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PubMed2005

Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X.

CONTEXT: Approximately 60% of families that meet the Amsterdam-I criteria (AC-I) for hereditary nonpolyposis colorectal cancer (HNPCC) have a hereditary abnormality in a DNA mismatch repair (MMR) gene. Cancer incidence in AC-I families with MMR gene mutations is reported to be very high, but cancer incidence for individuals in AC-I families with no evidence of an MMR defect is unknown. OBJECTIVE: To determine if cancer risks in AC-I families with no apparent deficiency in DNA MMR are different from cancer risks in AC-I families with DNA MMR abnormalities. DESIGN, SETTING, AND PARTICIPANTS: Identification (1997-2001) of 161 AC-I pedigrees from multiple population- and clinic-based sources in North America and Germany, with families grouped into those with (group A) or without (group B) MMR deficiency by tumor testing. A total of 3422 relatives were included in the analyses. MAIN OUTCOME MEASURES: Cancer incidence in groups A and B (excluding the 3 affected members used to define each pedigree as AC-I) and computed age- and sex-adjusted standardized incidence ratios (SIRs) using Surveillance, Epidemiology, and End Results data. RESULTS: Group A families from both population- and clinic-based series showed increased incidence of the HNPCC-related cancers. Group B families showed increased incidence only for colorectal cancer (SIR, 2.3; 95% confidence interval, 1.7-3.0) and to a lesser extent than group A (SIR, 6.1; 95% confidence interval, 5.2-7.2) (P<.001). CONCLUSIONS: Families who fulfill AC-I criteria but who have no evidence of a DNA MMR defect do not share the same cancer incidence as families with HNPCC-Lynch syndrome (ie, hereditary MMR deficiency). Relatives in such families have a lower incidence of colorectal cancer than those in families with HNPCC-Lynch syndrome, and incidence may not be increased for other cancers. These families should not be described or counseled as having HNPCC-Lynch syndrome. To facilitate distinguishing these entities, the designation of "familial colorectal cancer type X" is suggested to describe this type of familial aggregation of colorectal cancer.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Comorbidity and survival disparities among black and white patients with breast cancer.

CONTEXT: Reasons for the shorter survival of black breast cancer patients compared with their white counterparts are not completely understood. OBJECTIVE: To evaluate the role of comorbidity in this racial disparity among breast cancer patients. DESIGN, SETTING, AND PATIENTS: Historical cohort from the Henry Ford Health System (a large comprehensive health system in Detroit, Mich) followed up for a median of 10 years. Patients (n = 906) included 264 black (29.1%) and 642 white (70.9%) women diagnosed as having breast cancer between 1985 and 1990. Detailed comorbidity data (268 comorbidities) and study data were abstracted from medical records and institutional, Surveillance, Epidemiology, and End Results, and Michigan State registries. Associations were analyzed with logistic and Cox regression. MAIN OUTCOME MEASURES: Breast cancer recurrence/progression and survival to death from all, breast cancer, and competing (non-breast cancer) causes. RESULTS: Of blacks, 64 (24.9%) died of breast cancer and 95 (37.0%) died of competing causes. Comparable data for whites were 115 (18.3%) and 202 (32.1%). Blacks had worse all-cause survival (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.11-1.62), breast cancer-specific survival (HR, 1.47; 95% CI, 1.08-2.00), and competing-causes survival (HR, 1.27; 95% CI, 1.00-1.63). A total of 77 adverse comorbidities were associated with reduced survival. Adverse comorbidity count was associated with all-cause (adjusted HR, 1.29; 95% CI, 1.19-1.40) and competing-causes survival but was not associated with recurrence/progression or breast cancer-specific survival. At least 1 adverse comorbidity was observed in 221 (86.0%) blacks and 407 (65.7%) whites (odds ratio, 3.20; 95% CI, 2.17-4.72). Comparisons of unadjusted and comorbidity-adjusted HRs indicated that adverse comorbidity explained 49.1% of all-cause and 76.7% of competing-causes survival disparity. Diabetes and hypertension were particularly important in explaining disparity. CONCLUSIONS: More black breast cancer patients die of competing causes than of breast cancer. Effective control of comorbidity in black breast cancer patients should help improve life expectancy and lead to a reduction in survival disparities.

