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Impact of Facility Type on Survival Outcomes in Pancreatic Neuroendocrine Carcinoma: An Analysis of the National Cancer Database
Background
This study aims to evaluate the impact of treatment facility type on the long-term survival rates of patients with pancreatic neuroendocrine tumors, as well as the demographic and treatment differences between these groups. Pancreatic neuroendocrine tumors are a rare form of pancreatic cancer with a highly variable survival rate. While existing cancer research indicates that patients treated at academic facilities generally experience improved survival outcomes compared to low income patients, there is little research on this topic in the context of pancreatic neuroendocrine tumors.
Methods
The National Cancer Database (NCDB) was used to identify patients diagnosed with pancreatic neuroendocrine carcinoma from 2004 to 2019 using the histology code 8246 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA, and Chi-Square tests were performed. Data was analyzed using SPSS version 27 and statistical significance was set at α = 0.05.
Results
In this analysis of 13,987 patients, 6,957 (49.7%) were treated at academic facilities, while 7,012 (50.3%) were treated at non-academic facilities. Patients treated at academic facilities experienced a significantly increased mean survival rate of 100.5 months following diagnosis compared to the 75.6 month mean survival rate of patients treated at non-academic facilities (p< 0.05). Additionally, patients treated at academic facilities were more likely to be black, have private insurance, undergo surgery, and live in a metropolitan area with a population larger than 1 million (p< 0.05). Conversely, patients treated at non-academic facilities experienced a worse 30-day and 90-day mortality, had a higher average Charlson-Deyo Comorbidity Index, and lived closer to their treatment facility (p< 0.05). Patients’ income did not differ significantly.
Conclusions
This study showed that patients with pancreatic neuroendocrine carcinomas treated at academic facilities experienced a significantly improved overall survival rate compared to low income patients. This disparity may be attributed to differences in rates of surgical intervention or insurance status, among other factors. These observations are based on correlational data, and they underscore the necessity for further investigation to establish causality.
Background
This study aims to evaluate the impact of treatment facility type on the long-term survival rates of patients with pancreatic neuroendocrine tumors, as well as the demographic and treatment differences between these groups. Pancreatic neuroendocrine tumors are a rare form of pancreatic cancer with a highly variable survival rate. While existing cancer research indicates that patients treated at academic facilities generally experience improved survival outcomes compared to low income patients, there is little research on this topic in the context of pancreatic neuroendocrine tumors.
Methods
The National Cancer Database (NCDB) was used to identify patients diagnosed with pancreatic neuroendocrine carcinoma from 2004 to 2019 using the histology code 8246 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA, and Chi-Square tests were performed. Data was analyzed using SPSS version 27 and statistical significance was set at α = 0.05.
Results
In this analysis of 13,987 patients, 6,957 (49.7%) were treated at academic facilities, while 7,012 (50.3%) were treated at non-academic facilities. Patients treated at academic facilities experienced a significantly increased mean survival rate of 100.5 months following diagnosis compared to the 75.6 month mean survival rate of patients treated at non-academic facilities (p< 0.05). Additionally, patients treated at academic facilities were more likely to be black, have private insurance, undergo surgery, and live in a metropolitan area with a population larger than 1 million (p< 0.05). Conversely, patients treated at non-academic facilities experienced a worse 30-day and 90-day mortality, had a higher average Charlson-Deyo Comorbidity Index, and lived closer to their treatment facility (p< 0.05). Patients’ income did not differ significantly.
Conclusions
This study showed that patients with pancreatic neuroendocrine carcinomas treated at academic facilities experienced a significantly improved overall survival rate compared to low income patients. This disparity may be attributed to differences in rates of surgical intervention or insurance status, among other factors. These observations are based on correlational data, and they underscore the necessity for further investigation to establish causality.
Background
This study aims to evaluate the impact of treatment facility type on the long-term survival rates of patients with pancreatic neuroendocrine tumors, as well as the demographic and treatment differences between these groups. Pancreatic neuroendocrine tumors are a rare form of pancreatic cancer with a highly variable survival rate. While existing cancer research indicates that patients treated at academic facilities generally experience improved survival outcomes compared to low income patients, there is little research on this topic in the context of pancreatic neuroendocrine tumors.
Methods
The National Cancer Database (NCDB) was used to identify patients diagnosed with pancreatic neuroendocrine carcinoma from 2004 to 2019 using the histology code 8246 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA, and Chi-Square tests were performed. Data was analyzed using SPSS version 27 and statistical significance was set at α = 0.05.
Results
In this analysis of 13,987 patients, 6,957 (49.7%) were treated at academic facilities, while 7,012 (50.3%) were treated at non-academic facilities. Patients treated at academic facilities experienced a significantly increased mean survival rate of 100.5 months following diagnosis compared to the 75.6 month mean survival rate of patients treated at non-academic facilities (p< 0.05). Additionally, patients treated at academic facilities were more likely to be black, have private insurance, undergo surgery, and live in a metropolitan area with a population larger than 1 million (p< 0.05). Conversely, patients treated at non-academic facilities experienced a worse 30-day and 90-day mortality, had a higher average Charlson-Deyo Comorbidity Index, and lived closer to their treatment facility (p< 0.05). Patients’ income did not differ significantly.
Conclusions
This study showed that patients with pancreatic neuroendocrine carcinomas treated at academic facilities experienced a significantly improved overall survival rate compared to low income patients. This disparity may be attributed to differences in rates of surgical intervention or insurance status, among other factors. These observations are based on correlational data, and they underscore the necessity for further investigation to establish causality.
An NCDB Analysis of Factors Associated With the Receipt of Surgery in Myxoid/Round Cell Liposarcoma
Background
Myxoid/round cell liposarcoma (MRCLS) is a rare soft tissue sarcoma originating from adipocytes and most commonly occurs in patients aged 20 to 40. Though slow-growing, MRCLS has a high propensity to metastasize. Complete surgical resection is central in the treatment of MRCLS. However, no significant study has analyzed the factors that predict the utilization of surgical therapy in MRCLS patients. This study also aims to characterize the effect of different treatment modalities on overall survival of these patients.
Methods
The National Cancer Database (NCDB) was used to identify patients diagnosed with MRCLS from 2004 to 2019 using the histology code 8852 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Multilevel Logistic Regression were performed, and data were analyzed using SPSS version 29. Statistical significance was set at α = 0.05.
