Kristin Berry

Quality of life in long term survivors of colorectal cancer

Abstract OBJECTIVES: We aimed to determine the quality of life (QOL) for long term survivors of colorectal cancer. METHODS: Persons with colorectal cancer who had survived at least 5 yr from diagnosis were recruited from a local cancer registry to answer questions about general QOL and colon cancer-specific issues. Before the general survey, focus group interviews with long term survivors were conducted to select survey questions from a pool of general and cancer-specific QOL questionnaires. The survey included the Health Utilities Index, the Center for Epidemiological Studies Depression Scale, and questions from the Short Form 36 and Functional Assessment of Cancer Therapy-Colorectal Cancer. After permission was obtained from their primary physicians, long term survivors from the registry were mailed invitation letters, then telephoned. Those agreeing were mailed self-administered questionnaires with stamped return envelopes. RESULTS: Two hundred twenty-seven respondents (average age = 74 yr, 46% female) completed the survey. Survivors reported a relatively uniform and high QOL, irrespective of stage at diagnosis and time from diagnosis. Non-cancer related comorbid conditions and low income status had more influence on overall QOL than initial stage of colorectal cancer or time since diagnosis. Compared to age-matched populations, long term survivors reported higher overall QOL, but had higher rates of depression. Sixteen percent reported three or more bowel movements a day; 49% reported chronic recurrent diarrhea. CONCLUSIONS: Those who achieve long term remission from colorectal cancer may experience a relatively high QOL, although physical symptoms such as diarrhea and depressive symptoms remain a problem.

Prostate-specific antigen testing in black and white men: an analysis of medicare claims from 1991–1998

OBJECTIVES To describe the trends in prostate-specific antigen (PSA) use and associated cancer detection among black and white Medicare beneficiaries older than 65 years during the calendar period from January 1991 through December 1998. METHODS Medicare claims data were linked with cancer registry data from the Surveillance, Epidemiology and End Results program of the National Cancer Institute. Data from a 5% random sample of men without a diagnosis of prostate cancer were combined with data from prostate cancer cases diagnosed during the calendar period from 1991 to 1998. PSA tests conducted after a diagnosis of prostate cancer were excluded. RESULTS PSA use has stabilized among white men, reaching an annual rate of 38% by 1995 and remaining at this level through 1998. The annual rate of use among black men reached 31% by 1998, but was still increasing at that time. By 1996, at least 80% of tests in both blacks and whites were second or later tests. By the end of 1996, 35% of white men and 25% of black men were undergoing testing at least biannually or more frequently. In 1996, 83% of diagnoses in whites and 77% in blacks were preceded by a PSA test. CONCLUSIONS Older black men lag slightly behind older white men in their use of the PSA test; however, annual testing rates in blacks have yet to stabilize. In both race groups, an overwhelming majority of diagnoses are associated with a PSA test, whether for screening or diagnostic purposes. Regular screening rates in blacks are substantially lower than in whites, but the regular screening rates are relatively low in both race groups. Should PSA screening prove efficacious, efforts to promote regular use among both black and white men will likely be needed.

Excellent posttransplant survival for patients with nonalcoholic steatohepatitis in the United States

Because of the ongoing epidemics of obesity and diabetes, nonalcoholic steatohepatitis (NASH) may become a leading indication for liver transplantation. There are concerns about the posttransplant survival of patients with NASH because of associated cardiovascular and metabolic risk factors. We aimed to determine recent trends in the proportion of patients undergoing transplantation for NASH‐related cirrhosis in the United States and to estimate their posttransplant survival. We used data provided by the United Network for Organ Sharing for first‐time adult cadaveric liver transplants performed in the United States between January 1, 1997 and October 31, 2010 (n = 53,738). The proportion of liver transplants performed for NASH‐related cirrhosis increased dramatically from 1.2% in 1997‐2003 to 7.4% in 2010 when NASH was the fourth most common indication for transplantation. The posttransplant survival of patients with NASH (n = 1810) at 1 (87.6%), 3 (82.2%), and 5 years (76.7%) was superior to the survival of patients with hepatocellular carcinoma, hepatitis C virus, alcoholic liver disease, acute hepatic necrosis, hemochromatosis, or cryptogenic liver disease and was inferior to the survival of only 4 groups of patients (those with primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, or hepatitis B virus). In conclusion, NASH‐related cirrhosis is increasing rapidly as an indication for liver transplantation in the United States and is associated with excellent posttransplant survival. Liver Transpl 18:29–37, 2012.

