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Biomedical subjects

William J Mackillop

Publications and source records attributed to William J Mackillop.

15 recordsLinked to original sources
PubMed2006

Predictive validity of five comorbidity indices in prostate carcinoma patients treated with curative intent.

BACKGROUND: Comorbidity is important to consider in clinical research on curative prostate carcinoma because of the role of competing risks. Five chart-based comorbidity indices were assessed for their ability to predict survival. METHODS: This was a case-cohort study of prostate carcinoma patient cohort treated with curative intent in Toronto and Southeast Cancer Care Ontario regions between 1990 and 1996; the subcohort was drawn from these men, whereas cases were cohort members who died from causes other than prostate carcinoma. Comorbidity data were obtained from medical charts (269 subjects). Vital status, age, area of residence, and socioeconomic status information were available. Predictive validity was quantified by the percent variance explained (PVE) over and above age using proportional hazards modeling. RESULTS: The Chronic Disease Score (CDS) (PVE = 11.3%; 95% confidence interval [95% CI], 3.5-22.8%), Index of Coexistent Disease (ICED) (PVE = 9.0%; 95% CI, 2.9-17.9%), Cumulative Illness Rating Scale (CIRS) (PVE = 7.2%; 95% CI, 1.4-17.1%), Kaplan-Feinstein Index (PVE = 4.9%; 95% CI, 0.6-12.8%), and Charlson Index (PVE = 3.8%; 95% CI, 0.3-10.9%) each explained some outcome variability beyond age. PVE differences among indices were not statistically significant. A comorbidity identified at the time of cancer diagnosis was the cause of death in 59.2% of cases (75% for cardiac or vascular causes). CONCLUSIONS: The better-performing, more comprehensive indices (CDS, ICED, and CIRS) would be useful in measuring and controlling for comorbidity in this setting. The CDS was easiest to apply and explained the most outcome variability.

Aged↗
PubMed2006

Compromised local control due to treatment interruptions and late treatment breaks in early glottic cancer: Population-based outcomes study supporting need for intensified treatment schedules.

PURPOSE: This population-based study describes the treatment of early glottic cancer in Ontario, Canada and assesses whether treatment variations were associated with treatment effectiveness. METHODS AND MATERIALS: We studied 491 T1N0 and 213 T2N0 patients. Data abstracted from charts included age, sex, stage, treatment details, disease control, and survival. RESULTS: The total dose ranged from 50 to 70 Gy, and the daily dose ranged from 1.9 to 2.8 Gy. In 90%, treatment duration was between 25 and 50 days. Field sizes, field reductions, beam arrangement, and beam energy varied. Late treatment breaks occurred in 13.6% of T1N0 and 27.1% of T2N0 cases. Local control was comparable to other reports for T1N0 (82% at 5 years), but was only 63.2% in T2N0. Variables associated with local failure in T1N0 were age less than 49 years (relative risk [RR], 3.21; 95% confidence interval [CI], 1.49-6.90) and >3 treatment interruption days (RR, 2.43; 95% CI, 1.00-5.91). In T2N0, these were field reduction (RR, 2.33; 95% CI, 1.23-4.42) and late treatment breaks (RR, 2.19; 95% CI, 1.09-4.41). CONCLUSION: Some aspects of treatment for early glottic cancer were associated with worse local control. Problems with protracted treatment are of particular concern, underscoring the need for randomized studies to intensify radiotherapy.

Age Factors↗
PubMed2005

An evidence-based estimate of the appropriate rate of utilization of radiotherapy for cancer of the cervix.

