Stacey Slone

Intraclass correlation estimates for cancer screening outcomes: estimates and applications in the design of group-randomized cancer screening studies.

BACKGROUND Screening has become one of our best tools for early detection and prevention of cancer. The group-randomized trial is the most rigorous experimental design for evaluating multilevel interventions. However, identifying the proper sample size for a group-randomized trial requires reliable estimates of intraclass correlation (ICC) for screening outcomes, which are not available to researchers. We present crude and adjusted ICC estimates for cancer screening outcomes for various levels of aggregation (physician, clinic, and county) and provide an example of how these ICC estimates may be used in the design of a future trial. METHODS Investigators working in the area of cancer screening were contacted and asked to provide crude and adjusted ICC estimates using the analysis of variance method estimator. RESULTS Of the 29 investigators identified, estimates were obtained from 10 investigators who had relevant data. ICC estimates were calculated from 13 different studies, with more than half of the studies collecting information on colorectal screening. In the majority of cases, ICC estimates could be adjusted for age, education, and other demographic characteristics, leading to a reduction in the ICC. ICC estimates varied considerably by cancer site and level of aggregation of the groups. CONCLUSIONS Previously, only two articles had published ICCs for cancer screening outcomes. We have complied more than 130 crude and adjusted ICC estimates covering breast, cervical, colon, and prostate screening and have detailed them by level of aggregation, screening measure, and study characteristics. We have also demonstrated their use in planning a future trial and the need for the evaluation of the proposed interval estimator for binary outcomes under conditions typically seen in GRTs.

Impact of adding the multikinase inhibitor sorafenib to endocrine therapy in metastatic estrogen receptor-positive breast cancer.

BACKGROUND Targeting growth factor and survival pathways may delay endocrine-resistance in estrogen receptor-positive breast cancer. MATERIALS & METHODS A pilot Phase II study adding sorafenib to endocrine therapy in 11 patients with metastatic estrogen receptor-positive breast cancer was conducted. Primary end point was response by RECIST after 3 months of sorafenib. Secondary end points included safety, time to progression and biomarker modulation. The study closed early owing to slow accrual. RESULTS Eight out of 11 patients had progressive disease on study entry and three had stable disease. Of the ten evaluable patients, seven experienced stable disease (70%) and three experienced progressive diseas (30%), with a median time to progression of 6.1 months (8.4 months in the seven patients on tamoxifen). The serum samples demonstrated a significant reduction in VEGF receptor 2 and PDGF receptor-α. Microarray analysis identified 32 suppressed genes, no induced genes and 29 enriched Kyoto Encyclopedia of Genes and Genomes pathways. CONCLUSION The strategy of adding a targeted agent to endocrine therapy upon resistance may be worthwhile testing in larger studies.

Cytomegalovirus reactivation is associated with a lower rate of early relapse in myeloid malignancies independent of in-vivo T cell depletion strategy

The association between cytomegalovirus (CMV) reactivation and relapse risk has not been evaluated in relation to T cell depletion strategies. We evaluated 93 patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) and analyzed the association between T cell depletion strategies with the cumulative incidence of relapse and CMV reactivation. A total of 33% of patients who received ATG vs. 34% who received alemtuzumab developed CMV reactivation. The cumulative incidence of relapse was 3% at 1year and 20% at 3 years in patients with CMV reactivation vs. 30% at 1year and 38% at 3 years in patients without CMV reactivation (p=0.02). When analyzed separately, this effect persisted in the myeloid, but not the lymphoid group. There was a numerical trend towards increased non-relapse mortality (NRM) in patients with CMV reactivation, especially in the myeloid group. The choice of T cell depleting agent and the rate of CMV reactivation were not associated with different overall survival (OS) rates. These results suggest that the choice of T cell depletion strategy may have similar effects on rates of CMV reactivation, disease relapse, and survival. Further studies examining these variables in patients not exposed to in-vivo T cell depleting agents may be of interest.

