Cultivating a communities of practice for colorectal cancer screening in northern Canada.

BACKGROUND: Knowledge management systems such as a Communities of Practice (CoP) can improve healthcare processes but are challenging in complex multidisciplinary systems, and guidance on methods to establish a CoP are needed. This case illustrates the use of early stakeholder engagement and Nominal Group Technique (NGT) to cultivate a CoP in a complex multidisciplinary system: colorectal cancer screening in northern Canada. METHODS: Stakeholders in the Northwest Territories, Canada were recruited and co-designed a workshop with authors to introduce CoP concepts and identify priorities. At the workshop NGT was used to identify and prioritize gaps in process, practice, and evidence for the CoP to focus on. An anonymous polling system was used to obtain workshop participants' feedback on the process. RESULTS: The co-design process integrated stakeholders' perspectives in developing a workshop. Using NGT, the gap analysis identified 23 areas of focus for the CoP, among which, the highest priorities were identified: communication between clinicians and with patients, and identification of screening eligibility in the electronic medical record. Participants found the process to be useful, educational, and interesting. There was unanimous interest in moving forward with developing a CoP. CONCLUSION: A co-designed workshop and NGT were useful in laying the foundation for a CoP in a complex multidisciplinary environment. POLICY STATEMENT: This case shows the utility of a co-designed workshop and NGT in starting a CoP: a knowledge management system that would provide critical insight into colorectal cancer screening policies for the region.

Implementing a one-day testing model improves timeliness of workup for patients with lung cancer.

Background: Patients with lung cancer often experience stressful delays throughout the diagnostic phase of care. To address that situation, our multidisciplinary team created a "Navigation Day," during which patients partake in a single-day visit that comprises nurse-led teaching, social work, smoking cessation counselling, symptom control, and dedicated test slots for integrated positron-emission tomography and computed tomography (pet/ct), pulmonary function tests (pfts), and magnetic resonance imaging (mri) of the brain. We evaluated the effects of that program on wait times and patient satisfaction. Methods: Patients with a suspicion of lung cancer on chest ct imaging referred during 3 time periods were reviewed: 1 year before launch of the Navigation Day, 1 year post-launch, and 2 years post-launch. Patients were further stratified according to concordance of their test date with a Navigation Day date. Mean wait times for pet/ct, pfts, and mri brain were calculated for each group. Patient satisfaction was measured using a standardized provincial survey. The Student t-test and analysis of variance were used to assess for significance. Results: After implementation, mean wait times in the first year improved to 9.2 days from 15.5 days for pet/ct (p < 0.0001), to 9.6 days from 15.7 days for pfts (p < 0.0001), and to 10.2 days from 16.0 days for mri brain (p < 0.0001). Patients who used a dedicated test slot experienced the shortest wait times, at 5.8 days for pet/ct, 5.8 days for pfts, and 6.3 days for mri brain (p < 0.0001). Those improvements were sustained at 2 years post-launch. Patient satisfaction in the categories of assistance, emotional support, and clarity remained high post-launch. Conclusions: Navigation Day significantly improved the timeliness of diagnostic testing services in patients with suspected lung cancer.

The effect of surgery report cards on improving radical prostatectomy quality: the SuRep study protocol.

