Jack L. Finch

Spectrum of Cancer Risk Among US Solid Organ Transplant Recipients

CONTEXT Solid organ transplant recipients have elevated cancer risk due to immunosuppression and oncogenic viral infections. Because most prior research has concerned kidney recipients, large studies that include recipients of differing organs can inform cancer etiology. OBJECTIVE To describe the overall pattern of cancer following solid organ transplantation. DESIGN, SETTING, AND PARTICIPANTS Cohort study using linked data on solid organ transplant recipients from the US Scientific Registry of Transplant Recipients (1987-2008) and 13 state and regional cancer registries. MAIN OUTCOME MEASURES Standardized incidence ratios (SIRs) and excess absolute risks (EARs) assessing relative and absolute cancer risk in transplant recipients compared with the general population. RESULTS The registry linkages yielded data on 175,732 solid organ transplants (58.4% for kidney, 21.6% for liver, 10.0% for heart, and 4.0% for lung). The overall cancer risk was elevated with 10,656 cases and an incidence of 1375 per 100,000 person-years (SIR, 2.10 [95% CI, 2.06-2.14]; EAR, 719.3 [95% CI, 693.3-745.6] per 100,000 person-years). Risk was increased for 32 different malignancies, some related to known infections (eg, anal cancer, Kaposi sarcoma) and others unrelated (eg, melanoma, thyroid and lip cancers). The most common malignancies with elevated risk were non-Hodgkin lymphoma (n = 1504; incidence: 194.0 per 100,000 person-years; SIR, 7.54 [95% CI, 7.17-7.93]; EAR, 168.3 [95% CI, 158.6-178.4] per 100,000 person-years) and cancers of the lung (n = 1344; incidence: 173.4 per 100,000 person-years; SIR, 1.97 [95% CI, 1.86-2.08]; EAR, 85.3 [95% CI, 76.2-94.8] per 100,000 person-years), liver (n = 930; incidence: 120.0 per 100,000 person-years; SIR, 11.56 [95% CI, 10.83-12.33]; EAR, 109.6 [95% CI, 102.0-117.6] per 100,000 person-years), and kidney (n = 752; incidence: 97.0 per 100,000 person-years; SIR, 4.65 [95% CI, 4.32-4.99]; EAR, 76.1 [95% CI, 69.3-83.3] per 100,000 person-years). Lung cancer risk was most elevated in lung recipients (SIR, 6.13 [95% CI, 5.18-7.21]) but also increased among other recipients (kidney: SIR, 1.46 [95% CI, 1.34-1.59]; liver: SIR, 1.95 [95% CI, 1.74-2.19]; and heart: SIR, 2.67 [95% CI, 2.40-2.95]). Liver cancer risk was elevated only among liver recipients (SIR, 43.83 [95% CI, 40.90-46.91]), who manifested exceptional risk in the first 6 months (SIR, 508.97 [95% CI, 474.16-545.66]) and a 2-fold excess risk for 10 to 15 years thereafter (SIR, 2.22 [95% CI, 1.57-3.04]). Among kidney recipients, kidney cancer risk was elevated (SIR, 6.66 [95% CI, 6.12-7.23]) and bimodal in onset time. Kidney cancer risk also was increased in liver recipients (SIR, 1.80 [95% CI, 1.40-2.29]) and heart recipients (SIR, 2.90 [95% CI, 2.32-3.59]). CONCLUSION Compared with the general population, recipients of a kidney, liver, heart, or lung transplant have an increased risk for diverse infection-related and unrelated cancers.

Cancer risk in people infected with human immunodeficiency virus in the United States.

