After endoscopic resection, high-risk T1 colorectal cancer (CRC) may have a tenfold greater risk of recurrence than low-risk disease, based on a meta-analysis involving more than 5,000 patients.

These findings support personalized, histologically based surveillance strategies following endoscopic resection of T1 CRC, reported lead author Hao Dang of Leiden University Medical Center in the Netherlands, and colleagues.

“With the introduction of population-based screening programs, a growing number of early-invasive colorectal cancers (T1 CRCs) are detected and treated with local endoscopic resection,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Success with this approach, however, depends upon accurate risk recurrence data, which have been lacking.

Joseph Feuerstein, MD, of the department of medicine at Harvard Medical School, Boston, and associate clinical chief of gastroenterology at Beth Israel Deaconess Medical Center, Boston, said, “While attempting complete resection of an early cancer with a colonoscopy is appealing, given the very low morbidity associated with it, this technique is only advisable if the risk of recurrence is extremely low when comparing [it] to surgical resection.”

In addition to patient selection, accurate recurrence data could also inform postoperative surveillance.

“To determine the optimal frequency and method of surveillance, it is important to know how often, and at which moments in follow-up local or distant CRC recurrences exactly occur,” wrote Mr. Dang and colleagues. “However, for endoscopically treated T1 CRC patients, the definite answers to these questions have not yet been provided.”

To find answers, Mr. Dang and colleagues conducted a meta-analysis involving 71 studies and 5,167 patients with endoscopically treated T1 CRC. The primary outcome was cumulative incidence and time pattern of CRC recurrence. Data were further characterized by local and/or distant metastasis and CRC-specific mortality.

The pooled cumulative incidence of CRC recurrence was 3.3%, with local and distant recurrences occurring at similar, respective rates of 1.9% and 1.6%. Most recurrences (95.6%) occurred within 72 months of endoscopic resection.

Risk-based recurrence analysis revealed a distinct pattern, with high-risk T1 CRCs recurring at a rate of 7.0% (95% confidence interval, 4.9%-9.9%; I² = 48.1%), compared with just 0.7% for low-risk tumors (95%-CI, 0.4%-1.2%; I² = 0%). Mortality data emphasized the clinical importance of this disparity, as the CRC-related mortality rate was 1.7% across the entire population, versus 40.8% among patients with recurrence.

“Our meta-analysis provides quantitative measures of relevant follow-up outcomes, which can form the basis for evidence-based surveillance recommendations for endoscopically treated T1 CRC patients,” the investigators concluded.

According to Dr. Feuerstein, the findings highlight the importance of surveillance after endoscopic resection of CRC while adding clarity to appropriate timing.

“Current guidelines recommend a colonoscopy following a colon cancer diagnosis at 1 year and then 3 years and then every 5 years,” Dr. Feuerstein said. “Adhering to these guidelines would likely identify most cases of recurrence early on within the 72-month window identified in this study.” He noted that “high-risk T1 CRC should probably be monitored more aggressively.”

Anoop Prabhu, MD, of the department of medicine at the University of Michigan Medical Center and director of endoscopy at Ann Arbor Veterans Affairs Medical Center, drew similar conclusions from the findings, noting that “tumor histology appears to be a powerful risk-stratification tool for subsequent surveillance.”

“One of the most important take-home messages from this paper is that, in those patients with low-risk, endoscopically resected colon cancer, surveillance with a colonoscopy in 1 year (as opposed to more intense endoscopic or radiographic surveillance) is likely more than adequate and can save unnecessary testing,” Dr. Prabhu said.

To build upon these findings, Dr. Prabhu suggested that upcoming studies could directly compare different management pathways.

“A potential area for future research would be a cost-effectiveness analysis of competing surveillance strategies after upfront endoscopic resection, with a particular focus on cancer-specific survival,” he said.

The investigators disclosed relationships with Boston Scientific, Cook Medical, and Medtronics. Dr. Feuerstein and Dr. Prabhu reported no relevant conflicts of interest.

Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC. 

After endoscopic resection, high-risk T1 colorectal cancer (CRC) may have a tenfold greater risk of recurrence than low-risk disease, based on a meta-analysis involving more than 5,000 patients.

These findings support personalized, histologically based surveillance strategies following endoscopic resection of T1 CRC, reported lead author Hao Dang of Leiden University Medical Center in the Netherlands, and colleagues.

“With the introduction of population-based screening programs, a growing number of early-invasive colorectal cancers (T1 CRCs) are detected and treated with local endoscopic resection,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Success with this approach, however, depends upon accurate risk recurrence data, which have been lacking.

Joseph Feuerstein, MD, of the department of medicine at Harvard Medical School, Boston, and associate clinical chief of gastroenterology at Beth Israel Deaconess Medical Center, Boston, said, “While attempting complete resection of an early cancer with a colonoscopy is appealing, given the very low morbidity associated with it, this technique is only advisable if the risk of recurrence is extremely low when comparing [it] to surgical resection.”

In addition to patient selection, accurate recurrence data could also inform postoperative surveillance.

“To determine the optimal frequency and method of surveillance, it is important to know how often, and at which moments in follow-up local or distant CRC recurrences exactly occur,” wrote Mr. Dang and colleagues. “However, for endoscopically treated T1 CRC patients, the definite answers to these questions have not yet been provided.”

To find answers, Mr. Dang and colleagues conducted a meta-analysis involving 71 studies and 5,167 patients with endoscopically treated T1 CRC. The primary outcome was cumulative incidence and time pattern of CRC recurrence. Data were further characterized by local and/or distant metastasis and CRC-specific mortality.

The pooled cumulative incidence of CRC recurrence was 3.3%, with local and distant recurrences occurring at similar, respective rates of 1.9% and 1.6%. Most recurrences (95.6%) occurred within 72 months of endoscopic resection.

Risk-based recurrence analysis revealed a distinct pattern, with high-risk T1 CRCs recurring at a rate of 7.0% (95% confidence interval, 4.9%-9.9%; I² = 48.1%), compared with just 0.7% for low-risk tumors (95%-CI, 0.4%-1.2%; I² = 0%). Mortality data emphasized the clinical importance of this disparity, as the CRC-related mortality rate was 1.7% across the entire population, versus 40.8% among patients with recurrence.

“Our meta-analysis provides quantitative measures of relevant follow-up outcomes, which can form the basis for evidence-based surveillance recommendations for endoscopically treated T1 CRC patients,” the investigators concluded.

According to Dr. Feuerstein, the findings highlight the importance of surveillance after endoscopic resection of CRC while adding clarity to appropriate timing.

“Current guidelines recommend a colonoscopy following a colon cancer diagnosis at 1 year and then 3 years and then every 5 years,” Dr. Feuerstein said. “Adhering to these guidelines would likely identify most cases of recurrence early on within the 72-month window identified in this study.” He noted that “high-risk T1 CRC should probably be monitored more aggressively.”

Anoop Prabhu, MD, of the department of medicine at the University of Michigan Medical Center and director of endoscopy at Ann Arbor Veterans Affairs Medical Center, drew similar conclusions from the findings, noting that “tumor histology appears to be a powerful risk-stratification tool for subsequent surveillance.”

“One of the most important take-home messages from this paper is that, in those patients with low-risk, endoscopically resected colon cancer, surveillance with a colonoscopy in 1 year (as opposed to more intense endoscopic or radiographic surveillance) is likely more than adequate and can save unnecessary testing,” Dr. Prabhu said.

