33 results on '"Begg, Colin B."'
Search Results
2. Attribution of Deaths Following Cancer Treatment.
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Begg, Colin B. and Schrag, Deborah
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CANCER , *PATIENTS , *DEATH - Abstract
Determines the incidence and mortality rates of cancer in the U.S. Causes of death; Growth in the use of cancer-directed surgery; Classification of cancer mortality.
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- 2002
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3. Marketing Drugs Too Early in Testing.
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Begg, Colin B., Brawley, Otis, Califf, Robert M., Demets, David L., Ellenberg, Susan S., and Kaplan, Richard S.
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DRUG approval , *LEGISLATIVE bills , *DRUG laws , *DRUG traffic , *COMMERCIAL law , *DRUG side effects , *TOXICOLOGY - Abstract
This article reports that the U.S. Food and Drug Administration has had the authority to approve new drugs for sale in the United States on the basis of their demonstrated safety and efficacy since 1962. Since that time the agency has regularly come under attack by those who believe that access to drugs should be governed by market forces rather than the scientific evaluation of the balance of their benefits and risks. This view has now entered the political domain in the form of a bill before the U.S. Senate, entitled the "Access, Compassion, Care and Ethics for Seriously Ill Patients Act." This bill, if it becomes law will permit marketing of drugs for serious illnesses on the basis of results from non-human studies and a Phase I trial, a trial solely designed to establish a tolerable dose but not designed to assess whether the drug is actually effective or to develop an understanding of its risks. This bill has caused much consternation in the scientific community. The vast majority of drugs that enter Phase I testing turn out to be either ineffective or toxic. Consequently, if the bill becomes law, the market could be flooded with ineffective and possibly harmful agents.
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- 2006
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4. Clinical Trial Participation Among Older Adult Medicare Fee-for-Service Beneficiaries With Cancer.
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Green AK, Tabatabai SM, Aghajanian C, Landgren O, Riely GJ, Sabbatini P, Bach PB, Begg CB, Lipitz-Snyderman A, and Mailankody S
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- Aged, Humans, Male, Female, United States, Cohort Studies, Retrospective Studies, Fee-for-Service Plans, Medicare, Neoplasms therapy
- Abstract
Importance: Clinical trials play a critical role in the development of novel cancer therapies, and precise estimates of the frequency with which older adult patients with cancer participate in clinical trials are lacking., Objective: To estimate the proportion of older adult Medicare Fee-for-Service (FFS) beneficiaries with cancer who participate in interventional cancer clinical trials, using a novel population-based methodology., Design, Setting, and Participants: In this retrospective cohort study evaluating clinical trial participation among older adult patients with cancer from January 1, 2014, through June 30, 2020, claims data from Medicare FFS were linked with the ClinicalTrials.gov to determine trial participation through the unique National Clinical Trial (NCT) identifier. The proportion of patients with newly diagnosed or newly recurrent cancer in 2015 participating in an interventional clinical trial and receiving active cancer treatment from January 2014 to June 2020 was estimated. Data analysis was performed from November 18, 2020, to November 1, 2021., Exposures: Patients with cancer aged 65 years or older with Medicare FFS insurance, with and without active cancer treatment., Main Outcomes and Measures: Enrollment in clinical trials among all patients with cancer 65 years and older and among patients receiving active cancer treatments as defined by the presence of at least 1 NCT identifier corresponding to an interventional cancer clinical trial in Medicare claims., Results: Among 1 150 978 patients (mean [SD] age, 75.7 [8.4] years; 49.9% men and 50.1% women) with newly diagnosed or newly recurrent cancer in 2015, 12 028 (1.0%) patients had a billing claim with an NCT identifier indicating enrollment in an interventional cancer clinical trial between January 2014 and June 2020. In a subset of 429 343 patients with active cancer treatment, 8360 (1.9%) were enrolled in 1 or more interventional trials. Patients enrolled in a trial tended to be younger, male, a race other than Black, and residing in zip codes with high median incomes., Conclusions and Relevance: Findings of this cohort study show that clinical trial enrollment among older adult patients with cancer remains low, with only 1.0% to 1.9% of patients with newly diagnosed or recurrent cancer in 2015 participating in an interventional cancer clinical trial as measured by the presence of NCT identifiers in Medicare claims. These data provide a contemporary estimate of trial enrollment, persistent disparities in trial participation, and only limited progress in trial access over the past 2 decades.
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- 2022
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5. Validation of a Population-Based Data Source to Examine National Cancer Clinical Trial Participation.
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Green AK, Tabatabai SM, Bai X, Mishra Meza A, Lesny AM, Aghajanian C, Landgren O, Riely GJ, Sabbatini P, Salner A, Lipkin S, Ip A, Bach PB, Begg CB, Mailankody S, and Lipitz-Snyderman A
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- Adult, Aged, Cohort Studies, Humans, Information Storage and Retrieval, Retrospective Studies, United States, Medicare, Neoplasms epidemiology, Neoplasms therapy
- Abstract
Importance: The Centers for Medicare & Medicaid Services requires health care organizations to report the National Clinical Trial (NCT) identifier on claims for items and services related to clinical trials that qualify for coverage. This same NCT identifier is used to identify clinical trials in the ClinicalTrials.gov registry. If linked, this information could facilitate population-based analyses of clinical trial participation and outcomes., Objective: To evaluate the validity of a linkage between fee-for-service (FFS) Medicare claims and ClinicalTrials.gov through the NCT identifier for patients with cancer enrolled in clinical trials., Design, Setting, and Participants: This cohort study included 2 complementary retrospective analyses for a validation assessment. First, billing data from 3 health care institutions were used to estimate the missingness of the NCT identifier in claims by calculating the proportion of known participants in cancer clinical trials with no NCT identifier on any submitted Medicare claims. Second, the Surveillance Epidemiology and End Results-Medicare data set, which includes a subset of all FFS Medicare beneficiaries for whom health insurance claims are linked with cancer registry data, was used to identify adult patients diagnosed with cancer between 2006 and 2015 with an NCT identifier in claims corresponding to an interventional cancer clinical trial. To estimate the accuracy of the NCT identifier when present, the proportion of NCT identifiers that corresponded to trials that were aligned with the patients' known primary or secondary diagnoses was calculated. Data were analyzed from March 2020 to March 2021., Exposures: An NCT identifier present in Medicare claims., Main Outcomes and Measures: The main outcome was participating in a clinical trial relevant to patient's cancer diagnosis., Results: A total of 1 171 816 patients were included in analyses. Across the 3 participating institutions, there were 5061 Medicare patients enrolled in a clinical trial, including 3797 patients (75.0%) with an NCT identifier on at least 1 billing claim that matched the clinical trial on which the patient was participating. Among 1 171 816 SEER-Medicare patients, 29 138 patients (2.5%) had at least 1 claim with a value entered in the NCT identifier field corresponding to 32 950 unique patient-NCT identifier pairs. There were 26 694 pairs (81.0%) with an NCT identifier corresponding to a clinical trial registered in ClinicalTrials.gov, of which 10 170 pairs (38.1%) were interventional cancer clinical trials. Among these, 9805 pairs (96.4%) were considered appropriate., Conclusions and Relevance: In this cohort study, this data linkage provided a novel data source to study clinical trial enrollment patterns among Medicare patients with cancer on a population level. The presence of the NCT identifiers in claims for Medicare patients participating in clinical trials is likely to improve over time with increasing adherence with the Centers for Medicare & Medicaid Services mandate.
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- 2022
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6. The costs of cancer drugs.
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Begg CB
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- Antineoplastic Agents therapeutic use, Costs and Cost Analysis, Humans, Randomized Controlled Trials as Topic, United States, United States Food and Drug Administration, Antineoplastic Agents economics, Neoplasms drug therapy
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- 2020
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7. Expedited approval programs at the Food and Drug Administration.
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Begg CB and Ellenberg SS
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- Humans, Product Surveillance, Postmarketing standards, Randomized Controlled Trials as Topic, Research Design, United States, United States Food and Drug Administration, Drug Approval
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- 2018
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8. Vitamin D receptor polymorphisms and survival in patients with cutaneous melanoma: a population-based study.