BACKGROUND: The goal of radical prostatectomy is to achieve the optimal balance between complete cancer removal and preserving a patient's urinary and sexual function. Performing a wider excision of peri-prostatic tissue helps achieve negative surgical margins, but can compromise urinary and sexual function. Alternatively, sparing peri-prostatic tissue to maintain functional outcomes may result in an increased risk of cancer recurrence. The objective of this study is to determine the effect of providing surgeons with detailed information about their patient outcomes through a surgical report card. METHODS: We propose a prospective cohort quasi-experimental study. The intervention is the provision of feedback to prostate cancer surgeons via surgical report cards. These report cards will be distributed every 3 months by email and will present surgeons with detailed information, including urinary function, erectile function, and surgical margin outcomes of their patients compared to patients treated by other de-identified surgeons in the study. For the first 12 months of the study, pre-operative, 6-month, and 12-month patient data will be collected but there will be no report cards distributed to surgeons. This will form the pre-feedback cohort. After the pre-feedback cohort has completed accrual, surgeons will receive quarterly report cards. Patients treated after the provision of report cards will comprise the post-feedback cohort. The primary comparison will be post-operative function of the pre-feedback cohort vs. post-feedback cohort. The secondary comparison will be the proportion of patients with positive surgical margins in the two cohorts. Outcomes will be stratified or case-mix adjusted, as appropriate. Assuming a baseline potency of 20% and a baseline continence of 70%, 292 patients will be required for 80% power at an alpha of 5% to detect a 10% improvement in functional outcomes. Assuming 30% of patients may be lost to follow-up, a minimum sample size of 210 patients is required in the pre-feedback cohort and 210 patients in the post-feedback cohort. DISCUSSION: The findings from this study will have an immediate impact on surgeon self-evaluation and we hypothesize surgical report cards will result in improved overall outcomes of men treated with radical prostatectomy.

Regional process redesign of lung cancer care: a learning health system pilot project.

BACKGROUND: The Ottawa Hospital (toh) defined delay to timely lung cancer care as a system design problem. Recognizing the patient need for an integrated journey and the need for dynamic alignment of providers, toh used a learning health system (lhs) vision to redesign regional diagnostic processes. A lhs is driven by feedback utilizing operational and clinical information to drive system optimization and innovation. An essential component of a lhs is a collaborative platform that provides connectivity across silos, organizations, and professions. METHODS: To operationalize a lhs, we developed the Ottawa Health Transformation Model (ohtm) as a consensus approach that addresses process barriers, resistance to change, and conflicting priorities. A regional Community of Practice (cop) was established to engage stakeholders, and a dedicated transformation team supported process improvements and implementation. RESULTS: The project operationalized the lung cancer diagnostic pathway and optimized patient flow from referral to initiation of treatment. Twelve major processes in referral, review, diagnostics, assessment, triage, and consult were redesigned. The Ottawa Hospital now provides a diagnosis to 80% of referrals within the provincial target of 28 days. The median patient journey from referral to initial treatment decreased by 48% from 92 to 47 days. CONCLUSIONS: The initiative optimized regional integration from referral to initial treatment. Use of a lhs lens enabled the creation of a system that is standardized to best practice and open to ongoing innovation. Continued transformation initiatives across the continuum of care are needed to incorporate best practice and optimize delivery systems for regional populations.

OV21/PETROC: a randomized Gynecologic Cancer Intergroup phase II study of intraperitoneal versus intravenous chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer.

Background: The purpose of this multistage, adaptively, designed randomized phase II study was to evaluate the role of intraperitoneal (i.p.) chemotherapy following neoadjuvant chemotherapy (NACT) and optimal debulking surgery in women with epithelial ovarian cancer (EOC). Patients and methods: We carried out a multicenter, two-stage, phase II trial. Eligible patients with stage IIB-IVA EOC treated with platinum-based intravenous (i.v.) NACT followed by optimal (<1 cm) debulking surgery were randomized to one of the three treatment arms: (i) i.v. carboplatin/paclitaxel, (ii) i.p. cisplatin plus i.v./i.p. paclitaxel, or (iii) i.p. carboplatin plus i.v./i.p. paclitaxel. The primary end point was 9-month progressive disease rate (PD9). Secondary end points included progression-free survival (PFS), overall survival (OS), toxicity, and quality of life (QOL). Results: Between 2009 and 2015, 275 patients were randomized; i.p. cisplatin containing arm did not progress beyond the first stage of the study after failing to meet the pre-set superiority rule. The final analysis compared i.v. carboplatin/paclitaxel (n = 101) with i.p. carboplatin, i.v./i.p. paclitaxel (n = 102). The intention to treat PD9 was lower in the i.p. carboplatin arm compared with the i.v. carboplatin arm: 24.5% (95% CI 16.2% to 32.9%) versus 38.6% (95% CI 29.1% to 48.1%) P = 0.065. The study was underpowered to detect differences in PFS: HR PFS 0.82 (95% CI 0.57-1.17); P = 0.27 and OS HR 0.80 (95% CI 0.47-1.35) P = 0.40. The i.p. carboplatin-based regimen was well tolerated with no reduction in QOL or increase in toxicity compared with i.v. administration alone. Conclusion: In women with stage IIIC or IVA EOC treated with NACT and optimal debulking surgery, i.p. carboplatin-based chemotherapy is well tolerated and associated with an improved PD9 compared with i.v. carboplatin-based chemotherapy. Clinical trial number: clinicaltrials.gov, NCT01622543.

