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James J Dignam

Publications and source records attributed to James J Dignam.

15 recordsLinked to original sources
PubMed2007

A missing data approach to semi-competing risks problems.

For event time data involving multiple mutually exclusive competing causes of failure, classic competing risks results show that marginal survival distributions are not identifiable. In a related instance, one or more failure modes may be observed provided that the failure events occur in a specific order. In such situations, sometimes referred to as semi-competing risks problems, the observations may under realistic assumptions lend information about parameters of interest that would be nonidentifiable in the strict competing risks case. Here, we present an approach that makes use of partially observable multiple modes of failures to obtain an estimate of the marginal distribution of one event type that may occur prior to the occurrence of another event type or be precluded by it. We apply the proposed method to the problem of estimating the distribution of time to tumour recurrence at specific sites among breast cancer patients participating in randomized clinical trials.

Antineoplastic Agents↗
PubMed2006

Body mass index and outcomes in patients who receive adjuvant chemotherapy for colon cancer.

BACKGROUND: Although several studies have established a link between obesity and colon cancer risk, little is known about the effect of obesity on outcomes after diagnosis. We investigated the association of body mass index (BMI) with outcomes after colon cancer in patients from cooperative group clinical trials. METHODS: The study cohort consisted of 4288 patients with Dukes B and C colon cancer who were accrued from July 1989 to February 1994 to National Surgical Adjuvant Breast and Bowel Project randomized trials. Risk of recurrence, second primary cancer, and mortality (overall and by likely cause) were evaluated in relation to BMI at diagnosis using statistical modeling. Median follow-up time was 11.2 years. All statistical tests were two-sided. RESULTS: Very obese patients (BMI > or = 35 kg/m2) had greater risk of a colon cancer event (recurrence or secondary primary tumor; hazard ratio [HR] = 1.38, 95% confidence interval [CI] = 1.10 to 1.73) than normal weight patients (BMI = 18.5-24.9 kg/m2). Mortality was greater for very obese (HR = 1.28, 95% CI = 1.04 to 1.57) and underweight (BMI < 18.5 kg/m2) (HR = 1.49, 95% CI = 1.17 to 1.91) than for normal weight patients. The increased risk of mortality for underweight patients was dominated by non-colon cancer deaths (HR of such deaths compared with normal weight patients = 2.23, 95% CI = 1.50 to 3.31), whereas for the very obese, deaths likely due to colon cancer were increased (HR = 1.36, 95% CI = 1.06 to 1.73). CONCLUSIONS: Among colon cancer patients, a BMI greater than 35.0 kg/m2 at diagnosis was associated with an increased risk for recurrence of and death from colon cancer. Further studies are needed to determine pathways between obesity and recurrence risk and whether weight reduction or related interventions would improve prognosis.

Adult↗
PubMed2006

Colorectal cancer model of health disparities: understanding mortality differences in minority populations.

African Americans are more likely to be diagnosed with and die as a result of colorectal cancer than white patients. This review briefly documents these differences and explores the factors that may contribute to advanced stage at diagnosis and reduced survival once African Americans are diagnosed with colorectal cancer. Attention is focused on what is known about the role of socioeconomic status, cancer screening, comorbidities and lifestyle factors, tumor biology and genetics, and the differences in the receipt of and benefit of appropriate therapy. Finally, areas of ongoing and future research and policy initiatives aimed at reducing disparities are discussed.

Black or African American↗
PubMed2005

Effects of obesity and race on prognosis in lymph node-negative, estrogen receptor-negative breast cancer.

BACKGROUND: Several factors may contribute to poorer prognosis for obese breast cancer patients, including unfavorable disease features, the influence of fat on estrogen availability, co-morbidity, and socio-demographic factors. Both obesity and estrogen receptor negative (ER-) tumors are more prevalent in black women than in whites in North America. We evaluated obesity and race in relation to outcomes in women with ER-breast cancer. METHODS: Among 4,077 women from National Surgical Adjuvant Breast and Bowel Project clinical trials for node-negative, ER-breast cancer, we evaluated disease-free survival (DFS) and its constituents (tumor recurrence, contralateral breast cancer (CBC), second primary cancers, deaths prior to these events) and mortality in relation to body mass index (BMI) and race, using statistical modeling to account for other prognostic factors. RESULTS: Compared to those of normal weight (BMI< or =24.9), DFS hazard was greater for obese (BMI > or = 30) women [hazard ratio (HR)=1.16, 95% confidence interval (CI)=1.01-1.33]. Obesity did not increase recurrence hazard, but did influence CBC (HR=2.08, 95% CI=1.22-3.55 in postmenopausal women) and second cancers (HR=1.49, 95% CI=1.06-2.10). Mortality increased with obesity; when partitioned by likely cause, those with BMI > or = 35.0 had greater risk of non-breast cancer mortality (HR=1.86, 95% CI=1.21-2.84). Relative to whites and adjusted for BMI, black women had greater hazard for DFS (HR=1.17, 95% CI=1.00-1.38), CBC (HR=1.37, 95% CI=0.94-1.99), and non-breast cancer deaths (HR=2.10, 95% CI=1.45-3.03); risk for deaths likely due to breast cancer was closer to that in whites (HR=1.18; 95% CI=0.93-1.50). CONCLUSIONS: For women with node-negative, ER-breast cancer from clinical trials, obesity did not increase recurrence risk, but was associated with greater risk for second cancers, CBC, and mortality, particularly non-breast cancer deaths. Less favorable prognosis for black women persists in clinical trials, and is in part attributable to non-breast cancer outcomes.