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Orlow I, Reiner AS, Thomas NE, Roy P, Kanetsky PA, Luo L, Paine S, Armstrong BK, Kricker A, Marrett LD, Rosso S, Zanetti R, Gruber SB, Anton-Culver H, Gallagher RP, Dwyer T, Busam K, Begg CB, and Berwick M
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- Australia epidemiology, Canada epidemiology, Female, Genotype, Haplotypes, Humans, Italy epidemiology, Male, Melanoma mortality, Polymorphism, Single Nucleotide, Proportional Hazards Models, Skin Neoplasms mortality, United States epidemiology, Melanoma genetics, Receptors, Calcitriol genetics, Skin Neoplasms genetics
- Abstract
Factors known to affect melanoma survival include age at presentation, sex and tumor characteristics. Polymorphisms also appear to modulate survival following diagnosis. Result from other studies suggest that vitamin D receptor (VDR) polymorphisms (SNPs) impact survival in patients with glioma, renal cell carcinoma, lung, breast, prostate and other cancers; however, a comprehensive study of VDR polymorphisms and melanoma-specific survival is lacking. We aimed to investigate whether VDR genetic variation influences survival in patients with cutaneous melanoma. The analysis involved 3566 incident single and multiple primary melanoma cases enrolled in the international population-based Genes, Environment, and Melanoma Study. Melanoma-specific survival outcomes were calculated for each of 38 VDR SNPs using a competing risk analysis after adjustment for covariates. There were 254 (7.1%) deaths due to melanoma during the median 7.6 years follow-up period. VDR SNPs rs7299460, rs3782905, rs2239182, rs12370156, rs2238140, rs7305032, rs1544410 (BsmI) and rs731236 (TaqI) each had a statistically significant (trend P values < 0.05) association with melanoma-specific survival in multivariate analysis. One functional SNP (rs2239182) remained significant after adjustment for multiple testing using the Monte Carlo method. None of the SNPs associated with survival were significantly associated with Breslow thickness, ulceration or mitosis. These results suggest that the VDR gene may influence survival from melanoma, although the mechanism by which VDR exerts its effect does not seem driven by tumor aggressiveness. Further investigations are needed to confirm our results and to understand the relationship between VDR and survival in the combined context of tumor and host characteristics., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
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- 2016
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9. Association Between NRAS and BRAF Mutational Status and Melanoma-Specific Survival Among Patients With Higher-Risk Primary Melanoma.
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Thomas NE, Edmiston SN, Alexander A, Groben PA, Parrish E, Kricker A, Armstrong BK, Anton-Culver H, Gruber SB, From L, Busam KJ, Hao H, Orlow I, Kanetsky PA, Luo L, Reiner AS, Paine S, Frank JS, Bramson JI, Marrett LD, Gallagher RP, Zanetti R, Rosso S, Dwyer T, Cust AE, Ollila DW, Begg CB, Berwick M, and Conway K
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- Adult, Aged, Aged, 80 and over, DNA Mutational Analysis, Female, Gene Frequency, Genetic Predisposition to Disease, Humans, Kaplan-Meier Estimate, Lymphocytes, Tumor-Infiltrating, Male, Melanoma enzymology, Melanoma immunology, Melanoma mortality, Melanoma pathology, Melanoma therapy, Middle Aged, Multivariate Analysis, Neoplasm Grading, Neoplasm Staging, New South Wales, Odds Ratio, Phenotype, Proportional Hazards Models, Risk Assessment, Risk Factors, Skin Neoplasms enzymology, Skin Neoplasms immunology, Skin Neoplasms mortality, Skin Neoplasms pathology, Skin Neoplasms therapy, Time Factors, Tumor Microenvironment, United States, Biomarkers, Tumor genetics, GTP Phosphohydrolases genetics, Melanoma genetics, Membrane Proteins genetics, Mutation, Proto-Oncogene Proteins B-raf genetics, Skin Neoplasms genetics
- Abstract
Importance: NRAS and BRAF mutations in melanoma inform current treatment paradigms, but their role in survival from primary melanoma has not been established. Identification of patients at high risk of melanoma-related death based on their primary melanoma characteristics before evidence of recurrence could inform recommendations for patient follow-up and eligibility for adjuvant trials., Objective: To determine tumor characteristics and survival from primary melanoma by somatic NRAS and BRAF status., Design, Setting, and Participants: A population-based study with a median follow-up of 7.6 years (through 2007), including 912 patients from the United States and Australia in the Genes, Environment, and Melanoma (GEM) Study, with first primary cutaneous melanoma diagnosed in the year 2000 and analyzed for NRAS and BRAF mutations., Main Outcomes and Measures: Tumor characteristics and melanoma-specific survival of primary melanoma by NRAS and BRAF mutational status., Results: The melanomas were 13% NRAS+, 30% BRAF+, and 57% with neither NRAS nor BRAF mutation (wildtype [WT]). In a multivariable model including clinicopathologic characteristics, relative to WT melanoma (with results reported as odds ratios [95% CIs]), NRAS+ melanoma was associated with presence of mitoses (1.8 [1.0-3.3]), lower tumor-infiltrating lymphocyte (TIL) grade (nonbrisk, 0.5 [0.3-0.8]; and brisk, 0.3 [0.5-0.7] [vs absent TILs]), and anatomic site other than scalp/neck (0.1 [0.01-0.6] for scalp/neck vs trunk/pelvis), and BRAF+ melanoma was associated with younger age (ages 50-69 years, 0.7 [0.5-1.0]; and ages >70 years, 0.5 [0.3-0.8] [vs <50 years]), superficial spreading subtype (nodular, 0.5 [0.2-1.0]; lentigo maligna, 0.4 [0.2-0.7]; and unclassified/other, 0.2 [0.1-0.5] [vs superficial spreading]), and presence of mitoses (1.7 [1.1-2.6]) (P < .05 for all). There was no significant difference in melanoma-specific survival (reported as hazard ratios [95% CIs]) for melanoma harboring mutations in NRAS (1.7 [0.8-3.4]) or BRAF (1.5 [0.8-2.9]) compared with WT melanoma, as adjusted for age, sex, site, American Joint Committee on Cancer (AJCC) tumor stage, TIL grade, and study center. However, melanoma-specific survival was significantly poorer for higher-risk (T2b or higher stage) tumors with NRAS (2.9 [1.1-7.7]) or BRAF (3.1 [1.2-8.5]) mutations (P = .04) but not for lower-risk (T2a or lower) tumors with NRAS (0.9 [0.3-3.0]) or BRAF (0.6 [0.2-1.7]) (P = .65), as adjusted for age, sex, site, AJCC tumor stage, TIL grade, and study center., Conclusions and Relevance: Lower TIL grade for NRAS+ melanoma suggests it has a more immunosuppressed microenvironment, which may affect its response to immunotherapies. The approximate 3-fold increased risk of death for higher-risk tumors harboring NRAS or BRAF mutations after adjusting for other prognostic factors compared with WT melanomas indicates that the prognostic implication of these mutations deserves further investigation, particularly in higher–AJCC stage primary melanomas.
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- 2015
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10. Inherited genetic variants associated with occurrence of multiple primary melanoma.
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Gibbs DC, Orlow I, Kanetsky PA, Luo L, Kricker A, Armstrong BK, Anton-Culver H, Gruber SB, Marrett LD, Gallagher RP, Zanetti R, Rosso S, Dwyer T, Sharma A, La Pilla E, From L, Busam KJ, Cust AE, Ollila DW, Begg CB, Berwick M, and Thomas NE
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- Australia epidemiology, Canada epidemiology, Case-Control Studies, Europe epidemiology, Follow-Up Studies, Genome-Wide Association Study, Humans, International Agencies, Melanoma epidemiology, Melanoma pathology, Neoplasm Invasiveness, Neoplasm Staging, Phenotype, Prognosis, Skin Neoplasms epidemiology, Skin Neoplasms pathology, United States epidemiology, Biomarkers, Tumor genetics, Genetic Predisposition to Disease, Haplotypes genetics, Melanoma genetics, Polymorphism, Single Nucleotide genetics, Skin Neoplasms genetics
- Abstract
Recent studies, including genome-wide association studies, have identified several putative low-penetrance susceptibility loci for melanoma. We sought to determine their generalizability to genetic predisposition for multiple primary melanoma in the international population-based Genes, Environment, and Melanoma (GEM) Study. GEM is a case-control study of 1,206 incident cases of multiple primary melanoma and 2,469 incident first primary melanoma participants as the control group. We investigated the odds of developing multiple primary melanoma for 47 SNPs from 21 distinct genetic regions previously reported to be associated with melanoma. ORs and 95% confidence intervals were determined using logistic regression models adjusted for baseline features (age, sex, age by sex interaction, and study center). We investigated univariable models and built multivariable models to assess independent effects of SNPs. Eleven SNPs in 6 gene neighborhoods (TERT/CLPTM1L, TYRP1, MTAP, TYR, NCOA6, and MX2) and a PARP1 haplotype were associated with multiple primary melanoma. In a multivariable model that included only the most statistically significant findings from univariable modeling and adjusted for pigmentary phenotype, back nevi, and baseline features, we found TERT/CLPTM1L rs401681 (P = 0.004), TYRP1 rs2733832 (P = 0.006), MTAP rs1335510 (P = 0.0005), TYR rs10830253 (P = 0.003), and MX2 rs45430 (P = 0.008) to be significantly associated with multiple primary melanoma, while NCOA6 rs4911442 approached significance (P = 0.06). The GEM Study provides additional evidence for the relevance of these genetic regions to melanoma risk and estimates the magnitude of the observed genetic effect on development of subsequent primary melanoma., (©2015 American Association for Cancer Research.)
