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Available long-term survival figures for patients with Hodgkin's lymphoma (HL) from population-based cancer registries mostly refer to patients diagnosed in the 1980s and 1990s, and do not reflect recent progress in and spread of effective therapy at the population level. Using data from the Surveillance, Epidemiology, and End Results program, we employed a novel model-based projection method to estimate 5- and 10-year relative survival expectations of HL patients in the U.S. diagnosed in 2006-2010. Preliminary empirical evaluation of the method using historical data indicates excellent performance. Projections of 10-year relative survival percentages and their standard errors by age groups are as follows: 15-24 y: 94.7 (1.1), 25-34 years, 89.4 (1.5); 35-44 years, 90.1 (1.6); 45-54 years, 83.6 (2.7); 55-64 years, 70.5 (4.7); 65-74 years, 48.5 (5.9); and 75+ years, 24.0 (5.7). These estimates are 2.5-11.1 percentage points higher than those obtained by standard cohort analysis from the same database (pertaining to patients diagnosed in 1991-1995). Patients diagnosed with HL in 2006-2010 have higher long-term survival expectations than suggested by conventional survival statistics from population-based cancer registries. The 10-year survival expectations are now close to or exceed 90% in all age groups up to age 45, and exceed 80% and 70% in the 45-54 and 55-64 age groups, respectively. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic lymphocytic leukemia (CLL) is characterized by accumulation of mature appearing lymphocytes and is rarely complicated by thrombosis. One possible explanation for the paucity of thrombotic events in these patients may be the presence of the ecto-nucleotidase CD39/NTDPase-1 on the surface of the malignant cells in CLL. CD39 is the major promoter of platelet inhibition in vivo via its metabolism of ADP to AMP. We hypothesize that if CD39 is observed on CLL cells, then patients with CLL may be relatively protected against platelet aggregation and recruitment and that CD39 may have other effects on CLL, including modulation of the disease, via its metabolism of ATP. Methods Normal and malignant lymphocytes were isolated from whole blood from patients with CLL and healthy volunteers. Enzyme activity was measured via radio-TLC assay and expression via FACS. Semi-quantititative RT-PCR for CD39 splice variants and platelet function tests were performed on several samples. Results Functional assays demonstrated that ADPase and ATPase activities were much higher in CLL cells than in total lymphocytes from the normal population on a per cell basis (p-value < 0.00001). CD39 activity was elevated in stage 0–2 CLL compared to stage 3–4 (p < 0.01). FACS of lymphocytes demonstrated CD39 expression on > 90% of normal and malignant B-lymphocytes and ~8% of normal T-lymphocytes. RT-PCR showed increased full length CD39 and splice variant 1.5, but decreased variant 1.3 in CLL cells. Platelet function tests showed inhibition of platelet activation and recruitment to ADP by CLL cells. Conclusion CD39 is expressed and active on CLL cells. Enzyme activity is higher in earlier stages of CLL and decreased enzyme activity may be associated with worsening disease. These results suggest that CD39 may play a role in the pathogenesis of malignancy and protect CLL patients from thrombotic events.

Background: The association between excess weight and colorectal cancer (CRC) risk may have been underestimated due to potential weight loss during pre-clinical sojourn time of CRC. We aimed to investigate this association and the corresponding population attributable fraction (PAF), accounting for prediagnostic weight loss., Methods: Data from the UK Biobank prospective cohort were used. Multivariable adjusted hazard ratios (HR) and their 95% confidence intervals (CI) for various periods of follow-up and the corresponding PAF of excess weight were calculated., Results: During a median of 10.0 years of follow-up, of 453,049 participants, 4794 developed CRC. The excess weight-CRC association became substantially stronger with including increasing lengths of follow-up in the analyses and further excluding the initial years of follow-up. HRs (95% CIs) for overweight and obesity were 1.06 (0.97-1.16) and 1.14 (1.03-1.26) after 7 years of follow-up, 1.13 (1.05-1.21) and 1.23 (1.14-1.33) when including complete follow-up length, and 1.26 (1.12-1.43) and 1.42 (1.24-1.63) when excluding the initial 7 years of follow-up. The corresponding PAFs of excess weight were estimated as 6.8%, 11.3%, and 19.0%, respectively., Conclusions: Comprehensive consideration of the potential effect of prediagnostic weight loss discloses a much stronger impact of excess body weight on CRC risk than previously assumed., (© 2023. The Author(s).)