The cost-effectiveness of bevacizumab for the treatment of advanced ovarian cancer in Canada.

BACKGROUND: The overall survival (os) analysis of the icon7 trial demonstrated that frontline ovarian cancer patients with a high risk of progression (stage iii suboptimally debulked, and stage iii or iv with unresectable disease) benefited from the addition of bevacizumab to standard chemotherapy compared with standard chemotherapy alone. The objective of the present study was to investigate the cost-effectiveness, from a Canadian publicly funded perspective, of adding bevacizumab to frontline treatment of ovarian cancer at high risk of progression. METHODS: An area-under-the-curve, Markov-structured model was used to estimate the cost-effectiveness of the treatments. Long-term progression-free survival (pfs) and os were extracted from the icon7 trial (subgroup at high risk of relapse) and extrapolated by parametric time-to-event functions over a time horizon of 10 years. Canadian pfs health state utility values were obtained from the EQ-5D (EuroQoL Group, Rotterdam, Netherlands) questionnaires in the icon7 high-risk patient population. Canadian post-progression utility values were consistent with those for other gynecologic cancers. Cost inputs were informed by public sources. An annual 5% efficacy and cost discount rate was applied. A probabilistic sensitivity analysis and one-way sensitivity analyses were conducted. RESULTS: Ovarian cancer patients at high risk of progression receiving bevacizumab plus standard chemotherapy experienced a mean incremental quality-adjusted life year (qaly) gain of 0.374 years. At an additional cost of $35,901.54, the incremental cost-effectiveness ratio (icer) for the addition of bevacizumab to standard chemotherapy, relative to standard chemotherapy alone, was $95,942 per qaly. CONCLUSIONS: No formal health technology assessment willingness-to-pay threshold exists in Canada. However, at a threshold of $100,000 per qaly, bevacizumab in addition to chemotherapy is a cost-effective alternative for ovarian cancer patients who are at high risk of progression (stage iii suboptimally debulked, and stage iii or iv with unresectable disease). Using the $100,000 per qaly threshold in a probabilistic sensitivity analysis, it was determined that, compared with standard chemotherapy, the addition of bevacizumab to chemotherapy is cost-effective in 56% of tested scenarios.

The optimal organization of gynecologic oncology services: a systematic review.

