early years of Cancer Care Ontario’s Program in Evidence-Based Care

Background: Cancer Care Ontario’s Program in Evidence-Based Care (pebc) was formalized in 1997 to produce clinical practice guidelines for cancer management for the Province of Ontario. At the time, the gap between guideline development and implementation was beginning to be acknowledged. The Program implemented strategies to promote use of guidelines. Methods: The program had to overcome numerous social challenges to survive. (1) Prospective strategies useful to practitioners—including participation, transparent communication, a methodological vision, and methodology skills development offerings—were used to create a culture of research-informed oncology practice within a broad community of practitioners. (2) Reactive strategies ensured the survival of the program in the early years, when some within the influential academic community and among decision-makers were skeptical about the feasibility of a rigorous methodologic approach meeting the fast turnaround times necessary for policy. Results: The paper details the pebc strategies within the context of what was known about knowledge translation (kt) at the time, and it tries to identify key success factors. Conclusions: Many of the barriers faced in the implementation of kt—and the strategies for overcoming them—are unavailable in the public domain because the relevant reporting does not fit the traditional paradigm for publication. Telling the “stories behind the story” should be encouraged to enhance the practice of kt beyond the science.

Challenges in Knowledge Translation: The Early Years of Cancer Care Ontario’s Program in Evidence-Based Care

Cancer Care Ontario's Program in Evidence-Based Care (pebc) was formalized in 1997 to produce clinical practice guidelines for cancer management for the Province of Ontario. At the time, the gap between guideline development and implementation was beginning to be acknowledged. The Program implemented strategies to promote use of guidelines. The program had to overcome numerous social challenges to survive. Prospective strategies useful to practitioners-including participation, transparent communication, a methodological vision, and methodology skills development offerings-were used to create a culture of research-informed oncology practice within a broad community of practitioners.Reactive strategies ensured the survival of the program in the early years, when some within the influential academic community and among decision-makers were skeptical about the feasibility of a rigorous methodologic approach meeting the fast turnaround times necessary for policy. The paper details the pebc strategies within the context of what was known about knowledge translation (kt) at the time, and it tries to identify key success factors. Many of the barriers faced in the implementation of kt-and the strategies for overcoming them-are unavailable in the public domain because the relevant reporting does not fit the traditional paradigm for publication. Telling the "stories behind the story" should be encouraged to enhance the practice of kt beyond the science.

Effective interventions to facilitate the uptake of breast, cervical and colorectal cancer screening: an implementation guideline

BackgroundAppropriate screening may reduce the mortality and morbidity of colorectal, breast, and cervical cancers. Several high-quality systematic reviews and practice guidelines exist to inform the most effective screening options. However, effective implementation strategies are warranted if the full benefits of screening are to be realized. We developed an implementation guideline to answer the question: What interventions have been shown to increase the uptake of cancer screening by individuals, specifically for breast, cervical, and colorectal cancers?MethodsA guideline panel was established as part of Cancer Care Ontario's Program in Evidence-based Care, and a systematic review of the published literature was conducted. It yielded three foundational systematic reviews and an existing guidance document. We conducted updates of these reviews and searched the literature published between 2004 and 2010. A draft guideline was written that went through two rounds of review. Revisions were made resulting in a final set of guideline recommendations.ResultsSixty-six new studies reflecting 74 comparisons met eligibility criteria. They were generally of poor to moderate quality. Using these and the foundational documents, the panel developed a draft guideline. The draft report was well received in the two rounds of review with mean quality scores above four (on a five-point scale) for each of the items. For most of the interventions considered, there was insufficient evidence to support or refute their effectiveness. However, client reminders, reduction of structural barriers, and provision of provider assessment and feedback were recommended interventions to increase screening for at least two of three cancer sites studied. The final guidelines also provide advice on how the recommendations can be used and future areas for research.ConclusionUsing established guideline development methodologies and the AGREE II as our methodological frameworks, we developed an implementation guideline to advise on interventions to increase the rate of breast, cervical and colorectal cancer screening. While advancements have been made in these areas of implementation science, more investigations are warranted.