Results
5365 patients with MRCLS were queried. 4811 (89.8%) patients received surgery. Surgical patients experienced greater overall survival compared to nonsurgical patients (159.17 vs 93.72 months, p < 0.001). Wedge/segmental resection (1551 patients, 32.2%) and lobectomy resection (2724 patients, 56.6%) were associated with improved survival over other surgery types (OS =161.0 months, p < 0.001). Private insurance status and care at an academic facility were associated with an increased likelihood of receiving surgery (p< 0.001). Metastasis was associated with a decreased likelihood of receiving surgery (p< 0.001). On nominal regression, grades I-II, stages 1-3, and histologically well to moderately differentiated disease were associated with a greater likelihood of receiving surgery. Adjuvant therapy did not appear to impact survival.
Conclusions
This study reaffirms that tumor resection is associated with increased overall survival in MRCLS patients. Specifically, wedge/segmental and lobectomy surgery types are associated with improved outcomes. It appears that care at an academic facility, private insurance status, lower stage and grade of disease, and well-differentiated histology are correlated to an increased likelihood of receiving surgical treatment. Metastasis is associated with a decreased chance of receiving surgery. This research serves as the start to a better understanding of the factors involved in the receipt of tumor resection, as it is the mainstay of MRCLS treatment.
Background
Myxoid/round cell liposarcoma (MRCLS) is a rare soft tissue sarcoma originating from adipocytes and most commonly occurs in patients aged 20 to 40. Though slow-growing, MRCLS has a high propensity to metastasize. Complete surgical resection is central in the treatment of MRCLS. However, no significant study has analyzed the factors that predict the utilization of surgical therapy in MRCLS patients. This study also aims to characterize the effect of different treatment modalities on overall survival of these patients.
Methods
The National Cancer Database (NCDB) was used to identify patients diagnosed with MRCLS from 2004 to 2019 using the histology code 8852 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Multilevel Logistic Regression were performed, and data were analyzed using SPSS version 29. Statistical significance was set at α = 0.05.
Results
5365 patients with MRCLS were queried. 4811 (89.8%) patients received surgery. Surgical patients experienced greater overall survival compared to nonsurgical patients (159.17 vs 93.72 months, p < 0.001). Wedge/segmental resection (1551 patients, 32.2%) and lobectomy resection (2724 patients, 56.6%) were associated with improved survival over other surgery types (OS =161.0 months, p < 0.001). Private insurance status and care at an academic facility were associated with an increased likelihood of receiving surgery (p< 0.001). Metastasis was associated with a decreased likelihood of receiving surgery (p< 0.001). On nominal regression, grades I-II, stages 1-3, and histologically well to moderately differentiated disease were associated with a greater likelihood of receiving surgery. Adjuvant therapy did not appear to impact survival.
Conclusions
This study reaffirms that tumor resection is associated with increased overall survival in MRCLS patients. Specifically, wedge/segmental and lobectomy surgery types are associated with improved outcomes. It appears that care at an academic facility, private insurance status, lower stage and grade of disease, and well-differentiated histology are correlated to an increased likelihood of receiving surgical treatment. Metastasis is associated with a decreased chance of receiving surgery. This research serves as the start to a better understanding of the factors involved in the receipt of tumor resection, as it is the mainstay of MRCLS treatment.
Background
Myxoid/round cell liposarcoma (MRCLS) is a rare soft tissue sarcoma originating from adipocytes and most commonly occurs in patients aged 20 to 40. Though slow-growing, MRCLS has a high propensity to metastasize. Complete surgical resection is central in the treatment of MRCLS. However, no significant study has analyzed the factors that predict the utilization of surgical therapy in MRCLS patients. This study also aims to characterize the effect of different treatment modalities on overall survival of these patients.
Methods
The National Cancer Database (NCDB) was used to identify patients diagnosed with MRCLS from 2004 to 2019 using the histology code 8852 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Multilevel Logistic Regression were performed, and data were analyzed using SPSS version 29. Statistical significance was set at α = 0.05.
Results
5365 patients with MRCLS were queried. 4811 (89.8%) patients received surgery. Surgical patients experienced greater overall survival compared to nonsurgical patients (159.17 vs 93.72 months, p < 0.001). Wedge/segmental resection (1551 patients, 32.2%) and lobectomy resection (2724 patients, 56.6%) were associated with improved survival over other surgery types (OS =161.0 months, p < 0.001). Private insurance status and care at an academic facility were associated with an increased likelihood of receiving surgery (p< 0.001). Metastasis was associated with a decreased likelihood of receiving surgery (p< 0.001). On nominal regression, grades I-II, stages 1-3, and histologically well to moderately differentiated disease were associated with a greater likelihood of receiving surgery. Adjuvant therapy did not appear to impact survival.
Conclusions
This study reaffirms that tumor resection is associated with increased overall survival in MRCLS patients. Specifically, wedge/segmental and lobectomy surgery types are associated with improved outcomes. It appears that care at an academic facility, private insurance status, lower stage and grade of disease, and well-differentiated histology are correlated to an increased likelihood of receiving surgical treatment. Metastasis is associated with a decreased chance of receiving surgery. This research serves as the start to a better understanding of the factors involved in the receipt of tumor resection, as it is the mainstay of MRCLS treatment.
Clear Cell Sarcoma Incidence and Survival: A SEER Database Analysis
Background
Clear cell sarcoma (CCS) is a rare soft tissue cancer that predominantly affects young to middle-aged adults. Current literature lacks recent accurate estimates of patient outcomes due to the disease’s low incidence and the small sample sizes in studies, particularly at a national registry level. This study aims to examine the incidence and survival of patients with CCS.
Methods
Patients from the Surveillance, Epidemiology, and End Results (SEER) database diagnosed with CCS between 2000-2020 were selected. Additional variables were collected including age, sex, race, stage, presence of metastases, tumor size, treatment status for surgery, radiation, and chemotherapy, time to treatment, median household income, and population size. Descriptive statistics, population-based incidence, log-rank tests with Kaplan-Meier curves, and Cox regression analyses were performed.
Results
A total of 287 patients were included. The population-adjusted incidence ranged from 0.012/100000 in 2004 to 0.027/100000 in 2010. The total percent change over the study period was 16.751% and the annual percent change, which did not change significantly over the study period, was 0.561%. The survival rate was 78.4% at one year, 62.0% at three years, and 57.1% at five years. Log-rank results showed Black patients survived shorter than White and Hispanic patients. Further, greater staging and tumor size >4.0cm were associated with shorter survival (p’s< 0.001). After controlling for covariates, Cox regression results showed Black patients were associated with shorter survival compared to White patients (p=0.038, hazard ratio=2.590). No other covariates were significantly associated with survival.
Conclusions
The findings showed CCS incidence is unchanged in recent years and prognosis is poor. Additionally, Black patients were associated with shorter survival duration compared to White patients. Contrary to prior findings on CCS, staging and tumor size were only significantly associated during univariate analyses, but not on Cox regression. The study was limited by a small sample size and variables found in the SEER database. Nonetheless, future research will benefit from assessing how race is an independent risk factor for CCS survival and how the prognosis of CCS patients can be improved.