BACKGROUND: A system-level organizational guideline for gynecologic oncology was identified by a provincial cancer agency as a key priority based on input from stakeholders, data showing more limited availability of multidisciplinary or specialist care in lower-volume than in higher-volume hospitals in the relevant jurisdiction, and variable rates of staging for ovarian and endometrial cancer patients. METHODS: A systematic review assessed the relationship of the organization of gynecologic oncology services with patient survival and surgical outcomes. The electronic databases medline and embase (ovid: 1996 through 9 January 2015) were searched using terms related to gynecologic malignancies combined with organization of services, patterns of care, and various facility and physician characteristics. Outcomes of interest included overall or disease-specific survival, short-term survival, adequate staging, and degree of cytoreduction or optimal cytoreduction (or both) for ovarian cancer patients by hospital or physician type, and rate of discrepancy in initial diagnoses and intraoperative consultation between non-specialist pathologists and gyne-oncology-specialist pathologists. RESULTS: One systematic review and sixteen additional primary studies met the inclusion criteria. The evidence base as a whole was judged to be of lower quality; however, a trend toward improved outcomes with centralization of gynecologic oncology was found, particularly with respect to the gynecologic oncology care of patients with advanced-stage ovarian cancer. CONCLUSIONS: Improvements in outcomes with centralization of gynecologic oncology services can be attributed to a number of factors, including access to specialist care and multidisciplinary team management. Findings of this systematic review should be used with caution because of the limitations of the evidence base; however, an expert consensus process made it possible to create recommendations for implementation.

Systemic therapy for recurrent, persistent, or metastatic cervical cancer: a clinical practice guideline.

BACKGROUND: Systemic therapy options are needed for women with recurrent, metastatic, or persistent cervical cancer. This systematic review and clinical practice guideline were developed to address that need, and to update a 2007 guideline from Cancer Care Ontario's Program in Evidence-Based Care. METHODS: The literature between 2006 and April 2014 in the medline and embase databases, the Cochrane Database of Systematic Reviews (Issue 4, 2014), the Cochrane Central Register of Controlled Trials (Issue 3, 2014), relevant guideline databases, and conference proceedings of the American Society of Clinical Oncology (2007-2013) was searched. A working group developed draft guidelines and incorporated comments and feedback from internal and external reviewers. RESULTS: Four phase iii randomized controlled trials met the inclusion criteria for the review and provided the basis for draft recommendations. Feedback was obtained from Ontario practitioners and others abroad, which led to modifications to the draft recommendations. Three key recommendations were developed. CONCLUSIONS: The working group concluded that all patients should be offered the opportunity to participate in appropriate randomized clinical trials. Cisplatin-paclitaxel, cisplatin-vinorelbine, cisplatin-gemcitabine, and cisplatin-topotecan are recommended combinations for this patient population. The substitution of carboplatin for cisplatin in the foregoing combinations can also be recommended because carboplatin is associated with fewer adverse effects and greater ease of administration. Selection of combination chemotherapy will depend on the toxicity profile, patient preference, and other factors. Finally, bevacizumab in combination with cisplatin-paclitaxel or carboplatin-paclitaxel is recommended for a specific subset of the target population as outlined in Gynecologic Oncology Group study 0240.

Exploring a "community of practice" methodology as a regional platform for large-scale collaboration in cancer surgery-the Ottawa approach.

Pressing challenges have forced health care providers to rethink traditional silos and professional boundaries. Communities of practice (cops) have been identified as a means to share knowledge across silos and boundaries. However, clarity sufficient to enable their easy and uniform reproducibility is lacking, leading to a gap between cop conceptualization and implementation. This paper explores a cop structure and outlines a framework that is adaptable, measurable, and implementable across health disciplines in a regional cancer surgery program.

Piloting a regional collaborative in cancer surgery using a "community of practice" model.

