Lawrence Paszat

A Multicenter Randomized Trial of Breast Intensity-Modulated Radiation Therapy to Reduce Acute Radiation Dermatitis

PURPOSE Dermatitis is a frequent adverse effect of adjuvant breast radiotherapy. It is more likely in full-breasted women and when the radiation is distributed nonhomogeneously in the breast. Breast intensity-modulated radiation therapy (IMRT) is a technique that ensures a more homogeneous dose distribution. PATIENTS AND METHODS A multicenter, double-blind, randomized clinical trial was performed to test if breast IMRT would reduce the rate of acute skin reaction (notably moist desquamation), decrease pain, and improve quality of life compared with standard radiotherapy using wedges. Patients were assessed each week during and up to 6 weeks after radiotherapy. RESULTS A total of 358 patients were randomly assigned between July 2003 and March 2005 in two Canadian centers, and 331 were included in the analysis. Breast IMRT significantly improved the dose distribution compared with standard radiation. This translated into a lower proportion of patients experiencing moist desquamation during or up to 6 weeks after their radiation treatment; 31.2% with IMRT compared with 47.8% with standard treatment (P = .002). A multivariate analysis found the use of breast IMRT (P = .003) and smaller breast size (P < .001) were significantly associated with a decreased risk of moist desquamation. The use of IMRT did not correlate with pain and quality of life, but the presence of moist desquamation did significantly correlate with pain (P = .002) and a reduced quality of life (P = .003). CONCLUSION Breast IMRT significantly reduced the occurrence of moist desquamation compared with a standard wedged technique. Moist desquamation was correlated with increased pain and reduction in the quality of life.

Bleeding and Perforation After Outpatient Colonoscopy and Their Risk Factors in Usual Clinical Practice

BACKGROUND & AIMS The most widely quoted complication rates for colonoscopy are from case series performed by expert endoscopists. Our objectives were to evaluate the rates of bleeding, perforation, and death associated with outpatient colonoscopy and their risk factors in a population-based study. METHODS We identified all individuals 50 to 75 years old who underwent an outpatient colonoscopy during April 1, 2002, to March 31, 2003, in British Columbia, Alberta, Ontario, and Nova Scotia, Canada. Using administrative data, we identified all individuals who were admitted to hospital with bleeding or perforation within 30 days following the colonoscopy in each province. We calculated the pooled rates of bleeding and perforation from the 4 provinces. In Ontario, we abstracted the hospital charts of all deaths that occurred within 30 days following the procedure. We used generalized estimating equations models to evaluate factors associated with bleeding and perforation. RESULTS We identified 97,091 persons who had an outpatient colonoscopy. The pooled rates of colonoscopy-related bleeding and perforation were 1.64/1000 and 0.85/1000, respectively. The death rate was 0.074/1000 or approximately 1/14,000. Older age, male sex, having a polypectomy, and having the colonoscopy performed by a low-volume endoscopist were associated with increased odds of bleeding or perforation. CONCLUSIONS Although colonoscopy has established benefits for the detection of colorectal cancer and adenomatous polyps, the procedure is associated with risks of serious complications, including death. Older age, male sex, having a polypectomy, and having the procedure done by a low-volume endoscopist were independently associated with colonoscopy-related bleeding and perforation.

Analysis of Administrative Data Finds Endoscopist Quality Measures Associated With Postcolonoscopy Colorectal Cancer