Background
Clear cell sarcoma (CCS) is a rare soft tissue cancer that predominantly affects young to middle-aged adults. Current literature lacks recent accurate estimates of patient outcomes due to the disease’s low incidence and the small sample sizes in studies, particularly at a national registry level. This study aims to examine the incidence and survival of patients with CCS.
Methods
Patients from the Surveillance, Epidemiology, and End Results (SEER) database diagnosed with CCS between 2000-2020 were selected. Additional variables were collected including age, sex, race, stage, presence of metastases, tumor size, treatment status for surgery, radiation, and chemotherapy, time to treatment, median household income, and population size. Descriptive statistics, population-based incidence, log-rank tests with Kaplan-Meier curves, and Cox regression analyses were performed.
Results
A total of 287 patients were included. The population-adjusted incidence ranged from 0.012/100000 in 2004 to 0.027/100000 in 2010. The total percent change over the study period was 16.751% and the annual percent change, which did not change significantly over the study period, was 0.561%. The survival rate was 78.4% at one year, 62.0% at three years, and 57.1% at five years. Log-rank results showed Black patients survived shorter than White and Hispanic patients. Further, greater staging and tumor size >4.0cm were associated with shorter survival (p’s< 0.001). After controlling for covariates, Cox regression results showed Black patients were associated with shorter survival compared to White patients (p=0.038, hazard ratio=2.590). No other covariates were significantly associated with survival.
Conclusions
The findings showed CCS incidence is unchanged in recent years and prognosis is poor. Additionally, Black patients were associated with shorter survival duration compared to White patients. Contrary to prior findings on CCS, staging and tumor size were only significantly associated during univariate analyses, but not on Cox regression. The study was limited by a small sample size and variables found in the SEER database. Nonetheless, future research will benefit from assessing how race is an independent risk factor for CCS survival and how the prognosis of CCS patients can be improved.
Background
Clear cell sarcoma (CCS) is a rare soft tissue cancer that predominantly affects young to middle-aged adults. Current literature lacks recent accurate estimates of patient outcomes due to the disease’s low incidence and the small sample sizes in studies, particularly at a national registry level. This study aims to examine the incidence and survival of patients with CCS.
Methods
Patients from the Surveillance, Epidemiology, and End Results (SEER) database diagnosed with CCS between 2000-2020 were selected. Additional variables were collected including age, sex, race, stage, presence of metastases, tumor size, treatment status for surgery, radiation, and chemotherapy, time to treatment, median household income, and population size. Descriptive statistics, population-based incidence, log-rank tests with Kaplan-Meier curves, and Cox regression analyses were performed.
Results
A total of 287 patients were included. The population-adjusted incidence ranged from 0.012/100000 in 2004 to 0.027/100000 in 2010. The total percent change over the study period was 16.751% and the annual percent change, which did not change significantly over the study period, was 0.561%. The survival rate was 78.4% at one year, 62.0% at three years, and 57.1% at five years. Log-rank results showed Black patients survived shorter than White and Hispanic patients. Further, greater staging and tumor size >4.0cm were associated with shorter survival (p’s< 0.001). After controlling for covariates, Cox regression results showed Black patients were associated with shorter survival compared to White patients (p=0.038, hazard ratio=2.590). No other covariates were significantly associated with survival.
Conclusions
The findings showed CCS incidence is unchanged in recent years and prognosis is poor. Additionally, Black patients were associated with shorter survival duration compared to White patients. Contrary to prior findings on CCS, staging and tumor size were only significantly associated during univariate analyses, but not on Cox regression. The study was limited by a small sample size and variables found in the SEER database. Nonetheless, future research will benefit from assessing how race is an independent risk factor for CCS survival and how the prognosis of CCS patients can be improved.
Survival and Incidence of Gastric Neuroendocrine Tumors: A SEER Database Analysis
Background
Gastric neuroendocrine tumors (GNETs) are slow-growing tumors derived from enterochromaffinlike cells whose prognosis depends on the type. Prior GNET studies have shown an increasing incidence but survival analyses have been more limited. This study aims to investigate if the increasing incidence trend continues and better describe factors associated with survival for GNET patients.
Methods
Patients diagnosed with GNET between 2000-2020 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Additional variables collected were age, sex, race, stage, presence of metastases, tumor size, treatment status for surgery, radiation, and chemotherapy, median household income, and population size. Descriptive statistics, population-based incidence, log-rank tests with Kaplan-Meier curves, and Cox regression analyses were performed.
Results
A total of 6512 patients were included. The one-, three-, and five-year survival rates were 90.4%, 85.0%, and 83.8%, respectively. The population-adjusted incidence ranged from 0.272/100000 in 2000 to 0.680/100000 in 2018. The total percent change in incidence over the study range was 104.1% with an annual percent change of 4.27%, which met significance <2.0cm and >5.0cm were associated with shorter survival (p’s< 0.05). Additionally, females, Hispanic patients, and recipients of surgery were associated with longer survival (p’s< 0.05).
Conclusions
The findings show GNET incidence has continued to increase over the past two decades. Additionally, clinical factors including stage, extent of metastasis, tumor size and socioeconomic factors like age, gender, and race were associated with changes in GNET survival. In the context of increasing incidence of GNET these findings describe factors associated with lower- and higher-risk tumors. Further assessment of these risk factors can benefit future research to better understand why GNET incidence is increasing, aid in risk stratification of GNET patients, and improve the prognosis of GNET.
Background
Gastric neuroendocrine tumors (GNETs) are slow-growing tumors derived from enterochromaffinlike cells whose prognosis depends on the type. Prior GNET studies have shown an increasing incidence but survival analyses have been more limited. This study aims to investigate if the increasing incidence trend continues and better describe factors associated with survival for GNET patients.
Methods
Patients diagnosed with GNET between 2000-2020 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Additional variables collected were age, sex, race, stage, presence of metastases, tumor size, treatment status for surgery, radiation, and chemotherapy, median household income, and population size. Descriptive statistics, population-based incidence, log-rank tests with Kaplan-Meier curves, and Cox regression analyses were performed.
Results
A total of 6512 patients were included. The one-, three-, and five-year survival rates were 90.4%, 85.0%, and 83.8%, respectively. The population-adjusted incidence ranged from 0.272/100000 in 2000 to 0.680/100000 in 2018. The total percent change in incidence over the study range was 104.1% with an annual percent change of 4.27%, which met significance <2.0cm and >5.0cm were associated with shorter survival (p’s< 0.05). Additionally, females, Hispanic patients, and recipients of surgery were associated with longer survival (p’s< 0.05).
