TOPLINE:

Delaying surgery after neoadjuvant therapy may improve tumor regression and decrease recurrence in advanced rectal cancer but does not translate to better overall survival.

METHODOLOGY:

• A total of 1,506 patients with locally advanced rectal cancer who underwent neoadjuvant therapy followed by total mesorectal excision were divided into three groups based on the time interval between therapy and surgery: short (8 weeks), intermediate (> 8 to 12 weeks), and long (> 12 weeks).
• The primary outcome was pathologic complete response, and secondary outcomes included other histopathologic results, perioperative events, and survival outcomes.
• Median follow-up was 33 months.

TAKEAWAY:

• Overall, a pathologic complete response was observed in 255 patients (17.2%).
• Compared with the intermediate interval (reference) group, investigators found no association between time interval and pathologic complete response in the short-interval (odds ratio, 0.74; 95% CI, 0.55-1.01) or long-interval groups (OR, 1.07; P = .70).
• A long interval was significantly associated with a lower risk of a bad response as measured by tumor regression grade 2-3, compared with the reference category (OR, 0.47), but a higher risk of minor postoperative complications (OR, 1.43), conversion to open surgery (OR, 3.14), and longer operative time.
• The long-interval group was associated with a significantly reduced risk of systemic recurrence, compared with the reference group (hazard ratio, 0.59; P = .04), but not improved overall survival (HR, 1.38; P = .11) or locoregional recurrence (HR, 0.53; P = .18); no significant findings occurred for the short versus intermediate group.

IN PRACTICE:

“Findings suggest that delaying surgery may improve tumor regression and decrease risk of distant metastasis but increase surgical complexity,” the authors conclude. “Nonetheless, the reported improvements in tumor regression and systemic recurrence in the long-interval group were unexpectedly not followed by improved [overall survival].”

SOURCE:

F. Borja de Lacy, MD, PhD, Hospital Clinic of Barcelona, University of Barcelona, led the study, published online in JAMA Surgery, with an accompanying editorial.

LIMITATIONS:

• The study’s main limitation was its retrospective design, which could have resulted in missing or inconsistent data, as well as the short follow-up time.
• Decisions about time interval were based more on professional preference rather than specific tumor characteristics.

DISCLOSURES:

Dr. de Lacy has reported no relevant financial relationships. No outside funding source was disclosed.

A version of this article first appeared on Medscape.com.

TOPLINE:

Delaying surgery after neoadjuvant therapy may improve tumor regression and decrease recurrence in advanced rectal cancer but does not translate to better overall survival.

METHODOLOGY:

• A total of 1,506 patients with locally advanced rectal cancer who underwent neoadjuvant therapy followed by total mesorectal excision were divided into three groups based on the time interval between therapy and surgery: short (8 weeks), intermediate (> 8 to 12 weeks), and long (> 12 weeks).
• The primary outcome was pathologic complete response, and secondary outcomes included other histopathologic results, perioperative events, and survival outcomes.
• Median follow-up was 33 months.

TAKEAWAY:

• Overall, a pathologic complete response was observed in 255 patients (17.2%).
• Compared with the intermediate interval (reference) group, investigators found no association between time interval and pathologic complete response in the short-interval (odds ratio, 0.74; 95% CI, 0.55-1.01) or long-interval groups (OR, 1.07; P = .70).
• A long interval was significantly associated with a lower risk of a bad response as measured by tumor regression grade 2-3, compared with the reference category (OR, 0.47), but a higher risk of minor postoperative complications (OR, 1.43), conversion to open surgery (OR, 3.14), and longer operative time.
• The long-interval group was associated with a significantly reduced risk of systemic recurrence, compared with the reference group (hazard ratio, 0.59; P = .04), but not improved overall survival (HR, 1.38; P = .11) or locoregional recurrence (HR, 0.53; P = .18); no significant findings occurred for the short versus intermediate group.

IN PRACTICE:

“Findings suggest that delaying surgery may improve tumor regression and decrease risk of distant metastasis but increase surgical complexity,” the authors conclude. “Nonetheless, the reported improvements in tumor regression and systemic recurrence in the long-interval group were unexpectedly not followed by improved [overall survival].”

SOURCE:

F. Borja de Lacy, MD, PhD, Hospital Clinic of Barcelona, University of Barcelona, led the study, published online in JAMA Surgery, with an accompanying editorial.

LIMITATIONS:

• The study’s main limitation was its retrospective design, which could have resulted in missing or inconsistent data, as well as the short follow-up time.
• Decisions about time interval were based more on professional preference rather than specific tumor characteristics.

DISCLOSURES:

Dr. de Lacy has reported no relevant financial relationships. No outside funding source was disclosed.

A version of this article first appeared on Medscape.com.

TOPLINE:

Delaying surgery after neoadjuvant therapy may improve tumor regression and decrease recurrence in advanced rectal cancer but does not translate to better overall survival.

METHODOLOGY:

• A total of 1,506 patients with locally advanced rectal cancer who underwent neoadjuvant therapy followed by total mesorectal excision were divided into three groups based on the time interval between therapy and surgery: short (8 weeks), intermediate (> 8 to 12 weeks), and long (> 12 weeks).
• The primary outcome was pathologic complete response, and secondary outcomes included other histopathologic results, perioperative events, and survival outcomes.
• Median follow-up was 33 months.

TAKEAWAY:

• Overall, a pathologic complete response was observed in 255 patients (17.2%).
• Compared with the intermediate interval (reference) group, investigators found no association between time interval and pathologic complete response in the short-interval (odds ratio, 0.74; 95% CI, 0.55-1.01) or long-interval groups (OR, 1.07; P = .70).
• A long interval was significantly associated with a lower risk of a bad response as measured by tumor regression grade 2-3, compared with the reference category (OR, 0.47), but a higher risk of minor postoperative complications (OR, 1.43), conversion to open surgery (OR, 3.14), and longer operative time.
• The long-interval group was associated with a significantly reduced risk of systemic recurrence, compared with the reference group (hazard ratio, 0.59; P = .04), but not improved overall survival (HR, 1.38; P = .11) or locoregional recurrence (HR, 0.53; P = .18); no significant findings occurred for the short versus intermediate group.

IN PRACTICE:

“Findings suggest that delaying surgery may improve tumor regression and decrease risk of distant metastasis but increase surgical complexity,” the authors conclude. “Nonetheless, the reported improvements in tumor regression and systemic recurrence in the long-interval group were unexpectedly not followed by improved [overall survival].”

SOURCE:

F. Borja de Lacy, MD, PhD, Hospital Clinic of Barcelona, University of Barcelona, led the study, published online in JAMA Surgery, with an accompanying editorial.

LIMITATIONS:

• The study’s main limitation was its retrospective design, which could have resulted in missing or inconsistent data, as well as the short follow-up time.
• Decisions about time interval were based more on professional preference rather than specific tumor characteristics.

DISCLOSURES:

Dr. de Lacy has reported no relevant financial relationships. No outside funding source was disclosed.

A version of this article first appeared on Medscape.com.

The findings in this case are suggestive of invasive lobular carcinoma (ILC).

Globally, breast cancer remains the most common life-threatening cancer diagnosed and the second leading cause of cancer-related deaths in women. In the United States, approximately 287,850 new cases of invasive breast cancer were diagnosed in 2022 and 43,250 deaths were attributed to breast cancer in the same year. Worldwide, approximately 2.3 million new diagnoses and 685,000 breast cancer-related deaths were reported in 2020.