Five-year survival has increased for many hematologic malignancies in the 21st century. However, whether this has translated into greater long-term survival is unknown. Here, we examine 10- and 20-year survival for patients with multiple myeloma (MM), acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), chronic lymphoid leukemia (CLL), chronic myeloid leukemia (CML), non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma (HL). Data were extracted from the Surveillance, Epidemiology, and End Results-9 database. Patients age 15+ with the above malignancies were included. The newly developed boomerang method was used to examine 10- and 20-year relative survival (RS) for patients in 2002-2006 and 2012-16. Ten and 20-year RS increased for each malignancy examined, with increases ranging from +4.4% units for 20-year RS for AML to +23.1% units for 10-year RS for CML. Ten year RS was >50% in 2012-16 for patients with CLL, CML, HL, NHL, and DLBCL, at 77.1%, 62.1%, 63.9%, 64.5%, and 63.0%, respectively. Survival dropped between 10 and 20 years after diagnosis for most malignancies. Long-term survival is increasing for common hematologic malignancies, but late mortality is an ongoing issue. Further study of long-term outcomes in curable malignancies to determine the reason for these later decreases in survival is indicated.

Background: Rectal cancer (RC) is a common malignancy with a substantial mortality but good survival for patients with optimally treated nonmetastatic disease. Lack of insurance may compromise access to care and therefore compromise survival. Here, we examine RC survival by insurance type., Methods: Data from the Surveillance, Epidemiology, and End Results database were used to determine 1- to 3-year survival for patients with RC by insurance type (Medicaid, uninsured, other insurance)., Results: Patients with Medicaid or no insurance presented at later stages and were less likely to receive definitive surgery. Overall 3-year survival was higher for patients with other insurance compared with Medicaid-insured (+22.2% units) and uninsured (+18.8% units) patients. Major differences in survival were still observed after adjustment for stage. When patients with stage II and III RC were considered, 3-year survival was higher for patients with other insurance versus those with Medicaid (+16.2% units) and uninsured patients (+12.2% units). However, when the analysis was limited to patients with stage II and III disease who received radiation therapy followed by definitive surgery, the difference decreased to +11.8% units and +7.3% units, respectively, for Medicaid and no insurance., Conclusion: For patients with stage II and III RC, much of the difference in survival between uninsured patients and those with insurance other than Medicaid can be explained by differences in treatment. Further efforts to determine the cause of residual differences as well as efforts to improve access to standard-of-care treatment for uninsured patients may improve population-level survival for RC. The Oncologist 2017;22:351-358 IMPLICATIONS FOR PRACTICE: Insurance status affects survival for patients with rectal cancer, but a substantial proportion of the difference in survival can be corrected if standard-of-care treatment is given. Every effort should be made to ensure that uninsured or publically insured patients receive standard-of-care treatment with as little delay as possible to improve patient outcomes., (© AlphaMed Press 2017.)

Background: Recent population-based studies in the United States of America (USA) and other countries have shown improvements in survival for patients with chronic lymphocytic leukemia (CLL) diagnosed in the early twenty-first century. Here, we examine the survival for patients diagnosed with CLL in Germany in 1997-2011., Methods: Data were extracted from 12 cancer registries in Germany and compared to the data from the USA. Period analysis was used to estimate 5- and 10-year relative survival (RS)., Results: Five- and 10-year RS estimates in 2009-2011 of 80.2 and 59.5%, respectively, in Germany and 82.4 and 64.7%, respectively, in the USA were observed. Overall, 5-year RS increased significantly in Germany and the difference compared to the survival in the USA which slightly decreased between 2003-2005 and 2009-2011. However, age-specific analyses showed persistently higher survival for all ages except for 15-44 in the USA. In general, survival decreased with age, but the age-related disparity was small for patients younger than 75. In both countries, 5-year RS was >80% for patients less than 75 years of age but <70% for those age 75+., Conclusions: Overall, 5-year survival for patients with CLL is good, but 10-year survival is significantly lower, and survival was much lower for those age 75+. Major differences in survival between countries were not observed. Further research into ways to increase survival for older CLL patients are needed to reduce the persistent large age-related survival disparity.