Adult↗
PubMed2005

Colorectal cancer and race: understanding the differences in outcomes between African Americans and whites.

Understanding the differences in the incidence and mortality rate between African Americans and whites with CRC remains a perplexing problem. There is clearly not any one factor that explains the observed differences. Clinicians are just beginning to understand the importance of tumor biology, genetics, and lifestyle risk factors in explaining differences in how CRCs present and how they behave. This holds true regardless of a patient's race, sex, or age. Whether these factors will add disproportionately to the understanding of racial differences in presentation and outcome remains to be seen. Certainly, issues surrounding screening for CRC remain important in understanding the advanced stage of presentation for African Americans. In particular, a better understanding is needed of who is being screened and who is not and why. For example, are higher-risk African Americans being screened and if not what are the reasons for this? Importantly, even if one were able to eliminate the differences in stage at presentation between African Americans and whites, a survival disadvantage, albeit a much smaller one, would likely persist. Clearly, there is a need to understand better why African Americans are not receiving recommended therapy at the same rate as whites. This becomes even more important as the life-prolonging options for treating both localized and metastatic colon cancer continue to multiply. Finally, the apparent greater disparity in outcome for African Americans who have stage II disease should be explored in more detail, because this could have an immediate impact on treatment recommendations. For example, a 23-gene signature was recently found to be predictive of recurrence among patients with Dukes B colon cancer [66]. If this model is validated in further studies, one could look at whether African-American patients are more likely to have this predictive signature. The problem has been clearly defined: a higher incidence of and a higher mortality from CRC for African Americans than whites. The task now becomes to continue to understand the reasons for the disparities and ultimately to come up with workable solutions so that the amazing progress in CRC treatment benefits all groups in this country.

Black or African American↗
PubMed2004

Mammographic density and breast cancer after ductal carcinoma in situ.

Women with ductal carcinoma in situ (DCIS) are at substantially increased risk for a second breast cancer, but few strong predictors for these subsequent tumors have been identified. We used Cox regression modeling to examine the association between mammographic density at diagnosis of DCIS of 504 women from the National Surgical Adjuvant Breast and Bowel Project B-17 trial and risk of subsequent breast cancer events. In this group of patients, mostly 50 years old or older, approximately 6.6% had breasts categorized as highly dense (i.e., > or =75% of the breast occupied by dense tissue). After adjusting for treatment with radiotherapy, age, and body mass index, women with highly dense breasts had 2.8 (95% confidence interval [CI] = 1.3 to 6.1) times the risk of subsequent breast cancer (DCIS or invasive), 3.2 (95% CI = 1.2 to 8.5) times the risk of invasive breast cancer, and 3.0 (95% CI = 1.2 to 7.5) times the risk of any ipsilateral breast cancer, compared with women with less than 25% of the breast occupied by dense tissue. Our results provide initial evidence that the risk of second breast cancers may be increased among DCIS patients with highly dense breasts.

Adult↗
PubMed2004

MYC is amplified in BRCA1-associated breast cancers.

