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The incidence of metastatic colorectal cancer (mCRC) among adults younger than 50 years has been increasing, and although younger patients are treated with aggressive regimens similarly to older patients, outcomes data, including incidence of toxic effects, across age groups are limited, wrote Lingbin Meng, MD, of H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla., and colleagues, in their paper on the new research.
“Studies on the age-related disparity ... provided mixed findings,” said corresponding author Hao Xie, MD, of the Mayo Clinic in Rochester, Minn., in an interview.
According to the paper, published in JAMA Network Open, the researchers sought to evaluate the association between age and mCRC treatment-related adverse events and survival.
The study population included 1,223 mCRC patients who underwent first-line treatment with fluorouracil and oxaliplatin therapy in three clinical trials. An additional 736 patients with mCRC from the Moffitt Cancer Center were used to assess genomic alterations and serve as an external validation cohort.
Methods and results
Patients were divided into three age groups: younger than 50 years, 50-65 years, and 65 years and older. Early onset was defined as younger than 50 years. Approximately 58% of the study population was male.
The primary outcomes were treatment-related adverse events and survival rates. Overall survival (OS) and progression-free survival (PFS) were was significantly shorter in the early-onset group, compared with the 50-65 years group (hazard ratios, 1.48 and 1.46, respectively, P < .001 for both) in a multivariate analysis. The shorter OS in the early-onset group was confirmed in the validation cohort.
The early-onset patients had significantly higher incidence of nausea and vomiting, severe abdominal pain, severe anemia, and severe rash, compared with patients in both the 50- to 65-year-old group and the older than 65 years group. In addition, abdominal pain and severe liver toxicity effects were associated with shorter survival in the early-onset patients.
Genomic data from the Moffitt cohort showed a higher prevalence of CTNNB1 mutation among patients younger than 50 years, compared with the 50- to 65-year-old group and the older than 65 years group (6.6%, 3.1%, and 2.3%, respectively; P = .047), as well as ERBB2 amplification (5.1%, 0.6%, and 2.3%, respectively; P = .005), and CREBBP mutation (3.1%, 0.9%, and 0.5%; P = .05), although the prevalence of BRAF mutation was significantly lower in the younger patients, compared with patients in the older groups (7.7%, 8.5%, and 16.7%, respectively; P = .002).
These data suggest that distinct genomic profiles may play a role in the worse outcomes for patients with early-onset mCRC, the researchers said.
The findings were limited by several factors, including the timing of the trials prior to the use of biologics as standard first-line therapy, the researchers noted. Other limitations include a lack of data on treatment adherence and intensity and the location and number of metastases, and potential limited generalizability to other populations given that the majority of the participants were white, they said.
Data support individualized treatment
“We were surprised to find that patients with early-onset metastatic colorectal cancer had worse survival outcome, compared to older patients with metastatic colorectal cancer,” Dr. Xie said, in an interview. “On the other hand, we were not surprised to find unique adverse-event patterns in patients with early-onset metastatic colorectal cancer.”
For clinicians, “The take home message is that we should adopt individualized management approaches [regarding] cancer-direct treatments and treatment-related side effects in patients with early-onset metastatic colorectal cancer,” said Dr. Xie. However, more research is needed in the form of prospective and interventional studies to address treatment-related side effects and to develop novel and personalized therapeutics for patients with early-onset metastatic colorectal cancer, Dr. Xie added.
Early-onset cancer concerns persist
“The increasing shift in early colon cancers demands better understanding, in particular as we attempt a more patient-focused approach to treatments,” said David A. Johnson, MD, chief of gastroenterology at Eastern Virginia Medical School, Norfolk, in an interview. “Clearly, genetic amplifications and oncogene mutations play an essential role in tumorigenesis and tumor progression, but data on specifics are needed.”
With regard to the current study, “it makes sense that the pathways to CRC development and progression at least in part play a role in age-related cancers,” said Dr. Johnson, who was not involved in the study.
The clinical implications from the study are that early-onset CRC “can be aggressive and progressive,” Dr. Johnson said. “Younger patients need to recognize the earlier ages for beginning CRC screening, age 45 years for those at average risk, and certainly report any new sign or symptom to their care provider, in particular blood in the stool.”
As for additional research, “The oncogenetic markers will be helpful in guiding treatment approaches to be more individual specific, rather than just disease focused,” Dr. Johnson said. “The role of the gut microbiome will need evaluation as it relates to these oncogenetic factors,” he noted. Considerations include not only the potential influence of the gut microbiome on the expression of these factors, but also the impact of the gut microbiome on the chemotherapeutic response, as has been evident with checkpoint inhibitors, he added.
The study was supported by a Moffitt Support Grant to Dr. Xie and the University of South Florida Continuing Medical Education Funding. The researchers had no financial conflicts to disclose. Dr. Johnson had no relevant financial conflicts to disclose.