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- 2015
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11. Comparison of clinicopathologic features and survival of histopathologically amelanotic and pigmented melanomas: a population-based study.
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Thomas NE, Kricker A, Waxweiler WT, Dillon PM, Busman KJ, From L, Groben PA, Armstrong BK, Anton-Culver H, Gruber SB, Marrett LD, Gallagher RP, Zanetti R, Rosso S, Dwyer T, Venn A, Kanetsky PA, Orlow I, Paine S, Ollila DW, Reiner AS, Luo L, Hao H, Frank JS, Begg CB, and Berwick M
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- Adult, Aged, Australia epidemiology, Canada epidemiology, Female, Follow-Up Studies, Humans, Italy epidemiology, Male, Melanoma, Amelanotic mortality, Melanoma, Amelanotic pathology, Middle Aged, Mitotic Index, Neoplasm Staging, Registries, Survival Rate, United States epidemiology, Melanoma mortality, Melanoma pathology, Skin Neoplasms mortality, Skin Neoplasms pathology
- Abstract
IMPORTANCE Previous studies have reported that histopathologically amelanotic melanoma is associated with poorer survival than pigmented melanoma; however, small numbers of amelanotic melanomas, selected populations, lack of centralized pathologic review, or no adjustment for stage limit the interpretation or generalization of results from prior studies.OBJECTIVE To compare melanoma-specific survival between patients with histopathologically amelanotic and those with pigmented melanoma in a large international population-based study.DESIGN, SETTING, AND PARTICIPANTS Survival analysis with a median follow-up of 7.6 years.The study population comprised 2995 patients with 3486 invasive primary melanomas centrally scored for histologic pigmentation from the Genes, Environment, and Melanoma(GEM) Study, which enrolled incident cases of melanoma diagnosed in 1998 through 2003 from international population-based cancer registries.MAIN OUTCOMES AND MEASURES Clinicopathologic predictors and melanoma-specific survival of histologically amelanotic and pigmented melanoma were compared using generalized estimating equations and Cox regression models, respectively.RESULTS Of 3467 melanomas, 275 (8%) were histopathologically amelanotic. Female sex,nodular and unclassified or other histologic subtypes, increased Breslow thickness, presence of mitoses, severe solar elastosis, and lack of a coexisting nevus were independently associated with amelanotic melanoma (each P < .05). Amelanotic melanoma was generally ofa higher American Joint Committee on Cancer (AJCC) tumor stage at diagnosis (odds ratios[ORs] [95%CIs] between 2.9 [1.8-4.6] and 11.1 [5.8-21.2] for tumor stages between T1b and T3b and ORs [95%CIs] of 24.6 [13.6-44.4] for T4a and 29.1 [15.5-54.9] for T4b relative to T1a;P value for trend, <.001) than pigmented melanoma. Hazard of death from melanoma was higher for amelanotic than for pigmented melanoma (hazard ratio [HR], 2.0; 95%CI, 1.4-3.0)(P < .001), adjusted for age, sex, anatomic site, and study design variables, but survival did not differ once AJCC tumor stage was also taken into account (HR, 0.8; 95%CI, 0.5-1.2)(P = .36).CONCLUSIONS AND RELEVANCE At the population level, survival after diagnosis of amelanotic melanoma is poorer than after pigmented melanoma because of its more advanced stage at diagnosis. It is probable that amelanotic melanomas present at more advanced tumor stages because they are difficult to diagnose. The association of amelanotic melanoma with presence of mitoses independently of Breslow thickness and other clinicopathologic characteristics suggests that amelanotic melanomas might also grow faster than pigmented melanomas. New strategies for early diagnosis and investigation of the biological properties of amelanotic melanoma are warranted.
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- 2014
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12. "Right to Try" laws.
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Begg CB, Kim K, and Neaton JD
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- Humans, Patient Rights legislation & jurisprudence, United States, United States Food and Drug Administration legislation & jurisprudence, Compassionate Use Trials legislation & jurisprudence, Drug Approval legislation & jurisprudence
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- 2014
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13. Risk of asynchronous contralateral breast cancer in noncarriers of BRCA1 and BRCA2 mutations with a family history of breast cancer: a report from the Women's Environmental Cancer and Radiation Epidemiology Study.
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Reiner AS, John EM, Brooks JD, Lynch CF, Bernstein L, Mellemkjær L, Malone KE, Knight JA, Capanu M, Teraoka SN, Concannon P, Liang X, Figueiredo JC, Smith SA, Stovall M, Pike MC, Haile RW, Thomas DC, Begg CB, and Bernstein JL
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- Adult, Aged, BRCA1 Protein genetics, BRCA2 Protein genetics, Case-Control Studies, Female, Heterozygote, Humans, Middle Aged, Mutation, Odds Ratio, Reproductive History, Risk Assessment, Risk Factors, United States epidemiology, Breast Neoplasms epidemiology, Breast Neoplasms genetics, Neoplasms, Second Primary epidemiology
- Abstract
Purpose: To fully characterize the risk of contralateral breast cancer (CBC) in patients with breast cancer with a family history who test negative for BRCA1 and BRCA2 mutations., Patients and Methods: From our population-based case-control study comparing women with CBC to women with unilateral breast cancer (UBC), we selected women who tested negative for BRCA1 and BRCA2 mutations (594 patients with CBC/1,119 control patients with UBC). Rate ratios (RRs) and 95% CIs were estimated to examine the association between family history of breast cancer and risk of asynchronous CBC. Age- and family history-specific 10-year cumulative absolute risks of CBC were estimated., Results: Family history of breast cancer was associated with increased CBC risk; risk was highest among young women (< 45 years) with first-degree relatives affected at young ages (< 45 years; RR, 2.5; 95% CI, 1.1 to 5.3) or women with first-degree relatives with bilateral disease (RR, 3.6; 95% CI, 2.0 to 6.4). Women diagnosed with UBC before age 55 years with a first-degree family history of CBC had a 10-year risk of CBC of 15.6%., Conclusion: Young women with breast cancer who have a family history of breast cancer and who test negative for deleterious mutations in BRCA1 and BRCA2 are at significantly greater risk of CBC than other breast cancer survivors. This risk varies with diagnosis age, family history of CBC, and degree of relationship to an affected relative. Women with a first-degree family history of bilateral disease have risks of CBC similar to mutation carriers. This has important implications for the clinical management of patients with breast cancer with family history of the disease.
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- 2013
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14. Risk of non-melanoma cancers in first-degree relatives of CDKN2A mutation carriers.
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Mukherjee B, Delancey JO, Raskin L, Everett J, Jeter J, Begg CB, Orlow I, Berwick M, Armstrong BK, Kricker A, Marrett LD, Millikan RC, Culver HA, Rosso S, Zanetti R, Kanetsky PA, From L, and Gruber SB
- Subjects
- Adult, Age Distribution, Aged, Aged, 80 and over, Female, Genetic Predisposition to Disease, Genotype, Humans, Male, Middle Aged, Risk Assessment, Risk Factors, United States epidemiology, Cyclin-Dependent Kinase Inhibitor p16 genetics, Family, Heterozygote, Mutation, Neoplasms epidemiology, Neoplasms genetics
- Abstract
The purpose of this study was to quantify the risk of cancers other than melanoma among family members of CDKN2A mutation carriers using data from the Genes, Environment and Melanoma study. Relative risks (RRs) of all non-melanoma cancers among first-degree relatives (FDRs) of melanoma patients with CDKN2A mutations (n = 65) and FDRs of melanoma patients without mutations (n = 3537) were calculated as the ratio of estimated event rates (number of cancers/total person-years) in FDRs of carriers vs noncarriers with exact Clopper-Pearson-type tests and 95% confidence intervals (CIs). All statistical tests were two-sided. There were 56 (13.1%) non-melanoma cancers reported among 429 FDRs of mutation carriers and 2199 (9.4%) non-melanoma cancers in 23 452 FDRs of noncarriers. The FDRs of carriers had an increased risk of any cancer other than melanoma (56 cancers among 429 FDRs of carrier probands vs 2199 cancers among 23 452 FDRs of noncarrier probands; RR = 1.5, 95% CI = 1.2 to 2.0, P = .005), gastrointestinal cancer (20 cancers among 429 FDRs of carrier probands vs 506 cancers among 23 452 FDRs of noncarrier probands; RR = 2.4, 95% CI = 1.4 to 3.7, P = .001), and pancreatic cancer (five cancers among 429 FDRs of carrier probands vs 41 cancers among 23 452 FDRs of noncarrier probands; RR = 7.4, 95% CI = 2.3 to 18.7, P = .002). Wilms tumor was reported in two FDRs of carrier probands and three FDRs of noncarrier probands (RR = 40.4, 95% CI = 3.4 to 352.7, P = .005). The lifetime risk of any cancer other than melanoma among CDKN2A mutation carriers was estimated as 59.0% by age 85 years (95% CI = 39.0% to 75.4%) by the kin-cohort method, under the standard assumptions of Mendelian genetics on the genotype distribution of FDRs conditional on proband genotype.