Background: New treatment options and supportive care measures have greatly improved survival of patients with non-Hodgkin lymphoma (NHL) but may not be affordable for those with no insurance or inadequate insurance., Methods: Using data from the Surveillance, Epidemiology, and End Results database, we estimated overall and cause-specific survival according to insurance status within 3 years after diagnosis of patients diagnosed with NHL in the U.S. in the period 2007-2011. Because NHL is a heterogeneous condition, we also examined survival in diffuse large B-cell lymphoma (DLBCL)., Results: Survival was higher for patients with non-Medicaid insurance compared with either uninsured patients or patients with Medicaid. For patients with any NHL, the 3-year survival estimates were 68.0% for uninsured patients, 60.7% for patients with Medicaid, and 84.9% for patients with non-Medicaid insurance. Hazard ratios (HRs) for uninsured and Medicaid-only patients compared with insured patients were 1.92 (95% confidence interval [CI]: 1.76-2.10) and 2.51 (95% CI: 2.36-2.68), respectively. Results were similar for patients with DLBCL, with survival estimates of 68.5% for uninsured patients (HR: 1.78; 95% CI: 1.57-2.02), 58%, for patients with Medicaid (HR: 2.42; 95% CI: 2.22-2.64), and 83.3% for patients with non-Medicaid insurance. Cause-specific analysis showed survival estimates of 80.3% for uninsured patients (HR: 1.83; 95% CI: 1.62-2.05), 77.7% for patients with Medicaid (HR: 2.23; 95% CI: 2.05-2.42), and 90.5% for patients with non-Medicaid insurance., Conclusion: Lack of insurance and Medicaid only were associated with significantly lower survival for patients with NHL. Further evaluation of the reasons for this disparity and implementation of comprehensive coverage for medical care are urgently needed., (©AlphaMed Press.)

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.

Introduction: The advent of tyrosine kinase inhibitors has produced 5-year survival of 90 + % for chronic myelocytic leukemia (CML) patients in clinical trials. However, population level survival has been lower, especially in older patients. Here, we examine survival of patients with CML in Germany and compare it to survival of patients in the United States (US)., Methods: Data were extracted from the Surveillance, Epidemiology, and End Results database in the US and 11 cancer registries in Germany. Patients 15-69 years old diagnosed with CML were included in the analysis. Period analysis for 2002-2006 was used to provide the most up-to-date possible estimates of five-year relative survival., Results: Five-year relative survival was 68.7% overall in Germany and 72.7% in the US. Survival was higher in the US for all age groups except for ages 15-39 years, but the difference was only statistically significant for ages 50-59 years (at 67.5% vs 77.7% in Germany and the US, respectively). Survival decreased with age, ranging from 83.1% and 81.9%, respectively, in Germany and the US for patients 15-39 years old to 54.2% and 54.5%, respectively, in patients 65-69 years old. Survival increased between 2002 and 2006 by 12.0% points in Germany and 17.1% points in the US., Conclusions: Five-year survival estimates were higher in the US than in Germany overall, but the difference was only significant for ages 50-59 years. Survival did not equal that seen in clinical trials for either country, but strong improvement in survival was seen between 2002 and 2006.

The survival of younger patients with acute leukemia has improved in the early 21(st) 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 21(st) 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.