PURPOSE: Current estimates of the proportion of cancer patients who will require radiotherapy (RT) are based almost entirely on expert opinion. The objective of this study was to calculate the proportion of incident cases of cervical cancer that should receive RT by application of an evidence-based approach. METHODS AND MATERIALS: A systematic review of the literature was done to identify indications for RT for cervical cancer and to ascertain the level of evidence that supported each indication. A survey of Canadian gynecologic oncologists and radiation oncologists who treat cervical cancer was done to determine the level of acceptance of each indication among doctors who practice in the field. An epidemiologic approach was then used to estimate the incidence of each indication for RT in a typical North American population of patients with cervical cancer. RESULTS: The systematic review of the literature identified 29 different indications for RT for cervical cancer. The majority of the 75 experts who responded to the mail survey stated that they "usually" or "always" recommended RT in all but one of the clinical situations that were identified as indications for RT on the basis of the systematic review. The analysis of epidemiologic data revealed that, in a typical North American population, 65.4% +/- 2.5% of cervical cancer cases will develop one or more indications for RT at some point in the course of the illness, 63.4% +/- 2.3% will develop indications for RT as part of their initial management, and 2.0% +/- 0.9% will develop indications for RT for progressive or recurrent disease. The effects of variations in case mix on the need for RT was examined by sensitivity analysis, which suggested that the maximum plausible range for the appropriate rate of utilization of RT was 54.3% to 67.9%. The proportion of cases that required RT was stage dependent: 10.6% +/- 1.2% in Stage IA, 74.9% +/- 1.3% in Stage IB, 100% in Stages II and III, and 97.2% +/- 1.1% in Stage IV. CONCLUSIONS: This evidence-based estimate of the appropriate rate of use of RT for cervical cancer adds to the growing pool of knowledge about the need for RT that will ultimately provide a rational basis for long-term planning for RT programs and for auditing access to RT in the general population.

Canada↗
PubMed2005

A population-based study of the waiting times for prostatectomy in Ontario.

INTRODUCTION AND OBJECTIVE: Despite the high incidence of prostate cancer in Canada, there is currently limited information describing how these patients are being managed. The aim of this study was to review the surgical waiting times for radical prostatectomy in Ontario, utilizing existing population-based cancer databases, and to describe factors associated with prolonged waiting times. METHODS: This is a retrospective, population-based, observational study of men diagnosed with prostate cancer in Ontario between 1980 and 2000. The sources of data include the Ontario Cancer Registry linked to hospital discharge data, as well as census data from Statistics Canada. Study variables include age, county of residence, teaching hospital status, hospital surgical volume, area-level median household income and cause-specific survival. Waiting times were compared across study variables using univariate and graphical methods. Survival was compared across geographic regions with differing average wait times. RESULTS: We identified 9524 men treated with radical prostatectomy in Ontario over the study period and found the percentage of all patients with the disease who were treated surgically increasing from 3% to 20% over the last 2 decades. The overall time to prostatectomy has almost doubled with a median waiting time of 55 days in earlier eras to 91 days in 1996-2000. A few counties had significantly different wait times, whereas age and socio-economic factors were not associated with wait times across most eras. In the most recent eras, acute care hospitals and hospitals with higher surgical volumes had significantly higher waiting times (up to 20 days longer in 1996-2000, p<0.0001). Patients living in regions with the shortest wait times had statistically significant worse survival (p=0.02), implying that triaging has a greater impact than the potential effect of prolonged waits. CONCLUSIONS: The observed increases in waiting times for radical prostatectomy from this study are similar to the known increases in waiting times for radiotherapy. This increased time to treatment is an illustration of the stress on the health care system in Ontario.

Aged↗
PubMed2004

Monitoring trends in waiting periods in Canada for elective surgery: validation of a method using administrative data.

BACKGROUND: Provincial governments require timely, economical methods to monitor surgical waiting periods. Although use of prospective procedure-specific registers would be the ideal method, a less elaborate system has been proposed that is based on physician billing data. This study assessed the validity of using the date of the last service billed prior to surgery as a proxy for the beginning of the post-referral, pre-surgical waiting period. METHOD: We examined charts for 31,824 elective surgical encounters between 1992 and 1996 at an Ontario teaching hospital. The date of the last service before surgery (the last billing date) was compared with the date of the consultant's letter indicating a decision to book surgery (i.e., to begin waiting). RESULTS: Several surgical specialties (but excluding cardiac, orthopedic and gynecologic) had a close correlation between the dates of the last pre-surgery visit and those of the actual decision to place the patient on the waiting list. Similar results were found for 12 of 15 individually studied procedures, including some orthopedic and gynecological procedures. CONCLUSION: Used judiciously, billing data is a timely, inexpensive and generally accurate method by which provincial governments could monitor trends in waiting times for appropriately selected surgical procedures.

Analysis of Variance↗
PubMed2003

An evidence-based estimate of the appropriate radiotherapy utilization rate for colorectal cancer.

