Locoregional management of in-transit metastasis in melanoma: an Ontario Health (Cancer Care Ontario) clinical practice guideline.

Objective: The purpose of this guideline is to provide guidance on appropriate management of satellite and in-transit metastasis (itm) from melanoma. Methods: The guideline was developed by the Program in Evidence-Based Care (pebc) of Ontario Health (Cancer Care Ontario) and the Melanoma Disease Site Group. Recommendations were drafted by a Working Group based on a systematic review of publications in the medline and embase databases. The document underwent patient- and caregiver-specific consultation and was circulated to the Melanoma Disease Site Group and the pebc Report Approval Panel for internal review; the revised document underwent external review. Recommendations: "Minimal itm" is defined as lesions in a location with limited spread (generally 1-4 lesions); the lesions are generally superficial, often clustered together, and surgically resectable. "Moderate itm" is defined as more than 5 lesions covering a wider area, or the rapid development (within weeks) of new in-transit lesions. "Maximal itm" is defined as large-volume disease with multiple (>15-20) 2-3 cm nodules or subcutaneous or deeper lesions over a wide area.■ In patients presenting with minimal itm, complete surgical excision with negative pathologic margins is recommended. In addition to complete surgical resection, adjuvant treatment may be considered.■ In patients presenting with moderate unresectable itm, consider using this approach for localized treatment: intralesional interleukin 2 or talimogene laherparepvec as 1st choice, topical diphenylcyclopropenone as 2nd choice, or radiation therapy as 3rd choice. Evidence is insufficient to recommend intralesional bacille Calmette- Guérin or CO2 laser ablation outside of a research setting.■ In patients presenting with maximal itm confined to an extremity, isolated limb perfusion, isolated limb infusion, or systemic therapy may be considered. In extremely select cases, amputation could be considered as a final option in patients without systemic disease after discussion at a multidisciplinary case conference.■ In cases in which local, regional, or surgical treatments for itm might be ineffective or unable to be performed, or if a patient has systemic metastases at the same time, systemic therapy may be considered.

OCTANE (Ontario-wide Cancer Targeted Nucleic Acid Evaluation): a platform for intraprovincial, national, and international clinical data-sharing.

Cancer is a genetic disease resulting from germline or somatic genetic aberrations. Rapid progress in the field of genomics in recent years is allowing for increased characterization and understanding of the various forms of the disease. The Ontario-wide Cancer Targeted Nucleic Acid Evaluation (octane) clinical trial, open at cancer centres across Ontario, aims to increase access to genomic sequencing of tumours and to facilitate the collection of clinical data related to enrolled patients and their clinical outcomes. The study is designed to assess the clinical utility of next-generation sequencing (ngs) in cancer patient care, including enhancement of treatment options available to patients. A core aim of the study is to encourage collaboration between cancer hospitals within Ontario while also increasing international collaboration in terms of sharing the newly generated data. The single-payer provincial health care system in Ontario provides a unique opportunity to develop a province-wide registry of ngs testing and a repository of genomically characterized, clinically annotated samples. It also provides an important opportunity to use province-wide real-world data to evaluate outcomes and the cost of ngs for patients with advanced cancer. The octane study is attempting to translate knowledge to help deliver precision oncology in a Canadian environment. In this article, we discuss the background to the study and its implementation, current status, and future directions.

Patient indications for Mohs micrographic surgery: a clinical practice guideline.

Objective: The purpose of the present work was to develop evidence-based indications for Mohs micrographic surgery in patients with a diagnosis of skin cancer. Methods: The guideline was developed by Cancer Care Ontario's Program in Evidence-Based Care, together with the Melanoma Disease Site Group and the Surgical Oncology Program, through a systematic review of relevant literature, patient- and caregiver-specific consultation, and internal and external reviews. Recommendation 1: Given a lack of high-quality, comparative evidence, surgery (with postoperative or intraoperative margin assessment) or radiation (for those who are ineligible for surgery) should remain the standard of care for patients with skin cancer. Recommendation 2: Mohs micrographic surgery is recommended for patients with histologically confirmed recurrent basal cell carcinoma of the face and is appropriate for primary basal cell carcinomas of the face that are larger than 1 cm, have aggressive histology, or are located on the H zone of the face. Recommendation 3: Mohs micrographic surgery should be performed by physicians who have completed a degree in medicine or equivalent, including a Royal College of Physicians and Surgeons of Canada Specialist Certificate or equivalent, and have received advanced training in Mohs micrographic surgery.