BACKGROUND & AIMS Most quality indicators for colonoscopy measure processes; little is known about their relationship to patient outcomes. We investigated whether characteristics of endoscopists, determined from administrative data, are associated with development of postcolonoscopy colorectal cancer (PCCRC). METHODS We identified individuals diagnosed with colorectal cancer in Ontario from 2000 to 2005 using the Ontario Cancer Registry. We determined performance of colonoscopy using Ontario Health Insurance Plan data. Patients who had complete colonoscopies 7 to 36 months before diagnosis were defined as having a PCCRC. Patients who had complete colonoscopies within 6 months of diagnosis had detected cancers. We determined if endoscopist factors (volume, polypectomy and completion rate, specialization, and setting) were associated with PCCRC using logistic regression, controlling for potential covariates. RESULTS In the study, 14,064 patients had a colonoscopy examination within 36 months of diagnosis; 584 (6.8%) with distal and 676 (12.4%) with proximal tumors had PCCRC. The endoscopists specialty (nongastroenterologist/nongeneral surgeon) and setting (non-hospital-based colonoscopy) were associated with PCCRC. Those who underwent colonoscopy by an endoscopist with a high completion rate were less likely to have a PCCRC (distal: odds ratio [OR], 0.73; 95% confidence interval [CI], 0.54-0.97; P = .03; proximal: OR, 0.72; 95% CI, 0.53-0.97; P = .002). Patients with proximal cancers undergoing colonoscopy by endoscopists who performed polypectomies at high rates had a lower risk of PCCRC (OR, 0.61; 95% CI, 0.42-0.89; P < .0001). Endoscopist volume was not associated with PCCRC. CONCLUSIONS Endoscopist characteristics derived from administrative data are associated with development of PCCRC and have potential use as quality indicators.

Mortality from myocardial infarction after adjuvant radiotherapy for breast cancer in the surveillance, epidemiology, and end-results cancer registries.

PURPOSE To compare the risk for fatal myocardial infarction (MI) after adjuvant radiotherapy (RT) for left-sided breast cancer with the risk for MI after adjuvant RT for right-sided breast cancer. METHODS We studied women with local- and regional-stage breast cancer diagnosed from 1973 to 1992 from the Surveillance, Epidemiology, and End-Results (SEER) cancer registries. We performed life-table analysis, the log-rank test, and Cox proportional hazards regression to compare the time to fatal MI from diagnosis between left-sided and right-sided cases, censoring deaths from other causes. RESULTS Among irradiated patients, the relative risk (RR) for fatal MI in women with left-sided breast cancer was 1.17 (95% confidence interval [CI], 1.01 to 1.36), controlling for age, compared with those with right-sided breast cancer. The RR for fatal MI among left-sided cases was increased for those under the age of 60 years (RR = 1.98; 95% CI, 1.31 to 2.97) compared with right-sided cases, but not at age 60 years or older. Among women with irradiated regional-stage cancer who were younger than 60 years of age, the risk was significantly increased (RR = 2.24; 95% CI, 1.38 to 3.64) for those with left-sided compared with right-sided breast cancer, but not among patients aged 60 years or older. Among irradiated local-stage cases, the risk for those with left-sided breast cancer was not significantly elevated in either age category. Analysis of 5-year conditional survival cohorts showed an increased risk for irradiated left-sided cases among women younger than 60 years of age in the 10- to 15-year conditional survival cohort (RR = 5.28; 95% CI, 1.82 to 15.3). CONCLUSION Adjuvant RT for left-sided breast cancer diagnosed in women younger than 60 years of age is associated with a higher risk for fatal MI 10 to 15 years later compared with adjuvant RT for right-sided cases.

Impact of Androgen Deprivation Therapy on Cardiovascular Disease and Diabetes

PURPOSE Use of androgen deprivation therapy (ADT) may be associated with an increased risk of diabetes mellitus but the risk of both acute myocardial infarction (AMI) and cardiovascular mortality remain controversial because few outcomes and conflicting findings have been reported. We sought to clarify whether ADT is associated with these outcomes in a large, representative cohort. METHODS Using linked administrative databases in Ontario, Canada, men age 66 years or older with prostate cancer given continuous ADT for at least 6 months or who underwent bilateral orchiectomy (n = 19,079) were matched with men with prostate cancer who had never received ADT. Treated and untreated groups were matched 1:1 (ie, hard-matched) on age, prior cancer treatment, and year of diagnosis and propensity-matched on comorbidities, medications, cardiovascular risk factors, prior fractures, and socioeconomic variables. Primary outcomes were development of AMI, sudden cardiac death, and diabetes. Fragility fracture was also examined. Results The cohort was observed for a mean of 6.47 years. In time-to-event analyses, ADT use was associated with an increased risk of diabetes (hazard ratio [HR], 1.16; 95% CI, 1.11 to 1.21) and fragility fracture (HR, 1.65; 95% CI, 1.53 to 1.77) but not with AMI (HR, 0.91; 95% CI, 0.84 to 1.00) or sudden cardiac death (HR, 0.96; 95% CI, 0.83 to 1.10). Increasing duration of ADT was associated with an excess risk of fragility fractures and diabetes but not cardiac outcomes. CONCLUSION Continuous ADT use for at least 6 months in older men is associated with an increased risk of diabetes and fragility fracture but not AMI or sudden cardiac death.