PURPOSE: Current estimates of the proportion of cancer patients who will require RT are based almost entirely on expert opinion. The objective of this study was to estimate the proportion of incident cases of colorectal cancer that should receive RT using an evidence-based approach. METHODS AND MATERIALS: A systematic review of the literature was undertaken to identify indications for RT for colorectal cancer, and to ascertain the level of evidence that supported each indication. An epidemiologic approach was then used to estimate the incidence of each indication for RT in a typical North American population of colorectal cancer patients. The effect of sampling error on the estimated appropriate rate of RT was calculated mathematically, and the effect of systematic error was estimated by sensitivity analysis. RESULTS: It was estimated that 23.7% +/- 1.0% of colorectal cancer cases develop one or more indications for RT at some point in the course of the illness: 20.9% +/- 1.1% as part of their initial treatment, and 2.8% +/- 0.5% later for recurrence or progression. We estimated that 7.1% +/- 0.8% of colon carcinoma patients will require RT at some point in the course of the illness: 4.0% +/- 0.7% as part of their initial treatment, and 3.1% +/- 0.4% later for recurrence or progression. We estimated that 72.3% +/- 1.0% of rectal carcinoma patients will require RT at some point in the course of the illness: 69.6% +/- 0.9% as part of their initial treatment and 2.7% +/- 0.2% later for recurrence or progression. CONCLUSIONS: This method provides a rational starting point for the long-term planning of radiation services, and for the audit of access to RT at the population level. By completing such evaluations in the major cancer sites, it will be possible to estimate the appropriate RT treatment rate for the cancer population as a whole.

Colonic Neoplasms↗
PubMed2003

Performance of different radiotherapy workload models.

PURPOSE: The purpose of this study was to evaluate the performance of different radiotherapy workload models using a prospectively collected dataset of patient and treatment information from a single center. METHODS AND MATERIALS: Information about all individual radiotherapy treatments was collected for 2 weeks from the three linear accelerators (linacs) in our department. This information included diagnosis code, treatment site, treatment unit, treatment time, fields per fraction, technique, beam type, blocks, wedges, junctions, port films, and Eastern Cooperative Oncology Group (ECOG) performance status. We evaluated the accuracy and precision of the original and revised basic treatment equivalent (BTE) model, the simple and complex Addenbrooke models, the equivalent simple treatment visit (ESTV) model, fields per hour, and two local standards of workload measurement. RESULTS: Data were collected for 2 weeks in June 2001. During this time, 151 patients were treated with 857 fractions. The revised BTE model performed better than the other models with a mean [observed -predicted] of 2.62 (2.44-2.80). It estimated 88.0% of treatment times within 5 min, which is similar to the previously reported accuracy of the model. CONCLUSION: The revised BTE model had similar accuracy and precision for data collected in our center as it did for the original dataset and performed the best of the models assessed. This model would have uses for patient scheduling, and describing workloads and case complexity.

Appointments and Schedules↗
PubMed2003

Does delay in starting treatment affect the outcomes of radiotherapy? A systematic review.

PURPOSE: The objective of this study was to synthesize what is known about the relationship between delay in radiotherapy (RT) and the outcomes of RT. METHODS: A systematic review of the world literature was conducted to identify studies that described the association between delay in RT and the probability of local control, metastasis, and/or survival. Studies were classified by clinical and methodologic criteria and their results were combined using a random-effects model. RESULTS: A total of 46 relevant studies involving 15,782 patients met our minimum methodologic criteria of validity; most (42) were retrospective observational studies. Thirty-nine studies described rates of local recurrence, 21 studies described rates of distant metastasis, and 19 studies described survival. The relationship between delay and the outcomes of RT had been studied in diverse situations, but most frequently in breast cancer (21 studies) and head and neck cancer (12 studies). Combined analysis showed that the 5-year local recurrence rate (LRR) was significantly higher in patients treated with adjuvant RT for breast cancer more than 8 weeks after surgery than in those treated within 8 weeks of surgery (odds ratio [OR] = 1.62, 95% confidence interval [CI], 1.21 to 2.16). Combined analysis also showed that the LRR was significantly higher among patients who received postoperative RT for head and neck cancer more than 6 weeks after surgery than among those treated within 6 weeks of surgery (OR = 2.89; 95% CI, 1.60 to 5.21). There was little evidence about the impact of delay in RT on the risk of metastases or the probability of long-term survival in any situation. CONCLUSION: Delay in the initiation of RT is associated with an increase [corrected] in LRR in breast cancer and head and neck cancer. Delays in starting RT should be as short as reasonably achievable.

Breast Neoplasms↗
PubMed2003

Management and outcome differences in supraglottic cancer between Ontario, Canada, and the Surveillance, Epidemiology, and End Results areas of the United States.