Conclusions
The findings show GNET incidence has continued to increase over the past two decades. Additionally, clinical factors including stage, extent of metastasis, tumor size and socioeconomic factors like age, gender, and race were associated with changes in GNET survival. In the context of increasing incidence of GNET these findings describe factors associated with lower- and higher-risk tumors. Further assessment of these risk factors can benefit future research to better understand why GNET incidence is increasing, aid in risk stratification of GNET patients, and improve the prognosis of GNET.
Background
Gastric neuroendocrine tumors (GNETs) are slow-growing tumors derived from enterochromaffinlike cells whose prognosis depends on the type. Prior GNET studies have shown an increasing incidence but survival analyses have been more limited. This study aims to investigate if the increasing incidence trend continues and better describe factors associated with survival for GNET patients.
Methods
Patients diagnosed with GNET between 2000-2020 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Additional variables collected were age, sex, race, stage, presence of metastases, tumor size, treatment status for surgery, radiation, and chemotherapy, median household income, and population size. Descriptive statistics, population-based incidence, log-rank tests with Kaplan-Meier curves, and Cox regression analyses were performed.
Results
A total of 6512 patients were included. The one-, three-, and five-year survival rates were 90.4%, 85.0%, and 83.8%, respectively. The population-adjusted incidence ranged from 0.272/100000 in 2000 to 0.680/100000 in 2018. The total percent change in incidence over the study range was 104.1% with an annual percent change of 4.27%, which met significance <2.0cm and >5.0cm were associated with shorter survival (p’s< 0.05). Additionally, females, Hispanic patients, and recipients of surgery were associated with longer survival (p’s< 0.05).
Conclusions
The findings show GNET incidence has continued to increase over the past two decades. Additionally, clinical factors including stage, extent of metastasis, tumor size and socioeconomic factors like age, gender, and race were associated with changes in GNET survival. In the context of increasing incidence of GNET these findings describe factors associated with lower- and higher-risk tumors. Further assessment of these risk factors can benefit future research to better understand why GNET incidence is increasing, aid in risk stratification of GNET patients, and improve the prognosis of GNET.
Changes in Age-Related Mortality in Malignant Melanoma From 1999- 2022: A CDC Wonder Study
Background
Melanoma is one of the leading causes of solid tumor cancers. This study’s objective is to analyze temporal trends in melanoma-related mortality among age groups in the US before and during COVID-19. To date, no previous studies have analyzed year-to-year trends in melanoma mortality by age group using the CDC Wonder database. A 2011 analysis previously showed increasing death rates only among those over age 65 between 1992-2006.
Methods
The CDC Wonder database was used to collect data on melanoma-related mortality rates in the US from 1999-2022. Crude mortality rates per 100,000 and annual percentage change using Joinpoint regression were used to analyze yearly trends among age groups.
Results
From 1999 to 2022, overall mortality rate fell from 2.91 to 2.07, and mortality rates among all age groups decreased with the exception of those over age 85. Age 35-44 crude mortality rate decreased from 1.42 to .7. Age 45-54 crude mortality rate decreased from 3.2 to 1.51. Age 55-64 decreased from 5.6 to 3.61. Age 65-74 decreased from 9.91 to 7.79. Age 75-84 decreased from 15.44 to 15.43. Ages 85+ increased from 21.5 to 33.1. Notably, mortality among those age 75-85 decreased by only .01, and were increased across the timespan of 2000-2020.
Conclusions
These results show that there may be differences between age groups in how mortality due to melanoma of age groups has changed from 1992-2022. While overall mortality attributed to melanoma fell during this period, mortality in those over age 85 increased. Future studies should confirm these results with different data sets and further investigate the reasons for these disparities.
Background
Melanoma is one of the leading causes of solid tumor cancers. This study’s objective is to analyze temporal trends in melanoma-related mortality among age groups in the US before and during COVID-19. To date, no previous studies have analyzed year-to-year trends in melanoma mortality by age group using the CDC Wonder database. A 2011 analysis previously showed increasing death rates only among those over age 65 between 1992-2006.
Methods
The CDC Wonder database was used to collect data on melanoma-related mortality rates in the US from 1999-2022. Crude mortality rates per 100,000 and annual percentage change using Joinpoint regression were used to analyze yearly trends among age groups.
Results
From 1999 to 2022, overall mortality rate fell from 2.91 to 2.07, and mortality rates among all age groups decreased with the exception of those over age 85. Age 35-44 crude mortality rate decreased from 1.42 to .7. Age 45-54 crude mortality rate decreased from 3.2 to 1.51. Age 55-64 decreased from 5.6 to 3.61. Age 65-74 decreased from 9.91 to 7.79. Age 75-84 decreased from 15.44 to 15.43. Ages 85+ increased from 21.5 to 33.1. Notably, mortality among those age 75-85 decreased by only .01, and were increased across the timespan of 2000-2020.
Conclusions
These results show that there may be differences between age groups in how mortality due to melanoma of age groups has changed from 1992-2022. While overall mortality attributed to melanoma fell during this period, mortality in those over age 85 increased. Future studies should confirm these results with different data sets and further investigate the reasons for these disparities.
Background
Melanoma is one of the leading causes of solid tumor cancers. This study’s objective is to analyze temporal trends in melanoma-related mortality among age groups in the US before and during COVID-19. To date, no previous studies have analyzed year-to-year trends in melanoma mortality by age group using the CDC Wonder database. A 2011 analysis previously showed increasing death rates only among those over age 65 between 1992-2006.
Methods
The CDC Wonder database was used to collect data on melanoma-related mortality rates in the US from 1999-2022. Crude mortality rates per 100,000 and annual percentage change using Joinpoint regression were used to analyze yearly trends among age groups.
Results
From 1999 to 2022, overall mortality rate fell from 2.91 to 2.07, and mortality rates among all age groups decreased with the exception of those over age 85. Age 35-44 crude mortality rate decreased from 1.42 to .7. Age 45-54 crude mortality rate decreased from 3.2 to 1.51. Age 55-64 decreased from 5.6 to 3.61. Age 65-74 decreased from 9.91 to 7.79. Age 75-84 decreased from 15.44 to 15.43. Ages 85+ increased from 21.5 to 33.1. Notably, mortality among those age 75-85 decreased by only .01, and were increased across the timespan of 2000-2020.
Conclusions
These results show that there may be differences between age groups in how mortality due to melanoma of age groups has changed from 1992-2022. While overall mortality attributed to melanoma fell during this period, mortality in those over age 85 increased. Future studies should confirm these results with different data sets and further investigate the reasons for these disparities.