A Population-based Study of Survival Impact of New Targeted and Immune-based Therapies for Metastatic or Unresectable Melanoma.

AIMS: New targeted drugs and immune therapies reported since 2010 for metastatic or unresectable melanoma (MM) have shown improved survival in randomised trials. We studied the uptake of these new drugs and their impact on population-based survival. MATERIALS AND METHODS: This was a retrospective, population-based cohort study of all patients treated for MM in Ontario 2007-2015. Provincial administrative sources covering the whole population identified palliative systemic therapy, radiotherapy and metastasis surgery. Temporal trends in utilisation and survival were investigated, as was survival of treatments predefined as 'new drugs' (BRAF or MEK inhibitors, anti-CTLA4 and anti-PD-1 antibodies). RESULTS: We identified 2793 treated MM patients. First treatment was systemic therapy (46%), radiotherapy (41%) and metastasis surgery (14%). Systemic treatment increased from 53% of patients (2007) to 75% (2015). New drug treatments increased from <6% of known first-line regimens in 2007 to 82% in 2015. One and 2 year overall survival was 28% and 15%, respectively, for all MM 2007-2009, rising to 46% and 35% for 2014-2015 (adjusted hazard ratio 0.56, 95% confidence interval 0.49-0.63, P < 0.0001). Survival gains were observed primarily among those cases initially treated with systemic therapy, which became dominated by the use of new drugs over the study period (2 year overall survival 16% 2007-2009 versus 44% 2014-2015; adjusted hazard ratio 0.46, 95% confidence interval 0.38-0.56, P < 0.0001). CONCLUSIONS: Utilisation of new targeted drugs and immune therapies for MM has increased considerably in routine practice 2007-2015. Consistent with the results of clinical trials, adoption was associated with substantial increases in survival of patients in the general population.

The population benefit of evidence-based radiotherapy: 5-Year local control and overall survival benefits.

BACKGROUND: To describe the population benefit of radiotherapy in a high-income setting if evidence-based guidelines were routinely followed. METHODS: Australian decision tree models were utilized. Radiotherapy alone (RT) benefit was defined as the absolute proportional benefit of radiotherapy compared with no treatment for radical indications, and of radiotherapy over surgery alone for adjuvant indications. Chemoradiotherapy (CRT) benefit was the absolute incremental benefit of concurrent chemoradiotherapy over RT. Five-year local control (LC) and overall survival (OS) benefits were measured. Citation databases were systematically queried for benefit data. Meta-analysis and sensitivity analysis were performed. FINDINGS: 48% of all cancer patients have indications for radiotherapy, 34% curative and 14% palliative. RT provides 5-year LC benefit in 10.4% of all cancer patients (95% Confidence Interval 9.3, 11.8) and 5-year OS benefit in 2.4% (2.1, 2.7). CRT provides 5-year LC benefit in an additional 0.6% of all cancer patients (0.5, 0.6), and 5-year OS benefit for an additional 0.3% (0.2, 0.4). RT benefit was greatest for head and neck (LC 32%, OS 16%), and cervix (LC 33%, OS 18%). CRT LC benefit was greatest for rectum (6%) and OS for cervix (3%) and brain (3%). Sensitivity analysis confirmed a robust model. INTERPRETATION: Radiotherapy provides significant 5-year LC and OS benefits as part of evidence-based cancer care. CRT provides modest additional benefits.

Variation in Radiotherapy Referral and Treatment for High-risk Pathological Features after Radical Prostatectomy: Results from a Population-based Study.