Systemic therapy for advanced gastric cancer: a clinical practice guideline.

What is the optimal chemotherapy regimen in advanced gastric cancer? Gastric cancer is the second leading cause of cancer mortality worldwide. Despite low incidence rates for gastric cancer in Ontario, the overall prognosis is bleak, with 5-year survival rates of approximately 23% in Canada. Even with the considerable body of research available on chemotherapy for advanced gastric cancer, uncertainty remains. There is no recognized standard treatment, and there appears to be geographic variation in practice. Outcomes of interest were overall survival, objective response rate (complete plus partial responses), time to disease progression, adverse effects, and quality of life. After a systematic review, a practice guideline containing clinical recommendations relevant to patients in Ontario was drafted. The practice guideline was reviewed and approved by the Gastrointestinal Disease Site Group (gi dsg) and the Report Approval Panel of the Program in Evidence-Based Care. External review by Ontario practitioners was obtained through a survey, the results of which were incorporated into the practice guideline. The gi dsg makes the following recommendations: To improve survival, a platinum agent should be included in any combination chemotherapy regimen.Within a combination chemotherapy regimen, oral capecitabine is preferred over intravenous 5-fluorouracil (5fu)-that is, epirubicin-cisplatin-capecitabine is preferred over the prior standard regimen, epirubicin-cisplatin-5fu (ecf).Epirubicin-oxaliplatin-capecitabine (eox) is a reasonable alternative to ecf. The choice between ecf and eox should be based on patient preference.Trastuzumab in combination with cisplatin and a fluoropyrimidine (5fu or oral capecitabine) is recommended for advanced gastric cancer positive for the human epidermal growth factor receptor 2 (her2/neu).

Translation of evidence into funding policy: An overview of guidelines from the Cancer Care Ontario's Program in Evidence-Based Care (PEBC).

e16513 Background: PEBC develops clinical practice guidelines through synthesis of best evidence. Ontario’s universal health insurance program funds cancer therapies based on Ministry of Health and Long-Term Care (MOHLTC) decisions. We evaluated key evidence associated with PEBC recommendations for use of targeted therapies (TT) and MOHLTC drug-funding decisions. Methods: We identified PEBC TT guidelines published before June 1, 2010. Key evidence (KE) supporting recommendations was extracted, prioritized, and associated with funding decisions. When there was more than 1 citation of KE, the following hierarchy was used (i) type: evidence highlighted by authors>published article>abstract; and (ii) level: meta-analysis (MA) or phase 3 RCTs (P3)>phase II trials (P2)>largest sample size. Funding decisions were extracted from MOHLTC documents. Results: For 23 guidelines related to 17 TTs, we identified 43 treatment recommendations; 39 (91%) did and 4 (9%) did not endorse use of the TT. Key evidence cited included 35 MA/P3 (81%) and 8 P2 trials (19%); coming from published articles (40/43; 93%) and abstracts (3/43; 7%). Key evidence evaluated overall survival (OS) (18/43; 19%); another time-to-event endpoint (TTE) (14/43; 33%) or response rate (RR) (8/43; 19%). Funding decisions and KE are shown in the table. Conclusions: Funding was approved for 74% of PEBC recommendations. Factors trending to association with declined funding are key evidence from P2 trial and/or RR. Further evaluations are required to assess magnitude of benefit and pharmacoeconomics. Key evidence associated with MOHLTC funding decisions for 31 CCO PEBC recommendations endorsing targeted therapy (TT).* Trial design Outcome** Publication status MA/P3 P2 OS+ TTE+ RR+ Article Abstract Recommendations associated with approved funding (n=23) 20 (87%) 3 (13%) 13 (57%) 8 (35%) 2 (8%) 22 (96%) 1 (4%) Recommendations associated with declined funding (n=8) 6 (75%) 2 (25%) 3 (38%) 4 (50%) 1 (12%) 6 (75%) 2 (25%) * Data for 31 cases reviewed by MOHLTC; 8 remain under review. ** One outcome is shown for each recommendation. In the absence of improved OS, recommendations are classified as having improved TTE or RR.