BACKGROUND: Patients requiring assessment for cancer surgery encounter a complex series of steps in their cancer journey. Further complicating the process is the fact that care is often delivered in a fragmented, silo-based system. Isolated strategies to improve cancer outcomes within those systems have had inconsistent results. METHODS: A regional quality improvement collaborative was developed based on a community of practice (cop) platform, a hub-and-spoke infrastructure, and a regional steering committee linking cop improvement projects with affiliated hospitals and their strategic priorities. The cop provided an avenue for multidisciplinary teams to collect and compare their performance data and to institute regional standards through literature review, discussion, and consensus. Regional interdisciplinary teams developed a set of quality indicators linked to mutually agreed-upon care standards. A limited regional database supported feedback about performance against both provincial and regional standards. RESULTS: The cop approach helped to develop a multihospital collaboration that facilitated care quality improvements on a regional scale, with clinical outcomes of the improvements able to be measured. The 9 participating hospitals delivered cancer surgery in the specific disease sites according to practitioner-developed and provincially- or regionally-generated care standards and clinical pathways. Compliance with provincial evidence-based clinical guidelines improved (20% increase in 2010-2011 compared with 2006-2007). Other significant improvements included standardization and implementation of regional perioperative pathways in breast, colorectal, and prostate cancer disease sites; rectal cancer surgery centralization; increased use of sentinel lymph node biopsies in breast cancer surgery; and decreased positive surgical margin rates in prostate cancer. CONCLUSIONS: Improved quality is likely a result of diverse confounding factors. The deliberately cultivated multihospital multidisciplinary cops have contributed to positive structural and functional change in cancer surgery in the region. This regional cop model has the potential to play an important role in the development of successful collaborations in care quality improvement.

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

QUESTIONS: 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? PERSPECTIVES: 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: 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. METHODOLOGY: 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. 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.

Follow-up for women after treatment for cervical cancer.

QUESTION: What is the most appropriate follow-up strategy for patients with cervical cancer who are clinically disease-free after receiving primary treatment? PERSPECTIVES: 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: Outcomes of interest included recurrence, survival, and quality of life. METHODOLOGY: 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. RESULTS: 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. PRACTICE GUIDELINE: 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.

Adjuvant hormonal therapy for stage I endometrial cancer.

QUESTION: What is the role of hormonal therapy as adjuvant therapy in patients with stage i endometrial cancer? PERSPECTIVES: 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. OUTCOMES: 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. METHODOLOGY: 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). RESULTS: 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). TARGET POPULATION: This clinical recommendation applies to women with newly diagnosed stage i endometrial cancer. RECOMMENDATION: 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.

Prospective evaluation of weekly topotecan in recurrent platinum-resistant epithelial ovarian cancer.

Topotecan administered on a weekly basis has been reported to possess antineoplastic activities with lower toxicities than the standard 5-day regimen every 3 weeks. We studied the activity of weekly topotecan regimen in recurrent platinum-resistant epithelial ovarian cancer patients. Ovarian cancer patients with documented platinum-resistant recurrences were treated with weekly intravenous topotecan (4 mg/m(2)) on days 1, 8, and 15 on a 28-day cycle. Prospective data collection included patients' demographics together with disease- and treatment-related toxicities. Responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) and CA125 criteria. Progression-free survival and overall survival time from commencement of weekly treatment were estimated using the Kaplan-Meier method. All P values less than 0.05 were considered to be statistically significant. Twenty-two patients were treated. Weekly topotecan was used most commonly as third-line chemotherapy (range 1-5). A total of 244 weekly treatments were administered, with a median of 12 weekly treatments per patient. Two patients (9%) reported grade 3/4 gastrointestinal and two had grade 3/4 hematologic toxicities respectively. No dose reduction or treatment delay was required. Partial response was observed in two patients (9.1%) and another seven patients (31.8%) showed stable disease. No significant association was observed between best clinical response and patients' initial platinum sensitivity status. The estimated median progression-free survival was 20.9 weeks (95% CI 11.2-30.5) from the start of the weekly regimen. Weekly topotecan is well tolerated in patients with recurrent platinum-resistant ovarian cancer with modest activity.

Optimal chemotherapy treatment for women with recurrent ovarian cancer.