To build upon these findings, Dr. Prabhu suggested that upcoming studies could directly compare different management pathways.

“A potential area for future research would be a cost-effectiveness analysis of competing surveillance strategies after upfront endoscopic resection, with a particular focus on cancer-specific survival,” he said.

The investigators disclosed relationships with Boston Scientific, Cook Medical, and Medtronics. Dr. Feuerstein and Dr. Prabhu reported no relevant conflicts of interest.

Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC. 

After endoscopic resection, high-risk T1 colorectal cancer (CRC) may have a tenfold greater risk of recurrence than low-risk disease, based on a meta-analysis involving more than 5,000 patients.

These findings support personalized, histologically based surveillance strategies following endoscopic resection of T1 CRC, reported lead author Hao Dang of Leiden University Medical Center in the Netherlands, and colleagues.

“With the introduction of population-based screening programs, a growing number of early-invasive colorectal cancers (T1 CRCs) are detected and treated with local endoscopic resection,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Success with this approach, however, depends upon accurate risk recurrence data, which have been lacking.

Joseph Feuerstein, MD, of the department of medicine at Harvard Medical School, Boston, and associate clinical chief of gastroenterology at Beth Israel Deaconess Medical Center, Boston, said, “While attempting complete resection of an early cancer with a colonoscopy is appealing, given the very low morbidity associated with it, this technique is only advisable if the risk of recurrence is extremely low when comparing [it] to surgical resection.”

In addition to patient selection, accurate recurrence data could also inform postoperative surveillance.

“To determine the optimal frequency and method of surveillance, it is important to know how often, and at which moments in follow-up local or distant CRC recurrences exactly occur,” wrote Mr. Dang and colleagues. “However, for endoscopically treated T1 CRC patients, the definite answers to these questions have not yet been provided.”

To find answers, Mr. Dang and colleagues conducted a meta-analysis involving 71 studies and 5,167 patients with endoscopically treated T1 CRC. The primary outcome was cumulative incidence and time pattern of CRC recurrence. Data were further characterized by local and/or distant metastasis and CRC-specific mortality.

The pooled cumulative incidence of CRC recurrence was 3.3%, with local and distant recurrences occurring at similar, respective rates of 1.9% and 1.6%. Most recurrences (95.6%) occurred within 72 months of endoscopic resection.

Risk-based recurrence analysis revealed a distinct pattern, with high-risk T1 CRCs recurring at a rate of 7.0% (95% confidence interval, 4.9%-9.9%; I² = 48.1%), compared with just 0.7% for low-risk tumors (95%-CI, 0.4%-1.2%; I² = 0%). Mortality data emphasized the clinical importance of this disparity, as the CRC-related mortality rate was 1.7% across the entire population, versus 40.8% among patients with recurrence.

“Our meta-analysis provides quantitative measures of relevant follow-up outcomes, which can form the basis for evidence-based surveillance recommendations for endoscopically treated T1 CRC patients,” the investigators concluded.

According to Dr. Feuerstein, the findings highlight the importance of surveillance after endoscopic resection of CRC while adding clarity to appropriate timing.

“Current guidelines recommend a colonoscopy following a colon cancer diagnosis at 1 year and then 3 years and then every 5 years,” Dr. Feuerstein said. “Adhering to these guidelines would likely identify most cases of recurrence early on within the 72-month window identified in this study.” He noted that “high-risk T1 CRC should probably be monitored more aggressively.”

Anoop Prabhu, MD, of the department of medicine at the University of Michigan Medical Center and director of endoscopy at Ann Arbor Veterans Affairs Medical Center, drew similar conclusions from the findings, noting that “tumor histology appears to be a powerful risk-stratification tool for subsequent surveillance.”

“One of the most important take-home messages from this paper is that, in those patients with low-risk, endoscopically resected colon cancer, surveillance with a colonoscopy in 1 year (as opposed to more intense endoscopic or radiographic surveillance) is likely more than adequate and can save unnecessary testing,” Dr. Prabhu said.

To build upon these findings, Dr. Prabhu suggested that upcoming studies could directly compare different management pathways.

“A potential area for future research would be a cost-effectiveness analysis of competing surveillance strategies after upfront endoscopic resection, with a particular focus on cancer-specific survival,” he said.

The investigators disclosed relationships with Boston Scientific, Cook Medical, and Medtronics. Dr. Feuerstein and Dr. Prabhu reported no relevant conflicts of interest.

Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC. 

Many scientific problems are complex. Finding the solution can require the concerted efforts of a team. Producing a vaccine for COVID-19 involved a multidisciplinary team with a variety of highly specialized expertises, extensive technological resources, and a history of previous scientific discoveries upon whose shoulders today’s scientists can stand.

Many ethical problems are also complex. Finding the ideal, multifaceted answer that addresses all the nuances of a social problem requires brilliant minds, a refined ability for logical analysis and rhetoric, the empowerment of the voices of all stakeholders, and attention to social values such as diversity and justice.

In both endeavors, the typical scientists and ethicists involved tend to presume that if they can determine an ideal solution, it will be rapidly and enthusiastically adopted and implemented for the betterment of society. That is, after all, exactly how those researchers would choose to act. Scientists see moral actions as having two steps. The hard part is deciding what is right. Doing the right thing is the easier task. This delusion is ubiquitous. Many scientists and ethicists recognize the delusion of the existence of a rational society, but proceed anyhow as if one exists.

There is a chorus of voices capable of debunking this delusion. Any priest who hears confessions will testify that the vast majority of harm comes from the failure to do what people already know is right, not from uncertainty, confusion, or ignorance. Psychologists and substance abuse counselors are inundated with people who are stuck doing harmful and self-destructive acts. Internists discuss diet and exercise with their patients, but find the advice is infrequently adopted. Master in business administration programs are devoted to training graduates in methods of motivating people to do what is right.

The response of the scientific establishment to the COVID-19 pandemic was imperfect. There were gaps in knowledge and some early information from China was misleading. The initial CDC test kit production was flawed. The early appeal for the public not to buy masks was strongly driven by a desire to preserve supplies for health care workers. Despite these missteps, the overall advice of scientists was wildly successful and beneficial. The goal was to flatten the curve, and a comparison of the April-June time frame with the November-January period shows markedly fewer COVID-19 cases, hospitalizations, and deaths. Confronted with the pandemic of the century, my assessment is that scientific establishment has performed well.

I am far more negative in my assessment of the institutions that support morality, form the social order, establish justice, and promote the general welfare. For instance, misinformation on social media is rampant, including conspiracy theories and outright denials of the pandemic. Scientific advice has been undercut and impugned. Policy recommendations of esteemed scientific institutions have been ignored. The public’s cooperation has fatigued. Laws on public gatherings, quarantines, and social distancing have been broken. Communitarian ethics and devotion to the common good have been left in a trash heap. The consequences have been hundreds of thousands of lives lost in 2020 and some states are on the brink of much worse.

Medical ethicists have debated in fine detail how to triage ventilators, ration antibody treatments, and prioritize vaccinations. Those policy recommendations have had limited influence. Medical ethics has inadequately addressed the age old problem of morality, which is getting people to behave as they know they ought. Modern medical ethics may have exacerbated the deviancy. Medical ethics for 50 years has emphasized replacing paternalism with autonomy, but it has not adequately promoted communitarian virtues, self-regulation, and personal integrity.