Follow-Up for Women after Treatment for Cervical Cancer

What is the most appropriate follow-up strategy for patients with cervical cancer who are clinically disease-free after receiving primary treatment? For women with cervical cancer who have been treated with curative intent, follow-up includes identification of complications related to treatment and intervention in the event of recurrent disease. Most women who recur with cervical cancer are not curable; however, early identification of recurrence can alter disease management or treatment-planning options, and for those with a central pelvic recurrence and no evidence of distant disease, there is a potential for cure with additional therapy. Follow-up protocols in this population are variable, using a number of tests at a variety of intervals with questionable outcomes. Outcomes of interest included recurrence, survival, and quality of life. The Gynecology Cancer Disease Site Group (DSG) conducted a systematic review of the literature and a narrative review of emerging clinical issues to inform the most appropriate follow-up strategy for patients with cervical cancer. The evidence was insufficient to specify a clinically useful recommended follow-up schedule, and therefore, the expert consensus opinion of the Gynecology Cancer DSG was used to develop recommendations on patient surveillance. The resulting recommendations were reviewed and approved by the Gynecology Cancer DSG and by the Program in Evidence-Based Care Report Approval Panel. An external review by Ontario practitioners completed the final phase of the review process. Feedback from all parties was incorporated to create the final practice guideline. The systematic review of the literature identified seventeen retrospective studies. The Gynecology Cancer DSG used a consensus process to develop recommendations based on the available evidence from the systematic review, the narrative review, and the collective clinical experience and judgment of the DSG members. The recommendations in this practice guideline are based on the expert consensus opinion of the Gynecology Cancer DSG, informed by evidence from retrospective studies. These are some general features of an appropriate follow-up strategy: 1. At a minimum, follow-up visits with a complete physical examination, including a pelvic-rectal exam and a patient history, should be conducted by a physician experienced in the surveillance of cancer patients. 2. There is little evidence to suggest that vaginal vault cytology adds significantly to the clinical exam in detecting early disease recurrence. 3. Routine use of various other radiologic or biologic follow-up investigations in asymptomatic patients is not advocated, because the role of those investigations has yet to be evaluated in a definitive manner. 4. A reasonable follow-up schedule involves follow-up visits every 3-4 months in the first 2 years and every 6-12 months in years 3-5. Patients should return to annual population-based general physical and pelvic examinations after 5 years of recurrence-free follow-up.

Epidermal growth factor receptor targeted therapy in stages III and IV head and neck cancer.

Epidermal growth factor receptor targeted therapy in stages III and IV head and neck cancer.

Cancer Diagnostic Assessment Programs: Standards for the Organization of Care in Ontario

Improving access to better, more efficient, and rapid cancer diagnosis is a necessary component of a high-quality cancer system. How diagnostic services ought to be organized, structured, and evaluated is less understood and studied. Our objective was to address this gap. As a quality initiative of Cancer Care Ontario's Program in Evidence-Based Care, the Diagnostic Assessment Standards Panel, with representation from clinical oncology experts, institutional and clinical administrative leaders, health service researchers, and methodologists, conducted a systematic review and a targeted environmental scan of the unpublished literature. Standards were developed based on expert consensus opinion informed by the identified evidence. Through external review, clinicians and administrators across Ontario were given the opportunity to provide feedback. The body of evidence consists of thirty-five published studies and fifteen unpublished guidance documents. The evidence and consensus opinion consistently favoured an organized, centralized system with multidisciplinary team membership as the optimal approach for the delivery of diagnostic cancer assessment services. Independent external stakeholders agreed (with higher mean values, maximum 5, indicating stronger agreement) that DAP standards are needed (mean: 4.6), that standards should be formally approved (mean: 4.3), and importantly, that standards reflect an effective approach that will lead to quality improvements in the cancer system (mean: 4.5) and in patient care (mean: 4.3). Based on the best available evidence, standards for the organization of DAPS are offered. There is clear need to integrate formal and comprehensive evaluation strategies with the implementation of the standards to advance this field.