PURPOSE: We compared the management and outcome of supraglottic cancer in Ontario, Canada, with that in the Surveillance, Epidemiology, and End Results (SEER) Program areas in the United States. METHODS: Electronic, clinical, and hospital data were linked to cancer registry data and supplemented by chart review where necessary. Stage-stratified analyses compared initial treatment and survival in the SEER areas (n = 1,643) with a random sample from Ontario (n = 265). We also compared laryngectomy rates at 3 years in those patients 65 years and older at diagnosis. RESULTS: Radical surgery was more commonly used in SEER, with absolute differences increasing with increasing stage: I/II, 17%; III, 36%; and IV, 45%. The 5-year survival rates were 74% in Ontario and 56% in SEER for stage I/II disease (P =.01), 55.7% in Ontario and 46.8% in SEER for stage III disease (P =.40), and 28.5% in Ontario and 29.1% in SEER for stage IV disease (P =.28). Cancer-specific survival results mirrored the overall survival results with the exception of stage IV disease, for which 34.6% of Ontario patients survived their cancer compared with 38.1% in SEER (P =.10). This stage IV difference was more pronounced when we further controlled for possible cause of death errors by restricting the comparison to patients with a single primary cancer (P =.01). Three-year actuarial laryngectomy rates differed. In stage I/II, these rates were 3% in Ontario compared with 35% in SEER (P < 10(-3)). In stage III disease, the rates were 30% and 54%, respectively (P =.03), and in stage IV disease they were 33% and 64% (P =.002). CONCLUSION: There are large differences in the management of supraglottic cancer between the SEER areas of the United States and Ontario. Long-term larynx retention was higher in Ontario, where radiotherapy is widely regarded as the treatment of choice and surgery is reserved for salvage. In stages I to III, survival was similar in the two regions despite the differences in treatment policy. In stage IV, there may be a small survival advantage in the U.S. SEER areas related to the higher use of primary surgery.

Aged↗
PubMed2003

Evidence-based estimate of appropriate radiotherapy utilization rate for prostate cancer.

PURPOSE: Current estimates of the proportion of cancer patients who will require radiotherapy (RT) are based almost entirely on expert opinion. The objective of this study was to use an evidence-based approach to estimate the proportion of incident cases of prostate cancer that should receive RT at any point in the evolution of the illness. METHODS AND MATERIALS: A systematic review of the literature was undertaken to identify indications for RT for prostate cancer and to ascertain the level of evidence that supported each indication. An epidemiologic approach was then used to estimate the incidence of each indication for RT in a typical North American population of prostate cancer patients. The effect of sampling error on the estimated appropriate rate of RT was calculated mathematically, and the effect of systematic error using alternative sources of information was estimated by sensitivity analysis. RESULTS: It was estimated that 61.2% +/- 5.6% of prostate cancer cases develop one or more indications for RT at some point in the course of the illness. The plausible range for this rate was 57.3%-69.8% on sensitivity analysis. Of all prostate cancer patients, 32.2% +/- 3.8% should receive RT in their initial treatment and 29.0% +/- 4.1% later for recurrence or progression. The proportion of cases that ever require RT is risk grouping dependent; 43.9% +/- 2.2% in low-risk disease, 68.7% +/- 3.5% in intermediate-risk disease; and 79.0% +/- 3.8% in high-risk locoregional disease. For metastatic disease, the predicted rate was 66.4% +/- 0.3%. CONCLUSION: This method provides a rational starting point for the long-term planning of radiation services and for the audit of access to RT at the population level. By completing such evaluations in major cancer sites, it will be possible to estimate the appropriate RT rate for the cancer population as a whole.

Humans↗
PubMed2002

An evidence-based estimate of appropriate radiotherapy utilization rate for breast cancer.