AIMS: Guidelines recommend the discussion of adjuvant radiotherapy post-prostatectomy for prostate cancer patients with high-risk pathology to consider all of their treatment options. We determine whether patterns of radiotherapy referral and treatment post-prostatectomy reflect guideline-based use in a contemporary prostatectomy cohort. MATERIALS AND METHODS: Electronic treatment records were linked to Ontario's cancer registry. Multivariable regression was used to evaluate clinical and health systems factors associated with referral and the use of adjuvant radiotherapy within 6 months post-prostatectomy. RESULTS: Among 2663 patients treated with prostatectomy between 1 January 2012 and 30 November 2012, 1261 (47%) were found to have adverse pathology and 492 were referred to radiation oncology ≤6 months post-prostatectomy, of whom 51% received adjuvant radiotherapy. Multivariable analysis showed that patients were more likely to be referred to radiation oncology from a low-volume surgical facility (≤50 versus >50 radical prostatectomy cases, odds ratio 2.50 [1.80-3.48]), if they lived farther from a radiotherapy centre (>50 km versus <10 km, odds ratio 1.73 [1.22-2.46]), if they were seen by radiation oncology preoperatively (odds ratio 1.95 [1.51-2.52]), or if they had adverse pathology: high T-category (pT3b/T4 versus pT2, odds ratio 17.87 [12.14-26.30]; pT3a versus pT2, odds ratio 5.24 [3.95-6.97]), positive margins (non-apex positive versus negative, odds ratio 4.20 [3.19-5.53]; apex only positive versus negative, odds ratio 2.60 [1.71-3.94]) and high Gleason score (8-10 versus ≤6, odds ratio 11.32 [5.37-23.84]; 7 versus ≤6, odds ratio 4.18 [2.16-8.10]). Wide geographic variation in radiotherapy referral rates persisted (range 6-66%; P < 0.0001). After radiotherapy referral, only high T-category (pT3b/T4 versus pT2, odds ratio 5.37 [3.01-9.60]; pT3a versus pT2, odds ratio 2.72 [1.59-4.65]) and non-apex positive margins (odds ratio 2.81 [1.86-4.23]) remained significantly predictive of treatment. CONCLUSIONS: Variations in referral for a discussion of radiotherapy post-prostatectomy are not mainly explained by patient characteristics. After seeing radiation oncology, treatment decisions correlated most strongly with pathological findings. Understanding the reasons for the tremendous non-clinical variations in care is needed to ensure access to potentially curative radiotherapy post-prostatectomy for high-risk prostate cancer patients.

Mental health services use by melanoma patients receiving adjuvant interferon: association of pre-treatment mental health care with early discontinuation.

BACKGROUND: Although high-dose interferon (hd-ifn) is the sole approved adjuvant systemic treatment for melanoma in many jurisdictions, it is toxic. We sought to assess the population-level effects of hd-ifn toxicity, particularly neuropsychiatric toxicity, hypothesizing that such toxicity would have the greatest effect on mental health services use in advanced resected melanoma. METHODS: This retrospective population-based registry study considered all melanoma patients receiving adjuvant hd-ifn in Ontario during 2008-2012. Toxicity was investigated through health services use compatible with hd-ifn toxicity (for example, mental health physician billings). Using stage data reported from cancer centres about a subset of patients (stages iib-iiic), a propensity-matched analysis compared such service use in patients who did and did not receive hd-ifn. Associations between early hd-ifn discontinuation and health services use were examined. RESULTS: Of 718 melanoma patients who received hd-ifn, 12% were 65 years of age and older, and 83% had few or no comorbidities. One third of the patients experienced 1 or more toxicity-associated health care utilization events within 1 year of starting hd-ifn. Of 420 utilization events, 364 (87%) were mental health-related, with 54% being family practitioner visits, and 39% being psychiatrist visits. In the propensity-matched analysis, patients receiving hd-ifn were more likely than untreated matched controls to use a mental health service (p = 0.01), with 42% of the control group and 51% of the hd-ifn group using a mental health service in the period spanning the 12 months before to the 24 months after diagnosis. In the multivariable analysis, early drug discontinuation was more likely in the presence of pre-existing mental health issues (odds ratio: 2.0; 95% confidence limits: 1.1, 3.4). CONCLUSIONS: Stage iib-iiic melanoma patients carry a substantial burden of mental health services use whether or not receiving hd-ifn, highlighting an important survivorship issue for these patients. High-dose interferon is associated with more use of mental health services, and pre-treatment use of mental health services is associated with treatment discontinuation. That association should be kept in mind when hd-ifn is being considered.

