Dianne Pulte

Changes in survival in head and neck cancers in the late 20th and early 21st century: A period analysis

BACKGROUND Therapy for head and neck cancers has evolved over the past decade, but few detailed analyses of recent developments in survival on the population level have been published. METHODS We use period analysis and modeled period analysis to disclose recent trends in survival in patients with head and neck cancer. Data are derived from the Surveillance, Epidemiology, and End Results limited-use database. RESULTS A major, statistically significant improvement in survival was observed, with the overall 5-year relative survival rate going from 54.7% in 1992-1996 to 65.9% in 2002-2006. Subgroup analysis showed improvement in cancers of the oral cavity, tongue, tonsils, and nasopharynx, with the greatest improvements observed in tonsillar carcinoma (+22.2 percentage points) and carcinoma of the tongue (+14.4 percentage points). Further analysis of survival for oral cavity, tonsillar, and tongue carcinoma revealed improvements in survival at each stage and across all age groups except for patients aged ≥ 75 years, with the greatest improvement occurring in locally advanced disease and in patients aged 55-64 years for carcinoma of the tongue and tonsils and those aged 15-44 years for oral cavity cancers. CONCLUSIONS Survival has substantially improved for head and neck cancer patients over the past decade. The greatest improvement was seen in tonsillar and tongue cancers.

Improvement in Survival of Older Adults with Multiple Myeloma: Results of an Updated Period Analysis of SEER Data

BACKGROUND Treatment of multiple myeloma has changed significantly over the past several years with clinical trials reporting superior survival results using newer agents. Previous work has shown that the survival rate has improved for younger, but not older, patients with myeloma. Here, we update survival estimates for patients with myeloma in the early 21st century to determine whether continued improvement can be seen on a population level and whether or not it now extends to older patients. METHODS Using period analysis to examine data from the Surveillance, Epidemiology, and End Results database, we estimate changes in the 5- and 10-year relative survival rates (RSRs) from 1998-2002 to 2003-2007. RESULTS The 5- and 10-year RSRs have improved for patients with myeloma overall, from 32.8% and 15% in 1998-2002 to 40.3% and 20.8%, respectively, in 2003-2007. The greatest improvements were observed for patients aged 15-44 years, with 5- and 10-year RSRs reaching >70% and ~50%, respectively, but improvements were also seen for patients aged >70 years. CONCLUSION Overall, survival continues to improve for patients with myeloma, including older patients, suggesting that newer treatment options continue to make a population-wide impact.

Recent improvement in survival of patients with multiple myeloma: variation by ethnicity

Abstract Survival for patients with multiple myeloma has increased during the first decade of the 21st century. However, it is unknown whether the improvements in survival have extended equally in all ethnic groups. Using data from the United States Surveillance, Epidemiology and End Results Program, we assessed trends in survival and disease-related mortality for patients with myeloma by ethnic group, including non-Hispanic whites (nHw), African-Americans (AA), Hispanics and people of Asian and Pacific Islander descent (API) from 1998–2001 to 2006–2009. Overall, age adjusted 5-year relative survival increased, from 35.6% in 1998–2001 to 44% in 2006–2009. The greatest improvements were observed for patients aged 15–49, for whom survival increased by + 16.8% units for nHw and + 14.4% units for AA, whereas improvement was less pronounced and not statistically significant in Hispanics and API. Excess mortality hazard ratios were 1.20 (95% confidence interval [CI]: 1.09–1.33) for AA and 1.25 (95% CI: 1.11–1.41) for Hispanics compared to nHw in 2006–2009. Although survival increased greatly for nHw with myeloma between 1998–2001 and 2006–2009, smaller increases were observed for people of other ethnic groups. Persistent excess mortality was seen for AA and Hispanic patients with myeloma. Ethnic inequalities persisted or even increased from earlier periods to 2006–2009. The results suggest that ethnic minorities may not have benefited from newer treatments to the same extent as nHw patients have.