PURPOSE: Current estimates of the proportion of cancer patients who will require radiotherapy (RT) are based almost entirely on expert opinion. We sought to use an evidence-based approach to estimate the proportion of incident cases of breast cancer that will require RT at any point in the evolution of the illness. METHODS AND MATERIALS: We undertook a systematic review of the literature to identify indications for RT for breast cancer and to ascertain the level of evidence that supported each indication. An epidemiologic approach was then used to estimate the incidence of each indication for RT in a typical North American population of breast cancer patients. The effect of sampling error on the estimated appropriate rate of RT was calculated mathematically, and the effect of systematic error was estimated by sensitivity analysis. RESULTS: It was estimated that 66.4% +/- 4.8% of breast cancer patients develop one or more indications for RT at some point in the course of the illness. The plausible range for this rate was 56.3%-72.4% on sensitivity analysis. Of all breast cancer patients, 57.3% +/- 4.7% require RT in their initial treatment and 9.1% +/- 1.0% do so later for recurrence or progression. The proportion of patients who ever require RT is stage dependent: 39.8% +/- 1.1% in ductal carcinoma in situ; 68.6% +/- 4.1% in Stage I invasive carcinoma; 81.5% +/- 2.3% in Stage II; 95.3% +/- 0.3% in Stage III; and 63.7% +/- 0.3% in Stage IV. CONCLUSION: This method provides a rational starting point for the long-term planning of RT services and for the audit of access to RT at the population level. By completing such evaluations in the major cancer sites, it will be possible to estimate the appropriate RT treatment rate for the cancer population as a whole.

Algorithms↗
PubMed2002

A comparison of published head and neck stage groupings in laryngeal cancer using data from two countries.

The combination of T, N, and M classifications into stage groupings is meant to facilitate a number of activities including: the estimation of prognosis and the comparison of therapeutic interventions among similar groups of cases. We tested the UICC/AJCC fifth edition stage grouping and six other TNM-based groupings proposed for head and neck cancer for their ability to meet these expectations in laryngeal cancer using data from Ontario, Canada, and the area of Southern Norway surrounding Oslo. We defined four criteria to assess each grouping scheme: (1) the subgroups defined by T, N, and M comprising a given group within a grouping scheme have similar survival rates (hazard consistency); (2) the survival rates differ among the groups (hazard discrimination); (3) the prediction of cure is high (outcome prediction); and (4) the distribution of patients among the groups is balanced. We previously identified or derived a measure for each criterion, and the findings were summarized using a scoring system. The range of scores was from 0 (best) to 7 (worst). The data sets were population-based, with 861 cases from Ontario and 642 cases from Southern Norway. Clinical stage assignment was used and the outcome of interest was cause-specific survival. Summary scores across the seven schemes had similar ranges: 0.9 to 5.1 in Ontario and 1.8 to 5.7 in Southern Norway, but the ranking varied. Summing the scores across the two datasets, the TANIS-7 scheme (Head & Neck 1993;15:497-503) ranked first, and was ranked high in both datasets (first and second, respectively). The UICC/AJCC scheme ranked sixth out of seven schemes, and its ranking was fifth and seventh, respectively. UICC/AJCC stage groupings were defined without empirical investigation. When tested, this scheme did not perform best. Our results suggest that the usefulness of the TNM system could be enhanced by optimizing the design of stage groupings through empirical investigation.

Carcinoma, Squamous Cell↗
PubMed2002

Prognostic factors in non-small cell lung cancer: a decade of progress.

STUDY OBJECTIVES: To provide a systematic overview of the literature investigating patient and tumor factors that are predictive of survival for patients with non-small cell lung cancer (NSCLC), and to analyze patterns in the design of these studies in order to highlight problematic aspects of their design and to advocate for appropriate directions of future studies. DESIGN: A systematic search of the MEDLINE database and a synthesis of the identified literature. MEASUREMENTS AND RESULTS: The database search (January 1990 to July 2001) was carried out combining the MeSH terms prognosis and carcinoma, nonsmall cell lung. Eight hundred eighty-seven articles met the search criteria. These studies identified 169 prognostic factors relating either to the tumor or the host. One hundred seventy-six studies reported multivariate analyses. Concerning 153 studies reporting a multivariate analysis of prognostic factors in patients with early-stage NSCLC, the median number of patients enrolled per study was 120 (range, 31 to 1,281 patients). The median number of factors reported to be significant in univariate analyses was 4 (range, 2 to 14 factors). The median number of factors reported to be significant in multivariate analyses per study was 2 (range, 0 to 6 factors). The median number of studies examining each prognostic factor was 1 (range, 1 to 105 studies). Only 6% of studies addressed clinical outcomes other than patient survival. CONCLUSIONS: While the breadth of prognostic factors studied in the literature is extensive, the scope of factors evaluated in individual studies is inappropriately narrow. Individual studies are typically statistically underpowered and are remarkably heterogeneous with regard to their conclusions. Larger studies with clinically relevant modeling are required to address the usefulness of newly available prognostic factors in defining the management of patients with NSCLC.

Biomarkers, Tumor↗