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- 2012
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15. Adjuvant systemic therapy for breast cancer in BRCA1/BRCA2 mutation carriers in a population-based study of risk of contralateral breast cancer.
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Reding KW, Bernstein JL, Langholz BM, Bernstein L, Haile RW, Begg CB, Lynch CF, Concannon P, Borg A, Teraoka SN, Törngren T, Diep A, Xue S, Bertelsen L, Liang X, Reiner AS, Capanu M, and Malone KE
- Subjects
- Adult, Breast Neoplasms genetics, Breast Neoplasms pathology, Case-Control Studies, Chemotherapy, Adjuvant, DNA Mutational Analysis, Denmark, Female, Humans, Likelihood Functions, Logistic Models, Middle Aged, Neoplasm Recurrence, Local genetics, Registries, Risk Assessment, Risk Factors, SEER Program, Tamoxifen administration & dosage, Treatment Outcome, United States, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, BRCA1 Protein genetics, BRCA2 Protein genetics, Breast Neoplasms drug therapy, Mutation, Neoplasm Recurrence, Local prevention & control
- Abstract
Given the greatly elevated risks of contralateral breast cancer (CBC) observed in breast cancer patients who carry mutations in BRCA1 and BRCA2, it is critical to determine the effectiveness of standard adjuvant therapies in preventing CBC in mutation carriers. The WECARE study is a matched, case-control study of 708 women with CBC as cases and 1,399 women with unilateral breast cancer (UBC) as controls, including 181 BRCA1/BRCA2 mutation carriers. Interviews and medical record reviews provided detailed information on risk factors and breast cancer therapy. All study participants were screened for BRCA1 and BRCA2 mutations using denaturing high-performance liquid chromatography (DHPLC) to detect genetic variants in the coding and flanking regions of the genes. Conditional logistic regression was used to compare the risk of CBC associated with chemotherapy and tamoxifen in BRCA1/BRCA2 mutation carriers and non-carriers. Chemotherapy was associated with lower CBC risk both in non-carriers (RR = 0.6 [95% CI: 0.5-0.7]) and carriers (RR = 0.5 [95% CI: 0.2-1.0]; P value = 0.04). Tamoxifen was associated with a reduced CBC risk in non-carriers (RR = 0.7 [95% CI: 0.6-1.0]; P value = 0.03). We observed a similar but non-significant reduction associated with tamoxifen in mutation carriers (RR = 0.7 [95% CI: 0.3-1.8]). The tests of heterogeneity comparing carriers to non-carriers did not provide evidence for a difference in the associations with chemotherapy (P value = 0.51) nor with tamoxifen (P value = 0.15). Overall, we did not observe a difference in the relative risk reduction associated with adjuvant treatment between BRCA1/BRCA2 mutation carriers and non-carriers. However, given the higher absolute CBC risk in mutation carriers, the potentially greater impact of adjuvant therapy in reducing CBC risk among mutation carriers should be considered when developing treatment plans for these patients.
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- 2010
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16. Population-based study of the risk of second primary contralateral breast cancer associated with carrying a mutation in BRCA1 or BRCA2.
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Malone KE, Begg CB, Haile RW, Borg A, Concannon P, Tellhed L, Xue S, Teraoka S, Bernstein L, Capanu M, Reiner AS, Riedel ER, Thomas DC, Mellemkjaer L, Lynch CF, Boice JD Jr, Anton-Culver H, and Bernstein JL
- Subjects
- Adult, Age Factors, Apoptosis Regulatory Proteins, Breast Neoplasms mortality, Breast Neoplasms pathology, Breast Neoplasms therapy, Case-Control Studies, DNA Mutational Analysis, Denmark epidemiology, Female, Genetic Predisposition to Disease, Humans, Logistic Models, Middle Aged, Population Surveillance, Risk Assessment, Risk Factors, SEER Program, Time Factors, Treatment Outcome, United States epidemiology, BRCA1 Protein genetics, BRCA2 Protein genetics, Breast Neoplasms genetics, Mutation, Neoplasm Recurrence, Local
- Abstract
Purpose: Women with breast cancer diagnosed early in life comprise a substantial portion of those tested for BRCA1/BRCA2 mutations; however, little information is available on the subsequent risks of contralateral breast cancer in mutation carriers. This study assessed the risk of subsequent contralateral breast cancer associated with carrying a BRCA1 or BRCA2 mutation., Patients and Methods: In this nested case-control study, patients with contralateral breast cancer diagnosed 1 year or more after a first primary breast cancer (n = 705) and controls with unilateral breast cancer (n = 1,398) were ascertained from an underlying population-based cohort of 52,536 women diagnosed with a first invasive breast cancer before age 55 years. Interviews and medical record reviews were used to collect risk factor and treatment histories. All women were tested for BRCA1/BRCA2 mutations. Relative (rate ratios) and absolute (5- and 10-year cumulative) risks of developing contralateral breast cancer following a first invasive breast cancer were computed., Results: Compared with noncarriers, BRCA1 and BRCA2 mutation carriers had 4.5-fold (95% CI, 2.8- to 7.1-fold) and 3.4-fold (95% CI, 2.0- to 5.8-fold) increased risks of contralateral breast cancer, respectively. The relative risk of contralateral breast cancer for BRCA1 mutation carriers increased as age of first diagnosis decreased. Age-specific cumulative risks are provided for clinical guidance., Conclusion: The risks of subsequent contralateral breast cancer are substantial for women who carry a BRCA1/BRCA2 mutation. These findings have important clinical relevance regarding the assessment of BRCA1/BRCA2 status in patients with breast cancer and the counseling and clinical management of patients found to carry a mutation.
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- 2010
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17. Physician visits prior to treatment for clinically localized prostate cancer.
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Jang TL, Bekelman JE, Liu Y, Bach PB, Basch EM, Elkin EB, Zelefsky MJ, Scardino PT, Begg CB, and Schrag D
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- Aged, Aged, 80 and over, Analysis of Variance, Androgen Antagonists therapeutic use, Confounding Factors, Epidemiologic, Humans, Logistic Models, Male, Medicare, Neoplasm Staging, Physicians, Family, Practice Patterns, Physicians' trends, Prostatectomy, Prostatic Neoplasms drug therapy, Prostatic Neoplasms radiotherapy, Prostatic Neoplasms surgery, Radiation Oncology, Referral and Consultation statistics & numerical data, Research Design, Risk Factors, SEER Program, United States epidemiology, Workforce, Choice Behavior, Family Practice, Medical Oncology, Office Visits statistics & numerical data, Practice Patterns, Physicians' statistics & numerical data, Prostatic Neoplasms pathology, Prostatic Neoplasms therapy, Urology
- Abstract
Background: The 2 primary therapeutic interventions for localized prostate cancer are delivered by different types of physicians, urologists, and radiation oncologists. We evaluated how visits to specialists and primary care physicians (PCPs) by men with localized prostate cancer are related to treatment choice., Methods: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, we identified 85 088 men with clinically localized prostate cancer diagnosed at age 65 years or older, between 1994 and 2002. Men were categorized by primary treatment received within 9 months of diagnosis: radical prostatectomy (n = 18 201 [21%]), radiotherapy (n = 35 925 [42%]), androgen deprivation (n = 14 021 [17%]), or expectant management (n = 16 941 [20%]). Visits to specialists and PCPs were analyzed by patient characteristics and primary therapies received and were identified using Medicare claims and the American Medical Association Physician Masterfile., Results: Overall, 42 309 men (50%) were seen exclusively by urologists, 37 540 (44%) by urologists and radiation oncologists, 2329 (3%) by urologists and medical oncologists, and 2910 (3%) by all 3 specialists. There was a strong association between the type of specialist seen and primary therapy received. Visits to PCPs were infrequent between diagnosis and receipt of therapy (22% of patients visited any PCP and 17% visited an established PCP) and were not associated with a greater likelihood of specialist visits. Irrespective of age, comorbidity status, or specialist visits, men seen by PCPs were more likely to be treated expectantly., Conclusions: Specialist visits relate strongly to prostate cancer treatment choices. In light of these findings, prior evidence that specialists prefer the modality they themselves deliver and the lack of conclusive comparative studies demonstrating superiority of one modality over another, it is essential to ensure that men have access to balanced information before choosing a particular therapy for prostate cancer.