The incidence of metastatic colorectal cancer (mCRC) among adults younger than 50 years has been increasing, and although younger patients are treated with aggressive regimens similarly to older patients, outcomes data, including incidence of toxic effects, across age groups are limited, wrote Lingbin Meng, MD, of H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla., and colleagues, in their paper on the new research.
“Studies on the age-related disparity ... provided mixed findings,” said corresponding author Hao Xie, MD, of the Mayo Clinic in Rochester, Minn., in an interview.
According to the paper, published in JAMA Network Open, the researchers sought to evaluate the association between age and mCRC treatment-related adverse events and survival.
The study population included 1,223 mCRC patients who underwent first-line treatment with fluorouracil and oxaliplatin therapy in three clinical trials. An additional 736 patients with mCRC from the Moffitt Cancer Center were used to assess genomic alterations and serve as an external validation cohort.
Methods and results
Patients were divided into three age groups: younger than 50 years, 50-65 years, and 65 years and older. Early onset was defined as younger than 50 years. Approximately 58% of the study population was male.
The primary outcomes were treatment-related adverse events and survival rates. Overall survival (OS) and progression-free survival (PFS) were was significantly shorter in the early-onset group, compared with the 50-65 years group (hazard ratios, 1.48 and 1.46, respectively, P < .001 for both) in a multivariate analysis. The shorter OS in the early-onset group was confirmed in the validation cohort.
The early-onset patients had significantly higher incidence of nausea and vomiting, severe abdominal pain, severe anemia, and severe rash, compared with patients in both the 50- to 65-year-old group and the older than 65 years group. In addition, abdominal pain and severe liver toxicity effects were associated with shorter survival in the early-onset patients.
Genomic data from the Moffitt cohort showed a higher prevalence of CTNNB1 mutation among patients younger than 50 years, compared with the 50- to 65-year-old group and the older than 65 years group (6.6%, 3.1%, and 2.3%, respectively; P = .047), as well as ERBB2 amplification (5.1%, 0.6%, and 2.3%, respectively; P = .005), and CREBBP mutation (3.1%, 0.9%, and 0.5%; P = .05), although the prevalence of BRAF mutation was significantly lower in the younger patients, compared with patients in the older groups (7.7%, 8.5%, and 16.7%, respectively; P = .002).
These data suggest that distinct genomic profiles may play a role in the worse outcomes for patients with early-onset mCRC, the researchers said.
The findings were limited by several factors, including the timing of the trials prior to the use of biologics as standard first-line therapy, the researchers noted. Other limitations include a lack of data on treatment adherence and intensity and the location and number of metastases, and potential limited generalizability to other populations given that the majority of the participants were white, they said.
Data support individualized treatment
“We were surprised to find that patients with early-onset metastatic colorectal cancer had worse survival outcome, compared to older patients with metastatic colorectal cancer,” Dr. Xie said, in an interview. “On the other hand, we were not surprised to find unique adverse-event patterns in patients with early-onset metastatic colorectal cancer.”
For clinicians, “The take home message is that we should adopt individualized management approaches [regarding] cancer-direct treatments and treatment-related side effects in patients with early-onset metastatic colorectal cancer,” said Dr. Xie. However, more research is needed in the form of prospective and interventional studies to address treatment-related side effects and to develop novel and personalized therapeutics for patients with early-onset metastatic colorectal cancer, Dr. Xie added.
Early-onset cancer concerns persist
“The increasing shift in early colon cancers demands better understanding, in particular as we attempt a more patient-focused approach to treatments,” said David A. Johnson, MD, chief of gastroenterology at Eastern Virginia Medical School, Norfolk, in an interview. “Clearly, genetic amplifications and oncogene mutations play an essential role in tumorigenesis and tumor progression, but data on specifics are needed.”
With regard to the current study, “it makes sense that the pathways to CRC development and progression at least in part play a role in age-related cancers,” said Dr. Johnson, who was not involved in the study.
The clinical implications from the study are that early-onset CRC “can be aggressive and progressive,” Dr. Johnson said. “Younger patients need to recognize the earlier ages for beginning CRC screening, age 45 years for those at average risk, and certainly report any new sign or symptom to their care provider, in particular blood in the stool.”
As for additional research, “The oncogenetic markers will be helpful in guiding treatment approaches to be more individual specific, rather than just disease focused,” Dr. Johnson said. “The role of the gut microbiome will need evaluation as it relates to these oncogenetic factors,” he noted. Considerations include not only the potential influence of the gut microbiome on the expression of these factors, but also the impact of the gut microbiome on the chemotherapeutic response, as has been evident with checkpoint inhibitors, he added.
The study was supported by a Moffitt Support Grant to Dr. Xie and the University of South Florida Continuing Medical Education Funding. The researchers had no financial conflicts to disclose. Dr. Johnson had no relevant financial conflicts to disclose.
