Ethical aspects of participation in the Database of Genotypes and Phenotypes of the National Center for Biotechnology Information: The Cancer and Leukemia Group B Experience

BACKGROUND:

The rapid pace of genetics research, coupled with evolving standards for informed consent, can create ethical challenges regarding future use of tissue or information from completed clinical trials. The Cancer and Leukemia Group B (CALGB) Oncology Cooperative Group was faced with an ethical dilemma regarding sharing genetic data from a completed genome‐wide association study (GWAS) that was conducted as part of a large, multicenter breast cancer clinical trial with a national database: the Database of Genotypes and Phenotypes National Center for Biotechnology Information (dbGaP).

METHODS:

The CALGB Ethics Committee conducted a series of multidisciplinary meetings and teleconferences involving patient advocates, bioethicists, clinical researchers, and clinical oncologists to evaluate the ethical issues raised by this case and to identify lessons for improving informed consent to future genetics research in oncology trials.

RESULTS:

The Ethics Committee recommended that GWAS data be provided to dbGaP consistent with documented consent for future use of tissue among trial participants. Ethical issues, including adequacy of informed consent to future research, limitations of privacy in modern genetics research, the potential impact of population‐based genetics research on health disparities, and recontact of research participants for clinical care or further research, were identified as major ethical considerations in this area.

CONCLUSIONS:

Although modern standards for informed consent should not prohibit research or sharing of data consistent with participant's intent and the public interest, there is an urgent need for national consensus on the appropriate use of archived tissue and standardized informed consent for future research among cancer clinical trial participants. Cancer 2012. © 2012 American Cancer Society.     

Improved clinical trial enrollment in adolescent and young adult (AYA) oncology patients after the establishment of an AYA oncology program uniting pediatric and medical oncology divisions

BACKGROUND:

Since 1975, there has been a dramatic increase in the survival rates of pediatric and older cancer patients, but adolescent and young adult (AYA) patients ages 15 to 40 years have not had a similar improvement. Data indicate a direct correlation between increased cure rates and clinical trial enrollment.

METHODS:

The authors previously published data indicating inferior clinical trial enrollment when AYA patients were treated at an adult oncology center versus a pediatric oncology center. To address this deficit, a joint pediatric and adult AYA Oncology Program was established in July 2006 with the primary objective of improving outcomes by increasing therapeutic clinical trial enrollment in this population. Patients who were referred to that program from July 2006 through June 2010 were examined retrospectively to establish whether clinical trial enrollment increased compared with historic controls.

RESULTS:

Fifty‐seven patients were referred to the program from 2006 to 2010 (range, 12‐16 new patients per year). Eight patients were referred for consultation only and were not treated at the University of Pittsburgh Cancer Institute or Children's Hospital of Pittsburgh. Five of 22 patients (23%) who received treatment at the pediatric cancer center were enrolled onto a clinical trial, whereas 9 of 27 patients (33%) patients who received treatment at the adult cancer center were enrolled. There was superior trial participation compared with the previous 3 years for those shared AYA patients who were treated at the adult center (P < .001).

CONCLUSIONS:

Data from this study demonstrated that establishing a unified AYA oncology program can lead to improved clinical trial enrollment for patients who are treated at medical oncology centers. Cancer 2012;3614–3617. © 2011 American Cancer Society.     

General population norms for the Functional Assessment of Cancer Therapy–Kidney Symptom Index (FKSI)

BACKGROUND:

Metastatic renal cell cancer is associated with poor long‐term survival and has no cure. Traditional clinical endpoints are best supplemented by patient‐reported outcomes designed to assess symptoms and function. Normative data was obtained on the National Comprehensive Cancer Network‐Functional Assessment of Cancer Therapy–Kidney Symptom Index (NFKSI) to aid in score interpretation and planning of future trials.

METHODS:

General population data were obtained from 2000 respondents, who completed the 19‐item NFKSI‐19, as well the SF‐36 (Short Form 36‐item instrument) and the PROMIS‐29 (29‐item Patient Reported Outcomes Measurement Information System), both general health status measures. Basic demographic and self‐reported comorbidity data were also collected.

RESULTS:

The sample was 50% female, 85.7% caucasian, with an equal distribution across age bands from 18 years to 75 years and older. Most respondents (62.8%) had more than a high school education and reported an Eastern Cooperative Oncology Group performance status of normal activity without symptoms (63.4%). Score distributions on the NFKSI‐19, its subscales, and individual items are summarized.