There were many accomplishments and many people to admire in 2020 when compared to historical actions by the health care professionals during crises. Doctors, confronted with the COVID-19 plague, have not abandoned the cities as happened in prior centuries. Patients have not been shunned like lepers, though the total-body protective equipment and the no-visitor policies come very close. Nurses have heroically provided bedside care, though I am haunted by one dissident nurse during a protest carrying a sign saying “Don’t call me a hero. I am being martyred against my will.”

As a scientist, I am prone to the delusion that, if I can build a better mouse trap, people will use it. I’ve lived with that delusion for decades. It carries over into my medical ethics work. Yet I see hospitals in California being overwhelmed by the surge on top of a surge due to unwise and unsafe holiday travel. I can see that optimized solutions aren’t the answer – it is better behavior by the public. I recall when I was a child, my mother would simply command, “Behave yourself.” And never, in any of those recollections, was I in doubt about which correct behavior she meant.
 

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

Many scientific problems are complex. Finding the solution can require the concerted efforts of a team. Producing a vaccine for COVID-19 involved a multidisciplinary team with a variety of highly specialized expertises, extensive technological resources, and a history of previous scientific discoveries upon whose shoulders today’s scientists can stand.

Many ethical problems are also complex. Finding the ideal, multifaceted answer that addresses all the nuances of a social problem requires brilliant minds, a refined ability for logical analysis and rhetoric, the empowerment of the voices of all stakeholders, and attention to social values such as diversity and justice.

In both endeavors, the typical scientists and ethicists involved tend to presume that if they can determine an ideal solution, it will be rapidly and enthusiastically adopted and implemented for the betterment of society. That is, after all, exactly how those researchers would choose to act. Scientists see moral actions as having two steps. The hard part is deciding what is right. Doing the right thing is the easier task. This delusion is ubiquitous. Many scientists and ethicists recognize the delusion of the existence of a rational society, but proceed anyhow as if one exists.

There is a chorus of voices capable of debunking this delusion. Any priest who hears confessions will testify that the vast majority of harm comes from the failure to do what people already know is right, not from uncertainty, confusion, or ignorance. Psychologists and substance abuse counselors are inundated with people who are stuck doing harmful and self-destructive acts. Internists discuss diet and exercise with their patients, but find the advice is infrequently adopted. Master in business administration programs are devoted to training graduates in methods of motivating people to do what is right.

The response of the scientific establishment to the COVID-19 pandemic was imperfect. There were gaps in knowledge and some early information from China was misleading. The initial CDC test kit production was flawed. The early appeal for the public not to buy masks was strongly driven by a desire to preserve supplies for health care workers. Despite these missteps, the overall advice of scientists was wildly successful and beneficial. The goal was to flatten the curve, and a comparison of the April-June time frame with the November-January period shows markedly fewer COVID-19 cases, hospitalizations, and deaths. Confronted with the pandemic of the century, my assessment is that scientific establishment has performed well.

I am far more negative in my assessment of the institutions that support morality, form the social order, establish justice, and promote the general welfare. For instance, misinformation on social media is rampant, including conspiracy theories and outright denials of the pandemic. Scientific advice has been undercut and impugned. Policy recommendations of esteemed scientific institutions have been ignored. The public’s cooperation has fatigued. Laws on public gatherings, quarantines, and social distancing have been broken. Communitarian ethics and devotion to the common good have been left in a trash heap. The consequences have been hundreds of thousands of lives lost in 2020 and some states are on the brink of much worse.

Medical ethicists have debated in fine detail how to triage ventilators, ration antibody treatments, and prioritize vaccinations. Those policy recommendations have had limited influence. Medical ethics has inadequately addressed the age old problem of morality, which is getting people to behave as they know they ought. Modern medical ethics may have exacerbated the deviancy. Medical ethics for 50 years has emphasized replacing paternalism with autonomy, but it has not adequately promoted communitarian virtues, self-regulation, and personal integrity.

There were many accomplishments and many people to admire in 2020 when compared to historical actions by the health care professionals during crises. Doctors, confronted with the COVID-19 plague, have not abandoned the cities as happened in prior centuries. Patients have not been shunned like lepers, though the total-body protective equipment and the no-visitor policies come very close. Nurses have heroically provided bedside care, though I am haunted by one dissident nurse during a protest carrying a sign saying “Don’t call me a hero. I am being martyred against my will.”

As a scientist, I am prone to the delusion that, if I can build a better mouse trap, people will use it. I’ve lived with that delusion for decades. It carries over into my medical ethics work. Yet I see hospitals in California being overwhelmed by the surge on top of a surge due to unwise and unsafe holiday travel. I can see that optimized solutions aren’t the answer – it is better behavior by the public. I recall when I was a child, my mother would simply command, “Behave yourself.” And never, in any of those recollections, was I in doubt about which correct behavior she meant.
 

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

Many scientific problems are complex. Finding the solution can require the concerted efforts of a team. Producing a vaccine for COVID-19 involved a multidisciplinary team with a variety of highly specialized expertises, extensive technological resources, and a history of previous scientific discoveries upon whose shoulders today’s scientists can stand.

Many ethical problems are also complex. Finding the ideal, multifaceted answer that addresses all the nuances of a social problem requires brilliant minds, a refined ability for logical analysis and rhetoric, the empowerment of the voices of all stakeholders, and attention to social values such as diversity and justice.

In both endeavors, the typical scientists and ethicists involved tend to presume that if they can determine an ideal solution, it will be rapidly and enthusiastically adopted and implemented for the betterment of society. That is, after all, exactly how those researchers would choose to act. Scientists see moral actions as having two steps. The hard part is deciding what is right. Doing the right thing is the easier task. This delusion is ubiquitous. Many scientists and ethicists recognize the delusion of the existence of a rational society, but proceed anyhow as if one exists.

There is a chorus of voices capable of debunking this delusion. Any priest who hears confessions will testify that the vast majority of harm comes from the failure to do what people already know is right, not from uncertainty, confusion, or ignorance. Psychologists and substance abuse counselors are inundated with people who are stuck doing harmful and self-destructive acts. Internists discuss diet and exercise with their patients, but find the advice is infrequently adopted. Master in business administration programs are devoted to training graduates in methods of motivating people to do what is right.

The response of the scientific establishment to the COVID-19 pandemic was imperfect. There were gaps in knowledge and some early information from China was misleading. The initial CDC test kit production was flawed. The early appeal for the public not to buy masks was strongly driven by a desire to preserve supplies for health care workers. Despite these missteps, the overall advice of scientists was wildly successful and beneficial. The goal was to flatten the curve, and a comparison of the April-June time frame with the November-January period shows markedly fewer COVID-19 cases, hospitalizations, and deaths. Confronted with the pandemic of the century, my assessment is that scientific establishment has performed well.

I am far more negative in my assessment of the institutions that support morality, form the social order, establish justice, and promote the general welfare. For instance, misinformation on social media is rampant, including conspiracy theories and outright denials of the pandemic. Scientific advice has been undercut and impugned. Policy recommendations of esteemed scientific institutions have been ignored. The public’s cooperation has fatigued. Laws on public gatherings, quarantines, and social distancing have been broken. Communitarian ethics and devotion to the common good have been left in a trash heap. The consequences have been hundreds of thousands of lives lost in 2020 and some states are on the brink of much worse.