The incidence of metastatic colorectal cancer (mCRC) among adults younger than 50 years has been increasing, and although younger patients are treated with aggressive regimens similarly to older patients, outcomes data, including incidence of toxic effects, across age groups are limited, wrote Lingbin Meng, MD, of H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla., and colleagues, in their paper on the new research.
“Studies on the age-related disparity ... provided mixed findings,” said corresponding author Hao Xie, MD, of the Mayo Clinic in Rochester, Minn., in an interview.
According to the paper, published in JAMA Network Open, the researchers sought to evaluate the association between age and mCRC treatment-related adverse events and survival.
The study population included 1,223 mCRC patients who underwent first-line treatment with fluorouracil and oxaliplatin therapy in three clinical trials. An additional 736 patients with mCRC from the Moffitt Cancer Center were used to assess genomic alterations and serve as an external validation cohort.
Methods and results
Patients were divided into three age groups: younger than 50 years, 50-65 years, and 65 years and older. Early onset was defined as younger than 50 years. Approximately 58% of the study population was male.
The primary outcomes were treatment-related adverse events and survival rates. Overall survival (OS) and progression-free survival (PFS) were was significantly shorter in the early-onset group, compared with the 50-65 years group (hazard ratios, 1.48 and 1.46, respectively, P < .001 for both) in a multivariate analysis. The shorter OS in the early-onset group was confirmed in the validation cohort.
The early-onset patients had significantly higher incidence of nausea and vomiting, severe abdominal pain, severe anemia, and severe rash, compared with patients in both the 50- to 65-year-old group and the older than 65 years group. In addition, abdominal pain and severe liver toxicity effects were associated with shorter survival in the early-onset patients.
Genomic data from the Moffitt cohort showed a higher prevalence of CTNNB1 mutation among patients younger than 50 years, compared with the 50- to 65-year-old group and the older than 65 years group (6.6%, 3.1%, and 2.3%, respectively; P = .047), as well as ERBB2 amplification (5.1%, 0.6%, and 2.3%, respectively; P = .005), and CREBBP mutation (3.1%, 0.9%, and 0.5%; P = .05), although the prevalence of BRAF mutation was significantly lower in the younger patients, compared with patients in the older groups (7.7%, 8.5%, and 16.7%, respectively; P = .002).
These data suggest that distinct genomic profiles may play a role in the worse outcomes for patients with early-onset mCRC, the researchers said.
The findings were limited by several factors, including the timing of the trials prior to the use of biologics as standard first-line therapy, the researchers noted. Other limitations include a lack of data on treatment adherence and intensity and the location and number of metastases, and potential limited generalizability to other populations given that the majority of the participants were white, they said.
Data support individualized treatment
“We were surprised to find that patients with early-onset metastatic colorectal cancer had worse survival outcome, compared to older patients with metastatic colorectal cancer,” Dr. Xie said, in an interview. “On the other hand, we were not surprised to find unique adverse-event patterns in patients with early-onset metastatic colorectal cancer.”
For clinicians, “The take home message is that we should adopt individualized management approaches [regarding] cancer-direct treatments and treatment-related side effects in patients with early-onset metastatic colorectal cancer,” said Dr. Xie. However, more research is needed in the form of prospective and interventional studies to address treatment-related side effects and to develop novel and personalized therapeutics for patients with early-onset metastatic colorectal cancer, Dr. Xie added.
Early-onset cancer concerns persist
“The increasing shift in early colon cancers demands better understanding, in particular as we attempt a more patient-focused approach to treatments,” said David A. Johnson, MD, chief of gastroenterology at Eastern Virginia Medical School, Norfolk, in an interview. “Clearly, genetic amplifications and oncogene mutations play an essential role in tumorigenesis and tumor progression, but data on specifics are needed.”
With regard to the current study, “it makes sense that the pathways to CRC development and progression at least in part play a role in age-related cancers,” said Dr. Johnson, who was not involved in the study.
The clinical implications from the study are that early-onset CRC “can be aggressive and progressive,” Dr. Johnson said. “Younger patients need to recognize the earlier ages for beginning CRC screening, age 45 years for those at average risk, and certainly report any new sign or symptom to their care provider, in particular blood in the stool.”
As for additional research, “The oncogenetic markers will be helpful in guiding treatment approaches to be more individual specific, rather than just disease focused,” Dr. Johnson said. “The role of the gut microbiome will need evaluation as it relates to these oncogenetic factors,” he noted. Considerations include not only the potential influence of the gut microbiome on the expression of these factors, but also the impact of the gut microbiome on the chemotherapeutic response, as has been evident with checkpoint inhibitors, he added.
The study was supported by a Moffitt Support Grant to Dr. Xie and the University of South Florida Continuing Medical Education Funding. The researchers had no financial conflicts to disclose. Dr. Johnson had no relevant financial conflicts to disclose.
FROM JAMA NETWORK OPEN