PURPOSE: Germ-line mutations in the BRCA1 tumor suppressor gene predispose to early onset breast cancers with a distinct phenotype characterized by high tumor grade, aneuploidy, high proliferation rate, and estrogen receptor-negativity. The molecular mechanisms and cooperative oncogenes contributing to multistep tumor progression in cells lacking BRCA1 are not well defined. To examine whether C-MYC (MYC), a transforming oncogene associated with genetic instability, contributes to multistep tumor progression in BRCA1-associated breast cancer, we have analyzed tumors from women with hereditary BRCA1-mutated and sporadic breast cancers. EXPERIMENTAL DESIGN: We performed fluorescence in situ hybridization using a MYC:CEP8 assay on formalin-fixed paraffin-embedded tumor tissues from 40 women with known deleterious germ-line BRCA1 mutations and 62 sporadic cases, including 20 cases with hypermethylation of the BRCA1 gene promoter. RESULTS: We observed a MYC:CEP8 amplification ratio >/=2 in 21 of 40 (53%) BRCA1-mutated tumors compared with 14 of 62 (23%) sporadic tumors (P = 0.003). Of the 14 sporadic cases with MYC amplification, 8 (57%) were BRCA1-methylated. In total, MYC amplification was found in a significantly higher proportion of tumors with BRCA1 dysfunction (29 of 60, 48% versus 6 of 42, 14%; P = 0.0003). In a multivariable regression model controlling for age, tumor size, and estrogen receptor status, BRCA1-mutated tumors demonstrated significantly greater mean MYC:CEP8 ratio than sporadic tumors (P = 0.02). CONCLUSIONS: Our data indicate that MYC oncogene amplification contributes to tumor progression in BRCA1-associated breast cancers. Thus, we conclude that the aggressive histopathological features of BRCA1-associated tumors are in part due to dysregulated MYC activity.

Adult↗
PubMed2004

Semiparametric models for cumulative incidence functions.

In analyses of time-to-failure data with competing risks, cumulative incidence functions may be used to estimate the time-dependent cumulative probability of failure due to specific causes. These functions are commonly estimated using nonparametric methods, but in cases where events due to the cause of primary interest are infrequent relative to other modes of failure, nonparametric methods may result in rather imprecise estimates for the corresponding subdistribution. In such cases, it may be possible to model the cause-specific hazard of primary interest parametrically, while accounting for the other modes of failure using nonparametric estimators. The cumulative incidence estimators so obtained are simple to compute and are considerably more efficient than the usual nonparametric estimator, particularly with regard to interpolation of cumulative incidence at early or intermediate time points within the range of data used to fit the function. More surprisingly, they are often nearly as efficient as fully parametric estimators. We illustrate the utility of this approach in the analysis of patients treated for early stage breast cancer.

Analysis of Variance↗
PubMed2003

Obesity, tamoxifen use, and outcomes in women with estrogen receptor-positive early-stage breast cancer.

BACKGROUND: Obesity is associated with both increased breast cancer risk and poorer prognosis after disease onset. However, little is known about the effect of obesity on treatment efficacy. We evaluated the association of obesity with outcomes and with tamoxifen efficacy in women with early-stage, hormone-responsive breast cancer participating in a multicenter cancer cooperative group clinical trial. METHODS: The cohort consisted of 3385 women enrolled in National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-14, a randomized, placebo-controlled trial evaluating tamoxifen for lymph node-negative, estrogen receptor (ER)-positive breast cancer. Hazards of breast cancer recurrence, contralateral breast tumors, other new primary cancers, and several mortality endpoints were evaluated in relation to body mass index (BMI), using statistical modeling to adjust for other prognostic factors. Median follow-up time was 166 months. All statistical tests were two-sided. RESULTS: The hazard of breast cancer recurrence was the same among obese (BMI > or =30.0 kg/m2) women as compared with underweight and normal-weight women (BMI <25.0; hazard ratio [HR] = 0.98, 95% confidence interval [CI] = 0.80 to 1.18). Contralateral breast cancer hazard was higher in obese women than in underweight/normal-weight women (HR = 1.58, 95% CI = 1.10 to 2.25), as was the risk of other primary cancers (HR = 1.62, 95% CI = 1.16 to 2.24). Compared with normal-weight women, obese women had greater all-cause mortality (HR = 1.31, 95% CI = 1.12 to 1.54) and greater risk of deaths due to causes unrelated to breast cancer (HR = 1.49, 95% CI = 1.15 to 1.92). Breast cancer mortality was not statistically significantly increased for obese women (HR = 1.20, 95% CI = 0.97 to 1.49). Tamoxifen reduced breast cancer recurrence and mortality, regardless of BMI. CONCLUSIONS: For women with lymph node-negative, ER-positive breast cancer, obesity was not associated with a material increase in recurrence risk or a change in tamoxifen efficacy. However, because obesity was associated with increased risks of contralateral breast cancer, of other primary cancers, and of overall mortality, it may influence long-term outcomes for breast cancer survivors.

Adult↗
PubMed2003

Is patient travel distance associated with survival on phase II clinical trials in oncology?