Introduction: The survival of patients with chronic myelocytic leukemia (CML) has improved during the past decades. However, there have been discrepancies between results reported from clinical trials and population-based studies. We aimed to elucidate the extent of these discrepancies., Methods: We examined the 5-year survival rate of patients in clinical trials of CML treatment and compared these results with the survival of patients in the general population using the Surveillance, Epidemiology, and End Results (SEER) database, correcting for differences in the age structure of the patient populations., Results: Twenty-nine trials were identified for data extraction. The survival rate calculated from SEER data was lower than the survival rate in clinical trials in the corresponding period, with differences of 2.1%-50.7%. Age-adapted survival was similar for four trials, but differences up to 35.8% were seen in most. Limitations of the study include the lack of information on chemotherapy in the SEER database and possible heterogeneity of cases., Discussion: The survival rate in clinical trials of CML treatment is higher than the survival rate of all patients with CML. We speculate that the difference may be a result of access to better medications, selection of healthier patients for trials, and the time necessary for adoption of new treatments. This finding underscores the need for population-based studies to give a more realistic idea of survival for patients with a given malignancy in the general population.

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.

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.

Acute lymphoblastic leukemia (ALL) is an uncommon but highly fatal disease in adults. We used period analysis to data from the Surveillance, Epidemiology, and End Results (SEER) database to disclose changes in outcomes for patients diagnosed with ALL in the United States in the 2 decades between 1980-1984 and 2000-2004. Major improvement in survival was observed for patients less than 60 years of age. Improvement in survival was greater for women than for men, but was significant for both genders. The greatest improvement was seen in patients aged 15 to 19, in whom 5-year relative survival improved from 41.0% to 61.1%, and 10-year survival improved from 33.0% to 60.4%. Lesser but significant improvements were seen for age groups 20-29, 30-44, and 45-59. Survival for patients aged 60 and over remained essentially unchanged at levels around or below 10%, respectively. Survival has improved for patients with ALL over the time period studied, but treatment of older patients remains a difficult issue.

Background: Advances in the treatment of childhood hematologic malignancies have led to improvements in survival for several of these conditions during the past few decades, but most population-based survival data available to date refer only to patients diagnosed up to the mid-1990s., Methods: We used period analysis to assess trends in 5- and 10-year survival in US patients younger than 15 years of age at diagnosis with four hematologic malignancies--acute lymphoblastic leukemia, acute non-lymphoblastic leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma--over three recent 5-year intervals, 1990-1994, 1995-1999, and 2000-2004, using data on a total of 6957 patients from the Surveillance, Epidemiology, and End Results database. Expected survival for 2005-2009 was estimated by modeling from trends in the preceding intervals., Results: Major improvements in 5- and 10-year relative survival between 1990-1994 and 2000-2004 were seen for acute lymphoblastic leukemia (from 80.2% to 87.5% and from 73.4% to 83.8%, respectively), acute non-lymphoblastic leukemia (from 41.9% to 59.9% and from 38.7% to 59.1%, respectively), and non-Hodgkin lymphoma (from 76.6% to 87.7% and from 73.0% to 86.9%, respectively). For those diagnosed with Hodgkin lymphoma, 5- and 10-year survival rates for the 1990-1994 period were 96.1% and 94.4%, respectively, and these rates did not change substantially in the later time periods. Projected 10-year survival rates for children diagnosed in the 2005-2009 period were 88.0% for acute lymphoblastic leukemia, 63.9% for acute non-lymphoblastic leukemia, 90.6% for non-Hodgkin lymphoma, and 94.3% for Hodgkin lymphoma., Conclusions: Application of period analysis to a population-based study of childhood hematologic malignancies reveals ongoing increases in survival for three of the four common childhood hematologic malignancies.

Although chronic lymphocytic leukemia (CLL) has remained incurable with standard treatments, newer therapeutic approaches, such as chemoimmunotherapy or stem cell transplantation, bear the potential for prolonged survival. We estimated trends in age-specific 5- and 10-year absolute and relative survival of CLL patients in the United States between 1980-1984 and 2000-2004 from the 1973 to 2004 database of the Surveillance, Epidemiology, and End Results Program. Period analysis was used to disclose recent developments with minimum delay. Overall, 5- and 10-year absolute survival from diagnosis increased from 54.2% to 60.2% (+6 percentage points; P < .0001) and from 27.8% to 34.8% (+7 percentage points; P < .0001), respectively. Despite a strong age gradient in prognosis, increases in 5-year absolute and relative survival over time were rather homogeneous across age groups. In contrast, increases in 10-year absolute and relative survival close to or well above 10% units were observed for all patients younger than 80 years of age at diagnosis compared with no increase at all for older patients. Long-term survival expectations of patients with CLL have substantially improved over the past 2 decades except for patients 80 years of age or older at the time of diagnosis. Future studies are needed to confirm and expand our findings.