Medical ethicists have debated in fine detail how to triage ventilators, ration antibody treatments, and prioritize vaccinations. Those policy recommendations have had limited influence. Medical ethics has inadequately addressed the age old problem of morality, which is getting people to behave as they know they ought. Modern medical ethics may have exacerbated the deviancy. Medical ethics for 50 years has emphasized replacing paternalism with autonomy, but it has not adequately promoted communitarian virtues, self-regulation, and personal integrity.

There were many accomplishments and many people to admire in 2020 when compared to historical actions by the health care professionals during crises. Doctors, confronted with the COVID-19 plague, have not abandoned the cities as happened in prior centuries. Patients have not been shunned like lepers, though the total-body protective equipment and the no-visitor policies come very close. Nurses have heroically provided bedside care, though I am haunted by one dissident nurse during a protest carrying a sign saying “Don’t call me a hero. I am being martyred against my will.”

As a scientist, I am prone to the delusion that, if I can build a better mouse trap, people will use it. I’ve lived with that delusion for decades. It carries over into my medical ethics work. Yet I see hospitals in California being overwhelmed by the surge on top of a surge due to unwise and unsafe holiday travel. I can see that optimized solutions aren’t the answer – it is better behavior by the public. I recall when I was a child, my mother would simply command, “Behave yourself.” And never, in any of those recollections, was I in doubt about which correct behavior she meant.
 

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

Patients with knee osteoarthritis (OA) who wear stable supportive shoes for 6 months have greater average reductions in knee pain when walking, compared with patients who wear flat flexible shoes, according to a randomized trial that included more than 160 patients.

copyright Nandyphotos/Thinkstock

“Contrary to our hypothesis, flat flexible shoes were not superior to stable supportive shoes,” reported Kade L. Paterson, PhD, of the University of Melbourne, and colleagues. Their study was published Jan. 12 in Annals of Internal Medicine.
 

Research gap

Abnormal knee joint loading has been implicated in the pathogenesis of knee OA. Guidelines recommend that patients wear appropriate footwear, but research has not established which shoes are best.

The 2019 American College of Rheumatology clinical guidelines note that “optimal footwear is likely to be of considerable importance for those with knee and/or hip OA,” but “the available studies do not define the best type of footwear to improve specific outcomes for knee or hip OA.”

Some doctors call for thick, shock-absorbing soles and arch supports, based on expert opinion. On the other hand, studies have found that knee loading is lower with flat flexible shoes, and preliminary evidence has suggested that flat flexible shoes may improve OA symptoms, the investigators said.

To study this question, they enrolled in their trial 164 patients aged 50 years and older who had radiographic medial knee OA. Participants had knee pain on most days of the previous month, tibiofemoral osteophytes, and moderate to severe tibiofemoral OA.

The researchers randomly assigned 82 participants to flat flexible shoes and 82 participants to stable supportive shoes, worn for at least 6 hours a day for 6 months.

In the trial, flat flexible shoes included Merrell Bare Access (men’s and women’s), Vivobarefoot Primus Lite (men’s and women’s), Vivobarefoot Mata Canvas (men’s), Converse Dainty Low (women’s), and Lacoste Marice (men’s).

Stable supportive shoes included ASICS Kayano (men’s and women’s), Merrell Jungle Moc (men’s), Nike Air Max 90 Ultra (women’s), Rockport Edge Hill (men’s), and New Balance 624 (women’s).

After participants were randomly assigned to a group, they chose two different pairs of shoes from their assigned footwear group.

“Participants were not told that the purpose of the study was to compare flat flexible with stable supportive shoes,” the researchers noted. “Instead, they were informed only that the trial was comparing the effects of ‘different shoes’ on knee OA symptoms.”

The primary outcomes were changes in walking pain on a 0-10 scale and physical function as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index subscale at 6 months. The researchers also assessed other measures of pain and function, physical activity, and quality of life.

In all, 161 participants reported 6-month primary outcomes. The between-group difference in change in pain favored stable supportive shoes (mean difference, 1.1 units). In the flat flexible shoe group, overall average knee pain while walking decreased from 6.3 at baseline to 5.2 at 6 months. In the stable supportive shoe group, knee pain while walking decreased from 6.1 to 4.

In addition, improvements in knee-related quality of life and ipsilateral hip pain favored stable supportive shoes.

Participants who wore stable supportive shoes also were less likely to report adverse events, compared with those who wore flat flexible shoes (15% vs. 32%). Knee pain, ankle or foot pain, and shin or calf pain were among the adverse events reported.
 

‘Important work’

“This study suggests that more supportive shoes may help some patients with knee osteoarthritis feel better,” Constance R. Chu, MD, professor of orthopedic surgery at Stanford (Calif.) University, said in an interview. “Shoes, insoles, wedges, and high heels have been shown to change loading of the knee related to knee pain and osteoarthritis ... This is important work toward providing more specific information on the optimum shoes for people with different patterns and types of arthritis to reduce pain and disability from early knee OA.”

The reported changes in pain may be clinically meaningful for many but not all patients, the authors wrote. “Despite biomechanical evidence showing that flat flexible shoes reduce medial knee load compared with stable supportive shoes, our findings show that this does not translate to improved knee osteoarthritis symptoms,” they said. “This may be because relationships between knee loading and symptoms are not as strong as previously thought, or because the small reductions in medial knee load with flat flexible shoes are insufficient to substantively improve pain and function.”

The trial did not include a control group of patients who wore their usual shoes, and it focused on a select subgroup of patients with knee OA, which may limit the study’s generalizability, the authors noted. The study excluded people with lateral joint space narrowing greater than or equal to medial, those with recent or planned knee surgery, and those who were using shoe orthoses or customized shoes.

The study was supported by grants from the National Health and Medical Research Council. Dr. Chu had no relevant disclosures.

[email protected]

Patients with knee osteoarthritis (OA) who wear stable supportive shoes for 6 months have greater average reductions in knee pain when walking, compared with patients who wear flat flexible shoes, according to a randomized trial that included more than 160 patients.

copyright Nandyphotos/Thinkstock

“Contrary to our hypothesis, flat flexible shoes were not superior to stable supportive shoes,” reported Kade L. Paterson, PhD, of the University of Melbourne, and colleagues. Their study was published Jan. 12 in Annals of Internal Medicine.
 

Research gap

Abnormal knee joint loading has been implicated in the pathogenesis of knee OA. Guidelines recommend that patients wear appropriate footwear, but research has not established which shoes are best.

The 2019 American College of Rheumatology clinical guidelines note that “optimal footwear is likely to be of considerable importance for those with knee and/or hip OA,” but “the available studies do not define the best type of footwear to improve specific outcomes for knee or hip OA.”

Some doctors call for thick, shock-absorbing soles and arch supports, based on expert opinion. On the other hand, studies have found that knee loading is lower with flat flexible shoes, and preliminary evidence has suggested that flat flexible shoes may improve OA symptoms, the investigators said.

To study this question, they enrolled in their trial 164 patients aged 50 years and older who had radiographic medial knee OA. Participants had knee pain on most days of the previous month, tibiofemoral osteophytes, and moderate to severe tibiofemoral OA.

The researchers randomly assigned 82 participants to flat flexible shoes and 82 participants to stable supportive shoes, worn for at least 6 hours a day for 6 months.