Adult↗
PubMed2005

Risk of pelvic fractures in older women following pelvic irradiation.

CONTEXT: Pelvic fractures, including hip fractures, are a major source of morbidity and mortality in older women. Although therapeutic pelvic irradiation could increase the risk of such fractures, this effect has not been studied. OBJECTIVE: To determine if women who undergo pelvic irradiation for pelvic malignancies (anal, cervical, or rectal cancers) have a higher rate of pelvic fracture than women with pelvic malignancies who do not undergo irradiation. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked to Medicare claims data. A total of 6428 women aged 65 years and older diagnosed with pelvic malignancies from 1986 through 1999 were included. We compared results for women who did (n = 2855) vs did not (n = 3573) undergo radiation therapy. To assess the influence of selection bias, we also evaluated the effect of irradiation on osteoporotic fractures in nonirradiated sites (arm and spine). MAIN OUTCOME MEASURE: We evaluated the effect of irradiation on the incidence of pelvic fractures over time, and adjusted for potential confounders using a proportional hazards model. RESULTS: Women who underwent radiation therapy were more likely to have a pelvic fracture than women who did not undergo radiation therapy (cumulative 5-year fracture rate, 14.0% vs 7.5% in women with anal cancer, 8.2% vs 5.9% in women with cervical cancer, and 11.2% vs 8.7% in women with rectal cancer); the difference was statistically significant and most fractures (90%) were hip fractures. We controlled for potential confounders including age, race, cancer stage, and geographic location. The impact of irradiation varied by cancer site: treatment for anal cancer was associated with a higher risk of pelvic fractures (hazard ratio, 3.16; 95% confidence interval, 1.48-6.73); than for cervical cancer (hazard ratio, 1.66; 95% confidence interval, 1.06-2.59); or rectal cancer (hazard ratio, 1.65; 95% confidence interval, 1.33-2.05). No statistically significant difference was found in the rate of arm or spine fractures between the irradiated and nonirradiated groups (hazard ratio, 1.15; 95% confidence interval, 0.89-1.48). CONCLUSIONS: Pelvic irradiation substantially increases the risk of pelvic fractures in older women. Given the high baseline risk of pelvic fracture, this finding is of particular concern.

Aged↗
PubMed2006

Survival associated with treatment vs observation of localized prostate cancer in elderly men.

CONTEXT: Prostate-specific antigen screening has led to an increase in the diagnosis and treatment of localized prostate cancer. However, the role of active treatment of low- and intermediate-risk disease in elderly men is controversial. OBJECTIVE: To estimate the association between treatment (with radiation therapy or radical prostatectomy) compared with observation and overall survival in men with low- and intermediate-risk prostate cancer. DESIGN AND SETTING: Observational US cohort from Surveillance, Epidemiology, and End Results Medicare data. PATIENTS: At total of 44,630 men aged 65 to 80 years who were diagnosed between 1991 and 1999 with organ-confined, well- or moderately differentiated prostate cancer and who had survived more than a year past diagnosis. Patients were followed up until death or study end (December 31, 2002). Patients were classified as having received treatment (n=32,022) if they had claims for radical prostatectomy or radiation therapy during the first 6 months after diagnosis. They were classified as having received observation (n=12,608) if they did not have claims for radical prostatectomy, radiation, or hormonal therapy. Patients who received only hormonal therapy were excluded. MAIN OUTCOME MEASURE: Overall survival. RESULTS: At the end of the 12-year study period, 4663 men (37%) in the observational group and 7639 men (23.8%) in the treatment group had died. The treatment group had longer 5- and 10-year survival than the observation group. After using propensity scores to adjust for potential confounders (tumor characteristics, demographics, and comorbidities), there was a statistically significant survival advantage associated with treatment (hazard ratio, 0.69; 95% confidence interval, 0.66-0.72). A benefit associated with treatment was seen in all subgroups examined, including older men (aged 75-80 years at diagnosis), black men, and men with low-risk disease. CONCLUSIONS: This study suggests a survival advantage is associated with active treatment for low- and intermediate-risk prostate cancer in elderly men aged 65 to 80 years. Because observational data cannot completely adjust for potential selection bias and confounding, these results must be validated in randomized controlled trials of alternative management strategies in elderly men with localized prostate cancer.