Clinician–Patient Communication: Evidence-Based Recommendations to Guide Practice in Cancer

To develop recommendations for effective communication between cancer health care providers and patients based on a systematic review of methods of clinician-patient communication that may affect patient outcomes associated with distress at critical points in the course of cancer care. A systematic review of the literature was conducted, and evidence-based recommendations were formulated to guide clinician-patient communication in cancer care. A formal external review was conducted to validate the relevance of these recommendations. Recommendations for communication in cancer care are presented, based on guidelines from the Australian National Breast Cancer Centre and the Australian National Cancer Control Initiative,an updated systematic review of the research evidence, and a consensus by the Clinician-Patient Communications Working Panel of the Program in Evidence-Based Care of Cancer Care Ontario. The recommendations were sent to 110 Ontario practitioners for external review: 33 responded (30% response rate). Most of these respondents (87%) agreed with the draft recommendations and approved of their use as a practice guideline (90%). A condensed version of the recommendations, including 10 key points, was also created. There is evidence to support general clinician-patient communication approaches, although the preferences of cancer patients regarding such communication exhibit individual and cultural variability. Recommendations are provided, based on evidence, the consensus of an expert panel, and feedback from a survey of external practitioners. Evidence evaluating the role of decision aids and strategies to facilitate better communication is inconsistent, although such tools may be of value for some patients.

Poster — Wed Eve—03: Delivering Brachytherapy for Cervical Cancer: Organizational and Technical Advice to Facilitate Care

Many centres in Ontario are currently starting programs in HDR brachytherapy for cervical cancer. To provide guidance for establishing such programs, an Expert Working Group (EWG) was struck in collaboration with Cancer Care Ontario's Program in Evidence Based Care (PEBC) to examine the technical and organizational requirements for high‐quality delivery of HDR to women with cervical cancer. All components of brachytherapy were considered including required facilities, imaging technologies, team composition and qualifications, treatment planning, caseload/volumes, documentation, and quality control. Organizational recommendations for each of these areas were developed based on evidence gathered through an environmental scan and a systematic search of the literature. As such, they represent a synthesis, with adaptation to the environment in Ontario, of the most recent, comprehensive, and relevant existing documents combined with expert consensus opinion of the panel. Although designed for Ontario, these recommendations are generally applicable to other jurisdictions looking to put in place new brachytherapy services, or to improve existing ones. A particular focus of the EWG was the examination of evidence supporting the use of different imaging technologies for guiding and planning HDR brachytherapy of the cervix. Imaging is a key component of this technique and optimizing its use may improve both the quality of brachytherapy and treatment outcomes. We present the first systematic review of imaging for cervical brachytherapy. Although the studies reviewed varied in design and quality, all favoured planning with volumetric 3D imaging over conventional 2D imaging.

Assessing compliance with practice treatment guidelines by treatment centers and the reasons for noncompliance

e17506 Background: Cancer Care Ontario (CCO) is the chief advisor on cancer care to the government of Ontario, a province with a population of more than 12 million. One of the many roles of CCO is to develop evidence based consensus-derived treatment practice guidelines for all major cancer types, through its Program in Evidence-based Care (PEBC). To determine province-wide compliance with these guidelines, a pilot project assessed the proportion of patients with stage III colon cancer (CC) treated in concordance with the corresponding treatment guideline. Initial results are made available to the regional cancer centers (RCC) in the province and to the public through web based Cancer Systems Quality Index (CSQI, http://www.cancercare.on.ca/qualityindex2007/ ). Methods: The guideline (http://www.cancercare.on.ca/pdf/pebc2–29s.pdf) states that patients with resected stage 3 CC will have adjuvant fluoropyrimidine-based chemotherapy within eight weeks of resection. Patients at each of 11 RCC who presented in 2007/2008 with stage III CC and the proportion treated according to the guidelines were identified. Individual charts of those patients who were not treated according to guideline were reviewed to determine the reason. Results: Across eight RCC with complete chart results to date 376 patients with stage 3 CC were identified, 244 (65%, range 47% to 72%) treated in concordance with the guideline, including 13% treated with capecitabine and 6% on clinical trials. The reasons for non-concordance of the 132 remaining cases were: age and co morbid conditions 48 (13%), patient choice 36 (10%), referred for treatment outside the RCC system 16 (4%), stage incorrect and other 32 (9%). Conclusions: Adjuvant chemotherapy treatment of stage III CC at the RCC across the Province of Ontario was concordant with the guideline in the majority of patients, and appropriate clinical reasons for non-compliance were identified. Data from all 11 RCC will be presented along with concordance within the eight-week time frame stated in the guideline . Refinement in province-wide data collection and interpretation will allow results from this pilot to be expanded to other PEBC practice guidelines for dissemination through the CSQI. No significant financial relationships to disclose.