In the trial, flat flexible shoes included Merrell Bare Access (men’s and women’s), Vivobarefoot Primus Lite (men’s and women’s), Vivobarefoot Mata Canvas (men’s), Converse Dainty Low (women’s), and Lacoste Marice (men’s).

Stable supportive shoes included ASICS Kayano (men’s and women’s), Merrell Jungle Moc (men’s), Nike Air Max 90 Ultra (women’s), Rockport Edge Hill (men’s), and New Balance 624 (women’s).

After participants were randomly assigned to a group, they chose two different pairs of shoes from their assigned footwear group.

“Participants were not told that the purpose of the study was to compare flat flexible with stable supportive shoes,” the researchers noted. “Instead, they were informed only that the trial was comparing the effects of ‘different shoes’ on knee OA symptoms.”

The primary outcomes were changes in walking pain on a 0-10 scale and physical function as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index subscale at 6 months. The researchers also assessed other measures of pain and function, physical activity, and quality of life.

In all, 161 participants reported 6-month primary outcomes. The between-group difference in change in pain favored stable supportive shoes (mean difference, 1.1 units). In the flat flexible shoe group, overall average knee pain while walking decreased from 6.3 at baseline to 5.2 at 6 months. In the stable supportive shoe group, knee pain while walking decreased from 6.1 to 4.

In addition, improvements in knee-related quality of life and ipsilateral hip pain favored stable supportive shoes.

Participants who wore stable supportive shoes also were less likely to report adverse events, compared with those who wore flat flexible shoes (15% vs. 32%). Knee pain, ankle or foot pain, and shin or calf pain were among the adverse events reported.
 

‘Important work’

“This study suggests that more supportive shoes may help some patients with knee osteoarthritis feel better,” Constance R. Chu, MD, professor of orthopedic surgery at Stanford (Calif.) University, said in an interview. “Shoes, insoles, wedges, and high heels have been shown to change loading of the knee related to knee pain and osteoarthritis ... This is important work toward providing more specific information on the optimum shoes for people with different patterns and types of arthritis to reduce pain and disability from early knee OA.”

The reported changes in pain may be clinically meaningful for many but not all patients, the authors wrote. “Despite biomechanical evidence showing that flat flexible shoes reduce medial knee load compared with stable supportive shoes, our findings show that this does not translate to improved knee osteoarthritis symptoms,” they said. “This may be because relationships between knee loading and symptoms are not as strong as previously thought, or because the small reductions in medial knee load with flat flexible shoes are insufficient to substantively improve pain and function.”

The trial did not include a control group of patients who wore their usual shoes, and it focused on a select subgroup of patients with knee OA, which may limit the study’s generalizability, the authors noted. The study excluded people with lateral joint space narrowing greater than or equal to medial, those with recent or planned knee surgery, and those who were using shoe orthoses or customized shoes.

The study was supported by grants from the National Health and Medical Research Council. Dr. Chu had no relevant disclosures.

[email protected]

Patients with knee osteoarthritis (OA) who wear stable supportive shoes for 6 months have greater average reductions in knee pain when walking, compared with patients who wear flat flexible shoes, according to a randomized trial that included more than 160 patients.

copyright Nandyphotos/Thinkstock

“Contrary to our hypothesis, flat flexible shoes were not superior to stable supportive shoes,” reported Kade L. Paterson, PhD, of the University of Melbourne, and colleagues. Their study was published Jan. 12 in Annals of Internal Medicine.
 

Research gap

Abnormal knee joint loading has been implicated in the pathogenesis of knee OA. Guidelines recommend that patients wear appropriate footwear, but research has not established which shoes are best.

The 2019 American College of Rheumatology clinical guidelines note that “optimal footwear is likely to be of considerable importance for those with knee and/or hip OA,” but “the available studies do not define the best type of footwear to improve specific outcomes for knee or hip OA.”

Some doctors call for thick, shock-absorbing soles and arch supports, based on expert opinion. On the other hand, studies have found that knee loading is lower with flat flexible shoes, and preliminary evidence has suggested that flat flexible shoes may improve OA symptoms, the investigators said.

To study this question, they enrolled in their trial 164 patients aged 50 years and older who had radiographic medial knee OA. Participants had knee pain on most days of the previous month, tibiofemoral osteophytes, and moderate to severe tibiofemoral OA.

The researchers randomly assigned 82 participants to flat flexible shoes and 82 participants to stable supportive shoes, worn for at least 6 hours a day for 6 months.

In the trial, flat flexible shoes included Merrell Bare Access (men’s and women’s), Vivobarefoot Primus Lite (men’s and women’s), Vivobarefoot Mata Canvas (men’s), Converse Dainty Low (women’s), and Lacoste Marice (men’s).

Stable supportive shoes included ASICS Kayano (men’s and women’s), Merrell Jungle Moc (men’s), Nike Air Max 90 Ultra (women’s), Rockport Edge Hill (men’s), and New Balance 624 (women’s).

After participants were randomly assigned to a group, they chose two different pairs of shoes from their assigned footwear group.

“Participants were not told that the purpose of the study was to compare flat flexible with stable supportive shoes,” the researchers noted. “Instead, they were informed only that the trial was comparing the effects of ‘different shoes’ on knee OA symptoms.”

The primary outcomes were changes in walking pain on a 0-10 scale and physical function as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index subscale at 6 months. The researchers also assessed other measures of pain and function, physical activity, and quality of life.

In all, 161 participants reported 6-month primary outcomes. The between-group difference in change in pain favored stable supportive shoes (mean difference, 1.1 units). In the flat flexible shoe group, overall average knee pain while walking decreased from 6.3 at baseline to 5.2 at 6 months. In the stable supportive shoe group, knee pain while walking decreased from 6.1 to 4.

In addition, improvements in knee-related quality of life and ipsilateral hip pain favored stable supportive shoes.

Participants who wore stable supportive shoes also were less likely to report adverse events, compared with those who wore flat flexible shoes (15% vs. 32%). Knee pain, ankle or foot pain, and shin or calf pain were among the adverse events reported.
 

‘Important work’

“This study suggests that more supportive shoes may help some patients with knee osteoarthritis feel better,” Constance R. Chu, MD, professor of orthopedic surgery at Stanford (Calif.) University, said in an interview. “Shoes, insoles, wedges, and high heels have been shown to change loading of the knee related to knee pain and osteoarthritis ... This is important work toward providing more specific information on the optimum shoes for people with different patterns and types of arthritis to reduce pain and disability from early knee OA.”

The reported changes in pain may be clinically meaningful for many but not all patients, the authors wrote. “Despite biomechanical evidence showing that flat flexible shoes reduce medial knee load compared with stable supportive shoes, our findings show that this does not translate to improved knee osteoarthritis symptoms,” they said. “This may be because relationships between knee loading and symptoms are not as strong as previously thought, or because the small reductions in medial knee load with flat flexible shoes are insufficient to substantively improve pain and function.”

The trial did not include a control group of patients who wore their usual shoes, and it focused on a select subgroup of patients with knee OA, which may limit the study’s generalizability, the authors noted. The study excluded people with lateral joint space narrowing greater than or equal to medial, those with recent or planned knee surgery, and those who were using shoe orthoses or customized shoes.

The study was supported by grants from the National Health and Medical Research Council. Dr. Chu had no relevant disclosures.