ILC is one of the leading histologic types of invasive carcinoma, second in incidence only to invasive carcinoma of no special type. ILC accounts for 5%-15% of all invasive breast cancers, and its incidence has been steadily increasing — particularly among postmenopausal women — over the past two decades. ILC has distinct molecular and histopathologic features, including the loss of cell-cell adhesion molecule E-cadherin, resulting in small, discohesive cells proliferating in single-file strands; positivity for both the estrogen and progesterone receptor; and human epidermal growth factor receptor 2 negativity.

The diagnosis of ILC can be challenging, as it is difficult to detect both on physical examination and with standard imaging techniques. Patients are often diagnosed with late-stage disease, characterized by large tumors and lymph node involvement. The signs of ILC are often vague, such as skin thickening or dimpling. In addition, measuring the extent of ILC can be challenging, as traditional screening methods (eg, mammography and ultrasonography) have a low sensitivity for detecting ILC compared with other invasive breast tumors. This difficulty is usually ascribed to the diffuse infiltrative growth pattern of ILC. MRI has a greater sensitivity for detecting ILC.

Risk factors for the development of ILC have been identified and include:

•    Alcohol consumption
•    Use of combined hormone replacement therapy
•    Early menarche (menarche before the age of 12 years)
•    Late-onset menopause (menopause after the age of 55 years)
•    Nulliparity/low parity (defined by World Health Organization as fewer than five pregnancies with gestation periods of ≥ 20 weeks)
•    Late age at birth (> 30 years)
•    Family history (eg, hereditary diffuse gastric cancer syndrome)
•    Genetics (eg, CDH1 mutations)

Treatment protocols for ILC align with those used in other breast cancer subtypes and typically involve a multidisciplinary approach comprising surgery, radiotherapy, and systemic therapies. Cancers that are deemed resectable will typically be managed surgically upfront, although some patients may require neoadjuvant therapy to reduce tumor burden and facilitate surgical intervention. Breast-conserving surgery using a wide local excision can frequently be performed; however, in up to 65% of cases, a second surgery will be required (re-excision or mastectomy). Axillary lymph node status is a crucial factor in the prognosis of all breast cancers and affects surgical planning. Sentinel node biopsy is the standard method of assessing the axilla. 

Systemic therapy is an integral part of the multidisciplinary approach to treating breast cancer and usually involves the use of chemotherapy. However, because of the unique molecular biology of ILC, treatment response to chemotherapy is often poor, resulting in lower rates of complete pathologic response and higher rates of mastectomy. Conversely, ILC has been shown to respond well to endocrine therapy, making it the optimal treatment choice. Novel therapeutic approaches are under investigation. 

Detailed guidance on the treatment of ILC is available from the National Comprehensive Cancer Network.

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL.

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.
 

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The findings in this case are suggestive of invasive lobular carcinoma (ILC).

Globally, breast cancer remains the most common life-threatening cancer diagnosed and the second leading cause of cancer-related deaths in women. In the United States, approximately 287,850 new cases of invasive breast cancer were diagnosed in 2022 and 43,250 deaths were attributed to breast cancer in the same year. Worldwide, approximately 2.3 million new diagnoses and 685,000 breast cancer-related deaths were reported in 2020.

ILC is one of the leading histologic types of invasive carcinoma, second in incidence only to invasive carcinoma of no special type. ILC accounts for 5%-15% of all invasive breast cancers, and its incidence has been steadily increasing — particularly among postmenopausal women — over the past two decades. ILC has distinct molecular and histopathologic features, including the loss of cell-cell adhesion molecule E-cadherin, resulting in small, discohesive cells proliferating in single-file strands; positivity for both the estrogen and progesterone receptor; and human epidermal growth factor receptor 2 negativity.

The diagnosis of ILC can be challenging, as it is difficult to detect both on physical examination and with standard imaging techniques. Patients are often diagnosed with late-stage disease, characterized by large tumors and lymph node involvement. The signs of ILC are often vague, such as skin thickening or dimpling. In addition, measuring the extent of ILC can be challenging, as traditional screening methods (eg, mammography and ultrasonography) have a low sensitivity for detecting ILC compared with other invasive breast tumors. This difficulty is usually ascribed to the diffuse infiltrative growth pattern of ILC. MRI has a greater sensitivity for detecting ILC.

Risk factors for the development of ILC have been identified and include:

•    Alcohol consumption
•    Use of combined hormone replacement therapy
•    Early menarche (menarche before the age of 12 years)
•    Late-onset menopause (menopause after the age of 55 years)
•    Nulliparity/low parity (defined by World Health Organization as fewer than five pregnancies with gestation periods of ≥ 20 weeks)
•    Late age at birth (> 30 years)
•    Family history (eg, hereditary diffuse gastric cancer syndrome)
•    Genetics (eg, CDH1 mutations)

Treatment protocols for ILC align with those used in other breast cancer subtypes and typically involve a multidisciplinary approach comprising surgery, radiotherapy, and systemic therapies. Cancers that are deemed resectable will typically be managed surgically upfront, although some patients may require neoadjuvant therapy to reduce tumor burden and facilitate surgical intervention. Breast-conserving surgery using a wide local excision can frequently be performed; however, in up to 65% of cases, a second surgery will be required (re-excision or mastectomy). Axillary lymph node status is a crucial factor in the prognosis of all breast cancers and affects surgical planning. Sentinel node biopsy is the standard method of assessing the axilla. 

Systemic therapy is an integral part of the multidisciplinary approach to treating breast cancer and usually involves the use of chemotherapy. However, because of the unique molecular biology of ILC, treatment response to chemotherapy is often poor, resulting in lower rates of complete pathologic response and higher rates of mastectomy. Conversely, ILC has been shown to respond well to endocrine therapy, making it the optimal treatment choice. Novel therapeutic approaches are under investigation. 

Detailed guidance on the treatment of ILC is available from the National Comprehensive Cancer Network.

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL.

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.
 

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The findings in this case are suggestive of invasive lobular carcinoma (ILC).

Globally, breast cancer remains the most common life-threatening cancer diagnosed and the second leading cause of cancer-related deaths in women. In the United States, approximately 287,850 new cases of invasive breast cancer were diagnosed in 2022 and 43,250 deaths were attributed to breast cancer in the same year. Worldwide, approximately 2.3 million new diagnoses and 685,000 breast cancer-related deaths were reported in 2020.

ILC is one of the leading histologic types of invasive carcinoma, second in incidence only to invasive carcinoma of no special type. ILC accounts for 5%-15% of all invasive breast cancers, and its incidence has been steadily increasing — particularly among postmenopausal women — over the past two decades. ILC has distinct molecular and histopathologic features, including the loss of cell-cell adhesion molecule E-cadherin, resulting in small, discohesive cells proliferating in single-file strands; positivity for both the estrogen and progesterone receptor; and human epidermal growth factor receptor 2 negativity.