CONCLUSIONS:

The NFKSI‐19 and its subscales now have scores for the general US population, allowing comparability to generic questionnaires such as the SF‐36 and PROMIS‐29. These data can be used to guide treatment expectations and plan future comparative effectiveness research using the scales. Cancer 2013. © 2012 American Cancer Society.     

Implementing a breast cancer registry and treatment plan/summary program in clinical practice: A pilot program

BACKGROUND:

There is a need to better measure and improve the quality of oncology care and improve communication with patients and other providers. The American Society of Clinical Oncology Breast Cancer Registry (BCR) pilot evaluated the feasibility and acceptability of prospective data collection for quality assessment in daily clinical practice. Data were used to create and share treatment plans/summaries (TPSs) at the point of care.

METHODS:

Using a web‐based tool, 20 diverse practices entered clinical data on each new early‐stage breast cancer patient into the BCR for 14 months (September 2009 through November 2010). The tool created individual TPSs that were shared with patients. Practices received practice‐specific and aggregate BCR quality measures data, participated in a survey, and received a participation stipend.

RESULTS:

Twenty practices entered 2014 patients into the BCR, collecting demographic, clinical, and treatment information. Fifty‐two percent of practice participants replied to an end‐of‐pilot survey: 73% were satisfied with the BCR and web‐based tool, 31% expressed concern regarding time and effort, and 52% reported additional practice costs during the pilot. Among those who created or shared the TPSs, 90% thought the documents improved oncologist‐patient communication, and 95% favored using BCR data for practice quality improvement.

CONCLUSIONS:

Prospective data collection for quality assessment is feasible and allows sharing of TPSs with patients at the point of care. Future efforts should focus on decreasing implementation burden to practices, broadening participation, examining costs, and, most importantly, assessing its effects on patient outcomes. Cancer 2013. © 2012 American Cancer Society.     

A method for analyzing the business case for provider participation in the National Cancer Institute's Community Clinical Oncology Program and similar federally funded, provider-based research networks

BACKGROUND:

The Community Clinical Oncology Program (CCOP) plays an essential role in the efforts of the National Cancer Institute (NCI) to increase enrollment in clinical trials. Currently, there is little practical guidance in the literature to assist provider organizations in analyzing the return on investment (ROI), or business case, for establishing and operating a provider‐based research network (PBRN) such as the CCOP. In this article, the authors present a conceptual model of the business case for PBRN participation, a spreadsheet‐based tool and advice for evaluating the business case for provider participation in a CCOP organization.

METHODS:

A comparative, case‐study approach was used to identify key components of the business case for hospitals attempting to support a CCOP research infrastructure. Semistructured interviews were conducted with providers and administrators. Key themes were identified and used to develop the financial analysis tool.

RESULTS:

Key components of the business case included CCOP start‐up costs, direct revenue from the NCI CCOP grant, direct expenses required to maintain the CCOP research infrastructure, and incidental benefits, most notably downstream revenues from CCOP patients. The authors recognized the value of incidental benefits as an important contributor to the business case for CCOP participation; however, currently, this component is not calculated.

CONCLUSIONS:

The current results indicated that providing a method for documenting the business case for CCOP or other PBRN involvement will contribute to the long‐term sustainability and expansion of these programs by improving providers' understanding of the financial implications of participation. Cancer 2012. © 2011 American Cancer Society.     

Central pathology review in multicenter trials and studies

BACKGROUND:

Central pathology review (CPR) is an important component of multicenter tumor trials. The authors retrospectively analyzed the quality of pathology material submitted to determine the benefits and limitations of rapid CPR.

METHODS:

Analysis of pathology specimens from previous renal tumors in children trials (1980‐2007) included the number of cases submitted, the number of slides per case, discrepancies in diagnosis and staging between institutional pathologists and CPR, and the impact of rapid CPR on treatment.