[email protected]

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CP-CML), steady state plasma imatinib levels, MDR1 polymorphisms, and ABC transporter expression influence early molecular response (EMR)/major molecular response (MMR) to imatinib therapy, which in turn influence failure-free survival (FFS).

Major finding: Patients with low and intermediate Sokal scores showed better 2-year FFS vs. those with high Sokal score (P = .02). Patients with variant MDR1/ABCB1-C1236T had high day 29 plasma imatinib levels (P = .005), increased EMR at 3 months (P = .044), and a better 2 year FFS (P = .003) vs. those with wild type genotype. Patients with lower ABCB1 mRNA expression showed significantly higher intracellular imatinib levels (P = .029). The median plasma imatinib level on day 29 was significantly higher in patients who achieved EMR at 3 months (P = .022) and MMR at 12 months (P = .041) which essentially resulted in better 2-year FFS (P = .05).

Study details: This prospective single center observational study evaluated factors influencing EMR to imatinib and FFS in newly diagnosed CP-CML patients (n = 160).

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Rajamani BM et al. Sci Rep. 2020 Nov 26. doi: 10.1038/s41598-020-77140-9.

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CP-CML), steady state plasma imatinib levels, MDR1 polymorphisms, and ABC transporter expression influence early molecular response (EMR)/major molecular response (MMR) to imatinib therapy, which in turn influence failure-free survival (FFS).

Major finding: Patients with low and intermediate Sokal scores showed better 2-year FFS vs. those with high Sokal score (P = .02). Patients with variant MDR1/ABCB1-C1236T had high day 29 plasma imatinib levels (P = .005), increased EMR at 3 months (P = .044), and a better 2 year FFS (P = .003) vs. those with wild type genotype. Patients with lower ABCB1 mRNA expression showed significantly higher intracellular imatinib levels (P = .029). The median plasma imatinib level on day 29 was significantly higher in patients who achieved EMR at 3 months (P = .022) and MMR at 12 months (P = .041) which essentially resulted in better 2-year FFS (P = .05).

Study details: This prospective single center observational study evaluated factors influencing EMR to imatinib and FFS in newly diagnosed CP-CML patients (n = 160).

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Rajamani BM et al. Sci Rep. 2020 Nov 26. doi: 10.1038/s41598-020-77140-9.

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CP-CML), steady state plasma imatinib levels, MDR1 polymorphisms, and ABC transporter expression influence early molecular response (EMR)/major molecular response (MMR) to imatinib therapy, which in turn influence failure-free survival (FFS).

Major finding: Patients with low and intermediate Sokal scores showed better 2-year FFS vs. those with high Sokal score (P = .02). Patients with variant MDR1/ABCB1-C1236T had high day 29 plasma imatinib levels (P = .005), increased EMR at 3 months (P = .044), and a better 2 year FFS (P = .003) vs. those with wild type genotype. Patients with lower ABCB1 mRNA expression showed significantly higher intracellular imatinib levels (P = .029). The median plasma imatinib level on day 29 was significantly higher in patients who achieved EMR at 3 months (P = .022) and MMR at 12 months (P = .041) which essentially resulted in better 2-year FFS (P = .05).

Study details: This prospective single center observational study evaluated factors influencing EMR to imatinib and FFS in newly diagnosed CP-CML patients (n = 160).

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Rajamani BM et al. Sci Rep. 2020 Nov 26. doi: 10.1038/s41598-020-77140-9.

Key clinical point: Tyrosine kinase inhibitor (TKI) therapy is associated with a higher burden of adverse events in patients with chronic myelogenous leukemia (CML). Later-generation TKIs may have greater toxicity than imatinib.

Major finding: The 5-year cumulative incidence of almost all major organ system outcomes was significantly higher for the CML + TKI vs. noncancer group (P less than .05). In the first year, later-generation TKIs vs. imatinib were associated with primary infections (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.02-2.00), circulatory events (HR, 1.15; 95% CI, 1.01-1.31), and skin issues (HR, 1.43; 95% CI, 1.13-1.80). Musculoskeletal and nervous system/sensory issues were less common with later-generation TKIs vs. imatinib (HR, 0.83-0.84; P less than .05).

Study details: This real-world analysis of health plan enrollees evaluated adverse events in CML patients treated with TKI (n = 1,200) compared with a noncancer cohort (n = 7,635; median follow-up, approximately 3 years).

Disclosures: The study was funded by Stand Up To Cancer, the American Association for Cancer Research, and the U.S. National Institutes of Health. The authors declared no conflicts of interest.

Source: Chow EJ et al. Leuk Lymphoma. 2020 Dec 7. doi: 10.1080/10428194.2020.1855340.

Key clinical point: Tyrosine kinase inhibitor (TKI) therapy is associated with a higher burden of adverse events in patients with chronic myelogenous leukemia (CML). Later-generation TKIs may have greater toxicity than imatinib.

Major finding: The 5-year cumulative incidence of almost all major organ system outcomes was significantly higher for the CML + TKI vs. noncancer group (P less than .05). In the first year, later-generation TKIs vs. imatinib were associated with primary infections (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.02-2.00), circulatory events (HR, 1.15; 95% CI, 1.01-1.31), and skin issues (HR, 1.43; 95% CI, 1.13-1.80). Musculoskeletal and nervous system/sensory issues were less common with later-generation TKIs vs. imatinib (HR, 0.83-0.84; P less than .05).

Study details: This real-world analysis of health plan enrollees evaluated adverse events in CML patients treated with TKI (n = 1,200) compared with a noncancer cohort (n = 7,635; median follow-up, approximately 3 years).

Disclosures: The study was funded by Stand Up To Cancer, the American Association for Cancer Research, and the U.S. National Institutes of Health. The authors declared no conflicts of interest.

Source: Chow EJ et al. Leuk Lymphoma. 2020 Dec 7. doi: 10.1080/10428194.2020.1855340.

Key clinical point: Tyrosine kinase inhibitor (TKI) therapy is associated with a higher burden of adverse events in patients with chronic myelogenous leukemia (CML). Later-generation TKIs may have greater toxicity than imatinib.

Major finding: The 5-year cumulative incidence of almost all major organ system outcomes was significantly higher for the CML + TKI vs. noncancer group (P less than .05). In the first year, later-generation TKIs vs. imatinib were associated with primary infections (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.02-2.00), circulatory events (HR, 1.15; 95% CI, 1.01-1.31), and skin issues (HR, 1.43; 95% CI, 1.13-1.80). Musculoskeletal and nervous system/sensory issues were less common with later-generation TKIs vs. imatinib (HR, 0.83-0.84; P less than .05).

Study details: This real-world analysis of health plan enrollees evaluated adverse events in CML patients treated with TKI (n = 1,200) compared with a noncancer cohort (n = 7,635; median follow-up, approximately 3 years).

Disclosures: The study was funded by Stand Up To Cancer, the American Association for Cancer Research, and the U.S. National Institutes of Health. The authors declared no conflicts of interest.

Source: Chow EJ et al. Leuk Lymphoma. 2020 Dec 7. doi: 10.1080/10428194.2020.1855340.

Key clinical point: Bosutinib is effective in patients with Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) resistant/intolerant to prior therapy across age groups and the Charlson Comorbidity Index score without the age component (mCCI) scores.