The diagnosis of ILC can be challenging, as it is difficult to detect both on physical examination and with standard imaging techniques. Patients are often diagnosed with late-stage disease, characterized by large tumors and lymph node involvement. The signs of ILC are often vague, such as skin thickening or dimpling. In addition, measuring the extent of ILC can be challenging, as traditional screening methods (eg, mammography and ultrasonography) have a low sensitivity for detecting ILC compared with other invasive breast tumors. This difficulty is usually ascribed to the diffuse infiltrative growth pattern of ILC. MRI has a greater sensitivity for detecting ILC.

Risk factors for the development of ILC have been identified and include:

•    Alcohol consumption
•    Use of combined hormone replacement therapy
•    Early menarche (menarche before the age of 12 years)
•    Late-onset menopause (menopause after the age of 55 years)
•    Nulliparity/low parity (defined by World Health Organization as fewer than five pregnancies with gestation periods of ≥ 20 weeks)
•    Late age at birth (> 30 years)
•    Family history (eg, hereditary diffuse gastric cancer syndrome)
•    Genetics (eg, CDH1 mutations)

Treatment protocols for ILC align with those used in other breast cancer subtypes and typically involve a multidisciplinary approach comprising surgery, radiotherapy, and systemic therapies. Cancers that are deemed resectable will typically be managed surgically upfront, although some patients may require neoadjuvant therapy to reduce tumor burden and facilitate surgical intervention. Breast-conserving surgery using a wide local excision can frequently be performed; however, in up to 65% of cases, a second surgery will be required (re-excision or mastectomy). Axillary lymph node status is a crucial factor in the prognosis of all breast cancers and affects surgical planning. Sentinel node biopsy is the standard method of assessing the axilla. 

Systemic therapy is an integral part of the multidisciplinary approach to treating breast cancer and usually involves the use of chemotherapy. However, because of the unique molecular biology of ILC, treatment response to chemotherapy is often poor, resulting in lower rates of complete pathologic response and higher rates of mastectomy. Conversely, ILC has been shown to respond well to endocrine therapy, making it the optimal treatment choice. Novel therapeutic approaches are under investigation. 

Detailed guidance on the treatment of ILC is available from the National Comprehensive Cancer Network.

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL.

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.
 

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The International Agency for Research on Cancer announced on July 13 that it has officially classified the artificial sweetener aspartame as a possible carcinogen.

Although this means aspartame might cause cancer in humans, the Group 2B classification from the IARC means the evidence is “limited.” A summary of the working group’s evaluation, also published in The Lancet Oncology, explained that the classification was based on data from three studies assessing the link between aspartame intake and primary liver cancer.

Using that evidence, the World Health Organization and Food and Agriculture Organization Joint Expert Committee on Food Additives confirmed its existing stance that aspartame consumption of up to 40 mg/kg of body weight per day – the amount found in 9-14 diet soft drinks – is safe.

The decision, which was anticipated by Reuters in late June, drew praise from an array of experts who weighed in on the study results via the U.K.-based Science Media Centre. Many emphasized the lack of data showing a causal relationship between the low-calorie artificial sweetener and sought to temper any alarmism related to the decision.

“In short the evidence that aspartame causes primary liver cancer, or any other cancer in humans, is very weak,” said Paul Pharoah, MD, PhD, a professor of cancer epidemiology at Cedars-Sinai Medical Center, Los Angeles. “Group 2B is a very conservative classification in that almost any evidence of carcinogenicity, however flawed, will put a chemical in that category or above.”

Other examples of substances classified as Group 2B are extract of aloe vera, diesel oil, and caffeic acid found in coffee and tea, Dr. Pharoah explained, adding that “this is reflected in the view of the [JECFA] who concluded that there was no convincing evidence from experimental animal or human data that aspartame has adverse effects after ingestion.”

“The general public should not be worried about the risk of cancer associated with a chemical classed as Group 2B by IARC,” he stressed.

Alan Boobis, OBE, PhD, similarly noted that the Group 2B classification “reflects a lack of confidence that the data from experimental animals or from humans is sufficiently convincing to reach a clear conclusion that aspartame is carcinogenic.”

“Hence, exposure at current levels would not be anticipated to have any detrimental effects,” added Dr. Boobis, emeritus professor of toxicology, Imperial College London.

The IARC/JECFA opinion is “very welcome” and “ends the speculation about the safety of aspartame,” added Gunter Kuhnle, Dr. rer. nat., a professor of nutrition and food science at the University of Reading (England).

“It is unfortunate that leaking some information might have created unnecessary uncertainty and concern as consumers might be rightfully worried if they are told that something that is in many foods could cause cancer,” Dr. Kuhnle said. “The published opinion puts this into perspective and makes it very clear that there is no cause for concern when consumed at the current amounts.”

The data reviewed by the IARC Working Group included three studies, comprising four prospective cohorts, that “assessed the association of artificially sweetened beverage consumption with liver cancer risk,” the group reported.

The cohort studies – including one conducted within 10 European countries, one that pooled data from two large U.S. cohorts, and a prospective study also conducted in the United States – each “showed positive associations between artificially sweetened beverage consumption and cancer incidence or cancer mortality” in the overall study population or in relevant subgroups.

Although the studies were of “high quality and controlled for many potential confounders,” the Working Group concluded that “chance, bias, or confounding could not be ruled out with reasonable confidence.” Thus, the evidence for cancer in humans was deemed “limited” for hepatocellular carcinoma and “inadequate” for other cancer types.”

Dr. Pharoah and Dr. Kuhnle disclosed no relevant financial relationships. Dr. Boobis is a member of a number of advisory committees in the public and private sectors, including the International Life Science Institute and The Center for Research on Ingredient Safety at Michigan State University.

A version of this article first appeared on Medscape.com.

The International Agency for Research on Cancer announced on July 13 that it has officially classified the artificial sweetener aspartame as a possible carcinogen.

Although this means aspartame might cause cancer in humans, the Group 2B classification from the IARC means the evidence is “limited.” A summary of the working group’s evaluation, also published in The Lancet Oncology, explained that the classification was based on data from three studies assessing the link between aspartame intake and primary liver cancer.

Using that evidence, the World Health Organization and Food and Agriculture Organization Joint Expert Committee on Food Additives confirmed its existing stance that aspartame consumption of up to 40 mg/kg of body weight per day – the amount found in 9-14 diet soft drinks – is safe.

The decision, which was anticipated by Reuters in late June, drew praise from an array of experts who weighed in on the study results via the U.K.-based Science Media Centre. Many emphasized the lack of data showing a causal relationship between the low-calorie artificial sweetener and sought to temper any alarmism related to the decision.

“In short the evidence that aspartame causes primary liver cancer, or any other cancer in humans, is very weak,” said Paul Pharoah, MD, PhD, a professor of cancer epidemiology at Cedars-Sinai Medical Center, Los Angeles. “Group 2B is a very conservative classification in that almost any evidence of carcinogenicity, however flawed, will put a chemical in that category or above.”

Other examples of substances classified as Group 2B are extract of aloe vera, diesel oil, and caffeic acid found in coffee and tea, Dr. Pharoah explained, adding that “this is reflected in the view of the [JECFA] who concluded that there was no convincing evidence from experimental animal or human data that aspartame has adverse effects after ingestion.”

“The general public should not be worried about the risk of cancer associated with a chemical classed as Group 2B by IARC,” he stressed.

Alan Boobis, OBE, PhD, similarly noted that the Group 2B classification “reflects a lack of confidence that the data from experimental animals or from humans is sufficiently convincing to reach a clear conclusion that aspartame is carcinogenic.”