Serum alpha‐fetoprotein level independently predicts posttransplant survival in patients with hepatocellular carcinoma

We aimed to determine whether combining serum alpha‐fetoprotein (AFP) level with hepatocellular carcinoma (HCC) tumor burden would allow better stratification of posttransplant survival for patients with HCC undergoing liver transplantation. Adjusting for donor and recipient characteristics, we calculated the risk of posttransplant mortality associated with serum AFP level or HCC tumor burden for all first‐time adult liver transplants performed in the United States between 2002 and 2011 (n = 45,267). Serum AFP level, rather than tumor burden, was the tumor characteristic most strongly associated with posttransplant survival. Although recipients with HCC and a serum AFP level ≤ 15 ng/mL at the time of transplantation had no excess posttransplant mortality [adjusted hazard ratio (AHR) = 1.02, 95% confidence interval (CI) = 0.93‐1.12], patients with a serum AFP level of 16 to 65 ng/mL (AHR = 1.38, 95% CI = 1.23‐1.54), patients with a serum AFP level of 66 to 320 ng/mL (AHR = 1.65, 95% CI = 1.45‐1.88), and patients with a serum AFP level > 320 ng/mL (AHR = 2.37, 95% CI = 2.06‐2.73) had progressively worse posttransplant mortality in comparison with recipients without HCC. Patients with a tumor burden exceeding the Milan criteria (who are usually excluded from transplantation) had excellent posttransplant survival if their serum AFP level was 0 to 15 ng/mL (AHR = 0.97, 95% CI = 0.66‐1.43). In contrast, patients within the Milan criteria (who are routinely considered to be transplant candidates) had poor survival if their serum AFP level was substantially elevated (for a serum AFP level ≥ 66 ng/mL, AHR = 1.93, 95% CI = 1.74‐2.15). Changes in serum AFP level while patients were on the waiting list corresponded closely to changes in posttransplant mortality. In conclusion, the absolute serum AFP level and changes in the serum AFP level strongly predict posttransplant survival independently of the tumor burden. We hope that these data, in combination with other factors, can be used to inform future studies and ongoing discussions aimed at improving the eligibility criteria for liver transplantation for patients with HCC. Liver Transpl 19:634–645, 2013.

Lifetime cancer-attributable cost of care for long term survivors of colorectal cancer

OBJECTIVES: We aimed to determine cancer-related medical care costs for long term survivors of colorectal cancer. METHODS: The SEER-Medicare database was used to measure lifetime cancer-attributable costs of care for those with colorectal cancer surviving at least 5 yr versus age- and gender-matched controls. Costs were directly estimated, stratified by age at diagnosis and stage at diagnosis, for years 6–11 after diagnosis and then modeled to estimate lifetime costs. Cost differences between cancer cases and controls were compared to expected costs based on published guidelines for postcancer surveillance. RESULTS: Lifetime medical costs for long term survivors (future years not discounted) were up to

HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma

19,516 higher than control costs, and were highest for younger age groups and those with early-stage disease. Excess costs for cancer survivors exceeded expected surveillance costs by

Comparison of Liver Transplant–Related Survival Benefit in Patients With Versus Without Hepatocellular Carcinoma in the United States

2,223–8,822 for years 6–10 from the date of initial diagnosis. CONCLUSIONS: Cancer-attributable medical costs can be substantial for long term survivors, and exceed expected costs of surveillance. Future research is need to determine the components of excess cost in this survivor group.

The association between race/ethnicity and the effectiveness of direct antiviral agents for hepatitis C virus infection

BACKGROUND & AIMS It is unclear whether direct-acting antiviral (DAA) treatment-induced sustained virologic response (SVR) reduces the risk of hepatocellular carcinoma (HCC) in patients with HCV infection. Therefore, in the current study, our aim was to determine the impact of DAA-induced SVR on HCC risk. METHODS We identified 62,354 patients who initiated antiviral treatment in the Veterans Affairs (VA) national healthcare system from 1 January 1999 to 31 December 2015, including 35,871 (58%) interferon (IFN)-only regimens, 4,535 (7.2%) DAA + IFN regimens, and 21,948 (35%) DAA-only regimens. We retrospectively followed patients until 15 June 2017 to identify incident cases of HCC. We used Cox proportional hazards regression to determine the association between SVR and HCC risk or between type of antiviral regimen (DAA-only vs. DAA + IFN vs. IFN-only) and HCC risk. RESULTS We identified 3,271 incident cases of HCC diagnosed at least 180 days after initiation of antiviral treatment during a mean follow-up of 6.1 years. The incidence of HCC was highest in patients with cirrhosis and treatment failure (3.25 per 100 patient-years), followed by cirrhosis and SVR (1.97), no cirrhosis and treatment failure (0.87), and no cirrhosis and SVR (0.24). SVR was associated with a significantly decreased risk of HCC in multivariable models irrespective of whether the antiviral treatment was DAA-only (adjusted hazard ratio [AHR] 0.29; 95% CI 0.23-0.37), DAA + IFN (AHR 0.48; 95% CI 0.32-0.73) or IFN-only (AHR 0.32; 95% CI 0.28-0.37). Receipt of a DAA-only or DAA + IFN regimen was not associated with increased HCC risk compared with receipt of an IFN-only regimen. CONCLUSIONS DAA-induced SVR is associated with a 71% reduction in HCC risk. Treatment with DAAs is not associated with increased HCC risk compared with treatment with IFN. LAY SUMMARY It was unclear whether direct-acting antiviral treatment-induced sustained virologic response reduces the risk of liver cancer in patients with HCV infection. We demonstrated that eradication of HCV infection with direct-acting antiviral agents reduces the risk of liver cancer by 71%.