Adjuvant Hormonal Therapy for Stage I Endometrial Cancer

What is the role of hormonal therapy as adjuvant therapy in patients with stage i endometrial cancer? There is little consensus on the role of adjuvant treatment for patients with stage i endometrial cancer. Although the use of hormonal therapy has been established in advanced disease, less agreement has emerged concerning the benefits of adjuvant hormonal therapy for patients with early-stage disease. The objective of the present evidence series was to review the existing literature on the role of hormonal therapy as adjuvant therapy in patients with stage i endometrial cancer. REPORTS WERE SOUGHT THAT INCLUDED AT LEAST ONE OF THE FOLLOWING OUTCOMES: overall survival, disease-free survival, recurrence (local, or distant, or both), adverse effects, and quality of life. Because of the potential for long-term adverse effects with adjuvant hormonal treatment in this patient population, especially with regard to thromboembolic or cardiovascular events, the rates of non-cancer-related death were also of interest. The medline, embase, and Cochrane Library databases were systematically searched for randomized controlled trials, practice guidelines, systematic reviews, and meta-analyses. The resulting evidence informed the development of the clinical practice guideline. The systematic review with meta-analyses and practice guideline were approved by the Report Approval Panel of the Program in Evidence-Based Care, and by the Gynecology Cancer Disease Site Group (DSG). Nine randomized trials and one published meta-analysis comparing adjuvant hormonal therapy with no adjuvant therapy in women with stage i endometrial cancer constituted the evidence base. One trial reported a statistically significant survival benefit with adjuvant progestogen as compared with no further treatment (97% vs. 69%, p < 0.001). In that trial, the treatment group had a higher number of patients with less myometrial invasion, and a lower number of patients with advanced-stage disease. These differences in baseline characteristics between the randomized groups were considered to be clinically important. In addition, the results of that trial were not consistent with those of other trials, and the trial was a source of statistical heterogeneity when data were pooled across trials. In two of the nine randomized trials, statistically significant recurrence-free benefits were detected with adjuvant hormonal therapy as compared with no further therapy. In one trial, the difference between the rates of recurrence was 16%; however, the methodologic concerns related to that that trial limited its relevance. In the other trial, the difference between the rates of recurrence was 5%. In that trial, patients were at a high risk of recurrence. None of the remaining seven randomized trials reported any significant difference in recurrence rates between treatment groups. The meta-analysis identified in the literature detected no statistically significant recurrence-free or overall survival benefit associated with adjuvant hormonal therapy as compared with no adjuvant therapy [odds ratio (or): 1.05; 95% confidence interval (ci): 0.88 to 1.24). Those results are consistent with the results of the meta-analysis in the present report, which included an additional two trials (or: 1.10; 95% ci: 0.91 to 1.34). This clinical recommendation applies to women with newly diagnosed stage i endometrial cancer. The available evidence does not demonstrate any benefit for adjuvant hormonal therapy. The use of hormonal therapy is not recommended as adjuvant treatment for patients with stage i endometrial cancer.