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- 2010
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18. Alcohol intake and cigarette smoking and risk of a contralateral breast cancer: The Women's Environmental Cancer and Radiation Epidemiology Study.
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Knight JA, Bernstein L, Largent J, Capanu M, Begg CB, Mellemkjaer L, Lynch CF, Malone KE, Reiner AS, Liang X, Haile RW, Boice JD Jr, and Bernstein JL
- Subjects
- Adult, Cohort Studies, Comorbidity, Confidence Intervals, Humans, Logistic Models, Middle Aged, Risk Factors, United States epidemiology, Alcohol Drinking epidemiology, Breast Neoplasms epidemiology, Neoplasms, Second Primary epidemiology, Smoking epidemiology
- Abstract
Women with primary breast cancer are at increased risk of developing second primary breast cancer. Few studies have evaluated risk factors for the development of asynchronous contralateral breast cancer in women with breast cancer. In the Women's Environmental Cancer and Radiation Epidemiology Study (1985-2001), the roles of alcohol and smoking were examined in 708 women with asynchronous contralateral breast cancer (cases) compared with 1,399 women with unilateral breast cancer (controls). Cases and controls aged less than 55 years at first breast cancer diagnosis were identified from 5 population-based cancer registries in the United States and Denmark. Controls were matched to cases on birth year, diagnosis year, registry region, and race and countermatched on radiation treatment. Risk factor information was collected by telephone interview. Rate ratios and 95% confidence intervals were estimated by using conditional logistic regression. Ever regular drinking was associated with an increased risk of asynchronous contralateral breast cancer (rate ratio = 1.3, 95% confidence interval: 1.0, 1.6), and the risk increased with increasing duration (P = 0.03). Smoking was not related to asynchronous contralateral breast cancer. In this, the largest study of asynchronous contralateral breast cancer to date, alcohol is a risk factor for the disease, as it is for a first primary breast cancer.
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- 2009
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19. Variants in the ATM gene associated with a reduced risk of contralateral breast cancer.
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Concannon P, Haile RW, Børresen-Dale AL, Rosenstein BS, Gatti RA, Teraoka SN, Diep TA, Jansen L, Atencio DP, Langholz B, Capanu M, Liang X, Begg CB, Thomas DC, Bernstein L, Olsen JH, Malone KE, Lynch CF, Anton-Culver H, and Bernstein JL
- Subjects
- Ataxia Telangiectasia Mutated Proteins, Breast Neoplasms epidemiology, Case-Control Studies, DNA Mutational Analysis, Denmark epidemiology, Female, Humans, Middle Aged, Risk Factors, United States epidemiology, Breast Neoplasms genetics, Cell Cycle Proteins genetics, DNA-Binding Proteins genetics, Genetic Variation, Mutation genetics, Neoplasms, Second Primary genetics, Protein Serine-Threonine Kinases genetics, Tumor Suppressor Proteins genetics
- Abstract
Between 5% and 10% of women who survive a first primary breast cancer will subsequently develop a second primary cancer in the contralateral breast. The Women's Environment, Cancer, and Radiation Epidemiology Study was designed to identify genetic and environmental determinants of contralateral breast cancer (CBC). In this study, 708 women with asynchronous CBC served as cases and 1,397 women with unilateral breast cancer served as controls. ATM, a serine-threonine kinase, controls the cellular response to DNA double-strand breaks, and has been implicated in breast cancer risk. Complete mutation screening of the ATM gene in all 2,105 study participants identified 240 distinct sequence variants; only 15 were observed in >1% of subjects. Among the rare variants, deleterious alleles resulting in loss of ATM function were associated with a nonsignificant increase in risk of CBC. In contrast, carriers of common variants had a statistically significant reduction in risk of CBC. Four of these 15 variants were individually associated with a significantly decreased risk of second primary breast cancer [c.1899-55T>G, rate ratio (RR), 0.5; 95% confidence interval (CI), 0.3-0.8; c.3161C>G, RR, 0.5; 95% CI, 0.3-0.9; c.5558A>T, RR, 0.2; 95% CI, 0.1-0.6; c.6348-54T>C RR, 0.2; 95% CI, 0.1-0.8]. These data suggest that some alleles of ATM may exert an antineoplastic effect, perhaps by altering the activity of ATM as an initiator of DNA damage responses or a regulator of p53.
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- 2008
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20. Estimating the empirical Lorenz curve and Gini coefficient in the presence of error with nested data.
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Moskowitz CS, Seshan VE, Riedel ER, and Begg CB
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- Humans, Medicare, Quality of Health Care, United States, Black or African American, Black People statistics & numerical data, Models, Statistical, Primary Health Care statistics & numerical data
- Abstract
The Lorenz curve is a graphical tool that is widely used to characterize the concentration of a measure in a population, such as wealth. It is frequently the case that the measure of interest used to rank experimental units when estimating the empirical Lorenz curve, and the corresponding Gini coefficient, is subject to random error. This error can result in an incorrect ranking of experimental units which inevitably leads to a curve that exaggerates the degree of concentration (variation) in the population. We consider a specific data configuration with a hierarchical structure where multiple observations are aggregated within experimental units to form the outcome whose distribution is of interest. Within this context, we explore this bias and discuss several widely available statistical methods that have the potential to reduce or remove the bias in the empirical Lorenz curve. The properties of these methods are examined and compared in a simulation study. This work is motivated by a health outcomes application that seeks to assess the concentration of black patient visits among primary care physicians. The methods are illustrated on data from this study.
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- 2008
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21. Disenrollment from Medicare managed care among beneficiaries with and without a cancer diagnosis.
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Elkin EB, Ishill N, Riley GF, Bach PB, Gonen M, Begg CB, and Schrag D
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- Aged, Aged, 80 and over, Breast Neoplasms epidemiology, Case-Control Studies, Colorectal Neoplasms epidemiology, Fee-for-Service Plans statistics & numerical data, Female, Humans, Kaplan-Meier Estimate, Lung Neoplasms epidemiology, Male, Neoplasms diagnosis, Neoplasms therapy, Proportional Hazards Models, Prostatic Neoplasms epidemiology, SEER Program, United States, Managed Care Programs statistics & numerical data, Medicare, Neoplasms epidemiology
- Abstract
Background: Medicare managed care may offer enrollees lower out-of-pocket costs and provide benefits that are not available in the traditional fee-for-service Medicare program. However, managed care plans may also restrict provider choice in an effort to control costs. We compared rates of voluntary disenrollment from Medicare managed care to traditional fee-for-service Medicare among Medicare managed care enrollees with and without a cancer diagnosis., Methods: We identified Medicare managed care enrollees aged 65 years or older who were diagnosed with a first primary breast (n = 28 331), colorectal (n = 26 494), prostate (n = 29 046), or lung (n = 31 243) cancer from January 1, 1995, through December 31, 2002, in Surveillance, Epidemiology, and End Results (SEER) cancer registry records linked with Medicare enrollment files. Cancer patients were pair-matched to cancer-free enrollees by age, sex, race, and geographic location. We estimated rates of voluntary disenrollment to fee-for-service Medicare in the 2 years after each cancer patient's diagnosis, adjusted for plan characteristics and Medicare managed care penetration, by use of Cox proportional hazards regression., Results: In the 2 years after diagnosis, cancer patients were less likely to disenroll from Medicare managed care than their matched cancer-free peers (for breast cancer, adjusted hazard ratio [HR] for disenrollment = 0.78, 95% confidence interval [CI] = 0.74 to 0.82; for colorectal cancer, HR = 0.84, 95% CI = 0.80 to 0.88; for prostate cancer, HR = 0.86, 95% CI = 0.82 to 0.90; and for lung cancer, HR = 0.81, 95% CI = 0.76 to 0.86). Results were consistent across strata of age, sex, race, SEER registry, and cancer stage., Conclusion: A new cancer diagnosis between 1995 and 2002 did not precipitate voluntary disenrollment from Medicare managed care to traditional fee-for-service Medicare.