Adjuvant Chemotherapy for Stage II Colon Cancer: Practice Patterns and Effectiveness in the General Population.

AIMS: Although guidelines do not recommend adjuvant chemotherapy (ACT) for stage II colon cancer, many state that ACT may be considered in high-risk disease. Here we describe practice patterns and outcomes associated with ACT in the general population. MATERIALS AND METHODS: All cases of colon cancer diagnosed in Ontario 2002-2008 were identified using the Ontario Cancer Registry, which was linked to electronic treatment records. Pathology reports were obtained for a 25% random sample of cases. High-risk disease was defined as: T4 tumours, <12 lymph nodes, poorly differentiated histology, lymphovascular invasion. Modified Poisson regression was used to evaluate factors associated with ACT. The Cox proportional hazards model was used to explore the association between ACT and cancer-specific (CSS) and overall survival. RESULTS: The study population included 2488 patients with stage II colon cancer; 1175 (47%) with high-risk disease. ACT was delivered to 18% of all patients and 24% of patients with high-risk disease. ACT rates were higher among younger patients (51% age 20-49 years versus 16% age 70-79, P < 0.001) and varied considerably across geographic regions (range 10-39%, P < 0.001). Among all patients with stage II colon cancer, ACT was not associated with improved CSS (hazard ratio 1.41, 95% confidence interval 1.09-1.82) or overall survival (hazard ratio 1.16, 95% confidence interval 0.94-1.42). Stratified survival analysis for patients with high-risk disease did not show benefit to ACT (CSS hazard ratio 1.14, 95% confidence interval 0.84-1.55; overall survival hazard ratio 1.02, 95% confidence interval 0.79-1.31). CONCLUSION: ACT use varies across age groups and geographic regions. ACT is not associated with improved survival among patients with stage II colon cancer including those with high-risk disease.

The Benefits of Providing External Beam Radiotherapy in Low- and Middle-income Countries.

More than half of all cancer diagnoses worldwide occur in low- and middle-income countries (LMICs) and the incidence is projected to rise substantially within the next 20 years. Radiotherapy is a vital, cost-effective treatment for cancer; yet there is currently a huge deficit in radiotherapy services within these countries. The aim of this study was to estimate the potential outcome benefits if external beam radiotherapy was provided to all patients requiring such treatment in LMICs, according to the current evidence-based guidelines. Projected estimates of these benefits were calculated to 2035, obtained by applying the previously published Collaboration for Cancer Outcomes, Research and Evaluation (CCORE) demand and outcome benefit estimates to cancer incidence and projection data from the GLOBOCAN 2012 data. The estimated optimal radiotherapy utilisation rate for all LMICs was 50%. There were about 4.0 million cancer patients in LMICs who required radiotherapy in 2012. This number is projected to increase by 78% by 2035, a far steeper increase than the 38% increase expected in high-income countries. National radiotherapy benefits varied widely, and were influenced by case mix. The 5 year population local control and survival benefits for all LMICs, if radiotherapy was delivered according to guidelines, were estimated to be 9.6% and 4.4%, respectively, compared with no radiotherapy use. This equates to about 1.3 million patients who would derive a local control benefit in 2035, whereas over 615 000 patients would derive a survival benefit if the demand for radiotherapy in LMICs was met. The potential outcome benefits were found to be higher in LMICs. These results further highlight the urgent need to reduce the gap between the supply of, and demand for, radiotherapy in LMICs. We must attempt to address this 'silent crisis' as a matter of priority and the approach must consider the complex societal challenges unique to LMICs.

Quality of Radiation Therapy Referral and Utilisation Post-prostatectomy: A Population-based Study of Time Trends.