RESULTS:

The percentage of cases submitted for CPR increased from 76% in earlier trials to 100% in the current trial. The number of slides submitted rose from a median of 6 (International Pediatric Oncology Society [SIOP] 9301) to 25 for the SIOP‐UK Renal Tumors 2001 trial. Discrepancies between the institutional pathologists and CPR were as follows: diagnosis: SIOP 9, 17%; SIOP 93‐01, 14%; United Kingdom Wilms Tumour 3 Trial (UKWT3), 3.5%; SIOP‐UK 2001, 3.8%; staging: SIOP 6, 9%; SIOP 93‐01, 14%; UKWT3, 17%; SIOP‐UK 2001, 3.8% of cases. There were clinically significant discrepancies in diagnosis and/or stage in 30 of 152 (20%) cases submitted for delayed CPR in SIOP‐UK 2001.

CONCLUSIONS:

The number and quality of material submitted for CPR has markedly improved over time, predominantly due to the introduction of a simple standard operating procedure. Discrepancies in diagnosis and staging remain, but rapid review CPR allows clinicians to modify treatment if required. Benefits from the CPR system followed in SIOP‐UK 2001 have been clearly demonstrated, and similar systems should be considered for future trials of other tumors. Cancer 2009. © 2009 American Cancer Society.     

Feasibility and safety of sequential research‐related tumor core biopsies in clinical trials

BACKGROUND:

There has been increasing interest in serial research biopsies in studies of targeted therapies. Definition of patient characteristics and optimal target tissue for safe research tumor biopsy in the era of antiangiogenic and targeted agents is needed.

METHODS:

This institutional review board‐approved, retrospective study included chart and interventional radiology case review from 6 phase 1/2 studies at the National Cancer Institute.

RESULTS:

One hundred forty‐two of 150 protocol patients who were approached gave consent for research biopsies. Patients' median age was 56 years (range, 27‐78 years), their median body mass index was 25.8 kg/m² (range, 14.4‐46.2 kg/m²), they had an Eastern Cooperative Oncology Group performance status of 0 or 1, and they had normal end‐organ function. Baseline biopsies were collected from 138 of 142 patients (97%), and paired specimens were collected from 96 (70%). Most patients had metastatic gynecologic cancers (85%), and 78% had target disease below the diaphragm with a median size of 2.7 cm (range, 1‐14.5 cm). Protocol therapies included kinase inhibitors (35%), angiogenesis inhibitors (54%), and olaparib/carboplatin (11%); therapy was not interrupted for biopsies. All adverse events were uncomplicated and were observed in 4 patients (liver subcapsular hematoma in 1 patient, vasovagal syncope in 2 patients, and pneumothorax in 1 patient). The complication rate in obese patients was similar to that in nonobese patients (3 of 108 patients vs 1 of 34 patients, respectively). Sixty‐seven patients (48%) were receiving bevacizumab at the time of subsequent biopsies. The complication rate was not different between patients who were and were not receiving bevacizumab (3 of 67 patients vs 1 of 71 patients, respectively). Ninety‐five percent of biopsies yielded useable material.

CONCLUSIONS:

Serial percutaneous core‐needle biopsies can be obtained safely and yield material applicable for multiple translational applications. Obesity and/or concomitant antiangiogenic therapy and depth of disease did not increase the risk or preclude the successful acquisition of useful tissue. Cancer 2013. © 2012 American Cancer Society.     

American Society of Clinical Oncology‐recommended surveillance and physician specialty among long‐term breast cancer survivors

BACKGROUND:

It is unclear whether it is appropriate to transfer the follow‐up care of breast cancer (BrCa) survivors from cancer specialists to primary care physicians (PCPs). This contemporary study compared physician specialty and documented the long‐term surveillance of survivors who underwent surgery at an American academic center.

METHODS:

Women in this institutional review board‐approved study underwent breast surgery between 1996 and 2006. Data were collected for 270 patients with stage I to III BrCa (mean follow‐up, 6 years). Charts were reviewed based on American Society of Clinical Oncology (ASCO) guidelines for recommended surveillance frequency and care.

RESULTS:

The majority of patients (90%; n = 242) were followed by specialists with 10% (n = 28) followed by PCPs. Patients with advanced disease and a greater risk of disease recurrence more often received specialist care. Patients followed by specialists were more often seen at ASCO‐recommended intervals (eg, 89% vs 69% of patients followed by a PCP at follow‐up Year 6; P < .01); however, many patients were followed inconsistently. Breast disease was often not the focus of PCP visits or mentioned in clinic notes (18% patients). Women seen by specialists were more likely to have documented clinical examinations of the breast (93% vs 44% at Year 6), axilla (94% vs 52%), or annual mammograms (74% vs 48%; P = .001‐.02).