Evaluating Survivorship Care Plans: Results of a Randomized, Clinical Trial of Patients With Breast Cancer

PURPOSE An Institute of Medicine report recommends that patients with cancer receive a survivorship care plan (SCP). The trial objective was to determine if an SCP for breast cancer survivors improves patient-reported outcomes. PATIENTS AND METHODS Women with early-stage breast cancer who completed primary treatment at least 3 months previously were eligible. Consenting patients were allocated within two strata: less than 24 months and ≥ 24 months since diagnosis. All patients were transferred to their own primary care physician (PCP) for follow-up. In addition to a discharge visit, the intervention group received an SCP, which was reviewed during a 30-minute educational session with a nurse, and their PCP received the SCP and guideline on follow-up. The primary outcome was cancer-related distress at 12 months, assessed by the Impact of Event Scale (IES). Secondary outcomes included quality of life, patient satisfaction, continuity/coordination of care, and health service measures. RESULTS Overall, 408 survivors were enrolled through nine tertiary cancer centers. There were no differences between groups on cancer-related distress or on any of the patient-reported secondary outcomes, and there were no differences when the two strata were analyzed separately. More patients in the intervention than control group correctly identify their PCP as primarily responsible for follow-up (98.7% v 89.1%; difference, 9.6%; 95% CI, 3.9 to 15.9; P = .005). CONCLUSION The results do not support the hypothesis that SCPs are beneficial for improving patient-reported outcomes. Transferring follow-up to PCPs is considered an important strategy to meet the demand for scarce oncology resources. SCPs were no better than a standard discharge visit with the oncologist to facilitate transfer.

Risk of Developing Proximal Versus Distal Colorectal Cancer After a Negative Colonoscopy: A Population-Based Study

BACKGROUND & AIMS The incidence of colorectal cancer (CRC) overall is reduced for up to 10 years after a negative colonoscopy. The objective of this research was to determine the incidence of proximal and distal CRC after a negative complete colonoscopy. METHODS A cohort of Ontario residents aged 50 to 80 years who had a negative complete colonoscopy between January 1, 1992, and December 31, 1997, was identified by using linked administrative databases. Cohort members had no prior history of CRC, inflammatory bowel disease, or recent colonic resection. Each individual was followed up through December 31, 2005, and the relative rate (RR) of overall CRC, distal CRC, and proximal CRC was compared with the remaining Ontario population. RESULTS A cohort of 110,402 individuals with a negative complete colonoscopy was identified. The RR of CRC overall and the RR of distal CRC remained significantly lower than the Ontario population. For example, at year 14 the RR of distal CRC was 0.21 (95% confidence interval, 0.05-0.36). The RR of proximal CRC was significantly lower than the Ontario population in half of the follow-up years, mainly after 7 years of follow-up. CONCLUSIONS Over a 14-year follow-up period, negative complete colonoscopy was associated with a subsequent reduced incidence of CRC overall, and of incident CRC in the distal colon. However, the reduction in incidence of proximal CRC differed in magnitude and timing, and occurred in half the follow-up years, mainly after 7 years of follow-up. These results highlight an important limitation of colonoscopy in usual clinical practice.