Inconsistencies Between Medical Records and Patient-Reported Recommendations for Follow-Up After Abnormal Pap Tests

PURPOSE Adherence with recommended follow-up after an abnormal Pap test is a critical step in the prevention of cervical cancer. Here, we focused on identifying inconsistencies between self-reported and health department record recommendations for follow-up. METHODS Self-reported recommendations for follow-up were collected by questionnaire from 519 women with abnormal Pap tests in rural Appalachia as part of a trial of the efficacy of patient navigation. Health department medical records were reviewed to collect healthcare provider recommendations. Measures of inconsistency (discordance) were calculated for overall recommendations and each of three particular follow-up recommendations: repeat Pap test, referral for further tests, and other gynecologist referral. RESULTS The inconsistencies between the recommendation from the health department records and self-reports ranged from 15.0% (repeat Pap test) to 35.3% (gynecologist referral). Inconsistencies were most common among women with a history of abnormal Pap tests and those with more severe initial results. Recommendations for repeat Pap tests were correctly reported most often when the women recalled receiving a letter stating the results. Of greatest concern were the inconsistencies regarding recommendations for referral to a gynecologist. The more severe the Pap test result, the greater the odds of inaccurate self-reports of receiving a referral to a gynecologist for follow-up, p<0.001. CONCLUSIONS Clinicians should be aware that patients with a history of abnormal results and severe Pap test abnormalities are at risk of misreporting recommendations for follow up.

Short-term cardiac toxicity of autologous hematopoietic stem cell transplant for multiple myeloma

Th e last two decades have seen tremendous progress in the treatment of multiple myeloma, including the use of high-dose melphalan (HDM) with autologous hematopoietic stem cell transplant (auto-HCT) and the availability of various novel agents [1]. Th e incidence of cardiotoxicity after HDM is not known, even though there have been case reports of cardiac arrhythmias with HDM [2,3]. In this study, we evaluated the incidence of cardiac adverse events (AEs) in 325 patients within 30 days of undergoing auto-HCT using HDM at M. D. Anderson Cancer Center for multiple myeloma between January 2006 and December 2009. We excluded 78 patients with concurrent immunoglobulin light chain amyloidosis (AL). In the group who experienced cardiac AEs, melphalan doses of 200 mg/m 2 (19 patients) and 180 mg/m 2 (one patient) were used. Similarly, melphalan doses of 200 mg/m 2 (215 patients), 180 mg/m 2 (six patients), 160 mg/m 2 (one patient) and 140 mg/m 2 (two patients) were used in the group without cardiac AEs. In two patients without cardiac AEs the melphalan dose was missing. All patients received granulocyte colony stimulating factor (G-CSF), 5 μ g/kg/ day from day 1 until the absolute neutrophil count (ANC) was 0.5 109/L for 2 consecutive days, as per departmental guidelines. Supportive care measures, including blood product transfusion and electrolyte and weight management were done as per institutional guidelines. Cardiac toxicity was defi ned as any cardiac AE reported from the day of administration of melphalan to day 30 after auto-HCT. Th ese cardiac AEs included congestive heart failure (CHF), arrhythmias, ischemic chest pain and sudden cardiac death. CHF was defi ned as any structural or functional cardiac disorder that impaired the ability of the ventricles to fi ll or eject blood, with associated symptoms of fatigue, dyspnea and fl uid retention. Sudden cardiac death was defi ned as cessation of cardiac activity leading to unresponsiveness and demise of the patient. Ischemic chest pain was defi ned as typical substernal chest pain that was precipitated by exertion, radiating to the jaw and the inner aspect of the arms or shoulders, and relieved by nitroglycerin. Prior cardiac history was defi ned as a history of coronary artery disease, arrhythmias, valvular heart disease or cardiac light-chain amyloidosis before auto-HCT. Th e primary endpoint of the study was to evaluate the incidence of cardiac AEs after HDM and auto-HCT. We also evaluated the variables that could aff ect cardiac AEs. Th ese variables included a prior history of hypertension, diabetes, tobacco smoking, prior chemotherapy, interval between diagnosis and auto-HCT, cardiac biomarkers (troponin and brain natriuretic peptide [BNP]) and echocardiogram. Cardiac biomarkers are routinely collected as a part of pre-transplant evaluation.