CONCLUSIONS:

Consistent compliance with surveillance guidelines and chart documentation needs improvement among all providers; however, specialists more consistently met ASCO guidelines. If transfer of care to a PCP occurs, it should be formalized and include follow‐up recommendations and defined physician responsibilities. Providers and patients should be educated regarding surveillance care and current guidelines incorporated into standard clinical practice. Cancer 2010. © 2010 American Cancer Society.     

Fine‐needle aspiration of thyroid nodules: A study of 4703 patients with histologic and clinical correlations

BACKGROUND.

The Papanicolaou Society of Cytopathology recently proposed 6 diagnostic categories for the classification of thyroid fine‐needle aspiration (FNA) cytology. Using these categories, the experience with FNA from 2 institutions was studied with emphasis on cytologic‐histologic correlation, source of errors, and clinical management.

METHODS.

Patient cytology data were retrieved by a retrospective search of thyroid FNA in the institutional databases. Cytologic diagnoses were classified as unsatisfactory, benign, atypical cellular lesion (ACL), follicular neoplasm (FN), suspicious for malignancy, and positive for malignancy. Samples with a histologic discrepancy were re‐evaluated, and clinical follow‐up information was recorded.

RESULTS.

Of of 4703 FNA samples, 10.4% were classified as unsatisfactory, 64.6% were classified as benign, 3.2% were classified as ACL, 11.6% were classified as FN, 2.6% were classified as suspicious, and 7.6% were classified as malignant. Five hundred twelve patients had at least 1 repeat FNA, mainly for results in the unsatisfactory and ACL categories. One thousand fifty‐two patients had surgical follow‐up, including 14.9% of patients with unsatisfactory FNA results, 9.8% of patients with benign results, 40.6% of patients with ACL results, 63.1% of patients with FN results, 86.1% of patients with suspicious results, and 79.3% of patients with malignant results. The rates for histologically confirmed malignancy in these categories were 10.9%, 7.3%, 13.5%, 32.2%, 64.7%, and 98.6%, respectively. The cytologic‐histologic diagnostic discrepancy rate was 15.3%. Sources of errors included diagnoses on inadequate specimens, sample errors, and overlapping cytologic features between hyperplastic nodules and follicular adenoma. The sensitivity and specificity of thyroid FNA for the diagnosis of malignancy were 94% and 98.5%, respectively.

CONCLUSIONS.

The current results indicated that FNA provides an accurate diagnosis of thyroid malignancy. The 6 diagnostic categories were beneficial for triaging patients for either clinical follow‐up or surgical management. Cancer (Cancer Cytopathol) 2007. © 2007 American Cancer Society.     

Reclassification of serous ovarian carcinoma by a 2-tier system: a Gynecologic Oncology Group Study

BACKGROUND:

A study was undertaken to use the 2‐tier system to reclassify the grade of serous ovarian tumors previously classified using the International Federation of Gynecology and Obstetrics (FIGO) 3‐tier system and determine the progression‐free survival (PFS) and overall survival (OS) of patients treated on Gynecologic Oncology Group (GOG) Protocol 158.

METHODS:

The authors retrospectively reviewed demographic, pathologic, and survival data of 290 patients with stage III serous ovarian carcinoma treated with surgery and chemotherapy on GOG Protocol 158, a cooperative multicenter group trial. A blinded pathology review was performed by a panel of 6 gynecologic pathologists to verify histology and regrade tumors using the 2‐tier system. The association of tumor grade with PFS and OS was assessed.

RESULTS:

Of 241 cases, both systems demonstrated substantial agreement when combining FIGO grades 2 and 3 (overall agreement, 95%; kappa statistic, 0.68). By using the 2‐tier system, patients with low‐grade versus high‐grade tumors had significantly longer PFS (45.0 vs 19.8 months, respectively; P = .01). By using FIGO criteria, median PFS for patients with grade 1, 2, and 3 tumors was 37.5, 19.8, and 20.1 months, respectively (P = .07). There was no difference in clinical outcome in patients with grade 2 or 3 tumors in multivariate analysis. Woman with high‐grade versus low‐grade tumors demonstrated significantly higher risk of death (hazard ratio, 2.43; 95% confidence interval, 1.17‐5.04; P = .02).