Aged↗
PubMed2006

Relation between Medicare screening reimbursement and stage at diagnosis for older patients with colon cancer.

CONTEXT: Medicare's reimbursement policy was changed in 1998 to provide coverage for screening colonoscopies for patients with increased colon cancer risk, and expanded further in 2001 to cover screening colonoscopies for all individuals. OBJECTIVE: To determine whether the Medicare reimbursement policy changes were associated with an increase in either colonoscopy use or early stage colon cancer diagnosis. DESIGN, SETTING, AND PARTICIPANTS: Patients in the Surveillance, Epidemiology, and End Results Medicare linked database who were 67 years of age and older and had a primary diagnosis of colon cancer during 1992-2002, as well as a group of Medicare beneficiaries who resided in Surveillance, Epidemiology, and End Results areas but who were not diagnosed with cancer. MAIN OUTCOME MEASURES: Trends in colonoscopy and sigmoidoscopy use among Medicare beneficiaries without cancer were assessed using multivariate Poisson regression. Among the patients with cancer, stage was classified as early (stage I) vs all other (stages II-IV). Time was categorized as period 1 (no screening coverage, 1992-1997), period 2 (limited coverage, January 1998-June 2001), and period 3 (universal coverage, July 2001-December 2002). A multivariate logistic regression (outcome = early stage) was used to assess temporal trends in stage at diagnosis; an interaction term between tumor site and time was included. RESULTS: Colonoscopy use increased from an average rate of 285/100,000 per quarter in period 1 to 889 and 1919/100,000 per quarter in periods 2 (P<.001) and 3 (P vs 2<.001), respectively. During the study period, 44,924 eligible patients were diagnosed with colorectal cancer. The proportion of patients diagnosed at an early stage increased from 22.5% in period 1 to 25.5% in period 2 and 26.3% in period 3 (P<.001 for each pairwise comparison). The changes in Medicare coverage were strongly associated with early stage at diagnosis for patients with proximal colon lesions (adjusted relative risk period 2 vs 1, 1.19; 95% confidence interval, 1.13-1.26; adjusted relative risk period 3 vs 2, 1.10; 95% confidence interval, 1.02-1.17) but weakly associated, if at all, for patients with distal colon lesions (adjusted relative risk period 2 vs 1, 1.07; 95% confidence interval, 1.01-1.13; adjusted relative risk period 3 vs 2, 0.97; 95% confidence interval, 0.90-1.05). CONCLUSIONS: Expansion of Medicare reimbursement to cover colon cancer screening was associated with an increased use of colonoscopy for Medicare beneficiaries, and for those who were diagnosed with colon cancer, an increased probability of being diagnosed at an early stage. The selective effect of the coverage change on proximal colon lesions suggests that increased use of whole-colon screening modalities such as colonoscopy may have played a pivotal role.

Aged↗
PubMed1998

Time trends in distal colorectal cancer subsite location related to age and how it affects choice of screening modality.