Effectiveness of an Intervention for Adherence to Follow-up Recommendations for Abnormal Pap Tests in Appalachian Kentucky

OBJECTIVE In collaboration with rural county health departments (CHDs), we developed a patient navigation intervention to increase adherence to follow-up recommendations for women with abnormal Pap tests. METHODS Local women were recruited, trained and placed in CHDs. Navigation was tailored to the follow-up care recommended. Effectiveness was evaluated in a quasi-experimental trial that included 13 intervention CHDs and 13 comparison group CHDs. Participants were enrolled from September 2008 through July 2010. RESULTS A total of 478 participants were enrolled. The proportion that received recommended follow-up care was greater in the intervention CHDs (91.6%) than in the comparison group CHDs (80.8%) (p = .01). CONCLUSIONS These results suggest that development of policy to promote navigation with rural health care delivery systems has great potential to improve patient outcomes.

Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity

The basis for associations between lung cancer and major histocompatibility complex genes is not completely understood. Here the authors further consider genetic variation within the MHC region in lung cancer patients and identify independent associations within HLA genes that explain MHC lung cancer associations in Europeans and Asian populations.AbstractLung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter better represented by the amino acid Ala-104. These results implicate several HLA–tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility.

Abstract B30: Patient navigation for cervical cancer in Kentucky: Baseline results

Background: Although morbidity and mortality rates are low compared to other types of cancer, cervical cancer remains a high priority for the following reasons: 1) invasive cervical cancer is a disease that could be prevented in nearly all cases, with greater use of the Pap test; 2) the Pap test is a well‐established, low cost, widely available screening test that should present minimal barriers to its use; and 3) despite our ability to prevent and treat cervical cancer, the burden of cervical cancer morbidity and mortality continues to be higher among low‐income women with limited education, many of whom reside in rural areas. Despite public health recommendations for cervical cancer screening and follow‐up of abnormal Pap test results, adherence is still low among rural Appalachian women in Kentucky. In response to this concern, the University of Kentucky Prevention Research Center is implementing a National Cancer Institute‐funded project that is integrating patient navigators (PN) in cervical cancer screening programs in several rural health departments. Goal: To reduce the disproportionate burden of cervical cancer experienced by rural Appalachian women in Kentucky. Objectives: To: 1) improve our understanding of the barriers to follow‐up; 2) recruit, train, and utilize lay health workers as PNs in cervical cancer screening programs; 3) increase the proportion of women who adhere to recommended follow‐up; and 4) evaluate the efficacy of the intervention. Method: Intervention activities are as follows: 1) nurse case managers refer patients with abnormal pap tests to PNs in selected local health departments in Big Sandy, Lake Cumberland, and Kentucky River Area Development Districts; 2) PNs enroll patients in the study; 3) study participants complete a baseline interview; 4) PNs provide navigation services including outreach, education, and support; 5) PNs conduct follow‐up interviews; and 6) PNs document follow‐up recommendations, barriers, patient needs, and specific actions taken to ensure adherence to follow‐up recommendations. Evaluation: To assess the efficacy of the intervention, outcome data will be collected from health department records in intervention and control counties. Findings: The total number of referrals to date is 600. Among the referrals: 82 (14%) were ineligible (patient less than 18 years, refused services, dropped by health department for non‐compliance, or lost to follow‐up); 379 (63%) were offered enrollment; and enrollment is pending for 139 (23%). Among those offered enrollment, 297 (78%) agreed to participate in the study. Additional preliminary findings will be presented including reason for referral, characteristics of women enrolled, patient needs, adherence to follow‐up, etc. Conclusions: The program creates a unique opportunity to support rural cervical cancer screening programs, ensuring women obtain their recommended follow‐up care through the support of PNs. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B30.