BACKGROUND: Prior research has suggested that patients who travel out of their neighborhood for elective care from specialized medical centers may have better outcomes than local patients with the same illnesses who are treated at the same centers. We hypothesized that this phenomenon, often called "referral bias" or "distance bias," may also be evident in curative-intent cancer trials at specialized cancer centers. METHODS: We evaluated associations between overall survival and progression-free survival and the distance from the patient residence to the treating institution for 110 patients treated on one of four phase II curative-intent chemoradiotherapy protocols for locoregionally advanced squamous cell cancer of the head and neck conducted at the University of Chicago over 7 years. RESULTS: Using Cox regression that adjusted for standard patient-level disease and demographic factors and neighborhood-level economic factors, we found a positive association between the distance patients traveled from their residence to the treatment center and survival. Patients who lived more than 15 miles from the treating institution had only one-third the hazard of death of those living closer (hazard ratio [HR] = 0.32, 95% confidence interval [CI] = 0.12 to 0.84). Moreover, with every 10 miles that a patient traveled for care, the hazard of death decreased by 3.2% (HR = 0.97, 95% CI = 0.94 to 0.99). Similar results were obtained for progression-free survival. CONCLUSION: Results of phase II curative-intent clinical trials in oncology that are conducted at specialized cancer centers may be confounded by patient travel distance, which captures prognostic significance beyond cancer stage, performance status, and wealth. More work is needed to determine what unmeasured factors travel distance is mediating.

Adult↗
PubMed2003

Prognosis after rectal cancer in blacks and whites participating in adjuvant therapy randomized trials.

PURPOSE: National health statistics indicate that blacks have lower survival rates from colorectal cancer than do whites. This disparity has been attributed to differences in stage at diagnosis and other disease features, extent and quality of treatment, and socioeconomic factors. We evaluated outcomes for blacks and whites with rectal cancer who participated in randomized clinical trials of the National Surgical Adjuvant Breast and Bowel Project (NSABP). The randomized trial setting enhances uniformity in disease stage and treatment plan among all participants. PATIENTS AND METHODS: The study included black (N = 104) or white (N = 1,070) patients from two serially conducted NSABP randomized trials for operable rectal cancer. Recurrence-free survival and survival were compared using statistical modeling to account for differences in patient and disease characteristics between the groups. RESULTS: Blacks and whites had largely similar disease features at diagnosis. After adjustment for patient and tumor prognostic covariates, the black/white recurrence hazard ratio (HR) was 1.25 (95% confidence interval [CI], 0.94 to 1.66). The mortality HR was somewhat larger at 1.45 (95% CI = 1.09 to 1.93). Outcomes were improved for both groups in the more recent trial, which employed systemic adjuvant chemotherapy in all treatment arms. CONCLUSION: Recurrence-free survival was modestly less favorable for blacks, whereas overall survival was more disparate. Outcomes between groups were more comparable than those noted in national health statistics surveys and other studies. Adequate treatment access and the identification of new prognostic factors that can identify patients at high risk of recurrence are needed to ensure optimal outcomes for rectal cancer patients of all racial/ethnic backgrounds.

Aged↗
PubMed2002

Tamoxifen, radiation therapy, or both for prevention of ipsilateral breast tumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less.

PURPOSE: This trial was prompted by uncertainty about the need for breast irradiation after lumpectomy in node-negative women with invasive breast cancers of </= 1 cm, by speculation that tamoxifen (TAM) might be as or more effective than radiation therapy (XRT) in reducing the rate of ipsilateral breast tumor recurrence (IBTR) in such women, and by the thesis that both modalities might be more effective than either alone. PATIENTS AND METHODS: After lumpectomy, 1,009 women were randomly assigned to TAM (n = 336), XRT and placebo (n = 336), or XRT and TAM (n = 337). Rates of IBTR, distant recurrence, and contralateral breast cancer (CBC) were among the end points for analysis. Cumulative incidence of IBTR and of CBC was computed accounting for competing risks. Results with two-sided P values of.05 or less were statistically significant. RESULTS: XRT and placebo resulted in a 49% lower hazard rate of IBTR than did TAM alone; XRT and TAM resulted in a 63% lower rate than did XRT and placebo. When compared with TAM alone, XRT plus TAM resulted in an 81% reduction in hazard rate of IBTR. Cumulative incidence of IBTR through 8 years was 16.5% with TAM, 9.3% with XRT and placebo, and 2.8% with XRT and TAM. XRT reduced IBTR below the level achieved with TAM alone, regardless of estrogen receptor (ER) status. Distant treatment failures were infrequent and not significantly different among the groups (P =.28). When TAM-treated women were compared with those who received XRT and placebo, there was a significant reduction in CBC (hazard ratio, 0.45; 95% confidence interval, 0.21 to 0.95; P =.039). Survival in the three groups was 93%, 94%, and 93%, respectively (P =.93). CONCLUSION: In women with tumors </= 1 cm, IBTR occurs with enough frequency after lumpectomy to justify considering XRT, regardless of tumor ER status, and TAM plus XRT when tumors are ER positive.

Aged↗