BACKGROUND AND OBJECTIVES: A time trend analysis of colorectal cancer (CRC) incidence in the distal colorectum as a proportion of total CRC is presented for the period 1977-1994 as a function of age, to determine the age at which Americans might best be served by screening fiberoptic sigmoidoscopy. METHODS: CRC incidence rates were obtained for each anatomic subsite from SEER Public Use Files for 1977, 1986, and 1994. The colorectum was divided anatomically for these analyses at the junction of the descending colon and sigmoid colon. Incidence in the distal colorectum was divided by total CRC incidence to determine the proportion of CRC in that age/race/gender/year cohort located in the distal colorectum. RESULTS: The proportion of distal CRC among African Americans was without a clear trend as they grew older in each of the years of observation and in both genders. However, in whites, with increasing age, the proportion of distal disease declined progressively in both genders, with the greatest decline in 1994. Distal CRC became less prevalent than proximal at about age 72 years in white women and at age 82 in white men in 1994. CONCLUSIONS: As the white population becomes older, and for African Americans of all ages, more total colon screening modalities are needed, although at the onset of recommended screening, among 50- to 60-year-olds, fiberoptic sigmoidoscopy would appear efficacious.

Age Factors↗
PubMed1999

Carcinoma in situ of the colorectum: SEER trends by race, gender, and total colorectal cancer.

BACKGROUND AND OBJECTIVES: To determine if Americans of African origin (blacks) have less access to colonoscopic polypectomy than Americans of European origin (whites), the rate of carcinoma in situ of the colorectum (CIS), a disease more similar to benign adenoma of the colorectum than invasive cancer in its symptomatology, discovery, and treatment, was determined in the United States from 1973 to 1994. The hypothesis being tested is that CIS will be far less common in blacks than in whites and that rates of CIS should be increasing in whites from 1973 to 1994. METHODS: CIS and invasive carcinoma of the colorectum incidence data were obtained from Surveillance, Epidemiology, and End Results (SEER) Public Use Files from 1973 through 1994. Rates were age adjusted and proportions determined by division of CIS rates for each subsite by total carcinoma rates, for each year, race, and gender. The colorectum was divided anatomically in this analysis at the junction of the descending and sigmoid colon. RESULTS: The relationships between male/female and black/white CIS incidence rates were broadly similar to invasive cancer rates over the 21 years of SEER, demonstrating a white male predominance for distal disease, a black male predominance for proximal disease, and a decline in incidence since 1988. CIS as a proportion of total colorectal cancer increased in all races and genders from 1973 to 1987, but then declined in all groups. CONCLUSIONS: The majority of CIS is excised by endoscopic resection. Therefore, this might be considered a surrogate population for those individuals who have colonoscopic resection of benign adenomas. It is this latter treatment that has been hypothesized to be the cause for the declining incidence of invasive colorectal cancer. However, data presented herein do not support this hypothesis.

Black People↗
PubMed2000

Early deaths in childhood cancer.

BACKGROUND: Deaths prior to or shortly after the diagnosis of childhood cancer may reflect inadequacies in detection and appropriate referral for care. This study was performed to determine the extent of and factors associated with early death in childhood cancer. PROCEDURE: Patients with of primary cancer, aged <20 years at diagnosis, were identified from the SEER data (n = 23,470) from 1973 to 1995. Early deaths were defined as cases identified by 1) death certificate, 2) autopsy report, or 3) death within 1 month of initial diagnoses (n = 481). Cause of death was determined by ICD-8 and -9 codes. Age at diagnosis, year of diagnosis, morphology, site of disease, race, and gender were evaluated for association with early death. RESULTS: Age <1 year at diagnosis (6.2% early deaths), being diagnosed earlier in the observation period, and a diagnosis of a brain tumor, neuroblastoma, leukemia, or liver tumor were associated with increased early death. Gender and race were not associated with early death. Among the cases for whom the malignant diagnosis was made at the time of death (n = 119), the cause of death was nonmalignant for 36. For 22 of these cases the malignancy was an incidental finding and appeared not to contribute directly to the cause of death. Among these patients, 11 had neuroblastoma, 9 being <1 year of age. CONCLUSIONS: A decrease in the proportion of early deaths associated with childhood cancer has occurred during the past 2 decades. This decrease may reflect earlier diagnosis or improved imaging capabilities, surgical techniques, medical therapy, and supportive care. Awareness among pediatricians, general practitioners, and emergency physicians is warranted, with a focus on high-risk groups for early detection among childhood cancer patients.

Adolescent↗
PubMed1997

Risk of multiple primary cancers in prostate cancer patients in the Detroit metropolitan area: a retrospective cohort study.