Improvement in Glycemic Control of Type 2 Diabetes After Successful Treatment of Hepatitis C Virus

BACKGROUND & AIMS Patients with T2 hepatocellular carcinoma (HCC) can obtain an exception that allows them to undergo liver transplantation with much lower actual Model for End-Stage Liver Disease (MELD) scores than patients without HCC. We compared patients who received liver transplants, with and without HCC, with regard to transplantation-related survival benefit. METHODS We modeled the post-transplantation survival of adult, first-time liver transplant recipients with HCC (n = 9135) or without (n = 25,890) from 2002 through 2013 using Cox proportional hazards regression. We modeled waitlist survival of patients listed for transplantation with HCC (n = 15,605) or without (n = 85,229) using competing risks analysis and combined outcomes of death or liver failure (defined as MELD score ≥30). We used these survival models to calculate monthly transition probabilities and 5-year life expectancies. Survival benefit was calculated as the difference between post-transplantation and waitlist life expectancy. RESULTS The 5-year survival benefit increased with actual MELD score for patients with and without HCC, ranging from just a few months in patients with low MELD scores (ie, 6-8) to 4 years in patients with the highest MELD scores (ie, 36-40). The survival benefit of patients with HCC was similar to that of patients without HCC who had the same actual MELD score, irrespective of tumor burden or serum level of α-fetoprotein. However, because patients with HCC received liver transplants when they had a lower mean MELD score (13.3 ± 6.2) than patients without HCC (21.8 ± 8.0), a much lower mean 5-year survival benefit was achieved by providing liver transplants to patients with HCC (0.12 years/patient) than patients without HCC (1.47 years/patient). CONCLUSIONS The HCC MELD exception policy has unintentionally resulted in a large reduction in transplantation-related survival benefit.

Direct-acting antivirals are effective for chronic hepatitis C treatment in elderly patients: a real-world study of 17 487 patients.

Black race and Hispanic ethnicity were associated with lower rates of sustained virologic response (SVR) to interferon‐based treatments for chronic hepatitis C virus infection, whereas Asian race was associated with higher SVR rates compared to white patients. We aimed to describe the association between race/ethnicity and effectiveness of new direct‐acting antiviral regimens in the Veterans Affairs health care system nationally. We identified 21,095 hepatitis C virus–infected patients (11,029 [52%] white, 6,171 [29%] black, 1,187 [6%] Hispanic, 348 [2%] Asian/Pacific Islander/American Indian/Alaska Native, and 2,360 [11%] declined/missing race or ethnicity) who initiated antiviral treatment with regimens containing sofosbuvir, simeprevir + sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ombitasvir/ritonavir/dasabuvir during the 18‐month period from January 1, 2014, to June 30, 2015. Overall SVR rates were 89.8% (95% confidence interval [CI] 89.2‐90.4) in white, 89.8% (95% CI 89.0‐90.6) in black, 86.0% (95% CI 83.7‐88.0) in Hispanic, and 90.7% (95% CI 87.0‐93.5) in Asian/Pacific Islander/American Indian/Alaska Native patients. However, after adjustment for baseline characteristics, black (adjusted odds ratio = 0.77, P < 0.001) and Hispanic (adjusted odds ratio = 0.76, P = 0.007) patients were less likely to achieve SVR than white patients, a difference that was not explained by early treatment discontinuations. Among genotype 1–infected patients treated with ledipasvir/sofosbuvir monotherapy, black patients had significantly lower SVR than white patients when treated for 8 weeks but not when treated for 12 weeks. Conclusion: Direct‐acting antivirals produce high SVR rates in white, black, Hispanic, and Asian/Pacific Islander/American Indian/Alaska Native patients; but after adjusting for baseline characteristics, black race and Hispanic ethnicity remain independent predictors of treatment failure. Short 8‐week ledipasvir/sofosbuvir monotherapy regimens should perhaps be avoided in black patients with genotype 1 hepatitis C virus. (Hepatology 2017;65:426‐438).