“Hence, exposure at current levels would not be anticipated to have any detrimental effects,” added Dr. Boobis, emeritus professor of toxicology, Imperial College London.

The IARC/JECFA opinion is “very welcome” and “ends the speculation about the safety of aspartame,” added Gunter Kuhnle, Dr. rer. nat., a professor of nutrition and food science at the University of Reading (England).

“It is unfortunate that leaking some information might have created unnecessary uncertainty and concern as consumers might be rightfully worried if they are told that something that is in many foods could cause cancer,” Dr. Kuhnle said. “The published opinion puts this into perspective and makes it very clear that there is no cause for concern when consumed at the current amounts.”

The data reviewed by the IARC Working Group included three studies, comprising four prospective cohorts, that “assessed the association of artificially sweetened beverage consumption with liver cancer risk,” the group reported.

The cohort studies – including one conducted within 10 European countries, one that pooled data from two large U.S. cohorts, and a prospective study also conducted in the United States – each “showed positive associations between artificially sweetened beverage consumption and cancer incidence or cancer mortality” in the overall study population or in relevant subgroups.

Although the studies were of “high quality and controlled for many potential confounders,” the Working Group concluded that “chance, bias, or confounding could not be ruled out with reasonable confidence.” Thus, the evidence for cancer in humans was deemed “limited” for hepatocellular carcinoma and “inadequate” for other cancer types.”

Dr. Pharoah and Dr. Kuhnle disclosed no relevant financial relationships. Dr. Boobis is a member of a number of advisory committees in the public and private sectors, including the International Life Science Institute and The Center for Research on Ingredient Safety at Michigan State University.

A version of this article first appeared on Medscape.com.

The International Agency for Research on Cancer announced on July 13 that it has officially classified the artificial sweetener aspartame as a possible carcinogen.

Although this means aspartame might cause cancer in humans, the Group 2B classification from the IARC means the evidence is “limited.” A summary of the working group’s evaluation, also published in The Lancet Oncology, explained that the classification was based on data from three studies assessing the link between aspartame intake and primary liver cancer.

Using that evidence, the World Health Organization and Food and Agriculture Organization Joint Expert Committee on Food Additives confirmed its existing stance that aspartame consumption of up to 40 mg/kg of body weight per day – the amount found in 9-14 diet soft drinks – is safe.

The decision, which was anticipated by Reuters in late June, drew praise from an array of experts who weighed in on the study results via the U.K.-based Science Media Centre. Many emphasized the lack of data showing a causal relationship between the low-calorie artificial sweetener and sought to temper any alarmism related to the decision.

“In short the evidence that aspartame causes primary liver cancer, or any other cancer in humans, is very weak,” said Paul Pharoah, MD, PhD, a professor of cancer epidemiology at Cedars-Sinai Medical Center, Los Angeles. “Group 2B is a very conservative classification in that almost any evidence of carcinogenicity, however flawed, will put a chemical in that category or above.”

Other examples of substances classified as Group 2B are extract of aloe vera, diesel oil, and caffeic acid found in coffee and tea, Dr. Pharoah explained, adding that “this is reflected in the view of the [JECFA] who concluded that there was no convincing evidence from experimental animal or human data that aspartame has adverse effects after ingestion.”

“The general public should not be worried about the risk of cancer associated with a chemical classed as Group 2B by IARC,” he stressed.

Alan Boobis, OBE, PhD, similarly noted that the Group 2B classification “reflects a lack of confidence that the data from experimental animals or from humans is sufficiently convincing to reach a clear conclusion that aspartame is carcinogenic.”

“Hence, exposure at current levels would not be anticipated to have any detrimental effects,” added Dr. Boobis, emeritus professor of toxicology, Imperial College London.

The IARC/JECFA opinion is “very welcome” and “ends the speculation about the safety of aspartame,” added Gunter Kuhnle, Dr. rer. nat., a professor of nutrition and food science at the University of Reading (England).

“It is unfortunate that leaking some information might have created unnecessary uncertainty and concern as consumers might be rightfully worried if they are told that something that is in many foods could cause cancer,” Dr. Kuhnle said. “The published opinion puts this into perspective and makes it very clear that there is no cause for concern when consumed at the current amounts.”

The data reviewed by the IARC Working Group included three studies, comprising four prospective cohorts, that “assessed the association of artificially sweetened beverage consumption with liver cancer risk,” the group reported.

The cohort studies – including one conducted within 10 European countries, one that pooled data from two large U.S. cohorts, and a prospective study also conducted in the United States – each “showed positive associations between artificially sweetened beverage consumption and cancer incidence or cancer mortality” in the overall study population or in relevant subgroups.

Although the studies were of “high quality and controlled for many potential confounders,” the Working Group concluded that “chance, bias, or confounding could not be ruled out with reasonable confidence.” Thus, the evidence for cancer in humans was deemed “limited” for hepatocellular carcinoma and “inadequate” for other cancer types.”

Dr. Pharoah and Dr. Kuhnle disclosed no relevant financial relationships. Dr. Boobis is a member of a number of advisory committees in the public and private sectors, including the International Life Science Institute and The Center for Research on Ingredient Safety at Michigan State University.

A version of this article first appeared on Medscape.com.

MARSEILLE, FRANCE – Setmelanotide can lead to significant weight loss that lasts for at least 3 years, according to results presented at the latest French Pediatric Society conference. The treatment is effective for adults and children alike.

Setmelanotide is the culmination of two decades of research involving the identification of genes involved in early-onset obesity and the characterization of the melanocortin 4 receptor. It became available via early access in 2021.

Currently limited to use in treating obesity linked to a biallelic POMC/PCSK1 or LEPR deficiency, setmelanotide is being tested with respect to other mutations responsible for severe obesity, raising hopes that it will soon be indicated for use in a larger number of patients.

Fewer than 1% of patients who suffer from severe obesity have monogenic forms of obesity. In recent years, the hope for a targeted treatment for patients with these monogenic forms has become a reality.

Although only a small number of patients currently meet the criteria for setmelanotide treatment (namely, those with obesity linked to a biallelic POMC/PCSK1 enzyme or LEPR deficiency and patients with Bardet-Biedl syndrome), there is a real hope that patients with other forms of severe obesity will be able to benefit from this product, including those with heterozygous (not just homozygous) monoallelic variants, who account for more than 10% of patients with severe early-onset obesity.
 

Restoring satiety signaling

“Setmelanotide is a melanocortin 4 receptor agonist,” said Béatrice Dubern, MD, PhD, pediatrician at Trousseau Hospital, Paris, and member of the French medical research institute (INSERM)/Sorbonne University team on nutrition and obesity. “Its mode of action rests on activation of the leptin-melanocortin signaling pathway in the hypothalamus, which regulates hunger, satiety, energy expenditure, and, therefore, body weight. Rare genetic variants in the leptin-melanocortin pathway are associated with polyphagia and severe early-onset obesity. It is believed that more than 60 genes involved in this leptin-melanocortin pathway are currently associated with obesity.”

In July 2021, the European Medicines Agency approved setmelanotide for daily use via subcutaneous administration.
 