QUESTION: What is the optimal chemotherapy treatment for women with recurrent ovarian cancer who have previously received platinum-based chemotherapy? PERSPECTIVES: Currently, standard primary therapy for advanced disease involves a combination of maximal cytoreductive surgery and chemotherapy with carboplatin plus paclitaxel or with carboplatin alone. Despite initial high response rates, a large proportion of patients relapse, resulting in a therapeutic challenge. Because these patients are not curable, the goal of therapy becomes improvement in both quality and length of life. The search has therefore been to find active agents for women with recurrent disease following platinum-based chemotherapy. OUTCOMES: Outcomes of interest included any combination of tumour response rate, progression-free survival, overall survival, adverse events, and quality of life. METHODOLOGY: The MEDLINE, EMBASE, and Cochrane Library databases were systematically searched for primary articles and practice guidelines. The resulting evidence informed the development of clinical practice recommendations. The systematic review and recommendations were approved by the Report Approval Panel of the Program in Evidence-Based Care, and by the Gynecology Cancer Disease Site Group (DSG). The practice guideline was externally reviewed by a sample of practitioners from Ontario, Canada. RESULTS: Thirteen randomized trials compared various chemotherapy regimens for patients with recurrent ovarian cancer. In five of the thirteen trials in which 100% of patients were considered sensitive to platinum-containing chemotherapy, further platinum-based combination chemotherapy significantly improved response rates (two trials), progression-free survival (four trials), and overall survival (three trials) when compared with single-agent chemotherapy involving carboplatin or paclitaxel. Only two of these randomized trials compared the same chemotherapy regimens: carboplatin alone versus the combination of carboplatin and paclitaxel. Both trials were consistent in reporting improved survival outcomes with the combination of carboplatin and paclitaxel. In one trial, the combination of carboplatin and gemcitabine resulted in significantly higher response rates and improved progression-free survival when compared with carboplatin alone. Median survival with carboplatin alone ranged from 17 months to 24 months in four trials. In eight of the thirteen trials in which 35%-100% of patients had platinum-refractory or -resistant disease, one trial reported a statistically significant 2-month improvement in overall survival with liposomal doxorubicin as compared with topotecan (15 months vs. 13 months, p = 0.038; hazard ratio: 1.23; 95% confidence interval: 1.01 to 1.50). In that trial, because of the limited clinical benefit and the unusual finding that a survival difference emerged only after a year of treatment with no corresponding improvement in the rate of response or of progression-free survival, the authors concluded that further confirmation by results from randomized trials were needed to establish the superiority of one agent over another in their trial. In one trial, topotecan was superior to treosulphan in patient progression-free survival by a span of approximately 2 months (5.4 months vs. 3.0 months, p < 0.001). Toxicity was reported in all of the randomized trials, and although data on adverse events varied by treatment regimen, the observed adverse events correlated with known toxicity profiles. As expected, combination chemotherapy was associated with higher rates of adverse events. TARGET POPULATION: This clinical recommendation applies to women with recurrent epithelial ovarian cancer who have previously received platinum-based chemotherapy. Of specific interest are women who have previously shown sensitivity to platinum therapy and those who previously were refractory or resistant to platinum-based chemotherapy. As a general categorization within what is actually a continuum, "platinum sensitivity" refers to disease recurrence 6 months or more after prior platinum-containing chemotherapy, and "platinum resistance" refers to a response to platinum-based chemotherapy followed by relapse less than 6 months after chemotherapy is stopped. "Platinum-refractory disease" refers to a lack of response or to progression while on platinum-based chemotherapy. RECOMMENDATIONS: Although the body of evidence that informs the clinical recommendations is based on randomized trial data, those data are incomplete. Based on the available data and expert consensus opinion, the Gynecology Cancer DSG makes these recommendations: Systemic therapy for recurrent ovarian cancer is not curative. It is therefore recognized that each patient must be individually assessed to determine optimal therapy in terms of recurrence, sensitivity to platinum, toxicity, ease of administration, and patient preference. All suitable patients should be offered the opportunity to participate in randomized trials, if available.In the absence of contraindications, combination platinum-based chemotherapy should be considered for patients with prior sensitivity to platinum-containing chemotherapy. As compared with carboplatin alone, the combination of carboplatin and paclitaxel significantly improved both progression-free and overall survival.If combination platinum-based chemotherapy is not indicated, then a single platinum agent should be considered. Carboplatin has demonstrated efficacy across trials and has a manageable toxicity profile.If a single platinum agent is not being considered, then monotherapy with paclitaxel, topotecan, or pegylated liposomal doxorubicin are seen as reasonable treatment options.Some patients may be repeatedly sensitive to treatment and may benefit from multiple lines of chemotherapy.For patients with platinum-refractory or platinum-resistant disease, the goals of treatment should be to improve quality of life by extending the symptom-free interval, by reducing symptom intensity, and by increasing progression-free interval, and, if possible, to prolong life.With non-platinum agents, monotherapy should be considered because no advantage appears to accrue to the use of non-platinum-containing combination chemotherapy in this group of patients. Single-agent paclitaxel, topotecan, or pegylated liposomal doxorubicin have demonstrated activity in this patient population and are reasonable treatment options.No evidence either supports or refutes the use of more than one line of chemotherapy in patients with platinum-refractory or platinum-resistant recurrence. Many treatment options have shown modest response rates, but their benefits over best supportive care have not been studied in clinical trials.