Data are limited regarding cancer risk in human immunodeficiency virus (HIV)‐infected persons with modest immunosuppression, before the onset of acquired immunodeficiency syndrome (AIDS). For some cancers, risk may be affected by highly active antiretroviral therapy (HAART) widely available since 1996. We linked HIV/AIDS and cancer registries in Colorado, Florida and New Jersey. Standardized incidence ratios (SIRs) compared cancer risk in HIV‐infected persons (initially AIDS‐free) during the 5‐year period after registration with the general population. Poisson regression was used to compare incidence across subgroups, adjusting for demographic factors. Among 57,350 HIV‐infected persons registered during 1991–2002 (median CD4 count 491 cells/mm3), 871 cancers occurred during follow‐up. Risk was elevated for Kaposi sarcoma (KS, SIR 1,300 [n = 173 cases]), non‐Hodgkin lymphoma (NHL, 7.3 [n = 203]), cervical cancer (2.9 [n = 28]) and several non‐AIDS‐defining malignancies, including Hodgkin lymphoma (5.6 [n = 36]) and cancers of the lung (2.6 [n = 109]) and liver (2.7 [n = 14]). KS and NHL incidence declined over time but nonetheless remained elevated in 1996–2002. Incidence increased in 1996–2002 compared to 1991–1995 for Hodgkin lymphoma (relative risk 2.7, 95%CI 1.0–7.1) and liver cancer (relative risk infinite, one‐sided 95%CI 1.1‐infinity). Non‐AIDS‐defining cancers comprised 31.4% of cancers in 1991–1995, versus 58.0% in 1996–2002. For KS and NHL, risk was inversely related to CD4 count, but these associations attenuated after 1996. We conclude that KS and NHL incidence declined markedly in recent years, likely reflecting HAART‐related improvements in immunity, while incidence of some non‐AIDS‐defining cancers increased. These trends have led to a shift in the spectrum of cancer among HIV‐infected persons.

The Impact of Socioeconomic Status on Survival After Cancer in the United States : Findings From the National Program of Cancer Registries Patterns of Care Study

Understanding the ways in which socioeconomic status (SES) affects mortality is important for defining strategies to eliminate the unequal burden of cancer by race and ethnicity in the United States.

Rising Incidence of Oropharyngeal Cancer and the Role of Oncogenic Human Papilloma Virus

Objectives/Hypothesis: To document the increasing incidence of oropharyngeal (OP) cancer and to provide evidence that this increase is caused by oncogenic human papilloma virus (HPV).

The accuracy of cancer mortality statistics based on death certificates in the United States

BACKGROUND One measure of the accuracy of cancer mortality statistics is the concordance between cancer defined as the underlying cause of death from death certificates and cancer diagnoses recorded in central, population-based cancer registries. Previous studies of such concordance are outdated. OBJECTIVE To characterize the accuracy of cancer mortality statistics from the concordance between cancer cause of death and primary cancer site at diagnosis. DESIGN Central cancer registry records from California, Colorado, and Idaho in the U.S. were linked with state vital statistics data and evaluated by demographic and tumor information across 79 site categories. A retrospective arm (confirmation rate per 100 deaths) compared death certificate data from 2002 to 2004 with cancer registry diagnoses from 1993 to 2004, while a prospective arm (detection rate per 100 deaths) compared cancer registry diagnoses from 1993 to 1995 with death certificate data from 1993 to 2004 by International Statistical Classification of Diseases and Related Health Problems (ICD) version used to code deaths. RESULTS With n=265,863 deaths where cancer was recorded as the underlying cause based on the death certificate, the overall confirmation rate for ICD-10 was 82.8% (95% confidence interval [CI], 82.6-83.0%), the overall detection rate for ICD-10 was 81.0% (95% CI, 80.4-81.6%), and the overall detection rate for ICD-9 was 85.0% (95% CI, 84.8-85.2%). These rates varied across primary sites, where some rates were <50%, some were 95% or greater, and notable differences between confirmation and detection rates were observed. CONCLUSIONS Important unique information on the quality of cancer mortality data obtained from death certificates is provided. In addition, information is provided for future studies of the concordance of primary cancer site between population-based cancer registry data and data from death certificates, particularly underlying causes of death coded in ICD-10.

