Karleen Schulze

Mortality from myocardial infarction following postlumpectomy radiotherapy for breast cancer: a population-based study in Ontario, Canada.

PURPOSE To compare the risk of mortality from myocardial infarction (MI) after left-sided postlumpectomy radiotherapy (RT) to the risk after right-sided postlumpectomy RT. METHODS We conducted a population-based cohort study of cases of invasive female breast cancer in Ontario, diagnosed between January 1, 1982 and December 31, 1987 (n = 25,570). Records of the Ontario Cancer Registry (OCR) were linked to hospital procedure and discharge abstracts and to RT records from Ontario cancer centers. A case was labelled as lumpectomy if this was the maximum breast surgery within 4 months of diagnosis. Postlumpectomy RT occurred up to 1 year postdiagnosis. Laterality was assigned from the laterality descriptor of the RT records. A case was labelled as having had a fatal MI if ICD code 410 (myocardial infarction) was recorded as the cause of death in the OCR. We used logistic regression to compare the likelihood of utilization of: 1. Dose per fraction > 2.00 Gy; 2. cobalt vs. linac; and 3. boost RT. We used life table analysis and the log rank test comparing the time to fatal MI from diagnosis of breast cancer between women who received left-sided postlumpectomy RT and women who received right-sided. We used Cox proportional hazards models to study the relative risk for left-sided cases overall, and stratified by age, RT characteristics, and among conditional survival cohorts. RESULTS Postlumpectomy RT was received by 1,555 left-sided and 1,451 right-sided cases. With follow-up to December 31, 1995, 2% of women with left-sided RT had a fatal MI compared to 1% of women with right-sided RT. Comparison of the time to failure between women who had left-sided RT and women who had right-sided RT showed the left-sided RT group to be associated with a higher risk of fatal MI (p = 0.02). Adjusting for age at diagnosis, the relative risk for fatal MI with left-sided postlumpectomy RT was 2.10 (1.11, 3.95). CONCLUSION Among women who received postlumpectomy RT for breast cancer in Ontario between 1982-1987, left-sided postlumpectomy RT was associated with a higher risk of fatal MI compared to right-sided.

ESTIMATING THE NEED FOR RADIOTHERAPY FOR LUNG CANCER: AN EVIDENCE-BASED, EPIDEMIOLOGIC APPROACH

BACKGROUND AND OBJECTIVES 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 lung cancer that will require RT at any point in the evolution of the illness. METHODS A systematic review of the literature was undertaken to identify indications for RT for lung 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 lung 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 shown that 53.6% +/- 3.3% of small-cell lung cancer (SCLC) cases develop one or more indications for RT at some point in the course of the illness, 45.4% +/- 4.3% in their initial treatment, and 8.2% +/- 1.5% later for recurrence of progression. Overall, 64.3% +/- 4.7% of non-small-cell lung cancer (NSCLC) cases require RT, 45.9% +/- 4.3% in their initial treatment, and 18.3% +/- 1.8% later in the course of the illness. The proportion of NSCLC cases that ever require RT is stage dependent; 41.0% +/- 5.5% in Stage I; 54.5% +/- 6.5% in Stage II; 83.5% +/- 10.6% in Stage III; and 65.7% +/- 7.6% in Stage IV. In total, 61.0% +/- 3.9% of all patients with lung cancer will develop one or more indications for RT at some point in the illness, 44.6% +/- 3.6% in their initial treatment, and 16.5% +/- 1.5% later for recurrence or progression. 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. We now plan to extend this study to the other major cancer sites to enable us to estimate the appropriate RT treatment rate for the cancer population as a whole.

Association between age and the utilization of radiotherapy in Ontario.

PURPOSE The purpose of this study was to assess whether: (i) radiotherapy (RT) utilization varies with age in Ontario cancer patients; (ii) age-associated differences in the use of RT (if they exist) vary with cancer site and treatment intent; (iii) the age-associated variation in RT utilization is comparable to the decline in functional status in the general population; and (iv) the variation with age is due to differences in referral to a cancer center or to subsequent decisions. METHODS AND MATERIALS Details for several cancer sites diagnosed between 1984-1994 were obtained from the Ontario Cancer Registry (OCR). RT records from all treatment centers were linked to the OCR database. Information about the functional status of the Canadian population was obtained from the 1994 National Population Health Survey conducted by Statistics Canada. RESULTS The rate of RT use declined with age, particularly for adjuvant and palliative indications. The relative decline in RT with age exceeded the relative decline in functional status with age in the general population. Most of the decline in RT use was related to a decline in referral to cancer centers. CONCLUSIONS The referral for, and use of, palliative and adjuvant RT decreases more with age than can be explained by age-associated decline in functional status observed in the general population.