BACKGROUND: Patterns of excess risk for second primary cancers (SPC) in prostate cancer patients have been observed for urinary bladder, other sites in the urinary tract, and hematolymphopoietic tissues in several, but not all, previously reported cohort studies. METHODS: The risk of SPC was evaluated in 9,794 Detroit metropolitan-area men originally diagnosed with carcinoma of the prostate during 1973-1982. The cohort was assembled using Detroit Surveillance, Epidemiology, and End Results (SEER) Registry data and followed until December 31, 1993. RESULTS: The observed number of SPC of all sites was similar to the expected number in the cohort. A significant excess of invasive SPC of the urinary bladder [Standardized incidence ratio (SIR) = 1.57; 95% CI, 1.34-1.83] was observed in this cohort, but after excluding the first 2 months after prostate cancer diagnosis, the excess (SIR = 1.06) was no longer statistically significant. The cumulative proportion of patients with prostate cancer who developed bladder cancer during a follow-up interval of 20 years was 5.5% (95% CI, 4.1-6.9%). The patients who received first-course radiation treatment were observed to be at increased risk for bladder SPC (all stages; SIR = 1.49; 95% CI, 1.07-2.02) when compared to the Detroit-area male population. CONCLUSIONS: These results underscore the importance of continuing medical surveillance for urinary bladder second primary cancers in patients with prostate cancer, but are reassuring in that the magnitude of relative and absolute risks does not suggest deterring adverse effects of radiation treatment or intrinsic risks for neoplasms in other organs or tissues.

Adult↗
PubMed1996

The New Mexico Mammography Project. Screening mammography performance in Albuquerque, New Mexico, 1991 to 1993.

BACKGROUND: This project was designed to collect and link population-based mammography and breast carcinoma data to assess the performance of community mammography screening. METHODS: Computerized data were collected from all radiology practices in Albuquerque, New Mexico. The data were linked by computer match to breast carcinomas in a statewide cancer registry. Analysis is based on 126,466 screening mammogram studies performed on 87,443 female residents of New Mexico between the ages of 35 and 84 by 5 radiology groups. Sensitivity, specificity, positive predictive value, and call back rates were calculated as indicators of the discriminative performance of mammography. Carcinoma size and stage distribution were analyzed as outcome measurements. RESULTS: The computer match linked 634 breast carcinomas to the 126,466 screening mammogram series. The community-wide sensitivity was 79.9%, and specificity was 90.5%. The predictive value of an abnormal screen was 4.3%, and that of a biopsy recommendation result was 16.9%. The call back rate was 11.4%. The median invasive breast carcinoma size was 15 mm, 20.3% of carcinomas were in situ, 18.3% were lymph node positive, and 68.1% were Stage 0 or Stage 1. CONCLUSIONS: Mass screening mammography as practiced in Albuquerque, New Mexico, is able to detect breast carcinomas at early, treatable stages. The stage distribution of carcinomas is similar to that seen in successful clinical trials. However, measures of mammography performance show lower sensitivity, more additional studies, and more biopsy recommendations in this community setting than have been reported by expert mammographers.

Adult↗
PubMed1997

Computer-derived nuclear features compared with axillary lymph node status for breast carcinoma prognosis.

BACKGROUND: Both axillary lymph node involvement and tumor anaplasia, as expressed by visually assessed grade, have been shown to be prognostically important in breast carcinoma outcome. In this study, axillary lymph node involvement was used as the standard against which prognostic estimations based on computer-derived nuclear features were gauged. METHODS: The prognostic significance of nuclear morphometric features determined by computer-based image analysis were analyzed in 198 consecutive preoperative samples obtained by fine-needle aspiration (FNA) from patients with invasive breast carcinoma. A novel multivariate prediction method was used to model the time of distant recurrence as a function of the nuclear features. Prognostic predictions based on the nuclear feature data were cross-validated to avoid overly optimistic conclusions. The estimated accuracy of these prognostic determinations was compared with determinations based on the extent of axillary lymph node involvement. RESULTS: The predicted outcomes based on nuclear features were divided into three groups representing best, intermediate, and worst prognosis, and compared with the traditional TNM lymph node stratification. Nuclear feature stratification better separated the prognostically best from the intermediate group whereas lymph node stratification better separated the prognostically intermediate from the worst group. Prognostic accuracy was not increased by adding lymph node status or tumor size to the nuclear features. CONCLUSIONS: Computer analysis of a preoperative FNA more accurately identified prognostically favorable patients than did pathologic examination of axillary lymph nodes and may obviate the need for routine axillary lymph node dissection.