AIMS: Adjuvant radiotherapy post-prostatectomy has been shown to benefit patients with adverse pathology. It remains unclear whether salvage radiotherapy confers equivalent outcomes. Practice guidelines recommend referral to radiation oncology within 6 months after prostatectomy to discuss adjuvant and salvage radiotherapy. The study objectives were to assess, at a population level: (i) post-prostatectomy referral patterns for radiotherapy; (ii) adjuvant and salvage radiotherapy utilisation; and (iii) time trends in relation to clinical trials and guidelines. These findings provide indications of access to quality care. MATERIALS AND METHODS: This was a retrospective cohort study. Electronic radiotherapy consultation and treatment records were linked to the population-based Ontario Cancer Registry. The population included prostate cancer cases treated with prostatectomy in Ontario between 2003 and 2012. Radiotherapy referral and treatment rates over time were analysed using the chi-squared trend test. RESULTS: Over the study period, 30 447 prostate cancer patients received prostatectomy. The proportion seen by radiation oncology within 6 months after prostatectomy doubled from 10.7% in 2003-2004 to 21.7% in 2011-2012 (P < 0.0001 for trend), with the largest annual percentage difference in 2009-2011 (3.4%). Among 4641 patients seen within 6 months, adjuvant radiotherapy rates remained at 51.0% ± 3.0%. Contemporaneous with radiation oncology referral trends, overall adjuvant radiotherapy use increased from 6.2% in 2003-2004 to 11.0% in 2011-2012 (P < 0.001), while salvage radiotherapy remained at 8.4% ± 0.4%. Consequently, the total proportion receiving radiotherapy within 24 months increased from 14.1% in 2003-2004 to 17.7% in 2009-2010 (P < 0.0001). CONCLUSIONS: There was an increase in access to early radiation oncology referral post-prostatectomy and adjuvant radiotherapy in Ontario between 2003 and 2012, following guideline publication.

A Population-based Model of Local Control and Survival Benefit of Radiotherapy for Lung Cancer.

AIMS: To estimate the population-based locoregional control and overall survival benefits of radiotherapy for lung cancer if the whole population were treated according to evidence-based guidelines. These estimates were based on a published radiotherapy utilisation (RTU) model that has been used to estimate the demand and planning of radiotherapy services nationally and internationally. MATERIALS AND METHODS: The lung cancer RTU model was extended to incorporate an estimate of benefits of radiotherapy alone, and of radiotherapy in conjunction with concurrent chemotherapy (CRT). Benefits were defined as the proportional gains in locoregional control and overall survival from radiotherapy over no radiotherapy for radical indications, and from postoperative radiotherapy over surgery alone for adjuvant indications. A literature review (1990-2015) was conducted to identify benefit estimates of individual radiotherapy indications and summed to estimate the population-based gains for these outcomes. Model robustness was tested through univariate and multivariate sensitivity analyses. RESULTS: If evidence-based radiotherapy recommendations are followed for the whole lung cancer population, the model estimated that radiotherapy alone would result in a gain of 8.3% (95% confidence interval 7.4-9.2%) in 5 year locoregional control, 11.4% (10.8-12.0%) in 2 year overall survival and 4.0% (3.6-4.4%) in 5 year overall survival. For the use of CRT over radiotherapy alone, estimated benefits would be: locoregional control 1.7% (0.8-2.4%), 2 year overall survival 1.7% (0.5-2.8%) and 5 year overall survival 1.2% (0.7-1.9%). CONCLUSIONS: The model provided estimates of radiotherapy benefit that could be achieved if treatment guidelines are followed for all cancer patients. These can be used as a benchmark so that the effects of a shortfall in the utilisation of radiotherapy can be better understood and addressed. The model can be adapted to other populations with known epidemiological parameters to ensure the planning of equitable radiotherapy services.

The population benefit of radiotherapy for cervical cancer: local control and survival estimates for optimally utilized radiotherapy and chemoradiation.

PURPOSE: Population benefits of radiotherapy if evidence-based guidelines were routinely followed across the entire population are largely unknown. The aim of this study was to investigate population-based benefits for cervical cancer. METHODS: Overall survival (OS) and local control (LC) benefits were investigated. XRT benefit was defined as the absolute benefit of radiotherapy, over no treatment, for radical indications and defined as the benefit of adjuvant radiation over surgery alone for adjuvant indications. The concurrent chemoradiation (CRT) benefit was the incremental benefit of CRT over XRT. Australian population benefits were modeled using decision trees. Citation databases were systematically queried. Meta-analysis was performed if multiple sources of the same evidence level existed. Robustness of the model assumptions was tested through sensitivity analysis. RESULTS: 53% of all cervix patients had adjuvant or curative radiotherapy indications. 96% were for CRT. The estimated 5-year absolute benefits of optimally utilized radiotherapy alone were: LC: 31% (95% Confidence Interval 29%, 34%), OS: 17% (15%, 18%). These were over and above the contribution of other modalities to outcomes. The incremental 5-year absolute benefits of CRT were: LC 4% (2%, 5%), OS 3% (1%, 5%). In sensitivity analysis, the model was robust. CONCLUSIONS: Optimally utilized radiotherapy provides substantial population OS and LC benefits for cervical cancer. Chemoradiation provides a modest population benefit over XRT. The population-based model was robust.