Major finding: A substantial proportion of patients attained or maintained molecular response across age groups and mCCI scores molecular response. Older patients and those with mCCI ≥4 showed a trend towards higher rates of grade 3/4 treatment-related adverse events.

Study details: The data come from the ongoing, phase 4, single-arm, open-label BYOND study examining the safety and efficacy of bosutinib.

Disclosures: The study was sponsored by Pfizer. No data available regarding conflicts of interest.

Source: Gambacorti-Passerini C et al. Poster. Abstract 055. BSH 2020. 2020 Nov 9-14.

Key clinical point: Bosutinib is effective in patients with Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) resistant/intolerant to prior therapy across age groups and the Charlson Comorbidity Index score without the age component (mCCI) scores.

Major finding: A substantial proportion of patients attained or maintained molecular response across age groups and mCCI scores molecular response. Older patients and those with mCCI ≥4 showed a trend towards higher rates of grade 3/4 treatment-related adverse events.

Study details: The data come from the ongoing, phase 4, single-arm, open-label BYOND study examining the safety and efficacy of bosutinib.

Disclosures: The study was sponsored by Pfizer. No data available regarding conflicts of interest.

Source: Gambacorti-Passerini C et al. Poster. Abstract 055. BSH 2020. 2020 Nov 9-14.

Key clinical point: Bosutinib is effective in patients with Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) resistant/intolerant to prior therapy across age groups and the Charlson Comorbidity Index score without the age component (mCCI) scores.

Major finding: A substantial proportion of patients attained or maintained molecular response across age groups and mCCI scores molecular response. Older patients and those with mCCI ≥4 showed a trend towards higher rates of grade 3/4 treatment-related adverse events.

Study details: The data come from the ongoing, phase 4, single-arm, open-label BYOND study examining the safety and efficacy of bosutinib.

Disclosures: The study was sponsored by Pfizer. No data available regarding conflicts of interest.

Source: Gambacorti-Passerini C et al. Poster. Abstract 055. BSH 2020. 2020 Nov 9-14.

Key clinical point: Personalized treatment selection according to the LEukemia Artificial intelligence Program (LEAP) recommendations for patients with chronic myeloid leukemia in chronic phase (CML-CP) is associated with better likelihood of survival.

Major finding: The LEAP CML-CP recommendation was associated with an improved overall survival  (P less than 001).

Study details: A cohort of CML-CP patients was randomly assigned to training/validation (n = 504) and test cohorts (n = 126). The training/validation cohort was used to develop the LEAP CML-CP model using 101 variables at diagnosis. The test cohort was then applied to the LEAP CML-CP model and an optimum tyrosine kinase inhibitor therapy was selected for each patient.

Disclosures: The study was supported by the University of Texas MD Anderson Cancer Center Support Grant from the National Institutes of Health, the National Institutes of Health/National Cancer Institute under award, the University of Texas MD Anderson MDS/AML Moon Shot, and Leukemia Texas. K Sasaki, EJ Jabbour, F Ravandi, M Konopleva, G Garcia-Manero, JE Cortes,  C DiNardo reported relationships with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Sasaki K et al. Am J Hematol. 2020 Nov 12.  doi: 10.1002/ajh.26047.

Key clinical point: Personalized treatment selection according to the LEukemia Artificial intelligence Program (LEAP) recommendations for patients with chronic myeloid leukemia in chronic phase (CML-CP) is associated with better likelihood of survival.

Major finding: The LEAP CML-CP recommendation was associated with an improved overall survival  (P less than 001).

Study details: A cohort of CML-CP patients was randomly assigned to training/validation (n = 504) and test cohorts (n = 126). The training/validation cohort was used to develop the LEAP CML-CP model using 101 variables at diagnosis. The test cohort was then applied to the LEAP CML-CP model and an optimum tyrosine kinase inhibitor therapy was selected for each patient.

Disclosures: The study was supported by the University of Texas MD Anderson Cancer Center Support Grant from the National Institutes of Health, the National Institutes of Health/National Cancer Institute under award, the University of Texas MD Anderson MDS/AML Moon Shot, and Leukemia Texas. K Sasaki, EJ Jabbour, F Ravandi, M Konopleva, G Garcia-Manero, JE Cortes,  C DiNardo reported relationships with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Sasaki K et al. Am J Hematol. 2020 Nov 12.  doi: 10.1002/ajh.26047.

Key clinical point: Personalized treatment selection according to the LEukemia Artificial intelligence Program (LEAP) recommendations for patients with chronic myeloid leukemia in chronic phase (CML-CP) is associated with better likelihood of survival.

Major finding: The LEAP CML-CP recommendation was associated with an improved overall survival  (P less than 001).

Study details: A cohort of CML-CP patients was randomly assigned to training/validation (n = 504) and test cohorts (n = 126). The training/validation cohort was used to develop the LEAP CML-CP model using 101 variables at diagnosis. The test cohort was then applied to the LEAP CML-CP model and an optimum tyrosine kinase inhibitor therapy was selected for each patient.

Disclosures: The study was supported by the University of Texas MD Anderson Cancer Center Support Grant from the National Institutes of Health, the National Institutes of Health/National Cancer Institute under award, the University of Texas MD Anderson MDS/AML Moon Shot, and Leukemia Texas. K Sasaki, EJ Jabbour, F Ravandi, M Konopleva, G Garcia-Manero, JE Cortes,  C DiNardo reported relationships with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Sasaki K et al. Am J Hematol. 2020 Nov 12.  doi: 10.1002/ajh.26047.

Key clinical point: There is a decline in renal function among patients with chronic myeloid leukaemia (CML) treated with tyrosine kinase inhibitors (TKIs).

Major finding: There was a significant reduction between the first and final recorded estimated glomerular filtration rate across all patients, declining by a mean of -12 mL/minute/1.73m² over the 10 years of measurement.

Study details: The data come from a retrospective analysis of 50 patients with CML treated with TKI therapy for at least 2 years.

Disclosures: No information on funding was available. The presenting author R Hinton declared no conflicts of interest. The second author S Arami reported relationships with various pharmaceutical companies.

Source: Hinton R et al. Poster. Abstract 053. BSH 2020. 2020 Nov 9-14.

Key clinical point: There is a decline in renal function among patients with chronic myeloid leukaemia (CML) treated with tyrosine kinase inhibitors (TKIs).

Major finding: There was a significant reduction between the first and final recorded estimated glomerular filtration rate across all patients, declining by a mean of -12 mL/minute/1.73m² over the 10 years of measurement.

Study details: The data come from a retrospective analysis of 50 patients with CML treated with TKI therapy for at least 2 years.

Disclosures: No information on funding was available. The presenting author R Hinton declared no conflicts of interest. The second author S Arami reported relationships with various pharmaceutical companies.

Source: Hinton R et al. Poster. Abstract 053. BSH 2020. 2020 Nov 9-14.

Key clinical point: There is a decline in renal function among patients with chronic myeloid leukaemia (CML) treated with tyrosine kinase inhibitors (TKIs).

Major finding: There was a significant reduction between the first and final recorded estimated glomerular filtration rate across all patients, declining by a mean of -12 mL/minute/1.73m² over the 10 years of measurement.

Study details: The data come from a retrospective analysis of 50 patients with CML treated with TKI therapy for at least 2 years.

Disclosures: No information on funding was available. The presenting author R Hinton declared no conflicts of interest. The second author S Arami reported relationships with various pharmaceutical companies.