Weight loss maintained

In phase 3 studies, setmelanotide (melanocortin 4 receptor agonist) demonstrated its effectiveness in reducing weight and hunger for patients with obesity caused by a POMC/PCSK1 or LEPR deficiency.

Twenty-four patients aged 6 years and older showed a significant response to setmelanotide after 1 year of treatment and were included in the extension study. “Significant response” was defined as a reduction in body weight greater than or equal to 10% after 52 weeks for patients aged 18 years and older or a reduction in body mass index (BMI) z-score greater than or equal to 0.3 after 52 weeks for patients younger than 18 years.

Among all patients, the mean variation (standard deviation) in BMI was −24.8% (8.2%, n = 24), −21% (13%, n = 23), and −24% (17.9%, n = 15) at 12, 24, and 36 months, respectively.

For patients aged greater than or equal to 18 years (n = 11), the mean variation (standard deviation) in weight was −25.1% (7.7%, n = 11), −22.9% (12.5%, n = 11), and −24.4% (13.2%, n = 8) at 12, 24, and 36 months, respectively.

For children and adolescents (patients aged < 18 years, n = 13), the mean reduction (standard deviation) in BMI z-score was −1.31 ([0.66], n = 13), −1.10 ([0.79], n = 11), and −1.01 (1.22], n = 4) at 12, 24, and 36 months, respectively.

For patients younger than 18 years, the mean variation in BMI z-score was −1.01 SD after three years on setmelanotide (standard deviation, 1.22 [n = 4]). The mean BMI z-score was +2.42 SD (standard deviation, 1.22 [n = 4]) after 3 years of treatment with setmelanotide.

In sum, the patients who achieved a reduction in body weight of at least 10% or greater than or equal to 0.3 mean variation in BMI z-score after 1 year experienced long-lasting, clinically significant benefit after 3 years. The finding supports the long-term use of setmelanotide for this group.

“We feared that setmelanotide’s effectiveness would decrease over time, but after 3 years, this had not happened, and we are hopeful that this sustained efficacy will be long lasting. The first two patients who took the drug in 2016 have not noticed any loss of efficacy as it stands,” said Dr. Dubern.

This is all the more encouraging. In the study presented at the 2023 pediatric conference, setmelanotide’s safety profile was reassuring, and it was consistent with previous studies. Side effects reported in greater than or equal to 15% of patients include injection site reactions, skin hyperpigmentation, nausea, diarrhea, mood disturbances, abdominal pain, vomiting, gastroenteritis, and spontaneous erection.

In addition to the lack of control group, Dr. Dubern acknowledged one other constraint of this study. “Only the patients who responded to treatment with setmelanotide during early-phase trials (85.7%) were enrolled.”

Dr. Dubern summarized the clinical implications: “In patients with early-onset obesity, starting before 5 years of age, doctors should really be considering the possibility that genetics might be involved in such cases. For confirmation and to seek expert opinion, specialist obesity clinics can be found throughout France. Additionally, the INSERM NutriOmics research team headed by Prof Karine Clément, MD, PhD, Sorbonne University, in conjunction with Prof Christine Poitou, MD, PhD, has developed a diagnostic tool [called] ObsGen for practitioners faced with patients with potentially genetic causes of obesity. We can answer any questions they have about the likelihood of a particular patient having a genetic form of obesity and guide their next steps. Treating patients with genetic obesity early on helps limit the condition worsening during adolescence, prevents related complications, and can reduce the stigmatization and suffering experienced by these people. It’s a huge issue. A clinical trial with setmelanotide is currently being carried out in children over 2 years of age.”
 

Hypothalamic obesity

During the pediatric conference, another speaker presented the results of a phase 2 study that evaluated the efficacy and tolerability of setmelanotide as a new treatment for hypothalamic obesity. Lesions in the hypothalamus can alter melanocortin 4 receptor pathway signaling and thus lead to hypothalamic obesity. Eighteen patients aged 6-40 years with a BMI greater than or equal to the 95th percentile (for patients aged 6-18 years) or greater than or equal to 35 kg/m² (for adults aged ≥ 18 years) and hypothalamic obesity (craniopharyngioma or other benign brain tumors, surgical removal, and/or chemotherapy) were enrolled. A significant proportion of patients achieved a reduction of greater than or equal to 5% of their BMI (n = 16, 88.9%, CI 90%, 69%-89%, P < .0001), and 72.2% achieved a reduction of greater than or equal to 10% by week 16. The mean change in BMI was −14.9% (9.6%, n = 17). These early results may justify further studies of setmelanotide in treating hypothalamic obesity.

Dr. Dubern has collaborated with Rhythm Pharmaceuticals and Novo Nordisk.

This article was translated from the Medscape French Edition and a version appeared on Medscape.com.

MARSEILLE, FRANCE – Setmelanotide can lead to significant weight loss that lasts for at least 3 years, according to results presented at the latest French Pediatric Society conference. The treatment is effective for adults and children alike.

Setmelanotide is the culmination of two decades of research involving the identification of genes involved in early-onset obesity and the characterization of the melanocortin 4 receptor. It became available via early access in 2021.

Currently limited to use in treating obesity linked to a biallelic POMC/PCSK1 or LEPR deficiency, setmelanotide is being tested with respect to other mutations responsible for severe obesity, raising hopes that it will soon be indicated for use in a larger number of patients.

Fewer than 1% of patients who suffer from severe obesity have monogenic forms of obesity. In recent years, the hope for a targeted treatment for patients with these monogenic forms has become a reality.

Although only a small number of patients currently meet the criteria for setmelanotide treatment (namely, those with obesity linked to a biallelic POMC/PCSK1 enzyme or LEPR deficiency and patients with Bardet-Biedl syndrome), there is a real hope that patients with other forms of severe obesity will be able to benefit from this product, including those with heterozygous (not just homozygous) monoallelic variants, who account for more than 10% of patients with severe early-onset obesity.
 

Restoring satiety signaling

“Setmelanotide is a melanocortin 4 receptor agonist,” said Béatrice Dubern, MD, PhD, pediatrician at Trousseau Hospital, Paris, and member of the French medical research institute (INSERM)/Sorbonne University team on nutrition and obesity. “Its mode of action rests on activation of the leptin-melanocortin signaling pathway in the hypothalamus, which regulates hunger, satiety, energy expenditure, and, therefore, body weight. Rare genetic variants in the leptin-melanocortin pathway are associated with polyphagia and severe early-onset obesity. It is believed that more than 60 genes involved in this leptin-melanocortin pathway are currently associated with obesity.”

In July 2021, the European Medicines Agency approved setmelanotide for daily use via subcutaneous administration.
 

Weight loss maintained

In phase 3 studies, setmelanotide (melanocortin 4 receptor agonist) demonstrated its effectiveness in reducing weight and hunger for patients with obesity caused by a POMC/PCSK1 or LEPR deficiency.

Twenty-four patients aged 6 years and older showed a significant response to setmelanotide after 1 year of treatment and were included in the extension study. “Significant response” was defined as a reduction in body weight greater than or equal to 10% after 52 weeks for patients aged 18 years and older or a reduction in body mass index (BMI) z-score greater than or equal to 0.3 after 52 weeks for patients younger than 18 years.

Among all patients, the mean variation (standard deviation) in BMI was −24.8% (8.2%, n = 24), −21% (13%, n = 23), and −24% (17.9%, n = 15) at 12, 24, and 36 months, respectively.