Geographical Trends in Malignant Melanoma from 1999-2022: A CDC Wonder Study
Background
Melanoma is the fifth leading cause of cancer in the United States. This study’s objective is to analyze geographical trends in melanoma-related mortality in the US before and during COVID-19. To date, no previous studies have analyzed geographical trends in melanoma mortality using the CDC Wonder data base. Previous literature reports Utah, Vermont, Delaware, Minnesota and New Hampshire as having the highest UV-attributable incidence rates of melanoma.
Methods
The CDC Wonder database was used to collect data on melanoma-related mortality rates in the US from 1999-2022. Age-adjusted mortality rates (AAMR) per 100,000 and annual percentage change (APC) using Joinpoint regression were used to analyze state and regional trends.
Results
From 1999 to 2019, the states with the largest increase in AAMR were Idaho (0.91) and Colorado (0.63) while Oklahoma (-1.07), Nevada (-0.94), and Texas (-0.92) saw the largest decreases. During COVID-19 (2019 to 2021), the states with the largest increase in AAMR were South Dakota (1.42), Oregon (1.09), and Montana (1.08) while Vermont (-1.02), Minnesota (-0.45), and Connecticut (-0.38) had the largest declines. From 2006-2022, except 2020, the Northeast consistently had the lowest AAMR. From 2008-2012 the West consistently had the highest AAMR. From 2013-2022, except 2015, the Midwest had the highest AAMR. From 2009 onwards, all 4 regions have seen an overall decline in AAMR with their lowest values being in 2022.
Conclusions
Idaho had the highest AAMR before COVID-19 while Oklahoma had the lowest. During COVID-19, South Dakota saw the highest AAMR while Vermont had the lowest. AAMRs have been trending downwards across all 4 regions since 2009 and the Northeast has fared the best over that period. These results should be used to increase implementation and enforcement of preventative measures to reduce UV exposure, especially in states with higher AAMRs. Further research should examine statewide sun protection programs to search for any relationship with their AAMRs.
Background
Melanoma is the fifth leading cause of cancer in the United States. This study’s objective is to analyze geographical trends in melanoma-related mortality in the US before and during COVID-19. To date, no previous studies have analyzed geographical trends in melanoma mortality using the CDC Wonder data base. Previous literature reports Utah, Vermont, Delaware, Minnesota and New Hampshire as having the highest UV-attributable incidence rates of melanoma.
Methods
The CDC Wonder database was used to collect data on melanoma-related mortality rates in the US from 1999-2022. Age-adjusted mortality rates (AAMR) per 100,000 and annual percentage change (APC) using Joinpoint regression were used to analyze state and regional trends.
Results
From 1999 to 2019, the states with the largest increase in AAMR were Idaho (0.91) and Colorado (0.63) while Oklahoma (-1.07), Nevada (-0.94), and Texas (-0.92) saw the largest decreases. During COVID-19 (2019 to 2021), the states with the largest increase in AAMR were South Dakota (1.42), Oregon (1.09), and Montana (1.08) while Vermont (-1.02), Minnesota (-0.45), and Connecticut (-0.38) had the largest declines. From 2006-2022, except 2020, the Northeast consistently had the lowest AAMR. From 2008-2012 the West consistently had the highest AAMR. From 2013-2022, except 2015, the Midwest had the highest AAMR. From 2009 onwards, all 4 regions have seen an overall decline in AAMR with their lowest values being in 2022.
Conclusions
Idaho had the highest AAMR before COVID-19 while Oklahoma had the lowest. During COVID-19, South Dakota saw the highest AAMR while Vermont had the lowest. AAMRs have been trending downwards across all 4 regions since 2009 and the Northeast has fared the best over that period. These results should be used to increase implementation and enforcement of preventative measures to reduce UV exposure, especially in states with higher AAMRs. Further research should examine statewide sun protection programs to search for any relationship with their AAMRs.
Background
Melanoma is the fifth leading cause of cancer in the United States. This study’s objective is to analyze geographical trends in melanoma-related mortality in the US before and during COVID-19. To date, no previous studies have analyzed geographical trends in melanoma mortality using the CDC Wonder data base. Previous literature reports Utah, Vermont, Delaware, Minnesota and New Hampshire as having the highest UV-attributable incidence rates of melanoma.
Methods
The CDC Wonder database was used to collect data on melanoma-related mortality rates in the US from 1999-2022. Age-adjusted mortality rates (AAMR) per 100,000 and annual percentage change (APC) using Joinpoint regression were used to analyze state and regional trends.
Results
From 1999 to 2019, the states with the largest increase in AAMR were Idaho (0.91) and Colorado (0.63) while Oklahoma (-1.07), Nevada (-0.94), and Texas (-0.92) saw the largest decreases. During COVID-19 (2019 to 2021), the states with the largest increase in AAMR were South Dakota (1.42), Oregon (1.09), and Montana (1.08) while Vermont (-1.02), Minnesota (-0.45), and Connecticut (-0.38) had the largest declines. From 2006-2022, except 2020, the Northeast consistently had the lowest AAMR. From 2008-2012 the West consistently had the highest AAMR. From 2013-2022, except 2015, the Midwest had the highest AAMR. From 2009 onwards, all 4 regions have seen an overall decline in AAMR with their lowest values being in 2022.
Conclusions
Idaho had the highest AAMR before COVID-19 while Oklahoma had the lowest. During COVID-19, South Dakota saw the highest AAMR while Vermont had the lowest. AAMRs have been trending downwards across all 4 regions since 2009 and the Northeast has fared the best over that period. These results should be used to increase implementation and enforcement of preventative measures to reduce UV exposure, especially in states with higher AAMRs. Further research should examine statewide sun protection programs to search for any relationship with their AAMRs.
Implementation of an Intervention to Improve Efficiency and Accuracy of Data Entry into the Veterans Affairs Central Cancer Registry at the Lexington VA Healthcare System
Background
The Veterans Affairs Central Cancer Registry (VACCR) is an information system, which collects and organizes data on Veterans with cancer for use in cancer surveillance activities, such as epidemiologic based efforts to reduce the overall cancer burden. Unfortunately, there was no structured standardized data acquisition method in place to ensure accurate or timely data entry of Lexington VA Healthcare System (LVAHCS) statistics. This quality improvement study evaluated the implementation of a Structured Query Language (SQL) code to identify specific documents in the Computerized Patient Records System (CPRS) electronic medical record with associated ICD-10 codes matching the reportable cancer cases in the Surveillance, Epidemiology, and End Results (SEER) program.
Methods
Outcomes Studied: Accuracy of the SQL code, rates of data entry into the VACCR pre- and postintervention. Cancer Program leadership collaborated with the VISN 9 Program Analyst to write a SQL code identifying the Veteran’s name; social security number; location by city, state, and county; and visit associated data such as visit location, ICD-10 code documented by the provider, and visit year. This code can be run manually or at a pre-determined cadence.