Artificial Intelligence↗
PubMed1997

Second malignant neoplasms occuring in survivors of osteosarcoma.

BACKGROUND: Second malignant neoplasms have been noted infrequently in survivors of osteosarcoma treated before 1970. METHODS: For the above reason, the authors surveyed their patients to determine the actuarial incidence and relative risk of second malignancies among patients treated with adjuvant chemotherapy for osteosarcoma. RESULTS: Between March 1962 and March 1996, 334 patients received chemotherapy for newly diagnosed primary or metastatic osteosarcoma. Of these patients, 47 presented with metastases, 14 had multifocal osteosarcoma, and 273 had localized disease. Nine patients developed second malignant neoplasms 0.45-17.8 years (median, 6.3 years) after receiving definitive surgery and adjuvant chemotherapy for primary osteosarcoma; 2 of these patients had pulmonary metastasectomies before receiving adjuvant chemotherapy. The second neoplasms comprised two cases of malignant fibrous histiocytoma and one case each of melanoma, glioblastoma multiforme, chondrosarcoma, and carcinoma of the breast: stomach, colon, rectum. The overall 10-year cumulative incidence of second malignancies was 2% +/- 1%; by comparison, this rate was 2% +/- 1% for patients with localized osteosarcoma but was 8% +/- 5% (P = 0.15) for those who presented with metastatic disease. CONCLUSIONS: Since the advent of successful adjuvant chemotherapy, more patients are surviving primary osteosarcoma; therefore, the number of osteosarcoma patients who develop second malignancies can be expected to increase. Recognition of osteosarcoma patients who are members of families with Li-Fraumeni syndrome may lead to earlier intervention for these individuals.

Adolescent↗
PubMed1998

Use of Medicare claims data to measure county-level variations in the incidence of colorectal carcinoma.

BACKGROUND: Population-based cancer registries that can be used to compare cancer incidence and mortality across regions of the U.S. are currently lacking. The authors conducted this study to validate Medicare claims as a measure of county-level colorectal carcinoma incidence among older Americans. Variations found among counties are described in this article. METHODS: A total of 183,174 hospitalized patients age 65 years in 1991-1993 with newly diagnosed colorectal carcinoma who resided in one of 480 large counties were identified in Medicare files. The county-level truncated age, race, and gender adjusted incidence rates for the population age 65 years, the proportion of patients with a code indicating distant metastases, and the 2-year case-fatality rates were determined. Corresponding rates from the SEER database were compared. RESULTS: The median truncated adjusted 3-year incidence rate was 870 per 100,000 (Quartile 1-Quartile 3, 779-955), with almost twofold differences among counties even after the exclusion of outliers. The median proportion of patients with codes indicating distant metastases was 23.4% (range, 10.2-46.9%; Quartile 1-Quartile 3, 20.8-25.8), and the average 2-year case-fatality rate was 39.2% (range, 26.5-51.4%; Quartile 1-Quartile 3, 37.0-41.6). Medicare files tended to underestimate the truncated incidence rate according to SEER, but among counties the two sets of rates were closely correlated (r = 0.94, P < 0.0001). CONCLUSIONS: Medicare files are a potential alternative source of national data for the study of colorectal carcinoma incidence among the elderly at the county level. The data also suggest significant variations among counties in colorectal carcinoma incidence, stage, and mortality that could be used in public health initiatives.

Age Factors↗