A POPULATION-BASED STUDY OF GLIOBLASTOMA MULTIFORME

PURPOSE To describe (1) the use of surgery and radiotherapy (RT) in the treatment of patients with glioblastoma (GBM) in Ontario, (2) survival, and (3) proportion of survival time spent in the hospital after diagnosis. METHODS AND MATERIALS We performed a population-based cohort study of all Ontario Cancer Registry (OCR) cases of GBM diagnosed between 1982 and 1994. We linked OCR records, hospital files containing surgical procedure codes from the Canadian Institute for Health Information, and province-wide RT records. We studied the odds of treatment using multivariate logistic regression. We expressed the time spent in the hospital as the mean number of days per case, and as a proportion of the interval between diagnosis and death, or 24 months following diagnosis, whichever came first. We used the life-table method and Cox proportional hazards regression to describe survival. RESULTS The proportion of patients with GBM undergoing any surgery directed at the tumor varied with age (p < 0.0001) and region of residence (p < 0.0001). The proportion undergoing RT varied with age (p < 0.0001), region of residence (p < 0.0001), and year of diagnosis (p = 0.01). RT dose > or = 53.5 Gy varied with age (p < 0.0001), region of residence (p < 0.0001), and year of diagnosis (p = 0.0002). Median survival was 11 months among patients receiving RT and 3 months among those not receiving RT. The percentage of survival time spent in the hospital was similar among those who received from 49.5 to < 53.5 Gy, compared to > or = 53.5 Gy. Overall survival and the adjusted relative risk of death varied with age and region of residence. CONCLUSION We observed practice variation in the treatment of patients with GBM according to age, region of residence, and year of diagnosis. Survival did not increase during the study period. The variation in RT dose between those receiving from 49.5 to < 53.5 Gy compared to > or =53.5 Gy was not paralleled by variation in survival between regions where one or the other of the dose ranges predominated, nor was variation in dose ranges among the regions paralleled by variation in the proportion of survival time spent in the hospital.

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

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.

A comparison of published head and neck stage groupings in carcinomas of the tonsillar region

The combination of T, N, and M classifications into stage groupings was designed to facilitate a number of activities including: the estimation of prognosis and the comparison of therapeutic interventions among similar groups of cases. The authors tested the UICC/AJCC 5th edition stage grouping and seven other TNM‐based groupings proposed for head and neck cancer to determine their ability to meet these expectations in a specific site: carcinoma of the tonsillar region.

A prospective trial of short-course radiotherapy plus chemotherapy for palliation of dysphagia from advanced esophageal cancer

PURPOSE Between 1994 and 1997, 22 patients with dysphagia from advanced incurable esophageal cancer were enrolled in a phase I/II prospective study to assess the palliative benefit and toxicity of a short course of radiotherapy with chemotherapy. METHODS The study population included 17 men and five women with a median age of 69 (range 43-84). Patients were treated with 30 Gy in ten fractions to the mediastinum with a concurrent single course of chemotherapy (5-FU, 1000 mg/m(2), days 1-4 and mitomycin-C 10 mg/m(2), day 1). Swallowing ability was recorded each day on a self-administered diary card using the five point dysphagia index of the MRC (UK). The median baseline MRC swallowing score was 4 (cannot swallow solids). RESULTS Treatment was generally well tolerated, but seven (32%) patients had transient worsening of dysphagia scores immediately following treatment because of esophagitis; fifteen (68%) achieved a complete response (score 1: no difficulty on swallowing) with a median time to normalization of swallowing of 5 weeks. For these patients, the median dysphagia-free interval from time of onset of improvement was 11 weeks (range 1-131 weeks) and 11 (73%) remained dysphagia-free until death. The remaining patients had no or marginal improvement. Univariate analysis showed no difference between responders and non-responders with respect to age, gender, or histology. Median survival for the entire study population was 20 weeks (range 3-135 weeks). CONCLUSIONS This prospective trial shows that a short course of radiotherapy plus chemotherapy may produce complete relief of swallowing difficulties in a substantial proportion of patients with acceptable toxicity.

A population-based study of rectal cancer: permanent colostomy as an outcome

PURPOSE The objectives of this study are to describe the utilization of surgery and of radiotherapy in the treatment of newly diagnosed rectal cancer in Ontario between 1982 and 1994, and to describe the probability of permanent colostomy at any time after the diagnosis of rectal cancer, as an outcome of the treatment of newly diagnosed rectal cancer. METHODS AND MATERIALS Electronic records of rectal cancer (International Classification of Diseases code 154) from the Ontario Cancer Registry (n = 18,695, excluding squamous, basaloid, cloacogenic, and carcinoid histology) were linked to surgical records from all Ontario hospitals, and radiotherapy (RT) records from Ontario cancer centers. Procedures occurring within 4 months of diagnosis, or within 4 months of another procedure for rectal cancer, were considered part of initial treatment. Multivariate analyses controlled for age, sex, and year of diagnosis. RESULTS Resection plus permanent colostomy was performed in 33.1% of cases, whereas local excision or resection without permanent colostomy was performed in 38.2%. Multivariate logistic regression demonstrated higher odds ratios (OR) for resection plus permanent colostomy in all regions of Ontario relative to Toronto. The OR for postoperative RT following local excision or resection without permanent colostomy varied among the regions relative to Toronto (e.g., OR Ottawa = 0.59, OR Hamilton = 0.76, OR London = 1.25). The relative risk (RR) of colostomy conditional upon survival within 5 years from diagnosis varied among regions relative to Toronto (e.g., RR Ottawa = 1.21, RR Hamilton = 1.20). CONCLUSIONS There is regional variation in the utilization of resection with permanent colostomy, and in the utilization of postoperative RT among cases not undergoing permanent colostomy. Regions with higher initial rates of resection plus permanent colostomy continue to experience higher probability of permanent colostomy 5 years after diagnosis of rectal cancer. Higher initial rates of permanent colostomy may be malleable to interventions aimed at improving overall outcomes.

The role of computed tomography in the T classification of laryngeal carcinoma

The objectives of this study were 1) to describe patterns of use of computed tomography (CT) in laryngeal carcinoma, and 2) to characterize the contribution of CT to the T classification of laryngeal carcinoma.

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.