Factors associated with initial treatment and survival for clinically localized prostate cancer: results from the CDC-NPCR Patterns of Care Study (PoC1)

BackgroundDespite the large number of men diagnosed with localized prostate cancer, there is as yet no consensus concerning appropriate treatment. The purpose of this study was to describe the initial treatment patterns for localized prostate cancer in a population-based sample and to determine the clinical and patient characteristics associated with initial treatment and overall survival.MethodsThe analysis included 3,300 patients from seven states, diagnosed with clinically localized prostate cancer in 1997. We examined the association of sociodemographic and clinical characteristics with four treatment options: radical prostatectomy, radiation therapy, hormone therapy, and watchful waiting. Diagnostic and treatment information was abstracted from medical records. Socioeconomic measures were derived from the 2000 Census based on the patients residence at time of diagnosis. Vital status through December 31, 2002, was obtained from medical records and linkages to state vital statistics files and the National Death Index. Multiple logistic regression analysis and Cox proportional hazards models identified factors associated with initial treatment and overall survival, respectively.ResultsPatients with clinically localized prostate cancer received the following treatments: radical prostatectomy (39.7%), radiation therapy (31.4%), hormone therapy (10.3%), or watchful waiting (18.6%). After multivariable adjustment, the following variables were associated with conservative treatment (hormone therapy or watchful waiting): older age, black race, being unmarried, having public insurance, having non-screen detected cancer, having normal digital rectal exam results, PSA values above 20, low Gleason score (2-4), comorbidity, and state of residence. Among patients receiving definitive treatment (radical prostatectomy or radiation therapy), older age, being unmarried, PSA values above 10, unknown Gleason score, state of residence, as well as black race in patients under 60 years of age, were associated with receipt of radiation therapy. Overall survival was related to younger age, being married, Gleason score under 8, radical prostatectomy, and state of residence. Comorbidity was only associated with risk of death within the first three years of diagnosis.ConclusionsIn the absence of clear-cut evidence favoring one treatment modality over another, it is important to understand the factors that inform treatment selection. Since state of residence was a significant predictor of both treatment as well as overall survival, true regional differences probably exist in how physicians and patients select treatment options. Factors affecting treatment choice and treatment effectiveness need to be further explored in future population-based studies.

Risk of Merkel Cell Carcinoma After Solid Organ Transplantation

BACKGROUND Solid organ transplant recipients have elevated risks of virus-related cancers, in part because of long-term immunosuppression. Merkel cell carcinoma (MCC) is an aggressive skin cancer recently found to have a viral origin, but little is known regarding the occurrence of MCC after transplant. METHODS We linked the US Scientific Registry of Transplant Recipients with data from 15 population-based cancer registries to ascertain MCC occurrence among 189498 solid organ transplant recipients from 1987 to 2009. Risks for MCC following transplantation were compared with the general population using standardized incidence ratios, and Poisson regression was used to compare incidence rates according to key patient and transplant characteristics. All statistical tests were two-sided. RESULTS After solid organ transplantation, overall risk of MCC was increased 23.8-fold (95% confidence interval = 19.6 to 28.7, n = 110). Adjusted risks were highest among older recipients, increased with time since transplantation, and varied by organ type (all P ≤ .007). Azathioprine, cyclosporine, and mTOR inhibitors given for maintenance immunosuppression increased risk, and non-Hispanic white recipients on cyclosporine and azathioprine experienced increasing MCC risk with lower latitude of residence (ie, higher ultraviolet radiation exposure, P = .012). CONCLUSIONS MCC risk is sharply elevated after solid organ transplant, likely resulting from long-term immunosuppression. Immunosuppressive medications may act synergistically with ultraviolet radiation to increase risk.