Results
A total of 3,099 incidences of cancer were entered into the VACCR by local Oncology Data Specialists (ODSs) for calendar years 2015 to 2022. This is approximately 238 cases yearly. After the intervention, 1692 patients were entered into the VACCR in 2023. This is an increased rate of data entry of 611%.
Conclusions
This study demonstrated the feasibility of implementing a SQL code to accurately identify Veterans with diagnoses matching the SEER list. Increasing accuracy of identification has led to increased data entry efficiency into the VACCR by local ODS staff. After proving the feasibility of this intervention, we are partnering with the VISN 9 Program Analyst to create a static, daily recurring report provided to the ODS staff. Future application of this intervention could also include expansion into other VHA sites, increasing their accuracy and timeliness of data entry. Overall, improving the timeliness and accuracy of the VACCR would subsequently improve the ability of the VHA to target interventions aimed at reducing the overall cancer burden.
Background
The Veterans Affairs Central Cancer Registry (VACCR) is an information system, which collects and organizes data on Veterans with cancer for use in cancer surveillance activities, such as epidemiologic based efforts to reduce the overall cancer burden. Unfortunately, there was no structured standardized data acquisition method in place to ensure accurate or timely data entry of Lexington VA Healthcare System (LVAHCS) statistics. This quality improvement study evaluated the implementation of a Structured Query Language (SQL) code to identify specific documents in the Computerized Patient Records System (CPRS) electronic medical record with associated ICD-10 codes matching the reportable cancer cases in the Surveillance, Epidemiology, and End Results (SEER) program.
Methods
Outcomes Studied: Accuracy of the SQL code, rates of data entry into the VACCR pre- and postintervention. Cancer Program leadership collaborated with the VISN 9 Program Analyst to write a SQL code identifying the Veteran’s name; social security number; location by city, state, and county; and visit associated data such as visit location, ICD-10 code documented by the provider, and visit year. This code can be run manually or at a pre-determined cadence.
Results
A total of 3,099 incidences of cancer were entered into the VACCR by local Oncology Data Specialists (ODSs) for calendar years 2015 to 2022. This is approximately 238 cases yearly. After the intervention, 1692 patients were entered into the VACCR in 2023. This is an increased rate of data entry of 611%.
Conclusions
This study demonstrated the feasibility of implementing a SQL code to accurately identify Veterans with diagnoses matching the SEER list. Increasing accuracy of identification has led to increased data entry efficiency into the VACCR by local ODS staff. After proving the feasibility of this intervention, we are partnering with the VISN 9 Program Analyst to create a static, daily recurring report provided to the ODS staff. Future application of this intervention could also include expansion into other VHA sites, increasing their accuracy and timeliness of data entry. Overall, improving the timeliness and accuracy of the VACCR would subsequently improve the ability of the VHA to target interventions aimed at reducing the overall cancer burden.
Background
The Veterans Affairs Central Cancer Registry (VACCR) is an information system, which collects and organizes data on Veterans with cancer for use in cancer surveillance activities, such as epidemiologic based efforts to reduce the overall cancer burden. Unfortunately, there was no structured standardized data acquisition method in place to ensure accurate or timely data entry of Lexington VA Healthcare System (LVAHCS) statistics. This quality improvement study evaluated the implementation of a Structured Query Language (SQL) code to identify specific documents in the Computerized Patient Records System (CPRS) electronic medical record with associated ICD-10 codes matching the reportable cancer cases in the Surveillance, Epidemiology, and End Results (SEER) program.
Methods
Outcomes Studied: Accuracy of the SQL code, rates of data entry into the VACCR pre- and postintervention. Cancer Program leadership collaborated with the VISN 9 Program Analyst to write a SQL code identifying the Veteran’s name; social security number; location by city, state, and county; and visit associated data such as visit location, ICD-10 code documented by the provider, and visit year. This code can be run manually or at a pre-determined cadence.
Results
A total of 3,099 incidences of cancer were entered into the VACCR by local Oncology Data Specialists (ODSs) for calendar years 2015 to 2022. This is approximately 238 cases yearly. After the intervention, 1692 patients were entered into the VACCR in 2023. This is an increased rate of data entry of 611%.
Conclusions
This study demonstrated the feasibility of implementing a SQL code to accurately identify Veterans with diagnoses matching the SEER list. Increasing accuracy of identification has led to increased data entry efficiency into the VACCR by local ODS staff. After proving the feasibility of this intervention, we are partnering with the VISN 9 Program Analyst to create a static, daily recurring report provided to the ODS staff. Future application of this intervention could also include expansion into other VHA sites, increasing their accuracy and timeliness of data entry. Overall, improving the timeliness and accuracy of the VACCR would subsequently improve the ability of the VHA to target interventions aimed at reducing the overall cancer burden.
Data Elements Captured in Breast and Gynecologic Oncology System of Excellence Health Informatics Tool
Background
The VA National Oncology Program (NOP) Breast and Gynecologic Oncology System of Excellence (BGSOE) aims to ensure that Veterans with breast and gynecologic cancers receive state-of-the-art, guidelineadherent, Veteran-centric, timely, and well-coordinated care. Achieving these aims relies on a national multidisciplinary Cancer Care Navigation Team that provides tele-oncology navigation services. The teams connect with Veterans to identify and support clinical, psychological, system, coordination-related needs. To assist the navigation team to find these relatively rare diagnoses within VA, we developed a health informatics tool (HIT) that automatically identifies patients with breast or gynecologic cancers, displays demographic and clinical information, and facilitates systematic needs assessment and care coordination and tracking.
Methods
We used multiple frameworks to ensure alignment between HIT mission and coordinator workflow. A separate view was provided for each phase of the workflow: assessment of Veteran eligibility, intake assessment, and care coordination and tracking. Algorithmic identification of candidate Veterans was validated to ensure coordinators were not inundated with information on Veterans outside the scope of the program. User interface was implemented in accordance with Lean principles applied to HIT design, with close attention to information inventory, efficient user motion, information transportation, and avoidance of overprocessing.
Results
From January 1, 2021, to March 6, 2024, the HIT captured 5,561 breast cancer and 1,663 gynecologic cancer patients. 908 patients were reviewed by the coordinator, of whom 817 patients had a correct diagnosis assigned by the screening algorithm. From these, 332 patients were added to the intake process. The intake process is pending for 207 patients and complete for 102 patients; 23 patients declined intake. For patients who have completed intake, we have captured information that includes Veteran demographics, social history, insurance details, medical history, family history, hazards, barriers, and information specific to BGSOE care coordination.