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- 2008
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22. Reproductive history and risk of second primary breast cancer: the WECARE study.
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Largent JA, Capanu M, Bernstein L, Langholz B, Mellemkaer L, Malone KE, Begg CB, Haile RW, Lynch CF, Anton-Culver H, Wolitzer A, and Bernstein JL
- Subjects
- Adult, Age Factors, Aged, Breast Feeding, Breast Neoplasms pathology, Case-Control Studies, Cohort Studies, Denmark epidemiology, Female, Gravidity, Humans, Interviews as Topic, Logistic Models, Menarche, Menopause, Middle Aged, Neoplasm Invasiveness, Neoplasms, Second Primary pathology, Parity, Pregnancy, Registries, Risk Factors, Surveys and Questionnaires, United States epidemiology, Breast Neoplasms epidemiology, Neoplasms, Second Primary epidemiology, Reproductive History
- Abstract
Background: Women with an initial breast cancer diagnosis are at elevated risk of developing subsequent cancer in the contralateral breast. Studies of reproductive factors and contralateral breast cancer (CBC) have provided inconsistent results., Methods: We employed a case-control study nested within five population-based cancer registries in the United States and Denmark to examine associations between reproductive history and CBC risk. Cases were women with asynchronous CBC who had their first primary invasive breast cancer before age 55 years. Two controls, who had only one primary breast cancer diagnosis, were individually matched to each case on age and year of diagnosis, race, and registry. A total of 694 case-control triplets and 11 case-control pairs were enrolled. Information regarding possible CBC risk factors was obtained via telephone interviews. Multivariable conditional logistic regression was used to estimate rate ratios (RR) and 95% confidence intervals (95% CI) associated with risk factors of interest., Results: Increasing number of full-term pregnancies (FTP) was inversely associated with CBC risk (P trend, 0.001). Women who reported menarche before age 13 years had an increased risk of CBC (RR, 1.26; 95% CI, 1.01-1.58). Age at first FTP, breastfeeding history, and age at menopause were not significantly associated with CBC risk., Conclusions: These results suggest age at menarche and parity, which are established risk factors for first primary breast cancer, are associated with CBC, whereas other reproductive risk factors associated with first primary breast cancer, such as age at first FTP, are less important factors in the development of CBC.
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- 2007
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23. The prevalence of CDKN2A germ-line mutations and relative risk for cutaneous malignant melanoma: an international population-based study.
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Berwick M, Orlow I, Hummer AJ, Armstrong BK, Kricker A, Marrett LD, Millikan RC, Gruber SB, Anton-Culver H, Zanetti R, Gallagher RP, Dwyer T, Rebbeck TR, Kanetsky PA, Busam K, From L, Mujumdar U, Wilcox H, and Begg CB
- Subjects
- Aged, Australia epidemiology, Canada epidemiology, Case-Control Studies, Chromatography, High Pressure Liquid, Exons genetics, Female, Humans, International Agencies, Introns genetics, Italy epidemiology, Male, Melanoma epidemiology, Middle Aged, Neoplasms, Multiple Primary epidemiology, Polymerase Chain Reaction, Polymorphism, Genetic, Skin Neoplasms epidemiology, United States epidemiology, Cyclin-Dependent Kinase Inhibitor p16 genetics, Germ-Line Mutation, Melanoma genetics, Neoplasms, Multiple Primary genetics, Skin Neoplasms genetics
- Abstract
Germ-line mutations of CDKN2A have been identified as strong risk factors for melanoma in studies of multiple-case families. However, an assessment of their relative risk for melanoma in the general population has been difficult because they occur infrequently. We addressed this issue using a novel population-based case-control study design in which "cases" have incident second- or higher-order melanomas [multiple primary melanoma (MPM)] and "controls" have incident first primary melanoma [single primary melanoma (SPM)]. Participants were ascertained from nine geographic regions in Australia, Canada, Italy, and United States. In the 1,189 MPM cases and 2,424 SPM controls who were eligible and available for analysis, the relative risk of a subsequent melanoma among patients with functional mutations who have an existing diagnosis of melanoma, after adjustments for age, sex, center, and known phenotypic risk factors, is estimated to be 4.3 (95% confidence interval, 2.3-7.7). The odds ratio varied significantly depending on the type of mutation involved. The results suggest that the relative risk of mutation carriers in the population may be lower than currently believed and that different mutations on the CDKN2A gene may confer substantially different risks of melanoma.
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- 2006
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24. Cancer survivorship--genetic susceptibility and second primary cancers: research strategies and recommendations.
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Travis LB, Rabkin CS, Brown LM, Allan JM, Alter BP, Ambrosone CB, Begg CB, Caporaso N, Chanock S, DeMichele A, Figg WD, Gospodarowicz MK, Hall EJ, Hisada M, Inskip P, Kleinerman R, Little JB, Malkin D, Ng AK, Offit K, Pui CH, Robison LL, Rothman N, Shields PG, Strong L, Taniguchi T, Tucker MA, and Greene MH
- Subjects
- Antineoplastic Agents adverse effects, Biotechnology, Carcinogens, Case-Control Studies, Clinical Trials as Topic, Cohort Studies, Congresses as Topic, Genetic Predisposition to Disease, Humans, Medical Informatics, Multicenter Studies as Topic, Neoplasms drug therapy, Neoplasms mortality, Neoplasms radiotherapy, Neoplasms, Radiation-Induced chemically induced, Neoplasms, Radiation-Induced genetics, Neoplasms, Second Primary chemically induced, Neoplasms, Second Primary genetics, Radiotherapy adverse effects, Registries, Specimen Handling, Syndrome, United States epidemiology, Neoplasms genetics, Neoplasms, Radiation-Induced etiology, Neoplasms, Second Primary etiology, Survivors statistics & numerical data
- Abstract
Cancer survivors constitute 3.5% of the United States population, but second primary malignancies among this high-risk group now account for 16% of all cancer incidence. Although few data currently exist regarding the molecular mechanisms for second primary cancers and other late outcomes after cancer treatment, the careful measurement and documentation of potentially carcinogenic treatments (chemotherapy and radiotherapy) provide a unique platform for in vivo research on gene-environment interactions in human carcinogenesis. We review research priorities identified during a National Cancer Institute (NCI)-sponsored workshop entitled "Cancer Survivorship--Genetic Susceptibility and Second Primary Cancers." These priorities include 1) development of a national research infrastructure for studies of cancer survivorship; 2) creation of a coordinated system for biospecimen collection; 3) development of new technology, bioinformatics, and biomarkers; 4) design of new epidemiologic methods; and 5) development of evidence-based clinical practice guidelines. Many of the infrastructure resources and design strategies that would facilitate research in this area also provide a foundation for the study of other important nonneoplastic late effects of treatment and psychosocial concerns among cancer survivors. These research areas warrant high priority to promote NCI's goal of eliminating pain and suffering related to cancer.
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- 2006
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25. Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample.
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Begg CB, Orlow I, Hummer AJ, Armstrong BK, Kricker A, Marrett LD, Millikan RC, Gruber SB, Anton-Culver H, Zanetti R, Gallagher RP, Dwyer T, Rebbeck TR, Mitra N, Busam K, From L, and Berwick M
- Subjects
- Adult, Age Distribution, Aged, Australia epidemiology, Canada epidemiology, Case-Control Studies, Female, Genetic Predisposition to Disease, Genotype, Humans, Incidence, Italy epidemiology, Logistic Models, Male, Melanoma mortality, Middle Aged, Penetrance, Risk Assessment, Skin Neoplasms mortality, Survival Rate, United States epidemiology, Genes, p16, Germ-Line Mutation, Melanoma epidemiology, Melanoma genetics, Skin Neoplasms epidemiology, Skin Neoplasms genetics
- Abstract
Background: Germline mutations in the CDKN2A gene have been linked to melanoma incidence in many families with multiple cases of the disease. Previous studies of multiple-case families have indicated that the lifetime risk (i.e., penetrance) of melanoma in CDKN2A mutation carriers is very high, ranging from 58% in Europe to 91% in Australia by age 80 years. In this study, we examined lifetime melanoma risk among CDKN2A mutation carriers using carriers who were identified in a population-based study of melanoma., Methods: Probands for the study were incident case patients with either first or subsequent melanoma who were identified in nine geographic regions in Australia, Canada, the United States, and Italy. A total of 3626 probands (53% participation rate) with adequate DNA for analysis were recruited and genotyped for CDKN2A mutations. From the 3550 probands whose DNA could be amplified by polymerase chain reaction of CDKN2A exons 1alpha, 2, and 3 and surrounding regions, 65 mutation carriers were identified. Melanoma histories in first-degree relatives of these probands were used to calculate the lifetime risk in CDKN2A mutation carriers using the kin-cohort method., Results: The risk of melanoma in CDKN2A mutation carriers was approximately 14% (95% CI = 8% to 22%) by age 50 years, 24% (95% CI = 15% to 34%) by age 70 years, and 28% (95% CI = 18% to 40%) by age 80 years. Eighteen probands had three or more first-degree relatives with melanoma, but only one was a carrier of a CDKN2A mutation., Conclusions: CDKN2A mutation carriers in the general population have a much lower risk of melanoma than that suggested by estimates obtained from multiple-case families. The preponderance of familial clustering of melanoma occurs in families without identifiable mutations in CDKN2A.