HPV-Related Cancers After Solid Organ Transplantation in the United States

Transplant recipients have elevated cancer risk including risk of human papillomavirus (HPV)‐associated cancers of the cervix, anus, penis, vagina, vulva and oropharynx. We examined the incidence of HPV‐related cancers in 187 649 US recipients in the Transplant Cancer Match Study. Standardized incidence ratios (SIRs) compared incidence rates to the general population, and incidence rate ratios (IRRs) compared rates across transplant subgroups. We observed elevated incidence of HPV‐related cancers (SIRs: in situ 3.3–20.3, invasive 2.2–7.3), except for invasive cervical cancer (SIR 1.0). Incidence increased with time since transplant for vulvar, anal and penile cancers (IRRs 2.1–4.6 for 5+ vs. <2 years). Immunophenotype, characterized by decreased incidence with HLA DRB1:13 and increased incidence with B:44, contributed to susceptibility at several sites. Use of specific immunosuppressive medications was variably associated with incidence; for example, tacrolimus, was associated with reduced incidence for some anogenital cancers (IRRs 0.4–0.7) but increased incidence of oropharyngeal cancer (IRR 2.1). Thus, specific features associated with recipient characteristics, transplanted organs and medications are associated with incidence of HPV‐related cancers after transplant. The absence of increased incidence of invasive cervical cancer highlights the success of cervical screening in this population and suggests a need for screening for other HPV‐related cancers.

The impact of National Death Index linkages on population-based cancer survival rates in the United States.

BACKGROUND In order to ensure accurate survival estimates, population-based cancer registries must ascertain all, or nearly all, patients diagnosed with cancer in their catchment area, and obtain complete follow-up information on all deaths that occurred among registered cancer patients. In the US, linkage with state death records may not be sufficient to ascertain all deaths. Since 1979, all state vital statistics offices have reported their death certificate information to the National Death Index (NDI). OBJECTIVE This study was designed to measure the impact of linkage with the NDI on population-based relative and cancer cause-specific survival rates in the US. METHODS Central cancer registry records for patients diagnosed 1993-1995 from California, Colorado, and Idaho were linked with death certificate information (deaths 1993-2004) from their individual state vital statistics offices and with the NDI. Two databases were created: one contained incident records with deceased patients linked only to state death records and the second database contained incident records with deceased patients linked to both state death records and the NDI. Survival estimates and 95% confidence intervals from each database were compared by state and primary site category. RESULTS At 60 months follow-up, 42.1-48.1% of incident records linked with state death records and an additional 0.7-3.4% of records linked with the NDI. Survival point estimates from the analysis without NDI were not contained within the corresponding 95% CIs from the NDI augmented analysis for all sites combined and colorectal, pancreas, lung and bronchus, breast, prostate, non-Hodgkin lymphoma, and Kaposi sarcoma cases in all 3 states using relative survival methods. Additional combinations of state and primary site had significant survival estimate differences, which differed by method (relative versus cause-specific survival). CONCLUSION To ensure accurate population-based cancer survival rates, linkage with the National Death Index to ascertain out of state and late registered deaths is a necessary process for US central cancer registries.

Impact of using multiple causes of death codes to compute site-specific, death certificate-based cancer mortality statistics in the United States

BACKGROUND Cancer mortality statistics, an important indicator for monitoring cancer burden, are traditionally restricted to instances when cancer is determined to be the underlying cause of death (UCD) based on information recorded on standard certificates of death. This studys objective was to determine the impact of using multiple causes of death codes to compute site-specific cancer mortality statistics. METHODS The state cancer registries of California, Colorado and Idaho provided linked cancer registry and death certificate data for individuals who died between 2002 and 2004, had at least one cancer listed on their death certificate and were diagnosed with cancer between 1993 and 2004. These linked data were used to calculate the site-specific proportion of cancers not selected as the UCD (non-UCD) among all cancer-related deaths (any mention on the death certificate). In addition, the retrospective concordance between the death certificate and the population-based cancer registry, measured as confirmations rates, was calculated for deaths with cancer as the UCD, as a non-UCD, and for any mention. RESULTS Overall, non-UCD deaths comprised 9.5 percent of total deaths; 11 of the 79 cancer sites had proportions greater than 3 standard deviations from 9.5 percent. The confirmation rates for UCD and for any mention did not differ significantly for any of the cancer sites. CONCLUSION AND IMPACT The site-specific variation in proportions and rates suggests that for a few cancer sites, death rates might be computed for both UCD and any mention of the cancer site on the death certificate. Nevertheless, this study provides evidence that, in general, restricting to UCD deaths will not under report cancer mortality statistics.