Next-Generation Stool DNA Test Accurately Detects Colorectal Cancer and Large Adenomas

BACKGROUND & AIMS Technical advances have led to stool DNA (sDNA) tests that might accurately detect neoplasms on both sides of the colorectum. We assessed colorectal neoplasm detection by a next-generation sDNA test and effects of covariates on test performance. METHODS We performed a blinded, multicenter, case-control study using archived stool samples collected in preservative buffer from 252 patients with colorectal cancer (CRC), 133 with adenomas ≥ 1 cm, and 293 individuals with normal colonoscopy results (controls); two-thirds were randomly assigned to a training set and one-third to a test set. The sDNA test detects 4 methylated genes, a mutant form of KRAS, and the α-actin gene (as a reference value) using quantitative, allele-specific, real-time target and signal amplification; it also quantifies hemoglobin. We used a logistical model to analyze data. RESULTS The sDNA test identified 85% of patients with CRC and 54% of patients with adenomas ≥1 cm with 90% specificity. The test had a high rate of detection for all nonmetastatic stages of CRC (aggregate 87% detection rate for CRC stages I-III). Detection rates increased with adenoma size: 54% ≥ 1 cm, 63% >1 cm, 77% >2 cm, 86% >3 cm, and 92% >4 cm (P < .0001). Based on receiver operating characteristic analysis, the rate of CRC detection was slightly greater for the training than the test set (P = .04), whereas the rate of adenoma detection was comparable between sets. Sensitivities for detection of CRC and adenoma did not differ with lesion site. CONCLUSIONS Early-stage CRC and large adenomas can be detected throughout the colorectum and with high levels of accuracy by the sDNA test. Neoplasm size, but not anatomical site, affected detection rates. Further studies are needed to validate the findings in a larger population and optimize the sDNA test.

Socioeconomic status and cancer survival in Ontario.

BACKGROUND AND PURPOSE It is known that the socioeconomic status (SES) of the patient is associated with cancer survival in the United States. The purpose of this study was to determine whether the association between SES and survival is also present in Canada, a society with a comprehensive, universal, health insurance program. METHODS A population-based cancer registry was used to identify the 357,530 cases of invasive cancer diagnosed in the Canadian province of Ontario between 1982 and 1991. Information from the 1986 Canadian census was linked to the registry and used to describe the SES of the area in which each patient resided. Cox regression was used to describe the association between median household income and survival while controlling for age, sex, and the region in which the patient resided. The Cox model was fitted in a competing risk framework to assess the association between income and the probability of specific causes of death. RESULTS Lung cancer and cancers of the head and neck region were relatively more common in poor-income communities, and cancers of the breast, CNS, and testis were relatively more common in richer communities. A strong and statistically significant association between community income and survival was observed in cancers of the head and neck region, cervix, uterus, breast, prostate, bladder, and esophagus. Smaller, but significant associations were seen in cancers of the lung and rectum. No significant association between community income and survival was observed in cancers of the stomach, colon, pancreas, or ovary. Analysis of the cause of death showed that community income is associated both with the probability of death from cancer and with the probability of death from other causes. CONCLUSION Although Canadas health care system was designed to provide equitable access to equivalent standards of care, it does not prevent a difference in cancer survival between rich and poor communities.

A comparison of risk perception and psychological morbidity in women with ductal carcinoma in situ and early invasive breast cancer.

AbstractPurpose. To assess how women with ductal carcinoma in situ (DCIS) perceive their risks of recurrence, dying from breast cancer, and psychological distress compared to women with early stage invasive breast cancer (EIBC). Patients and methods. Eligible patients included those with DCIS or EIBC (T1 or T2, N0) referred to one cancer center between November 1998 and June 1999. Participants completed a self-administered survey regarding their views of their risks of developing recurrent cancer, of dying of breast cancer and the presence of psychological symptoms of distress. Responses were scored and compared between the two groups. Results. In total, 495 patients were screened, 240 found ineligible, 228 patients who agreed to participate. No significant difference between the two groups was observed in perceptions of risk related to the likelihood of developing local recurrence (DCIS: 53%, EIBC 45%, P = 0.14), distant recurrence (DCIS: 36%; EIBC: 39%, P = 0.35) or dying of breast cancer (DCIS: 27%, EIBC 27%, P = 0.5). Both groups expressed similar levels of psychological distress (anxiety, DCIS: 56%, EIBC 54%, P = 0.38; depression, DCIS: 41%, EIBC, 48%, P = 0.17). Conclusions. Despite the excellent prognosis, women with DCIS express serious concerns and report similar psychological morbidity as women with invasive cancer.