Source: Hinton R et al. Poster. Abstract 053. BSH 2020. 2020 Nov 9-14.

Key clinical point: This analysis of more than 400 conceptions revealed that the rate of malformations was 2.5% in offsprings of fathers who did not discontinue tyrosine kinase inhibitors (TKIs) before conception, comparable to that measured in the general population.

Major finding: A total of 428 pregnancies from 374 fathers conceived without treatment discontinuation, 400 of which (93.5%) ended up in a live birth. Malformation was reported in 10 offsprings (2.5% of total live births): 6 with imatinib (1.9% of 313 live births), 2 with nilotinib (7.7% of 26 live births), 1 with dasatinib (2.3% of 43 live births), and none with bosutinib (0% of 12 live births).

Study details: A systematic review of 27 nonoverlapping cohorts of patients or case studies.

Disclosures: Study costs were covered by the Economic Development and Innovation Operative Programme Grant; Human Resources Development Operational Programme Grants; and the New National Excellence Programme, Ministry of Human Capacities. The authors declared no conflicts of interest.

Source: Szakács Z et al. PLoS One. 2020 Dec 3. doi: 10.1371/journal.pone.0243045.

Key clinical point: This analysis of more than 400 conceptions revealed that the rate of malformations was 2.5% in offsprings of fathers who did not discontinue tyrosine kinase inhibitors (TKIs) before conception, comparable to that measured in the general population.

Major finding: A total of 428 pregnancies from 374 fathers conceived without treatment discontinuation, 400 of which (93.5%) ended up in a live birth. Malformation was reported in 10 offsprings (2.5% of total live births): 6 with imatinib (1.9% of 313 live births), 2 with nilotinib (7.7% of 26 live births), 1 with dasatinib (2.3% of 43 live births), and none with bosutinib (0% of 12 live births).

Study details: A systematic review of 27 nonoverlapping cohorts of patients or case studies.

Disclosures: Study costs were covered by the Economic Development and Innovation Operative Programme Grant; Human Resources Development Operational Programme Grants; and the New National Excellence Programme, Ministry of Human Capacities. The authors declared no conflicts of interest.

Source: Szakács Z et al. PLoS One. 2020 Dec 3. doi: 10.1371/journal.pone.0243045.

Key clinical point: This analysis of more than 400 conceptions revealed that the rate of malformations was 2.5% in offsprings of fathers who did not discontinue tyrosine kinase inhibitors (TKIs) before conception, comparable to that measured in the general population.

Major finding: A total of 428 pregnancies from 374 fathers conceived without treatment discontinuation, 400 of which (93.5%) ended up in a live birth. Malformation was reported in 10 offsprings (2.5% of total live births): 6 with imatinib (1.9% of 313 live births), 2 with nilotinib (7.7% of 26 live births), 1 with dasatinib (2.3% of 43 live births), and none with bosutinib (0% of 12 live births).

Study details: A systematic review of 27 nonoverlapping cohorts of patients or case studies.

Disclosures: Study costs were covered by the Economic Development and Innovation Operative Programme Grant; Human Resources Development Operational Programme Grants; and the New National Excellence Programme, Ministry of Human Capacities. The authors declared no conflicts of interest.

Source: Szakács Z et al. PLoS One. 2020 Dec 3. doi: 10.1371/journal.pone.0243045.

Key clinical point: In patients with chronic myeloid leukemia (CML), tyrosine kinase inhibitor (TKI) discontinuation seems safe and feasible and is associated with improvements in patient-reported outcomes (PROs).

Major finding: Overall, 65.5% of patients stayed in major molecular response loss, 60.8% achieved treatment-free remission (TFR), and 34.5% had molecular recurrence (MRec). Detectable BCR-ABL1 by real-time quantitative polymerase chain reaction (PCR) or droplet digital PCR at the time of TKI discontinuation was associated with a greater risk of MRec. In patients who had reached TFR at 12 months, TKI discontinuation was associated with improvements in patient-reported fatigue, diarrhea, depression, and sleep disturbance.

Study details: In this prospective single-group nonrandomized LAST study, MRec and PROs after TKI discontinuation for 172 patients with CML in chronic phase (median age, 60 years) from 14 U.S. sites were evaluated. Included patients had well-controlled disease while treated with imatinib, dasatinib, nilotinib, or bosutinib.

Disclosures: This research was supported by a grant from the U.S. National Cancer Institute. The presenting author reported receiving personal fees from Novartis, Bristol Myers Squibb, and Takeda and research support from Novartis and Takeda.

Source: Atallah E et al. JAMA Oncol. 2020 Nov 12. doi: 10.1001/jamaoncol.2020.5774.

Key clinical point: In patients with chronic myeloid leukemia (CML), tyrosine kinase inhibitor (TKI) discontinuation seems safe and feasible and is associated with improvements in patient-reported outcomes (PROs).

Major finding: Overall, 65.5% of patients stayed in major molecular response loss, 60.8% achieved treatment-free remission (TFR), and 34.5% had molecular recurrence (MRec). Detectable BCR-ABL1 by real-time quantitative polymerase chain reaction (PCR) or droplet digital PCR at the time of TKI discontinuation was associated with a greater risk of MRec. In patients who had reached TFR at 12 months, TKI discontinuation was associated with improvements in patient-reported fatigue, diarrhea, depression, and sleep disturbance.

Study details: In this prospective single-group nonrandomized LAST study, MRec and PROs after TKI discontinuation for 172 patients with CML in chronic phase (median age, 60 years) from 14 U.S. sites were evaluated. Included patients had well-controlled disease while treated with imatinib, dasatinib, nilotinib, or bosutinib.

Disclosures: This research was supported by a grant from the U.S. National Cancer Institute. The presenting author reported receiving personal fees from Novartis, Bristol Myers Squibb, and Takeda and research support from Novartis and Takeda.

Source: Atallah E et al. JAMA Oncol. 2020 Nov 12. doi: 10.1001/jamaoncol.2020.5774.

Key clinical point: In patients with chronic myeloid leukemia (CML), tyrosine kinase inhibitor (TKI) discontinuation seems safe and feasible and is associated with improvements in patient-reported outcomes (PROs).

Major finding: Overall, 65.5% of patients stayed in major molecular response loss, 60.8% achieved treatment-free remission (TFR), and 34.5% had molecular recurrence (MRec). Detectable BCR-ABL1 by real-time quantitative polymerase chain reaction (PCR) or droplet digital PCR at the time of TKI discontinuation was associated with a greater risk of MRec. In patients who had reached TFR at 12 months, TKI discontinuation was associated with improvements in patient-reported fatigue, diarrhea, depression, and sleep disturbance.

Study details: In this prospective single-group nonrandomized LAST study, MRec and PROs after TKI discontinuation for 172 patients with CML in chronic phase (median age, 60 years) from 14 U.S. sites were evaluated. Included patients had well-controlled disease while treated with imatinib, dasatinib, nilotinib, or bosutinib.

Disclosures: This research was supported by a grant from the U.S. National Cancer Institute. The presenting author reported receiving personal fees from Novartis, Bristol Myers Squibb, and Takeda and research support from Novartis and Takeda.

Source: Atallah E et al. JAMA Oncol. 2020 Nov 12. doi: 10.1001/jamaoncol.2020.5774.