CONCLUSIONS:

Women with high‐grade versus low‐grade serous carcinoma of the ovary are 2 distinct patient populations. Adoption of the 2‐tier grading system provides a simple yet precise framework for predicting clinical outcomes. Cancer 2012;118: 3087–94. © 2011 American Cancer Society.     

Overall survival of newly diagnosed glioblastoma patients receiving carmustine wafers followed by radiation and concurrent temozolomide plus rotational multiagent chemotherapy

BACKGROUND:

Glioblastoma multiforme (GBM), the most lethal type of brain tumor, has a 1‐year median survival. The effect of carmustine wafers on the survival of newly diagnosed GBM patients treated with radiotherapy (RT) and concurrent temozolomide (TMZ) plus RT plus rotational chemotherapy was investigated.

METHODS:

An institutional review board‐approved retrospective study was conducted in 85 newly diagnosed GBM patients who received surgical resection with and without carmustine wafers followed by RT and concurrent TMZ plus rotational chemotherapy. Treatment group comparisons were conducted using the log‐rank test. Survival experience of the Duke cohort was examined within specific patient subgroups defined by the original Radiation Therapy Oncology Group (RTOG) recursive partition analysis (RPA) class and compared with the European Organization for Research and Treatment of Cancer (Stupp) and RTOG trial.

RESULTS:

Overall 1‐ and 2‐year survival for the noncarmustine wafer cohort were 69% and 29%, respectively, with a median survival of 72.7 weeks. One‐ and 2‐year survival for the carmustine wafer cohort were 81% and 47%, with median survival of 89.5 weeks. Carmustine wafer was not an independent predictor (P = .110) of survival after adjustment for RPA class. The proportion of patients in the carmustine wafer cohort who lived longer than predicted based upon Stupp regimen results was significantly greater than 0.5 (P<.006); similar results based upon the RTOG trial data were observed (P < .001).

CONCLUSIONS:

Carmustine wafer with concurrent TMZ and radiation followed by rotational chemotherapy is a well tolerated, effective therapy, and has a survival benefit compared with radiation alone. Prospective randomized trials are needed to rigorously compare the carmustine wafer regimen to the Stupp and postradiation multimodality regimens. Cancer 2009. © 2009 American Cancer Society.     

Combination external beam radiation and brachytherapy boost with androgen deprivation for treatment of intermediate-risk prostate cancer: long-term results of CALGB 99809

BACKGROUND:

Combined transperineal prostate brachytherapy and external beam radiation therapy (EBRT) is widely used for treatment of prostate cancer. Long‐term efficacy and toxicity results of a multicenter phase 2 trial assessing combination of EBRT and transperineal prostate brachytherapy boost with androgen deprivation therapy (ADT) for intermediate‐risk prostate cancer are presented.

METHODS:

Intermediate‐risk patients per Memorial Sloan‐Kettering Cancer Center/National Comprehensive Cancer Network criteria received 6 months of ADT, and 45 grays (Gy) EBRT to the prostate and seminal vesicles, followed by transperineal prostate brachytherapy with I¹²⁵ (100 Gy) or Pd¹⁰³ (90 Gy). Toxicity was graded using the National Cancer Institute Common Toxicity Criteria version 2 and Radiation Therapy Oncology Group late radiation morbidity scoring systems. Disease‐free survival (DFS) was defined as time from enrollment to progression (biochemical, local, distant, or prostate cancer death). In addition to the protocol definition of biochemical failure (3 consecutive prostate‐specific antigen rises >1.0 ng/mL after 18 months from treatment start), the 1997 American Society for Therapeutic Radiology and Oncology (ASTRO) consensus and Phoenix definitions were also assessed in defining DFS. The Kaplan‐Meier method was used to estimate DFS and overall survival.

RESULTS:

Sixty‐one of 63 enrolled patients were eligible. Median follow‐up was 73 months. Late grade 2 and 3 toxicity, excluding sexual dysfunction, occurred in 20% and 3% of patients. Six‐year DFS applying the protocol definition, 1997 ASTRO consensus, and Phoenix definitions was 87.1%, 75.1%, and 84.9%. Six deaths occurred; only 1 was attributed to prostate cancer. Six‐year overall survival was 96.1%.

CONCLUSIONS:

In a cooperative setting, combination of EBRT and transperineal prostate brachytherapy boost plus ADT resulted in excellent DFS with acceptable late toxicity for patients with intermediate‐risk prostate cancer. Cancer 2011;. © 2011 American Cancer Society.     