Factors affecting the use of single-fraction radiotherapy for the palliation of bone metastases in Australia.

AIMS: Palliative radiotherapy for bone metastases remains an important treatment in patients with metastatic malignancy. Previous studies have indicated a reluctance to adopt single-fraction treatment despite considerable evidence. This study aims to describe the factors determining the use of palliative radiotherapy in patients with bone metastases and assess whether fractionation patterns have changed over time with emerging evidence. MATERIALS AND METHODS: A retrospective review of radiotherapy databases at Liverpool/Macarthur Cancer Therapy Centre and the Royal Brisbane and Women's Hospital was conducted for the period 1997-2009. Patients receiving palliative radiotherapy for bony metastases were identified and treatment sites were grouped into 'spine', 'limb', 'multiple' or 'other'. Treatment courses were divided into single- or multiple-fraction treatments. The effects of socioeconomic and geographical factors on radiotherapy utilisation and fractionation were assessed. RESULTS: In total, 5683 patients were identified in the cohort; they received a total of 8211 bone treatments. The overall proportion of single-fraction radiotherapy was 29%, with significant variation over the study period (P < 0.001). Age under 70 years and spine or multiple treatment sites were all associated with lower usage of single-fraction radiotherapy on multivariate analysis. Prostate and lung primary sites were associated with higher usage of single-fraction treatment. The proportion of single-fraction treatment remained low (35%), even for patients who survived less than 22 days from their last treatment. Socioeconomic and geographical factors had little effect on the number of fractions used. CONCLUSIONS: The rate of single-fraction radiotherapy for bone metastases has remained low in two large Australian institutions, despite considerable evidence that single-fraction treatment provides equivalent pain relief to fractionated therapy. This trend towards fractionated treatment was largely maintained, even in patients with limited life expectancy. Further measures to increase the rate of single-fraction therapy are needed.

Estimating the population benefit of radiotherapy: using demand models to estimate achievable cancer outcomes.

The measurement of population benefits is important for priority setting, economic evaluation and quality improvement. It also informs advocacy. In this article, the use of demand models to estimate the achievable benefit of cancer therapy is reviewed. Achievable benefit refers to the treatment benefit achievable under optimal conditions. The population benefit of radiotherapy has been used as an example. Demand models provide a means of estimating the optimal proportion of patients with treatment indications when guidelines are followed. They may be used to estimate achievable benefit. The choice of end point should reflect the range of benefits associated with the treatment of interest. In some cases, further model development is needed if a pre-existing demand model is used. The benefit of treatment for each indication is estimated using a systematic review process. The highest level of evidence is used to define the benefit for each indication. In cases where multiple sources of the same level and quality of evidence exist, a meta-analysis is carried out. Population-based effectiveness data sources are considered, but three major challenges to their use are: (i) generalisability of the observed outcomes, (ii) data resolution and (iii) confounding and bias. The population benefit determined from this process describes the population proportion achieving a benefit due to the use of guideline-based treatment, compared with no use of that treatment. Sensitivity analysis provides a means for modelling the effect of model uncertainties. The predominant uncertainty is most often due to uncertainty in indication proportion. Preference-sensitive treatment decisions are a common example. The described approach to estimating the achievable benefit of cancer therapy is robust to model uncertainties, rapidly adaptable and is transparent. However, estimates rely on the quality of model data sources and may be affected by model assumptions. Models should be developed for a broader range of modalities of cancer therapy and relevant end points.

A population-based study of factors affecting the use of radiotherapy for endometrial cancer.