Conclusions
We applied a novel framework to design and implement mission-driven, workflow-aligned HIT that achieves high user efficiency using Lean principles. This facilitated an exciting new model in tele-oncology care navigation delivery. Although the program is still in early phases, it has improved care coordination for Veterans with breast and gynecologic cancers across the United States.
Background
The VA National Oncology Program (NOP) Breast and Gynecologic Oncology System of Excellence (BGSOE) aims to ensure that Veterans with breast and gynecologic cancers receive state-of-the-art, guidelineadherent, Veteran-centric, timely, and well-coordinated care. Achieving these aims relies on a national multidisciplinary Cancer Care Navigation Team that provides tele-oncology navigation services. The teams connect with Veterans to identify and support clinical, psychological, system, coordination-related needs. To assist the navigation team to find these relatively rare diagnoses within VA, we developed a health informatics tool (HIT) that automatically identifies patients with breast or gynecologic cancers, displays demographic and clinical information, and facilitates systematic needs assessment and care coordination and tracking.
Methods
We used multiple frameworks to ensure alignment between HIT mission and coordinator workflow. A separate view was provided for each phase of the workflow: assessment of Veteran eligibility, intake assessment, and care coordination and tracking. Algorithmic identification of candidate Veterans was validated to ensure coordinators were not inundated with information on Veterans outside the scope of the program. User interface was implemented in accordance with Lean principles applied to HIT design, with close attention to information inventory, efficient user motion, information transportation, and avoidance of overprocessing.
Results
From January 1, 2021, to March 6, 2024, the HIT captured 5,561 breast cancer and 1,663 gynecologic cancer patients. 908 patients were reviewed by the coordinator, of whom 817 patients had a correct diagnosis assigned by the screening algorithm. From these, 332 patients were added to the intake process. The intake process is pending for 207 patients and complete for 102 patients; 23 patients declined intake. For patients who have completed intake, we have captured information that includes Veteran demographics, social history, insurance details, medical history, family history, hazards, barriers, and information specific to BGSOE care coordination.
Conclusions
We applied a novel framework to design and implement mission-driven, workflow-aligned HIT that achieves high user efficiency using Lean principles. This facilitated an exciting new model in tele-oncology care navigation delivery. Although the program is still in early phases, it has improved care coordination for Veterans with breast and gynecologic cancers across the United States.
Background
The VA National Oncology Program (NOP) Breast and Gynecologic Oncology System of Excellence (BGSOE) aims to ensure that Veterans with breast and gynecologic cancers receive state-of-the-art, guidelineadherent, Veteran-centric, timely, and well-coordinated care. Achieving these aims relies on a national multidisciplinary Cancer Care Navigation Team that provides tele-oncology navigation services. The teams connect with Veterans to identify and support clinical, psychological, system, coordination-related needs. To assist the navigation team to find these relatively rare diagnoses within VA, we developed a health informatics tool (HIT) that automatically identifies patients with breast or gynecologic cancers, displays demographic and clinical information, and facilitates systematic needs assessment and care coordination and tracking.
Methods
We used multiple frameworks to ensure alignment between HIT mission and coordinator workflow. A separate view was provided for each phase of the workflow: assessment of Veteran eligibility, intake assessment, and care coordination and tracking. Algorithmic identification of candidate Veterans was validated to ensure coordinators were not inundated with information on Veterans outside the scope of the program. User interface was implemented in accordance with Lean principles applied to HIT design, with close attention to information inventory, efficient user motion, information transportation, and avoidance of overprocessing.
Results
From January 1, 2021, to March 6, 2024, the HIT captured 5,561 breast cancer and 1,663 gynecologic cancer patients. 908 patients were reviewed by the coordinator, of whom 817 patients had a correct diagnosis assigned by the screening algorithm. From these, 332 patients were added to the intake process. The intake process is pending for 207 patients and complete for 102 patients; 23 patients declined intake. For patients who have completed intake, we have captured information that includes Veteran demographics, social history, insurance details, medical history, family history, hazards, barriers, and information specific to BGSOE care coordination.
Conclusions
We applied a novel framework to design and implement mission-driven, workflow-aligned HIT that achieves high user efficiency using Lean principles. This facilitated an exciting new model in tele-oncology care navigation delivery. Although the program is still in early phases, it has improved care coordination for Veterans with breast and gynecologic cancers across the United States.
A Phase II Study With Androgen Deprivation Therapy and Up-Front Radiotherapy in High-Intermediate and High-Risk Prostate Cancer With Stereotactic Body Radiation Therapy to Pelvic Nodes and Concomitant Prostate Boost by Simultaneous Integrated Boost
Background
The adoption of Stereotactic Body Radiation Therapy (SBRT) for prostate cancer has allowed treatment to be completed in less than 2 weeks, but has predominantly been given to the prostate only. Currently, very few prospective studies have compared delivery of SBRT versus hypofractionated radiotherapy (HFX) when giving concurrent pelvic radiation. The aim of the study is to evaluate the tolerance and efficacy of pelvic node radiotherapy and SIB to the prostate in prostate patients requiring nodal irradiation.
Methods
A total of 58 patients were irradiated with SBRT and initiated ADT therapy between 2014 and 2023. 57 patients were treated with 7.5 Gy to the prostate and 1 to 7.25 Gy. All patients were treated with 5 Gy x 5 fraction to the pelvis. This group was compared to a preselected historical cohort of 65 HFX patients with 57 of these patients treated with 67.5/50 Gy in 25 fractions, 1 with patient 67.5/45 Gy in 25 fractions, and 6 patients with 60/44-46 Gy in 20 fractions. Patients were evaluated for GU and GI toxicities according to Radiation Therapy Oncology Group Toxicity criteria at one year post radiation therapy.
Results
There were 31 grade 0 (53.4%), 1 grade 1 (1.7%), 25 grade 2 (43.1%), 1 grade 3 (1.7%) events in the SBRT group and 29 GU grade 0 (44.6%), 3 grade 1 (4.6%), and 33 grade 2 (50.8%) GU toxicities in the HFX group with no significant difference between the groups (p=0.464). There were 55 grade 0 (94.8%), 1 grade 1 (1.7%), and 2 grade 2 (3.4%) GI toxicities in the SBRT group and 59 grade 0 (90.8%), 1 grade 1 (1.5%), and 5 grade 2 (7.7%) events in the HFX group with no significant difference between the groups (p=0.381).
Conclusions
This prospective study provides data to support the use of concurrent pelvic radiation with SBRT to the prostate. Our findings suggest there is no difference in toxicity between HFX and 25 Gy pelvic radiation (5 Gy/5 fractions) concurrent with SBRT to the prostate, therefore it appears to be a safe and convenient option for veterans with prostate cancer.