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- 2005
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26. The effect of changes in tumor size on breast carcinoma survival in the U.S.: 1975-1999.
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Elkin EB, Hudis C, Begg CB, and Schrag D
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- Age Factors, Female, Humans, Time Factors, United States, Breast Neoplasms mortality, Breast Neoplasms pathology
- Abstract
Background: Temporal comparisons of case survival are commonly used to assess improvement in cancer treatment at the population level. However, such comparisons may be confounded by secular trends in disease prognosis, even within conventional stage categories. The objective of the current study was to characterize within-stage migration of tumor size in breast carcinoma, and to estimate the effect of this shift on reported breast carcinoma survival., Methods: Population-based Surveillance, Epidemiology, and End Results (SEER) cancer registry data were used to evaluate secular trends in tumor size at the time of diagnosis and relative survival among localized and regional invasive breast carcinoma patients diagnosed between 1975-1999. Outcomes were stage-specific tumor size distribution, 5-year relative survival, relative survival standardized to the tumor size distribution of the cohort diagnosed between 1975-1979, and the percentage of improvement in relative survival attributable to shifts in tumor size distribution., Results: Within each stage category, the proportion of smaller tumors increased significantly over time. Comparing patients diagnosed between 1995-1999 with those diagnosed between 1975-1979, within-stage migration of tumor size accounted for 61% and 28%, respectively, of the relative survival increases noted in localized and regional breast carcinoma., Conclusions: The tumor size distribution of incident breast carcinomas in SEER has shifted toward smaller tumors. A substantial fraction of the improvement in breast carcinoma survival noted since 1975 may be attributable to within-stage migration of tumor size., (Copyright 2005 American Cancer Society.)
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- 2005
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27. Variations among high volume surgeons in the rate of complications after radical prostatectomy: further evidence that technique matters.
- Author
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Bianco FJ Jr, Riedel ER, Begg CB, Kattan MW, and Scardino PT
- Subjects
- Aged, Cohort Studies, Cross-Sectional Studies, Humans, Male, New York, Outcome Assessment, Health Care statistics & numerical data, Postoperative Complications etiology, Prostatic Neoplasms pathology, Quality of Life, SEER Program, Statistics as Topic, United States, Urinary Incontinence epidemiology, Urologic Diseases epidemiology, Clinical Competence statistics & numerical data, Health Facility Size statistics & numerical data, Postoperative Complications epidemiology, Practice Patterns, Physicians' statistics & numerical data, Prostatectomy adverse effects, Prostatic Neoplasms surgery
- Abstract
Purpose: A strong association between surgeon, hospital volume and postoperative morbidity of radical prostatectomy has been demonstrated. While better outcomes are associated with high volume surgeons, the degree of variation in outcomes among surgeons has not been fully examined., Materials and Methods: Using a linked database from Surveillance, Epidemiology and End Results registries and federal Medicare claims data, we analyzed outcomes of consecutive patients treated with radical prostatectomy between 1992 and 1996. We focused on variations in several measures of morbidity (perioperative complications, late urinary complications and long-term incontinence) among patients of high volume surgeons, defined as those with 20 or more patients in the study period. After adjusting for hospital, surgeon volume and case mix, we examined the extent to which variations in the rates of adverse outcomes differed among surgeons for all 3 end points., Results: Of the 999 surgeons 16% (159) performed 48.7% (5,238) of the 10,737 radical prostatectomies during the study. The 30-day mortality rate was 0.5%, the major postoperative complication rate was 28.6%, late urinary complications 25.2% (major events 16%) and long-term incontinence 6.7%. For all 3 morbidity outcomes the variation among surgeons in the rate of complications was significantly greater than that expected by chance (p =0.001 for each) after adjustment of covariates. Furthermore, surgeons with better (or worse) than average results with regard to 1 outcome were likely to have better (or worse, respectively) results with regard to the other 2 outcome measures., Conclusions: Morbidity end points that directly affect quality of life showed significant variability among high volume providers. Surgeons who performed well in 1 area (eg postoperative complications) performed well in others. These results further suggest that variations in surgical technique and postoperative care lead to variations in outcomes after radical prostatectomy, indicating that outcomes of this operation are sensitive to small differences in performance.
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- 2005
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28. Resurrecting treatment histories of dead patients: a study design that should be laid to rest.
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Bach PB, Schrag D, and Begg CB
- Subjects
- Bias, Humans, Medical History Taking, Neoplasms mortality, Neoplasms therapy, Quality of Health Care, Treatment Outcome, United States, Outcome and Process Assessment, Health Care, Patient Care, Terminal Care
- Abstract
In this article we address whether studies of care rendered to patients prior to their death ("studies of decedents") produce an accurate portrait of care provided to patients who are dying. Studies of decedents typically analyze the care provided to patients over a defined interval antecedent to death. Studies of dying patients analyze care provided to patients subsequent to the time that their terminal status is perceived. We address whether 2 fundamental differences between studies of decedents and studies of the dying--the ways that subjects are identified and the time periods that are examined--lead to differences in interpretation of study results. Using examples from population-based cohorts of individuals with cancer, we show that both the differences in subject selection and time period introduce very substantial biases into studies of decedents. We conclude that studying care received prior to death can lead to invalid conclusions about the quality or type of care provided to dying patients.
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- 2004
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29. The effect of clustering of outcomes on the association of procedure volume and surgical outcomes.
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Panageas KS, Schrag D, Riedel E, Bach PB, and Begg CB
- Subjects
- Clinical Competence, Cluster Analysis, Colectomy statistics & numerical data, Female, Humans, Male, SEER Program, United States, Colonic Neoplasms surgery, Digestive System Surgical Procedures statistics & numerical data, Hospitals statistics & numerical data, Outcome Assessment, Health Care, Prostatectomy statistics & numerical data, Prostatic Neoplasms surgery, Rectal Neoplasms surgery
- Abstract
Background: A large body of literature documents associations between the volume of cases a hospital or surgeon treats and clinical outcomes. Most of these studies have used conventional statistical methods that do not recognize the fact that hospitals or surgeons with similar volumes may have very different outcomes because of systematic differences in processes of care, a phenomenon that exaggerates the true statistical significance of the effect of volume on outcome., Objective: To describe methods to assess the degree of this "clustering" of outcomes and to explore the impact of available statistical techniques that correct for clustering., Design: Reanalysis of 3 previously published volume-outcome studies., Setting: Medicare beneficiaries 65 years of age or older undergoing surgery for colon, prostate, or rectal cancer in the population defined by the Surveillance, Epidemiology, and End Results cancer registries during 1992 to 1996., Patients: 3 data sets were analyzed to assess the impact of surgeon volume on outcomes: 1) 24 166 colectomies performed by 2682 surgeons, 2) 10 737 prostatectomies performed by 999 surgeons, and 3) 2603 rectal resections performed by 1141 surgeons., Measurements: Volume-outcome trends were analyzed by a conventional method (logistic regression) and corrected for clustering. Two widely used statistical methods for analyzing clustered data, a random-effects model and generalized estimating equations, were used and compared, and the degree of clustering was presented graphically., Results: Substantial clustering was observed in the analyses involving morbidity end points. The 2 statistical techniques produced noticeably different results in some analyses., Conclusions: The presence of clustering represents variations in outcomes among providers with similar volumes. Thus, in volume-outcome studies, the degree of clustering of outcomes should be characterized because it may provide insight into variations in quality of care.
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- 2003
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30. Adherence to surveillance among patients with superficial bladder cancer.