Phase 2 study of bevacizumab plus erlotinib in patients with advanced hepatocellular cancer

BACKGROUND:

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are rational targets for therapy in hepatocellular cancer (HCC).

METHODS:

Patients with histologically proven HCC and not amenable to curative or liver directed therapy were included in this 2‐stage phase 2 trial. Eligibility included an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 and Child's Pugh score of A or B, and 1 prior systemic therapy. Patients received erlotinib 150 mg daily and bevacizumab 10 mg/kg on days 1 and 15 every 28 days. Objective tumor response was the primary end point.

RESULTS:

Twenty‐seven patients with advanced HCC (median age, 60 years) were enrolled in this multi‐institutional study. The proportion of patients with Child's A classification was 74%. One patient had a confirmed partial response and 11 (48%) achieved stable disease. Median time to disease progression was 3.0 months (95% confidence interval [CI], 1.8‐7.1). Median survival time was 9.5 months (95% CI, 7.1‐17.1). Grade 3 toxicities included rash, hypertension, fatigue, and diarrhea.

CONCLUSIONS:

In this trial, erlotinib combined with bevacizumab had minimal activity in patients with advanced HCC based on objective response and progression‐free survival. The role of targeting EGFR and VEGF in HCC needs further evaluation in molecularly selected patients. Cancer 2012. © 2011 American Cancer Society.     

Presentation,patterns of care,and survival in patients with brain metastases

BACKGROUND:

It is largely unknown to what extent new oncologic treatment options have improved survival of patients with brain metastasis in recent decades. Therefore, a multi‐institutional time‐staggered analysis was performed.

METHODS:

Two cohorts of 103 patients each were analyzed, one treated between 2005 and 2009 and the other between 1983 and 1989, ie, approximately 20 years earlier. Stratified analyses by prognostic groups were also performed (graded prognostic assessment [GPA] and Radiation Therapy Oncology Group recursive partitioning analysis [RTOG‐RPA]).

RESULTS:

Patterns of care have changed significantly. Contemporary patients received focal treatments such as stereotactic radiosurgery and surgical resection far more frequently. Furthermore, systemic treatment was used more often in contemporary patients, both before and after diagnosis of brain metastasis. Improved survival was observed in the contemporary cohort (P = .03). The 1‐year survival rate increased from 15% (95% confidence interval [CI], 7%‐25%) to 34% (95% CI, 25%‐44%). However, this improvement was largely driven by patients with favorable prognostic features. More than 40% of the patients still belong to unfavorable prognostic groups with limited median survival and little improvement.

CONCLUSIONS:

Contemporary patients were managed on a much more individualized basis, requiring multidisciplinary case discussion and thorough assessment of prognostic features. Progress has been made, but the overall outcome needs to be improved further. Avoiding overtreatment in patients with poor prognosis is as important as aggressive treatment in patients who might survive for several years. Cancer 2011. © 2010 American Cancer Society.     

Mapping cancer mortality‐to‐incidence ratios to illustrate racial and sex disparities in a high‐risk population

BACKGROUND:

Comparisons of incidence and mortality rates are the metrics used most commonly to define cancer‐related racial disparities. In the US, and particularly in South Carolina, these largely disfavor African Americans (AAs). Computed from readily available data sources, the mortality‐to‐incidence rate ratio (MIR) provides a population‐based indicator of survival.

METHODS:

South Carolina Central Cancer Registry incidence data and Vital Registry death data were used to construct MIRs. ArcGIS 9.2 mapping software was used to map cancer MIRs by sex and race for 8 Health Regions within South Carolina for all cancers combined and for breast, cervical, colorectal, lung, oral, and prostate cancers.

RESULTS:

Racial differences in cancer MIRs were observed for both sexes for all cancers combined and for most individual sites. The largest racial differences were observed for female breast, prostate, and oral cancers, and AAs had MIRs nearly twice those of European Americans (EAs).

CONCLUSIONS:

Comparing and mapping race‐ and sex‐specific cancer MIRs provides a powerful way to observe the scope of the cancer problem. By using these methods, in the current study, AAs had much higher cancer MIRs compared with EAs for most cancer sites in nearly all regions of South Carolina. Future work must be directed at explaining and addressing the underlying differences in cancer outcomes by region and race. MIR mapping allows for pinpointing areas where future research has the greatest likelihood of identifying the causes of large, persistent, cancer‐related disparities. Other regions with access to high‐quality data may find it useful to compare MIRs and conduct MIR mapping. Cancer 2009. © 2009 American Cancer Society.     