For patients aged greater than or equal to 18 years (n = 11), the mean variation (standard deviation) in weight was −25.1% (7.7%, n = 11), −22.9% (12.5%, n = 11), and −24.4% (13.2%, n = 8) at 12, 24, and 36 months, respectively.

For children and adolescents (patients aged < 18 years, n = 13), the mean reduction (standard deviation) in BMI z-score was −1.31 ([0.66], n = 13), −1.10 ([0.79], n = 11), and −1.01 (1.22], n = 4) at 12, 24, and 36 months, respectively.

For patients younger than 18 years, the mean variation in BMI z-score was −1.01 SD after three years on setmelanotide (standard deviation, 1.22 [n = 4]). The mean BMI z-score was +2.42 SD (standard deviation, 1.22 [n = 4]) after 3 years of treatment with setmelanotide.

In sum, the patients who achieved a reduction in body weight of at least 10% or greater than or equal to 0.3 mean variation in BMI z-score after 1 year experienced long-lasting, clinically significant benefit after 3 years. The finding supports the long-term use of setmelanotide for this group.

“We feared that setmelanotide’s effectiveness would decrease over time, but after 3 years, this had not happened, and we are hopeful that this sustained efficacy will be long lasting. The first two patients who took the drug in 2016 have not noticed any loss of efficacy as it stands,” said Dr. Dubern.

This is all the more encouraging. In the study presented at the 2023 pediatric conference, setmelanotide’s safety profile was reassuring, and it was consistent with previous studies. Side effects reported in greater than or equal to 15% of patients include injection site reactions, skin hyperpigmentation, nausea, diarrhea, mood disturbances, abdominal pain, vomiting, gastroenteritis, and spontaneous erection.

In addition to the lack of control group, Dr. Dubern acknowledged one other constraint of this study. “Only the patients who responded to treatment with setmelanotide during early-phase trials (85.7%) were enrolled.”

Dr. Dubern summarized the clinical implications: “In patients with early-onset obesity, starting before 5 years of age, doctors should really be considering the possibility that genetics might be involved in such cases. For confirmation and to seek expert opinion, specialist obesity clinics can be found throughout France. Additionally, the INSERM NutriOmics research team headed by Prof Karine Clément, MD, PhD, Sorbonne University, in conjunction with Prof Christine Poitou, MD, PhD, has developed a diagnostic tool [called] ObsGen for practitioners faced with patients with potentially genetic causes of obesity. We can answer any questions they have about the likelihood of a particular patient having a genetic form of obesity and guide their next steps. Treating patients with genetic obesity early on helps limit the condition worsening during adolescence, prevents related complications, and can reduce the stigmatization and suffering experienced by these people. It’s a huge issue. A clinical trial with setmelanotide is currently being carried out in children over 2 years of age.”
 

Hypothalamic obesity

During the pediatric conference, another speaker presented the results of a phase 2 study that evaluated the efficacy and tolerability of setmelanotide as a new treatment for hypothalamic obesity. Lesions in the hypothalamus can alter melanocortin 4 receptor pathway signaling and thus lead to hypothalamic obesity. Eighteen patients aged 6-40 years with a BMI greater than or equal to the 95th percentile (for patients aged 6-18 years) or greater than or equal to 35 kg/m² (for adults aged ≥ 18 years) and hypothalamic obesity (craniopharyngioma or other benign brain tumors, surgical removal, and/or chemotherapy) were enrolled. A significant proportion of patients achieved a reduction of greater than or equal to 5% of their BMI (n = 16, 88.9%, CI 90%, 69%-89%, P < .0001), and 72.2% achieved a reduction of greater than or equal to 10% by week 16. The mean change in BMI was −14.9% (9.6%, n = 17). These early results may justify further studies of setmelanotide in treating hypothalamic obesity.

Dr. Dubern has collaborated with Rhythm Pharmaceuticals and Novo Nordisk.

This article was translated from the Medscape French Edition and a version appeared on Medscape.com.

MARSEILLE, FRANCE – Setmelanotide can lead to significant weight loss that lasts for at least 3 years, according to results presented at the latest French Pediatric Society conference. The treatment is effective for adults and children alike.

Setmelanotide is the culmination of two decades of research involving the identification of genes involved in early-onset obesity and the characterization of the melanocortin 4 receptor. It became available via early access in 2021.

Currently limited to use in treating obesity linked to a biallelic POMC/PCSK1 or LEPR deficiency, setmelanotide is being tested with respect to other mutations responsible for severe obesity, raising hopes that it will soon be indicated for use in a larger number of patients.

Fewer than 1% of patients who suffer from severe obesity have monogenic forms of obesity. In recent years, the hope for a targeted treatment for patients with these monogenic forms has become a reality.

Although only a small number of patients currently meet the criteria for setmelanotide treatment (namely, those with obesity linked to a biallelic POMC/PCSK1 enzyme or LEPR deficiency and patients with Bardet-Biedl syndrome), there is a real hope that patients with other forms of severe obesity will be able to benefit from this product, including those with heterozygous (not just homozygous) monoallelic variants, who account for more than 10% of patients with severe early-onset obesity.
 

Restoring satiety signaling

“Setmelanotide is a melanocortin 4 receptor agonist,” said Béatrice Dubern, MD, PhD, pediatrician at Trousseau Hospital, Paris, and member of the French medical research institute (INSERM)/Sorbonne University team on nutrition and obesity. “Its mode of action rests on activation of the leptin-melanocortin signaling pathway in the hypothalamus, which regulates hunger, satiety, energy expenditure, and, therefore, body weight. Rare genetic variants in the leptin-melanocortin pathway are associated with polyphagia and severe early-onset obesity. It is believed that more than 60 genes involved in this leptin-melanocortin pathway are currently associated with obesity.”

In July 2021, the European Medicines Agency approved setmelanotide for daily use via subcutaneous administration.
 

Weight loss maintained

In phase 3 studies, setmelanotide (melanocortin 4 receptor agonist) demonstrated its effectiveness in reducing weight and hunger for patients with obesity caused by a POMC/PCSK1 or LEPR deficiency.

Twenty-four patients aged 6 years and older showed a significant response to setmelanotide after 1 year of treatment and were included in the extension study. “Significant response” was defined as a reduction in body weight greater than or equal to 10% after 52 weeks for patients aged 18 years and older or a reduction in body mass index (BMI) z-score greater than or equal to 0.3 after 52 weeks for patients younger than 18 years.

Among all patients, the mean variation (standard deviation) in BMI was −24.8% (8.2%, n = 24), −21% (13%, n = 23), and −24% (17.9%, n = 15) at 12, 24, and 36 months, respectively.

For patients aged greater than or equal to 18 years (n = 11), the mean variation (standard deviation) in weight was −25.1% (7.7%, n = 11), −22.9% (12.5%, n = 11), and −24.4% (13.2%, n = 8) at 12, 24, and 36 months, respectively.

For children and adolescents (patients aged < 18 years, n = 13), the mean reduction (standard deviation) in BMI z-score was −1.31 ([0.66], n = 13), −1.10 ([0.79], n = 11), and −1.01 (1.22], n = 4) at 12, 24, and 36 months, respectively.