Changes in survival by ethnicity of patients with cancer between 1992–1996 and 2002–2006: is the discrepancy decreasing?

BACKGROUND Patients of minority race/ethnicity have lower survival after diagnosis with most types of cancer. Little data are available concerning changes in disparity over time. Here, we examine changes in survival by race/ethnicity of patients with common cancers in two recent time periods. PATIENTS AND METHODS We used modeled period analysis to determine relative survival (RS) for non-Hispanic white (nHw), African-American (AA), and Hispanic patients in the Surveillance, Epidemiology, and End Results database diagnosed with common solid and hematological malignancies. RESULTS Five-year RS improved overall and for nHw for each tumor examined, ranging from+2%points (pancreatic cancer) to+16.4%points [non-Hodgkins lymphoma, (NHL)]. Greater improvement was observed for AA and Hispanics than nHw in breast and prostate cancer and NHL. Less improvement was observed for AA and Hispanics than for nHw for lung and pancreatic cancer. No statistically significant improvement was observed for AA and Hispanics with myeloma or acute leukemia. Survival disparities ranging from 0.5%points (myeloma) to 13.1%points (breast) between nHw and AA remained. CONCLUSIONS Progress has been made in decreasing disparities in survival between nHw and minorities in breast cancer, prostate cancer, and NHL. Little progress has been made in reducing disparities for the other studied cancers.BACKGROUND Patients of minority race/ethnicity have lower survival after diagnosis with most types of cancer. Little data are available concerning changes in disparity over time. Here, we examine changes in survival by race/ethnicity of patients with common cancers in two recent time periods. PATIENTS AND METHODS We used modeled period analysis to determine relative survival (RS) for non-Hispanic white (nHw), African-American (AA), and Hispanic patients in the Surveillance, Epidemiology, and End Results database diagnosed with common solid and hematological malignancies. RESULTS Five-year RS improved overall and for nHw for each tumor examined, ranging from + 2% points (pancreatic cancer) to + 16.4% points [non-Hodgkins lymphoma, (NHL)]. Greater improvement was observed for AA and Hispanics than nHw in breast and prostate cancer and NHL. Less improvement was observed for AA and Hispanics than for nHw for lung and pancreatic cancer. No statistically significant improvement was observed for AA and Hispanics with myeloma or acute leukemia. Survival disparities ranging from 0.5% points (myeloma) to 13.1% points (breast) between nHw and AA remained. CONCLUSIONS Progress has been made in decreasing disparities in survival between nHw and minorities in breast cancer, prostate cancer, and NHL. Little progress has been made in reducing disparities for the other studied cancers.

Recent trends in survival of adult patients with acute leukemia: overall improvements, but persistent and partly increasing disparity in survival of patients from minority groups

The survival of younger patients with acute leukemia has improved in the early 21st century, but it is unknown whether people of all ethnic and racial backgrounds have benefited equally. Using cancer registry data from the Surveillance, Epidemiology and End Results Program, we assessed trends in 5-year relative survival for patients aged 15 years or more with acute lymphoblastic leukemia and acute myeloblastic leukemia divided by racial and ethnic group, including non-Hispanic whites, African-Americans, Hispanics, and Asian-Pacific Islanders in the 1990s and the early 21st century. Modeled period analysis was used to obtain the most up-to-date estimates of survival. Overall, the 5-year survival increased from 31.6% in 1997-2002 to 39.0% in 2003-2008 for patients with acute lymphoblastic leukemia and from 15.5% in 1991-1996 to 22.5% in 2003-2008 for those with acute myeloblastic leukemia. Nevertheless, among patients with acute lymphoblastic leukemia, age-adjusted 5-year relative survival rates remained lower for African-Americans and Hispanics than for non-Hispanic whites. Among patients with acute myeloblastic leukemia, the increase in survival was greatest (from 32.6% in 1991-1996 to 47.1% in 2003-2008) for younger patients (15-54 years), and was more pronounced for non-Hispanic whites (+16.4% units) than for other patients (+10.8% units). Increases in survival are observed in all ethnic or racial groups. Nevertheless, among patients with acute leukemias, disparities in survival persist between non-Hispanic white people and people of other ethnic or racial groups. Disparities are increasing in younger patients with acute myeloblastic leukemia. Improvements in access to treatment, especially for minority patients, may improve outcomes.