AIMS: To describe the use of adjuvant radiotherapy for endometrial cancer in Ontario, and identify factors associated with its use, and to determine whether variation in the use of radiation is associated with differences in survival. MATERIALS AND METHODS: This was a retrospective, population-based, cohort study of all patients who had a hysterectomy for endometrial cancer in Ontario between 1992 and 2003. We used multiple logistic regression to identify health system-related factors associated with the use of radiotherapy, while controlling for disease- and patient-related factors. Survival and cancer cause-specific survival were compared among regions of the province with higher and lower rates of use of radiotherapy. RESULTS: The study population included a total of 9411 women with a median age of 63 years. Overall, 26.2% received adjuvant radiotherapy. Patients living further from regional cancer centres were slightly less likely to receive radiation (P = 0.02). Patients who had their surgery during longer prevailing waiting times for radiotherapy were less likely to receive radiation (P = 0.04). The use of radiotherapy varied widely from 18.0 to 34.3% among the catchment areas of provincial radiotherapy centres (P < 0.0001). In the overall population, there was no difference in survival among regions with higher and lower rates of use of radiotherapy. However, in the subgroup of cases with clear cell and serous carcinomas, both overall survival and cancer cause-specific survival were significantly lower in regions with lower rates of use of radiotherapy (P < 0.05). This difference remained significant after controlling for other factors (P < 0.05; hazard ratio 1.43; 95% confidence limits 1.06-1.93). CONCLUSIONS: Health system-related factors unrelated to patients' needs affect the use of adjuvant radiotherapy in Ontario. Lower rates of use of adjuvant radiotherapy are associated with lower rates of survival in patients with serous and clear cell carcinomas.

A population-based study of cervix cancer: incidence, management and outcome in the Canadian province of Saskatchewan.

AIMS: To document the incidence, management and outcome of uterine cervix cancer in the Canadian province of Saskatchewan. To compare provincial results of low dose rate (LDR) and high dose rate (HDR) brachytherapy in this population. MATERIALS AND METHODS: We carried out a retrospective population-based cohort study of all uterine cervix cancer cases in Saskatchewan diagnosed between 1985 and 2001. We used data from the provincial cancer registry for incident cases, the provincial death registry for vital status information and chart reviews for treatment and toxicity information. RESULTS: In total, 714 cases of uterine cervix cancer were identified. Stage distribution was IA 22.7%, IB 31.8%, II 19.1%, III 18.4%, IV 6.8%; 81.2% were squamous cell carcinoma, 13.4% adenocarcinoma, 1.5% adenosquamous, 0.9% small cell and 3.1% other. The annual crude incidence rate of uterine cervix cancer in Saskatchewan ranged from 6.5 to 12.3% between 1985 and 2001. The 5-year cause-specific survival rate ranged from 100% for stage IA1 to 22% for stage IV. One hundred and seven patients were treated with LDR and 37 with HDR with similar stage distribution. The 5-year cause-specific survival rate was 56% for HDR and 67% for LDR (P = 0.72). For 43 patients managed with external beam radiotherapy alone, outcome was poor for stage IIB to IIIB. The most common acute toxicities of radiation treatment were diarrhoea (60%) and abdominal cramps (12.5%). The common chronic toxicities were vaginal stenosis (5.5%) and small bowel obstruction (4%). CONCLUSIONS: Our population-level outcomes are in keeping with published observed results and provide some of the first Canadian population-level data on HDR and LDR outcomes. We found no significant different in cause-specific survival between patients managed with HDR and LDR, although interpretation is limited by patient numbers. Our results for external beam radiotherapy alone emphasise the vital role brachytherapy plays in the management of cervical cancer.

The knowledge authoring tool: an XML-based knowledge acquisition environment.

As part of an enterprise effort to develop new clinical information systems at Intermountain Health Care, we are developing a Knowledge Authoring Tool that facilitates the development of medical knowledge. At present, users of the application can compose order sets and other clinical knowledge documents based upon XML schemas. The flexible nature of the application allows for the authoring of new types of documents once an XML schema and accompanying web form have been developed and stored in a shared repository. The need for a knowledge acquisition tool stems largely from the desire for medical practitioners to be able to write their own content for clinical use. We hypothesize that knowledge content for clinical use can be successfully implemented around XML-based document frameworks containing structured and coded knowledge.