For patients younger than 18 years, the mean variation in BMI z-score was −1.01 SD after three years on setmelanotide (standard deviation, 1.22 [n = 4]). The mean BMI z-score was +2.42 SD (standard deviation, 1.22 [n = 4]) after 3 years of treatment with setmelanotide.

In sum, the patients who achieved a reduction in body weight of at least 10% or greater than or equal to 0.3 mean variation in BMI z-score after 1 year experienced long-lasting, clinically significant benefit after 3 years. The finding supports the long-term use of setmelanotide for this group.

“We feared that setmelanotide’s effectiveness would decrease over time, but after 3 years, this had not happened, and we are hopeful that this sustained efficacy will be long lasting. The first two patients who took the drug in 2016 have not noticed any loss of efficacy as it stands,” said Dr. Dubern.

This is all the more encouraging. In the study presented at the 2023 pediatric conference, setmelanotide’s safety profile was reassuring, and it was consistent with previous studies. Side effects reported in greater than or equal to 15% of patients include injection site reactions, skin hyperpigmentation, nausea, diarrhea, mood disturbances, abdominal pain, vomiting, gastroenteritis, and spontaneous erection.

In addition to the lack of control group, Dr. Dubern acknowledged one other constraint of this study. “Only the patients who responded to treatment with setmelanotide during early-phase trials (85.7%) were enrolled.”

Dr. Dubern summarized the clinical implications: “In patients with early-onset obesity, starting before 5 years of age, doctors should really be considering the possibility that genetics might be involved in such cases. For confirmation and to seek expert opinion, specialist obesity clinics can be found throughout France. Additionally, the INSERM NutriOmics research team headed by Prof Karine Clément, MD, PhD, Sorbonne University, in conjunction with Prof Christine Poitou, MD, PhD, has developed a diagnostic tool [called] ObsGen for practitioners faced with patients with potentially genetic causes of obesity. We can answer any questions they have about the likelihood of a particular patient having a genetic form of obesity and guide their next steps. Treating patients with genetic obesity early on helps limit the condition worsening during adolescence, prevents related complications, and can reduce the stigmatization and suffering experienced by these people. It’s a huge issue. A clinical trial with setmelanotide is currently being carried out in children over 2 years of age.”
 

Hypothalamic obesity

During the pediatric conference, another speaker presented the results of a phase 2 study that evaluated the efficacy and tolerability of setmelanotide as a new treatment for hypothalamic obesity. Lesions in the hypothalamus can alter melanocortin 4 receptor pathway signaling and thus lead to hypothalamic obesity. Eighteen patients aged 6-40 years with a BMI greater than or equal to the 95th percentile (for patients aged 6-18 years) or greater than or equal to 35 kg/m² (for adults aged ≥ 18 years) and hypothalamic obesity (craniopharyngioma or other benign brain tumors, surgical removal, and/or chemotherapy) were enrolled. A significant proportion of patients achieved a reduction of greater than or equal to 5% of their BMI (n = 16, 88.9%, CI 90%, 69%-89%, P < .0001), and 72.2% achieved a reduction of greater than or equal to 10% by week 16. The mean change in BMI was −14.9% (9.6%, n = 17). These early results may justify further studies of setmelanotide in treating hypothalamic obesity.

Dr. Dubern has collaborated with Rhythm Pharmaceuticals and Novo Nordisk.

This article was translated from the Medscape French Edition and a version appeared on Medscape.com.

An unapproved gene therapy for Leber hereditary optic neuropathy (LHON) led to a marked improvement in the eyesight of patients with a severe, progressive form of the disease who received the therapy as part of an early access program.

Results of a study of more than 60 patients who received lenadogene nolparvovec (Lumevoq, GenSight Biologics) as a unilateral or bilateral intravitreal injection showed that at 2-year follow-up, 60% had experienced a clinically relevant improvement in the number of letters they could read on a visual acuity chart.

The results, said study presenter Chiara La Morgia, MD, PhD, IRCCS Istituto delle Scienze Neurologiche di Bologna (Italy), confirm in a “real-life setting” the efficacy and safety of the treatment as previously shown in clinical trials.

The findings were presented at the Congress of the European Academy of Neurology (EAN) 2023.
 

Severe disease

LHON is a maternally inherited genetic condition that leads to rapid loss of vision. It is caused by alterations in mitochondrial DNA that increase oxidative stress in retinal ganglion cells, leading to cell damage and death. The m.11778G>A MT-ND4 mutation (MT-ND4-LHON) is the most common and is seen in approximately 75% of LHON patients in Europe and North America.

It also leads to the most severe form of the disease, in which patients experience rapid, progressive, and painless bilateral loss of vision, either simultaneously or sequentially in both eyes. Within 1 year of onset, 97% of patients have bilateral involvement.

Lenadogene nolparvovec uses an adeno-associated virus vector to deliver the wild-type ND4 gene directly to the mitochondrial membrane of the retinal ganglion cells. This compensates for the mutation and leads to protein synthesis and restoration of energy production.

Dr. La Morgia said that, so far, five clinical studies are or have been conducted with the gene therapy with patients in France, Italy, the United Kingdom, and the United States.

In the current analysis, patients who received the therapy as part of an early access program underwent unilateral or bilateral intravitreal injection at a dose of 9x10¹⁰ viral genomes per eye. Efficacy and safety data, as well as patient baseline characteristics, were collected.

Between August 2018 and March 2022, 63 patients with MT-ND4-LHON received lenadogene nolparvovec. Individual-level data were pooled and analyzed. The mean age at first injection was 33.7 years; 90.5% of participants were aged 60 years or younger. The majority (77.8%) were male; just over half (55.6%) were from France, while 28.6% were from the United States.

The average disease duration at first injection was 11.3 years. Sixty-seven percent of patients were injected in both eyes, and 81.0% had previously received idebenone, a short-chain benzoquinone, the only treatment for LHON that has marketing authorization.

At 2-year follow-up, there was a marked improvement in best-corrected visual acuity (BCVA) scores. Moreover, among all 90 treated eyes for which data were available, the mean change in BCVA from nadir at 1 year was –0.45 log of the minimum angle of resolution (LogMAR), or +22.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters on a chart.

Among 58 bilaterally treated eyes, the mean improvement was –0.49 LogMAR, or +24.5 ETDRS letters, over the same period. In 32 unilaterally treated eyes, mean improvement was –0.39 LogMAR, or +19.5 ETDRS letters.

Overall, 64.4% of treated eyes showed an improvement from nadir of ≥ 0.3 LogMAR. A clinically relevant response, defined as an improvement of ≥ 10 ETDRS letters, was achieved by 60.0% of patients.

Regarding safety, Dr. La Morgia showed that 42.9% of eyes had at least one episode of intraocular inflammation, a rate she described as “quite high.” The episodes lasted for an average of 155.8 days.

“But all of this inflammation was very easily treatable in a majority of cases without using oral steroids,” she added, “just topical steroids.”

She also noted that in most cases, the inflammation was not severe.
 

Approval status

Session cochair Gianfranco De Stefano, MD, department of human neuroscience, Sapienza University of Rome, asked Dr. La Morgia about the current approval status of lenadogene nolparvovec.

She said that it was presented to the European Medicines Agency for approval, but the application was withdrawn earlier this year. The “main criticism” was that bilateral improvement was seen even in patients who received only a unilateral injection.