Post-transplant Burkitt lymphoma is a more aggressive and distinct form of post-transplant lymphoproliferative disorder

BACKGROUND:

Although the literature reports a low incidence of Burkitt lymphoma (BL) as a post‐transplant lymphoproliferative disorder (PTLD), this entity appears to be different from other monomorphic PTLDs (M‐PTLDs), both in its aggressive clinical presentation and its distinct pathologic profile.

METHODS:

Patients with BL, diagnosed in the post‐transplant setting, (patients aged ≤18 years) were retrieved from the pathology archives at Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center from 1982 to 2010. Clinical outcomes were obtained along with pathologic review.

RESULTS:

Twelve patients with pediatric BL in the post‐transplant setting (9 boys, 3 girls) were retrieved. The patients displayed a monomorphic population of small to intermediate‐sized, noncleaved, lymphoid elements with a “starry‐sky” pattern. The immunophenotype for patients available to the study was CD20+ (n = 9/10), CD10+ (n = 8/8), bcl‐6+ (n = 11/11), with a near 100% Ki‐67/MIB‐1 proliferation index (n = 7/7), and negative for TdT (n = 7/7). Most pretransplant Epstein‐Barr virus titers were negative (n = 8/10), with post‐transplant titers positive in all tested patients (n = 11), and with positive Epstein‐Barr–encoded RNA in situ hybridization in most cases (n = 9/11). The median time from transplantation to diagnosis was 52 months (range, 6‐107 months). Nine patients were currently alive after immediate antineoplastic chemotherapy, with median disease‐free time of 93 months from diagnosis (range, 2‐199 months).

CONCLUSIONS:

BL‐PTLD had a higher Epstein‐Barr virus incidence compared with sporadic and immunodeficiency‐associated BL and represented a distinct monomorphic PTLD. Although some M‐PTLDs can be managed less aggressively with decreased immunosuppression alone, immediate lymphoma‐specific chemotherapy was associated with a favorable outcome and was strongly recommended. Cancer 2011;. © 2011 American Cancer Society.     

Increasing accrual in cancer clinical trials with a focus on minority enrollment: The William Beaumont Hospital Community Clinical Oncology Program Experience

BACKGROUND:

The authors reviewed changes in accrual to cancer clinical trials over the last 2 decades at their institution with a focus on minority participation after the implementation of a community clinical oncology program (CCOP) and an aggressive, education‐orientated minority outreach program (MOP).

METHODS:

Data on patient enrollment in clinical trials for the years 1988 to 2010 was obtained from the William Beaumont Hospital (WBH) Cancer Clinical Trials Office. The type and number of cancers diagnosed and treated during the same period were obtained from the WBH tumor registry data. The MOP was initiated in the fall of 2003 with a focus on culture‐specific cancer education.

RESULTS:

With the development of the CCOP, clinical trials accrual increased significantly by 10‐fold (P = .001). The primary service area for the CCOP consistently averaged an 85% to 90% Caucasian population. During the same period, the minority population for the service area remained stable between 8.8% and 10% and did not change significantly. From 1999 to 2004, the WBH tumor registry data demonstrated that minorities represented 8.6% of cancers registered, whereas the average yearly minority enrollment from 2002 to 2004 was 5.4%. After initiation of the MOP, minority accrual doubled to 11% by 2010 with stable minority demographics.

CONCLUSIONS:

The current findings support the importance of a CCOP in supporting the accrual of patients to national clinical trials and increasing access to state‐of‐the art research. These data also strongly support focusing additional energy and educational efforts on targeting minority representation in clinical trials. Cancer 2011;. © 2011 American Cancer Society.     

Racial disparities in recurrence among patients with early‐stage endometrial cancer

BACKGROUND.

Population‐based studies suggest that, because of inequalities in treatment, black women with localized endometrial cancer have shorter survival compared with white women. The objective of the current investigation was to determine whether there is a racial disparity in outcome between black patients and white patients with early‐stage endometrial cancer treated similarly in a clinical trial setting.

METHODS.