Chemotherapy for recurrent, metastatic, or persistent cervical cancer: a systematic review.

To determine the front-line chemotherapeutic options for women with recurrent, metastatic, or persistent cervical cancer. The Medline, Embase, and Cochrane Library databases were searched for randomized controlled trials (RCTs) comparing chemotherapy regimens for patients with recurrent, metastatic, or persistent cervical cancer. Studies were included if response rate, survival, toxicity, or quality of life data were reported. Fifteen RCTs were identified. The proportion of patients with prior chemoradiotherapy ranged from 0% to 57%. Four of the 15 RCTs detected significant improvements in overall response with combination cisplatin-based chemotherapy when compared with single-agent cisplatin. One of the 15 RCTs reported a significant median survival advantage with topotecan and cisplatin when compared with single-agent cisplatin (9.4 vs 6.5 months, P = 0.017); 57% of patients in this trial had previous chemoradiotherapy. Significant increases in grade 3 and 4 adverse events, especially severe hematologic toxicities, were detected among patients treated with that combination of chemotherapy. Thus, we conclude that cisplatin and topotecan should be discussed as a reasonable treatment option for appropriate patients who may wish to maximize the response and survival benefits associated with combination chemotherapy. Patients should understand that prior chemoradiotherapy with cisplatin may moderate the benefits observed, and that the relative benefits in response and survival outcomes come at the expense of increased toxicity. The improvement in median survival of 2.9 months represents a novel survival benefit in this difficult-to-treat patient population. Further randomized trials are needed to inform the role of single-agent or combination chemotherapy regimens, particularly in patients with prior chemoradiotherapy.

Omental chemotherapy effects as a prognostic factor in ovarian cancer patients treated with neoadjuvant chemotherapy and delayed primary surgical debulking.

BACKGROUND: We sought to assess the prognostic significance of chemotherapy effect on upper abdominal metastatic disease. METHODS: Retrospective chart reviews were carried out from 1997 to 2005 to identify ovarian cancer patients treated with neoadjuvant chemotherapy. Pathologic examinations of resected omental and ovarian tumors for the presence of chemotherapy effect were performed. Cox proportional hazard models were built to model time to progression and death by using predictor variables of age, tumor grade, amount and location of largest residual disease, and the presence of chemotherapy effects on resected tumors. RESULTS: Sixty-six patients with available slides and clinical information were identified. The presence of omental chemotherapy effects was observed in 58 patients (88%). Identified independent statistically significant predictors for progression-free survival included presence of omental chemotherapy effect (hazard ratio [HR], .38; 95% confidence interval [95% CI], .17-.89; P = .026) and suboptimal tumor residuals in upper abdominal location compared with pelvic location (HR, 2.41; 95% CI, 1.06-5.48; P = .035). The presence of omental chemotherapy effect was the only statistically significant predictor of disease specific survival (HR, .21; 95% CI, .068-.639; P = .006). The estimated median survival for the group with positive omental chemotherapy effect was 84.45 months (95% CI, 69.63-99.28). The corresponding statistic in patients with no observed response to chemotherapy was 31.15 months (95% CI, 21.84-40.47). CONCLUSIONS: Upper abdominal disease location and its response to chemotherapy were independent prognostic factors for progression-free survival. Aggressive upper abdominal debulking procedures are recommended to improve oncologic outcomes.