Since the breakthroughs in combination chemotherapy of patients with Hodgkin disease (HD) starting in the 1960s, prognosis of patients has been rising steadily. Trends in long-term survival of patients with HD on the population level should therefore be monitored in an as timely as possible manner. We assessed trends in age specific 5- and 10-year relative survival of patients with HD in the United States from 1980-1984 to 2000-2004 from the 1973-2004 database of the Surveillance, Epidemiology, and End Results (SEER) Program. Period analysis was used to disclose recent developments with minimum delay. Overall, 5-year relative survival steadily increased from 73.5% to 85.2% (+11.7 percentage units), and 10-year relative survival increased from 62.1% to 80.1% (+18.0 percentage units) between 1980-1984 and 2000-2004, according to period analysis. The increase was particularly pronounced for patients aged 45 to 59 years and 60 years and older (increases in 10-year relative survival by 24.8 and 23.3 percentage points, respectively). Nevertheless, a strong age gradient persisted, with 10-year relative survival of 92.7%, 88.7%, 84.9%, 76.2%, and 44.9% in patients aged 15 to 24 years, 25 to 34 years, 35 to 44 years, 45 to 54 years, and 60 years and older, respectively, in 2000-2004. Our period analysis discloses ongoing, major improvement in long-term survival of patients with HD in recent years, particularly among older patients.

In the past, most patients with multiple myeloma (MM) died within 5 to 10 years after diagnosis. Within the past decade, several new therapeutic interventions have been introduced, including autologous stem-cell transplantation, thalidomide, lenalidomide, and bortezomib. We estimated trends in age-specific 5- and 10-year relative survival of patients with MM in the United States from 1990-1992 to 2002-2004 from the 1973-2004 database of the Surveillance, Epidemiology, and End Results (SEER) Program. Techniques of period analysis were used to show most recent developments. Overall, 5-year relative survival increased from 28.8% to 34.7% (P < .001), and 10-year relative survival increased from 11.1% to 17.4% (P < .001) between 1990-1992 and 2002-2004. Much stronger increases were seen in the age group younger than 50 years, leading to 5- and 10-year relative survival of 56.7% and 41.3% in 2002-2004, and in the age group 50 to 59 years, leading to 5- and 10-year relative survival of 48.2% and 28.6% in 200-2004. By contrast, only moderate improvement was seen in the age group 60 to 69 years, and essentially no improvement was achieved among older patients. Our period analysis discloses a major increase in long-term survival of younger patients with MM in recent years, which most likely reflects the effect of recent advances in therapy and their dissemination in clinical practice.

Ikaros is a critical transcriptional regulator of hematopoietic cell differentiation. In addition to its effects on the lymphoid system and hematopoietic stem-cell compartment, we have previously shown that Ikaros is also required for normal erythroid development. In this report, we compare Ikaros-dependent gene expression in erythroid cells of mice lacking the Ikaros protein with that of normal mice in purified adult bone-marrow erythroid cells (BMRC). Gene expression, measured by Affymetrix microarray analysis, indicates that in the BMRC of Ikaros-null mice, there is significant up-regulation of SMADs 6 and 7, serine protease inhibitor 3, and immediate-early protein 3 (IER3), all proteins that play a modulating role in apoptosis. We investigate the role of Ikaros in oxidative stress-induced apoptosis using Annexin-V staining and FACS analysis. We find a decrease in apoptosis in the BMRC of Ikaros-null mice compared to normal mice. This effect is also seen in nonerythroid cells but is stronger in BMRC. We conclude that normal Ikaros function increases normal apoptosis in erythroid cells. The data also suggest that Ikaros plays a role in apoptosis-mediated events in other normal hematopoietic cell lineages., ((c) 2005 Wiley-Liss, Inc.)