Trends in survival of multiple myeloma patients in Germany and the United States in the first decade of the 21st century

Multiple myeloma is a chronic, incurable but highly treatable neoplasm. Recent population‐based studies have shown improvements in survival for patients diagnosed in the early 21st century. Here, we examine trends in survival for patients diagnosed with multiple myeloma in Germany and the United States (US) between 2002 and 2010. Data were extracted from 11 population‐based cancer registries in Germany and from the Surveillance, Epidemiology and End Results database in the US. Myeloma patients aged 15–74 years with diagnosis and follow‐up between 1997 and 2010 from Germany and the US were included. Period analysis was employed to assess trends in 5‐year relative survival in Germany and the US between 2002–04 and 2008–10. Age‐adjusted 5‐year relative survival increased from 47·3% to 53·8% in Germany and from 39·8% to 53·2% in the US between 2002–04 and 2008–10. There was a strong age gradient with lower survival among older patients, which persisted over time and was more pronounced in Germany than the US. Five‐year relative survival estimates for patients diagnosed with multiple myeloma below 75 years of age steadily increased throughout the first decade of the 21st century and reached levels above 50% in both Germany and the US, probably reflecting the increased use of newer agents in myeloma treatment.

Subsite-specific colorectal cancer risk in the colorectal endoscopy era

BACKGROUND Colorectal endoscopy (sigmoidoscopy and colonoscopy) is thought to reduce colorectal cancer (CRC) risk. Since the 1980s, its use has increased in the United States, which may be a reason for decreasing CRC incidence rates. OBJECTIVE To investigate the plausibility of a contribution of colorectal endoscopy use to the decrease in CRC risk. DESIGN Descriptive analysis of temporal trends. SETTING U.S. population from 1978 to 2007. MAIN OUTCOME MEASUREMENTS Using incidence data from the Surveillance, Epidemiology and End Results Program, we assessed the subsite-specific cumulative risk of CRC developing until age 79 years. RESULTS The cumulative risk of proximal CRC remained relatively stable over the observation period, varying between 2.09% (95% CI, 2.06%-2.11%) and 2.66% (95% CI,2.62%-2.69%) for men and between 1.90% (95% CI, 1.88%-1.93%) and 2.24% (95% CI, 2.21%-2.27%) for women. By contrast, the cumulative risk of distal CRC decreased from 4.68% (95% CI, 4.64%-4.73%) to 3.03% (95% CI, 3.00%-3.06%) for men and from 3.15% (95% CI, 3.11%-3.18%) to 1.93% (95% CI, 1.91%-1.95%) for women, which was largely attributable to the reduced cumulative risk of cancer in the sigmoid colon. The observed pattern was restricted to the population aged 50 to 79 years, whereas the magnitude of the decrease was greater for older age groups and similar across stages. LIMITATIONS The study is based on aggregated registry data only; therefore, no inferences about causal effects can be drawn. CONCLUSIONS The results show a major reduction of CRC risk, particularly in the sigmoid colon. Increased use of colorectal endoscopy in the population aged 50 years and older along with environmental factors may have contributed to the decreasing risk.

Survival of adults with acute lymphoblastic leukemia in Germany and the United States.