Background
The adoption of Stereotactic Body Radiation Therapy (SBRT) for prostate cancer has allowed treatment to be completed in less than 2 weeks, but has predominantly been given to the prostate only. Currently, very few prospective studies have compared delivery of SBRT versus hypofractionated radiotherapy (HFX) when giving concurrent pelvic radiation. The aim of the study is to evaluate the tolerance and efficacy of pelvic node radiotherapy and SIB to the prostate in prostate patients requiring nodal irradiation.
Methods
A total of 58 patients were irradiated with SBRT and initiated ADT therapy between 2014 and 2023. 57 patients were treated with 7.5 Gy to the prostate and 1 to 7.25 Gy. All patients were treated with 5 Gy x 5 fraction to the pelvis. This group was compared to a preselected historical cohort of 65 HFX patients with 57 of these patients treated with 67.5/50 Gy in 25 fractions, 1 with patient 67.5/45 Gy in 25 fractions, and 6 patients with 60/44-46 Gy in 20 fractions. Patients were evaluated for GU and GI toxicities according to Radiation Therapy Oncology Group Toxicity criteria at one year post radiation therapy.
Results
There were 31 grade 0 (53.4%), 1 grade 1 (1.7%), 25 grade 2 (43.1%), 1 grade 3 (1.7%) events in the SBRT group and 29 GU grade 0 (44.6%), 3 grade 1 (4.6%), and 33 grade 2 (50.8%) GU toxicities in the HFX group with no significant difference between the groups (p=0.464). There were 55 grade 0 (94.8%), 1 grade 1 (1.7%), and 2 grade 2 (3.4%) GI toxicities in the SBRT group and 59 grade 0 (90.8%), 1 grade 1 (1.5%), and 5 grade 2 (7.7%) events in the HFX group with no significant difference between the groups (p=0.381).
Conclusions
This prospective study provides data to support the use of concurrent pelvic radiation with SBRT to the prostate. Our findings suggest there is no difference in toxicity between HFX and 25 Gy pelvic radiation (5 Gy/5 fractions) concurrent with SBRT to the prostate, therefore it appears to be a safe and convenient option for veterans with prostate cancer.
Background
The adoption of Stereotactic Body Radiation Therapy (SBRT) for prostate cancer has allowed treatment to be completed in less than 2 weeks, but has predominantly been given to the prostate only. Currently, very few prospective studies have compared delivery of SBRT versus hypofractionated radiotherapy (HFX) when giving concurrent pelvic radiation. The aim of the study is to evaluate the tolerance and efficacy of pelvic node radiotherapy and SIB to the prostate in prostate patients requiring nodal irradiation.
Methods
A total of 58 patients were irradiated with SBRT and initiated ADT therapy between 2014 and 2023. 57 patients were treated with 7.5 Gy to the prostate and 1 to 7.25 Gy. All patients were treated with 5 Gy x 5 fraction to the pelvis. This group was compared to a preselected historical cohort of 65 HFX patients with 57 of these patients treated with 67.5/50 Gy in 25 fractions, 1 with patient 67.5/45 Gy in 25 fractions, and 6 patients with 60/44-46 Gy in 20 fractions. Patients were evaluated for GU and GI toxicities according to Radiation Therapy Oncology Group Toxicity criteria at one year post radiation therapy.
Results
There were 31 grade 0 (53.4%), 1 grade 1 (1.7%), 25 grade 2 (43.1%), 1 grade 3 (1.7%) events in the SBRT group and 29 GU grade 0 (44.6%), 3 grade 1 (4.6%), and 33 grade 2 (50.8%) GU toxicities in the HFX group with no significant difference between the groups (p=0.464). There were 55 grade 0 (94.8%), 1 grade 1 (1.7%), and 2 grade 2 (3.4%) GI toxicities in the SBRT group and 59 grade 0 (90.8%), 1 grade 1 (1.5%), and 5 grade 2 (7.7%) events in the HFX group with no significant difference between the groups (p=0.381).
Conclusions
This prospective study provides data to support the use of concurrent pelvic radiation with SBRT to the prostate. Our findings suggest there is no difference in toxicity between HFX and 25 Gy pelvic radiation (5 Gy/5 fractions) concurrent with SBRT to the prostate, therefore it appears to be a safe and convenient option for veterans with prostate cancer.
Do Clonal Hematopoiesis and Mosaic Chromosomal Alterations Increase Solid Tumor Risk?
Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.
These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
How This Study Differs From Others of Breast Cancer Risk Factors
“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.
In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.
But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.
“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”
In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?
To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.
In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.
More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.
The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.
“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.
“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.
“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.
Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
How Do Findings Compare With Those of the UK Biobank Study?
CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.
In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.
“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.
As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.
Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).
The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.
The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.
She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
Why Do Results Differ Between These Types of Studies?
Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.
“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.
“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.
Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?
“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”
Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.
“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
Future research and therapeutic development
Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.
“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.
Available data support both possibilities.
On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.
When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”
The presence of a causal association could be promising from a therapeutic standpoint.
“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.
Yet earlier intervention may still hold promise, according to experts.
“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.
The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.
A version of this article first appeared on Medscape.com.
Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.
These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
How This Study Differs From Others of Breast Cancer Risk Factors
“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.
In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.
But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.
“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”
In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?
To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.
In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.
More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.
The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.
“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.
“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.
“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.
Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
How Do Findings Compare With Those of the UK Biobank Study?
CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.
In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.
“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.
As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.
Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).
The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.
The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.
She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
Why Do Results Differ Between These Types of Studies?
Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.
“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.
“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.
Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?
“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”
Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.
“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
Future research and therapeutic development
Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.
“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.
Available data support both possibilities.
On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.
When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”
The presence of a causal association could be promising from a therapeutic standpoint.
“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.
Yet earlier intervention may still hold promise, according to experts.
“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.
The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.
A version of this article first appeared on Medscape.com.
Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.
These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
How This Study Differs From Others of Breast Cancer Risk Factors
“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.
In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.
But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.
“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”
In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?
To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.
In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.
More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.
The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.
“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.
“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.
“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.
Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
How Do Findings Compare With Those of the UK Biobank Study?
CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.
In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.
“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.
As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.
Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).
The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.
The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.
She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
Why Do Results Differ Between These Types of Studies?
Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.
“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.
“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.
Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?
“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”
Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.
“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
Future research and therapeutic development
Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.
“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.
Available data support both possibilities.
On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.
When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”
The presence of a causal association could be promising from a therapeutic standpoint.
“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.
Yet earlier intervention may still hold promise, according to experts.
“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.
The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.
A version of this article first appeared on Medscape.com.
FROM CANCER