Biochemotherapy for the Treatment of Metastatic Malignant Melanoma: A Clinical Practice Guideline

Questions What is the role of biochemotherapy in the treatment of metastatic malignant melanoma? For the purposes of this report, “biochemotherapy” is defined as a therapeutic regimen that includes, at a minimum, chemotherapy (either single agent or combination) and interleukin-2. What are the adverse effects and effects on quality of life using biochemotherapy as a treatment option? Perspectives While early detection, appropriate surgery and, in some cases, adjuvant therapy have improved outcomes, at least one third of patients with early-stage melanoma will develop metastases. Recently, in an effort to potentially maximize outcomes, the combination of chemotherapy and immunotherapy (biochemotherapy) has been evaluated The level of interest that this approach has generated, particularly with reference to the apparently high response rates seen in this otherwise devastating illness, was sufficient to merit closer examination of this approach by the Melanoma Disease Site Group (DSG) of Cancer Care Ontario’s Program in Evidence-based Care (PEBC). Outcomes Outcomes of interest include response rate, disease-free survival, overall survival, quality of life, and incidence of grade 3 and 4 toxicities. Methodology Evidence was selected and reviewed by three members of the Program in Evidence-based Care Melanoma Disease Site Group (DSG) and by two methodologists. The present practice guideline report has been reviewed and approved by the Melanoma DSG, compromised of medical and radiation oncologists, surgeons and dermatologists. External review by Ontario practitioners was obtained through a mailed survey, the results of which were incorporated into the practice guideline. Final approval of the original guideline report was obtained from the Program in Evidence-based Care Report Approval Panel (RAP). Results Clinical recommendations were drafted, based on the evidence identified through a systematic review. This practice guideline report with draft recommendations was mailed to Ontario practitioners for external review and to the Report Approval Panel, Feedback from both groups were incorporated into this report to create the final practice guideline. Practice Guideline The recommendations apply to adult patients with metastatic malignant melanoma. Due to the inconsistent results of the available studies with regard to benefit (response, time-to-progression, and survival) and consistently high toxicity rates, biochemotherapy is not recommended for the treatment of metastatic melanoma.

The delivery of high-dose-rate brachytherapy for cervix cancer: a systematic review. A quality initiative of the program in evidence-based care, Cancer Care Ontario

The delivery of high-dose-rate brachytherapy for cervix cancer: a systematic review. A quality initiative of the program in evidence-based care, Cancer Care Ontario

Cancer Care Ontario and American Society of Clinical Oncology Adjuvant Chemotherapy and Adjuvant Radiation Therapy for Stages I-IIIA Resectable Non–Small-Cell Lung Cancer Guideline

To determine the role of adjuvant chemotherapy and radiation therapy in patients with completely resected stage IA-IIIA non-small-cell lung cancer (NSCLC). The Cancer Care Ontario Program in Evidence-Based Care and the American Society of Clinical Oncology convened a Joint Expert Panel in August 2006 to review the evidence and draft recommendations for these therapies. Available data support the use of adjuvant cisplatin-based chemotherapy in completely resected NSCLC; however, the strength of the data and consequent recommendations vary by disease stage. Adjuvant radiation therapy appears detrimental to survival in stages IB and II, with a possible modest benefit in stage IIIA. Adjuvant cisplatin-based chemotherapy is recommended for routine use in patients with stages IIA, IIB, and IIIA disease. Although there has been a statistically significant overall survival benefit seen in several randomized clinical trials (RCTs) enrolling a range of people with completely resected NSCLC, results of subset analyses for patient populations with stage IB disease were not significant, and adjuvant chemotherapy in stage IB disease is not currently recommended for routine use. To date, very few patients with stage IA NSCLC have been enrolled onto RCTs of adjuvant therapy; adjuvant chemotherapy is not recommended in these cases. Evidence from RCTs demonstrates a survival detriment for adjuvant radiotherapy with limited evidence for a reduction in local recurrence. Adjuvant radiation therapy appears detrimental to survival in stage IB and II, and may possibly confer a modest benefit in stage IIIA.