Background Adulthood acute lymphoblastic leukemia (ALL) is a rare disease. In contrast to childhood ALL, survival for adults with ALL is poor. Recently, new protocols, including use of pediatric protocols in young adults, have improved survival in clinical trials. Here, we examine population level survival in Germany and the United States (US) to gain insight into the extent to which changes in clinical trials have translated into better survival on the population level. Methods Data were extracted from the Surveillance, Epidemiology, and End Results database in the US and 11 cancer registries in Germany. Patients age 15–69 diagnosed with ALL were included. Period analysis was used to estimate 5-year relative survival (RS). Results Overall 5-year RS was estimated at 43.4% for Germany and 35.5% for the US (p = 0.004), with a decrease in survival with increasing age. Survival was higher in Germany than the US for men (43.6% versus 37.7%, p = 0.002) but not for women (42.4% versus 40.3%, p>0.1). Five-year RS estimates increased in Germany and the US between 2002 and 2006 by 11.8 and 7.3 percent units, respectively (p = 0.02 and 0.04, respectively). Conclusions Survival for adults with ALL continues to be low compared with that for children, but a substantial increase in 5-year survival estimates was seen from 2002 to 2006 in both Germany and the US. The reasons for the survival differences between both countries require clarification.

INHIBITION OF JNK SIGNALING DIMINISHES EARLY BUT NOT LATE CELLULAR STRESS-INDUCED APOPTOSIS

The human leukemic T‐cell line Jurkat was used to define the role of the cellular stress pathway with its key player kinase JNK in cancer therapy‐induced apoptosis. JNK activity was inhibited by stable transfection with a dominant negative mutant of the upstream kinase JNKK/MKK4 or with the novel, potent and selective JNK1, ‐2 and ‐3 inhibitor SP600125. Inhibition of JNK activity delayed the onset of apoptosis induced by cisplatin, doxorubicin, γ‐irradiation and CD95‐L but did not prevent apoptosis per se. Early events during apoptosis such as induction of CD95‐L, activation of caspase‐8 and exposure of phosphatidylserine on the cell surface were strongly inhibited. Also, at early time points of apoptosis, loss of the mitochondrial membrane potential and release of cytochrome c were markedly impaired. However, late signaling events during apoptosis such as cleavage of PARP and DNA fragmentation apoptosis were only marginally affected. These findings are in accordance with the activity of initiator and effector caspases. Whereas activity of the initiator caspase‐8 was strongly inhibited early and late after induction, an inhibition of caspase‐3 activity was only observed early after induction of apoptosis. We therefore suggest that cellular stress signaling contributes to the initiation of apoptosis, whereas it might be dispensable for the progression of apoptosis. Dysfunction of this pathway under pathological conditions might contribute to therapy resistance of cancer cells.

Expected long-term survival of older patients diagnosed with non-Hodgkin lymphoma in 2008-2012.

BACKGROUND New therapeutic options have led to substantial increases in survival expectations of patients with non-Hodgkin lymphoma (NHL) in recent years. In contrast to many malignancies, survival in older patients has improved in NHL at a rate similar to that in younger patients. In the past, the impact of innovations on long-term survival of NHL patients on the population level has been disclosed only with substantial delay. METHODS We employ a novel model-based projection method to estimate survival expectations of NHL patients age 60+ diagnosed in 2008-2012. Preliminary empirical evaluation of the method using historical data indicates excellent performance in projection of age specific and overall 5- and 10-year relative survival. RESULTS Overall 5- and 10-year survival projections for 2008-2012 were 67.5% and 56.9%, respectively, 8.2 percentage units (% units) and 15.2% units, respectively, higher than the most recent survival estimates available from traditional cohort analysis. Projected survival decreased with age, ranging from 79.1% for patients age 60-64 to 54.3% for patients age 80+. Projected survival estimates for diffuse large B-cell lymphoma and follicular lymphoma were 59% and 84.9%, respectively. Survival estimates by model-based projection were substantially higher than available cohort estimates for all age groups including 80+, each specific morphology examined, nodal and extranodal disease, and both genders. CONCLUSIONS Patients over 60 diagnosed with NHL in 2008-2012 have much higher long-term survival expectations than suggested by previously available survival statistics.