A retrospective review of 110 black patients and 1049 white patients with stage I and II endometrial cancer (graded according to the International Federation of Gynecology and Obstetrics grading system) was performed using data from a randomized, placebo‐controlled trial performed by the Gynecologic Oncology Group that evaluated postoperative estrogen replacement therapy (ERT) and the risk of cancer recurrence. Demographic, pathologic, treatment, and outcome‐related data were collected and analyzed using regression and survival analysis.

RESULTS.

Estimates of recurrence‐free survival suggested that black patients may be more likely to have disease recurrence, particularly those receiving ERT. Within a median follow‐up of 3 years, 5 of 56 black patients with endometrial cancer in the ERT group were identified with recurrent disease compared with only 8 of 521 white patients. Adjusted for age, body mass index, and tumor grade, the relative risk of recurrence among blacks in the ERT group was 11.2 (95% confidence interval, 2.86‐43.59; P = .0005).

CONCLUSIONS.

The findings of the current study suggested that recurrence‐free survival may be shorter among black women with stage I endometrial cancer, even in a clinical trials setting in which patients receive similar treatment and follow‐up. This increased risk of recurrence appeared to be most evident in black women with endometrial cancer who maintained ERT after primary treatment. Cancer 2008. Published 2008 by the American Cancer Society.     

Radiation therapy at the end of life in patients with incurable nonsmall cell lung cancer

BACKGROUND:

Receipt of chemotherapy at the end of life (EOL) is considered an indicator of poor quality of care for medical oncology. The objective of this study was to characterize the use of radiotherapy (RT) in patients with nonsmall cell lung cancer (NSCLC) during the same period.

METHODS:

Treatment characteristics of patients with incurable NSCLC who received RT at the EOL, defined as within 14 days of death, were analyzed from the National Comprehensive Cancer Network NSCLC Outcomes Database.

RESULTS:

Among 1098 patients who died, 10% had received EOL RT. Patients who did and did not receive EOL RT were similar in terms of sex, race, comorbid disease, and Eastern Cooperative Oncology Group performance status. On multivariable logistic regression analysis, independent predictors of receiving EOL RT included stage IV disease (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.09‐3.83) or multiorgan involvement (OR, 1.75; 95% CI, 1.08‐2.84) at diagnosis, age <65 years at diagnosis (OR, 1.85; 95% CI, 1.21‐2.83), and treating institution (OR, 1.24‐5.94; P = .02). Nearly 50% of EOL RT recipients did not complete it, most commonly because of death or patient preference.

CONCLUSIONS:

In general, EOL RT was received infrequently, was delivered more commonly to younger patients with more advanced disease, and often was not completed as planned. There also was considerable variation in its use among National Comprehensive Cancer Network institutions. Next steps include expanding this research to other cancers and settings and investigating the clinical benefit of such treatment. Cancer 2012. © 2012 American Cancer Society.     

Prevalence and clinical impact of anaplasia in childhood rhabdomyosarcoma : a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group

BACKGROUND.

Anapalsia is rare in childhood rhabdomyosarcoma and has not been included in the International Classification of Rhabdomyosarcoma (ICR). A recent review of cases from the Soft Tissue Sarcoma Committee of the Children's Oncology Group (COG) suggests that anaplasia might be more common than previously reported and may impact clinical outcome.

METHODS.

The prevalence of anaplasia (focal or diffuse) was prospectively assessed in 546 eligible cases who were registered in an Intergroup Rhabdomyosarcoma Study Group (IRSG) or COG therapeutic trial from 1995 through 1998. The incidence of anaplasia in tumor samples and its impact in predicting clinical outcome was assessed.

RESULTS.

Overall, 71 (13%) of all samples analyzed had anaplasia. Anaplasia was more common in patients with tumors in favorable sites and was less commonly observed in younger patients and in those with stage II, III, or clinical group III disease. Regardless of its distribution (focal or diffuse), on univariate analysis the presence of anaplasia negatively influenced the failure‐free survival rate (63% vs 77% at 5 years) and overall survival (68% vs 82% at 5 years) rates in patients with embryonal rhabdomyosarcoma. This effect was most pronounced in children with intermediate‐risk tumors. Anaplasia did not affect outcome in patients with alveolar tumors.

CONCLUSIONS.

The incidence of anaplasia in patients with rhabdomyosarcoma is higher than previously described and may be of prognostic significance in children with intermediate‐risk embryonal rhabdomyosarcoma. Cancer 2008. © 2008 American Cancer Society.