- Author
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Schrag D, Hsieh LJ, Rabbani F, Bach PB, Herr H, and Begg CB
- Subjects
- Aged, Aged, 80 and over, Comorbidity, Female, Guideline Adherence, Humans, Male, Odds Ratio, Practice Guidelines as Topic, Risk, SEER Program, Secondary Prevention, United States, Urinary Bladder Neoplasms pathology, Urinary Bladder Neoplasms surgery, Cystectomy, Patient Compliance statistics & numerical data, Physicians statistics & numerical data, Population Surveillance, Urinary Bladder Neoplasms diagnosis
- Abstract
Background: Patients diagnosed with superficial bladder cancer who have not undergone total cystectomy are at high risk for recurrence, and bladder surveillance with cystoscopy is recommended for such patients every 3-6 months. We examined the degree to which bladder cancer patients undergo the recommended surveillance procedures and identified patient and primary care provider characteristics associated with nonadherence to these recommendations., Methods: We used information obtained from the Surveillance, Epidemiology, and End Results (SEER) Program-Medicare-linked database to identify 6717 patients aged 65 years or older who were diagnosed with superficial bladder cancer from 1992 through 1996 and who survived for at least 3 years after diagnosis but did not have a total cystectomy. We used information obtained from Medicare claims forms to examine the frequency with which these patients had a surveillance examination of the bladder during each of five contiguous 6-month intervals from month 7 to month 36 following diagnosis. We examined characteristics of patients and their physicians that were associated with low-intensity surveillance (defined as having an examination during fewer than two of the five possible follow-up intervals). Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided., Results: Only 40% of the entire cohort had an examination during all five intervals; 1216 patients (18.1%) had low-intensity surveillance. Patient characteristics that were independently associated with low-intensity surveillance were being age 75 years or older (adjusted OR = 1.54, 95% CI = 1.35 to 1.74), nonwhite (adjusted OR = 1.94, 95% CI = 1.57 to 2.40), and having favorable tumor histology (adjusted OR = 0.59, 95% CI = 0.48 to 0.72 for poorly differentiated versus referent well-differentiated tumor grade) and high comorbidity (adjusted OR = 1.72, 95% CI = 1.30 to 2.27). Residence in an urban area or in a census tract with low median income was also associated with low-intensity surveillance., Conclusions: The actual practice of surveillance for patients with superficial bladder cancer differs substantially from the standards recommended in clinical guidelines.
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- 2003
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31. Adjuvant chemotherapy use for Medicare beneficiaries with stage II colon cancer.
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Schrag D, Rifas-Shiman S, Saltz L, Bach PB, and Begg CB
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- Aged, Chemotherapy, Adjuvant, Cohort Studies, Colonic Neoplasms epidemiology, Colonic Neoplasms pathology, Female, Humans, Logistic Models, Male, Medicare, Proportional Hazards Models, SEER Program, Treatment Outcome, United States epidemiology, Antineoplastic Agents therapeutic use, Colonic Neoplasms drug therapy
- Abstract
Purpose: Clinical trials have not demonstrated that adjuvant chemotherapy improves survival for patients with resected stage II colon cancer. Nevertheless, patients may receive this treatment despite its uncertain benefit. The objective of this study was to determine the extent to which adjuvant chemotherapy is used for patients with stage II colon cancer., Patients and Methods: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified 3,151 patients aged 65 to 75 with resected stage II colon cancer and no adverse prognostic features. The primary outcome was chemotherapy use within 3 months of surgery ascertained from claims submitted to Medicare. Relationships between patient characteristics and adjuvant chemotherapy use were measured and their significance was assessed using multivariable logistic regression. Survival for treated and untreated patients was compared using a Cox model., Results: Twenty-seven percent of patients received chemotherapy during the 3 postoperative months. Younger age at diagnosis, white race, unfavorable tumor grade, and low comorbidity were each associated with a greater likelihood of receiving treatment. Sex, the number of examined lymph nodes in the tumor specimen, the urgency of the surgical admission, and median income was each unrelated to treatment. Five-year survival was 75% for untreated patients and 78% for treated patients. After adjusting for known between-group differences, the hazard ratio for survival associated with adjuvant treatment was 0.91 (95% confidence interval, 0.77 to 1.09)., Conclusion: A substantial percentage of Medicare beneficiaries with resected stage II colon cancer receive adjuvant chemotherapy despite its uncertain benefit.
- Published
- 2002
- Full Text
- View/download PDF
32. Measuring complications of cancer treatment using the SEER-Medicare data.
- Author
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Potosky AL, Warren JL, Riedel ER, Klabunde CN, Earle CC, and Begg CB
- Subjects
- Aged, Antineoplastic Agents adverse effects, Female, Health Services Research, Humans, Insurance Claim Reporting, Male, Medical Record Linkage, Neoplasms epidemiology, Postoperative Complications, Radiotherapy adverse effects, United States epidemiology, Medicare, Neoplasms therapy, Outcome Assessment, Health Care, SEER Program
- Abstract
Background: The linkage of SEER registry data with Medicare claims allows the longitudinal tracking of health care and outcomes for patients after a cancer diagnosis. One category of outcomes amenable to research using Medicare claims is complications of cancer treatments: the unintentional, adverse side effects or sequelae of interventions used to treat or palliate cancer patients., Research Design: The authors review some of the methods and limitations of using Medicare claims to identify both acute and chronic complications of cancer treatments, and present an original analysis comparing survey-based and claims-based complications following radical prostatectomy for prostate cancer to illustrate some of the potential limitations inherent in using claims for this purpose., Results: Utility of the Medicare claims for identifying postdischarge complications varies by the patient type, the initial treatment used, and any subsequent treatment of complications. For patients undergoing surgical interventions, Medicare claims can be used to identify most acute inpatient complications. However, claims data cannot be used as effectively in the long-term to capture chronic complications, particularly when the complication does not consistently prompt an intervention., Conclusion: Researchers who use the SEER-Medicare-linked database to assess long-term complications of cancer treatments should exercise caution when designing and interpreting studies. Ideally, for studies of most chronic complications of cancer care, validation studies similar to the one performed here would provide valuable additional evidence to assess the credibility of conclusions based on claims data.
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- 2002
- Full Text
- View/download PDF
33. Variations in morbidity after radical prostatectomy.
- Author
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Begg CB, Riedel ER, Bach PB, Kattan MW, Schrag D, Warren JL, and Scardino PT
- Subjects
- Aged, General Surgery statistics & numerical data, Humans, Male, Medicare, Postoperative Complications mortality, Prostatectomy adverse effects, Prostatic Neoplasms surgery, SEER Program, United States epidemiology, Urinary Incontinence epidemiology, Urinary Incontinence etiology, Urologic Diseases epidemiology, Urologic Diseases etiology, Workforce, Hospitals statistics & numerical data, Outcome Assessment, Health Care, Postoperative Complications epidemiology, Prostatectomy mortality, Prostatectomy statistics & numerical data
- Abstract
Background: Recent studies of surgery for cancer have demonstrated variations in outcomes among hospitals and among surgeons. We sought to examine variations in morbidity after radical prostatectomy for prostate cancer., Methods: We used the Surveillance, Epidemiology, and End Results-Medicare linked data base to evaluate health-related outcomes after radical prostatectomy. The rates of postoperative complications, late urinary complications (strictures or fistulas 31 to 365 days after the procedure), and long-term incontinence (more than 1 year after the procedure) were inferred from the Medicare claims records of 11,522 patients who underwent prostatectomy between 1992 and 1996. These rates were analyzed in relation to hospital volume and surgeon volume (the number of procedures performed at individual hospitals and by individual surgeons, respectively)., Results: Neither hospital volume nor surgeon volume was significantly associated with surgery-related death. Significant trends in the relation between volume and outcome were observed with respect to postoperative complications and late urinary complications. Postoperative morbidity was lower in very-high-volume hospitals than in low-volume hospitals (27 percent vs. 32 percent, P=0.03) and was also lower when the prostatectomy was performed by very-high-volume surgeons than when it was performed by low-volume surgeons (26 percent vs. 32 percent, P<0.001). The rates of late urinary complications followed a similar pattern. Results for long-term preservation of continence were less clear-cut. In a detailed analysis of the 159 surgeons who had a high or very high volume of procedures, wide surgeon-to-surgeon variations in these clinical outcomes were observed, and they were much greater than would be predicted on the basis of chance or observed variations in the case mix., Conclusions: In men undergoing prostatectomy, the rates of postoperative and late urinary complications are significantly reduced if the procedure is performed in a high-volume hospital and by a surgeon who performs a high number of such procedures.
- Published
- 2002
- Full Text
- View/download PDF
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