Use of systemic therapy in women with recurrent ovarian cancer--development of a national clinical practice guideline.

OBJECTIVE: To develop a guidance document concerning the use of systemic therapy for women with recurrent ovarian cancer that would be applicable for the Canadian health care system. This will be done using a standardized systematic review process, guideline evaluation instruments, multi-disciplinary expert consensus opinion and evidence-rating systems. DATA SELECTION: The primary data sources were MEDLINE, National Guideline Clearinghouse and Cochrane Library. METHODS: Clinical practice guidelines, technology assessments, systematic reviews and randomized controlled trials addressing systemic therapy for women with recurrent ovarian cancer were eligible. DATA EXTRACTION: Data was identified and extracted by the methodology team and reviewed by the authors. Results were reviewed and discussed by members of an expert working group comprised of a multidisciplinary and geographic divergent group of practitioners. DATA SYNTHESIS: The existing 7 practice guidelines underwent formal evaluation for quality, currency and content using the AGREE tool. Recommendations with evidence-ratings were developed. This data was used by a pan-Canadian panel in an informal consensus process, which resulted in the initial draft of a guideline. The guideline team reviewed the draft and made further edits to ensure the guideline's appropriateness for a national context. Practitioner feedback was requested from 165 health care providers who treat ovarian cancer from across Canada. Overall response rate was 37% and was very positive. Comments were reviewed and the guideline was edited appropriately. CONCLUSION: The development of a national practice guideline on the use of systemic therapy for recurrent ovarian cancer was feasible using systematic literature review, expert consensus, guideline evaluation instruments, evidence-rating systems, independent internal and external review measures and final approval by a national discipline specific society (GOC). Recommendations for practice are offered.

Histopathologic assessment of chemotherapy effects in epithelial ovarian cancer patients treated with neoadjuvant chemotherapy and delayed primary surgical debulking.

OBJECTIVES: To assess the prognostic significance of pathologic tumour response to neoadjuvant chemotherapy. METHODS: Retrospective chart reviews were carried out from 1997 to 2005 to identify ovarian cancer cases treated with neoadjuvant chemotherapy. Pathologic assessments of the extent of: tumour necrosis, fibrosis, macrophage infiltration, and tumour induced inflammation were graded on an ordinal scale of 0 to 2 (none/minimal, moderate, extensive). All pathology slides were reviewed and graded by one gynecologic pathologist. A composite pathologic tumour response score was calculated by summing all above pathologic assessments for each sample. Cox proportional hazard models were built to model time to clinical progression and death using predictor variables of: age, tumour grade, residual disease, and pathologic tumour response score. All p values less than 0.05 were considered to be statistically significant. RESULTS: Sixty-two cases with available slides for reviews were identified retrospectively. Optimal debulking was achieved in 46 cases (74%). Significant predictors for prolonged progression free survival included: younger age (p=0.05), optimal tumour residual status (p=0.016), and higher composite pathologic tumour response score (HR 0.848, 95% CI 0.742-0.970, p=0.0016). Cox regression modeling revealed only one significant predictive variable of time to disease related death being the composite pathologic tumour response score (HR 0.695, 95% CI=0.515-0.938, p=0.017). CONCLUSION: Pathologic assessments of tumour response to chemotherapy are helpful in determining prognosis and could be used to guide subsequent therapeutic decisions. The proposed composite pathologic tumour response score warrants further studies and validation.