This is “not easily explainable,” said Dr. La Morgia, although it was found that the viral vector was present in the uninjected eye.

There was also a question regarding the heterogeneity of the patient data, which it is hoped will be addressed in future clinical trials.

Commenting after the session, De Stefano said in an interview that the results are “very interesting” and “very promising.”

He pointed out that idebenone may be the only currently available therapy for LHON, but it is “not very effective, and it’s something you give the patient just for the sake of doing something” in light of the possibility that he or she might have “even a small improvement” in eyesight.

However, he believes that lenadogene nolparvovec is a long way from becoming available in the clinic, primarily because longer follow-up is required to determine whether just one injection is enough.

“It may be likely that this gene therapy does not have a long-lasting effect,” he explained.

Currently, the longest follow-up is just 2 years; “I don’t know if there will be a need for repeat injection,” De Stefano said.

No funding was declared. Dr. La Morgia has relationships with Chiesi Farmaceutici, GenSight Biologics, Regulatory Pharma Net, Thenewway, Santhera Pharmaceuticals, First Class srl, Biologix, Stoke Therapeutics, and Reneo.

A version of this article first appeared on Medscape.com.

An unapproved gene therapy for Leber hereditary optic neuropathy (LHON) led to a marked improvement in the eyesight of patients with a severe, progressive form of the disease who received the therapy as part of an early access program.

Results of a study of more than 60 patients who received lenadogene nolparvovec (Lumevoq, GenSight Biologics) as a unilateral or bilateral intravitreal injection showed that at 2-year follow-up, 60% had experienced a clinically relevant improvement in the number of letters they could read on a visual acuity chart.

The results, said study presenter Chiara La Morgia, MD, PhD, IRCCS Istituto delle Scienze Neurologiche di Bologna (Italy), confirm in a “real-life setting” the efficacy and safety of the treatment as previously shown in clinical trials.

The findings were presented at the Congress of the European Academy of Neurology (EAN) 2023.
 

Severe disease

LHON is a maternally inherited genetic condition that leads to rapid loss of vision. It is caused by alterations in mitochondrial DNA that increase oxidative stress in retinal ganglion cells, leading to cell damage and death. The m.11778G>A MT-ND4 mutation (MT-ND4-LHON) is the most common and is seen in approximately 75% of LHON patients in Europe and North America.

It also leads to the most severe form of the disease, in which patients experience rapid, progressive, and painless bilateral loss of vision, either simultaneously or sequentially in both eyes. Within 1 year of onset, 97% of patients have bilateral involvement.

Lenadogene nolparvovec uses an adeno-associated virus vector to deliver the wild-type ND4 gene directly to the mitochondrial membrane of the retinal ganglion cells. This compensates for the mutation and leads to protein synthesis and restoration of energy production.

Dr. La Morgia said that, so far, five clinical studies are or have been conducted with the gene therapy with patients in France, Italy, the United Kingdom, and the United States.

In the current analysis, patients who received the therapy as part of an early access program underwent unilateral or bilateral intravitreal injection at a dose of 9x10¹⁰ viral genomes per eye. Efficacy and safety data, as well as patient baseline characteristics, were collected.

Between August 2018 and March 2022, 63 patients with MT-ND4-LHON received lenadogene nolparvovec. Individual-level data were pooled and analyzed. The mean age at first injection was 33.7 years; 90.5% of participants were aged 60 years or younger. The majority (77.8%) were male; just over half (55.6%) were from France, while 28.6% were from the United States.

The average disease duration at first injection was 11.3 years. Sixty-seven percent of patients were injected in both eyes, and 81.0% had previously received idebenone, a short-chain benzoquinone, the only treatment for LHON that has marketing authorization.

At 2-year follow-up, there was a marked improvement in best-corrected visual acuity (BCVA) scores. Moreover, among all 90 treated eyes for which data were available, the mean change in BCVA from nadir at 1 year was –0.45 log of the minimum angle of resolution (LogMAR), or +22.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters on a chart.

Among 58 bilaterally treated eyes, the mean improvement was –0.49 LogMAR, or +24.5 ETDRS letters, over the same period. In 32 unilaterally treated eyes, mean improvement was –0.39 LogMAR, or +19.5 ETDRS letters.

Overall, 64.4% of treated eyes showed an improvement from nadir of ≥ 0.3 LogMAR. A clinically relevant response, defined as an improvement of ≥ 10 ETDRS letters, was achieved by 60.0% of patients.

Regarding safety, Dr. La Morgia showed that 42.9% of eyes had at least one episode of intraocular inflammation, a rate she described as “quite high.” The episodes lasted for an average of 155.8 days.

“But all of this inflammation was very easily treatable in a majority of cases without using oral steroids,” she added, “just topical steroids.”

She also noted that in most cases, the inflammation was not severe.
 

Approval status

Session cochair Gianfranco De Stefano, MD, department of human neuroscience, Sapienza University of Rome, asked Dr. La Morgia about the current approval status of lenadogene nolparvovec.

She said that it was presented to the European Medicines Agency for approval, but the application was withdrawn earlier this year. The “main criticism” was that bilateral improvement was seen even in patients who received only a unilateral injection.

This is “not easily explainable,” said Dr. La Morgia, although it was found that the viral vector was present in the uninjected eye.

There was also a question regarding the heterogeneity of the patient data, which it is hoped will be addressed in future clinical trials.

Commenting after the session, De Stefano said in an interview that the results are “very interesting” and “very promising.”

He pointed out that idebenone may be the only currently available therapy for LHON, but it is “not very effective, and it’s something you give the patient just for the sake of doing something” in light of the possibility that he or she might have “even a small improvement” in eyesight.

However, he believes that lenadogene nolparvovec is a long way from becoming available in the clinic, primarily because longer follow-up is required to determine whether just one injection is enough.

“It may be likely that this gene therapy does not have a long-lasting effect,” he explained.

Currently, the longest follow-up is just 2 years; “I don’t know if there will be a need for repeat injection,” De Stefano said.

No funding was declared. Dr. La Morgia has relationships with Chiesi Farmaceutici, GenSight Biologics, Regulatory Pharma Net, Thenewway, Santhera Pharmaceuticals, First Class srl, Biologix, Stoke Therapeutics, and Reneo.

A version of this article first appeared on Medscape.com.

An unapproved gene therapy for Leber hereditary optic neuropathy (LHON) led to a marked improvement in the eyesight of patients with a severe, progressive form of the disease who received the therapy as part of an early access program.

Results of a study of more than 60 patients who received lenadogene nolparvovec (Lumevoq, GenSight Biologics) as a unilateral or bilateral intravitreal injection showed that at 2-year follow-up, 60% had experienced a clinically relevant improvement in the number of letters they could read on a visual acuity chart.

The results, said study presenter Chiara La Morgia, MD, PhD, IRCCS Istituto delle Scienze Neurologiche di Bologna (Italy), confirm in a “real-life setting” the efficacy and safety of the treatment as previously shown in clinical trials.

The findings were presented at the Congress of the European Academy of Neurology (EAN) 2023.
 

Severe disease

LHON is a maternally inherited genetic condition that leads to rapid loss of vision. It is caused by alterations in mitochondrial DNA that increase oxidative stress in retinal ganglion cells, leading to cell damage and death. The m.11778G>A MT-ND4 mutation (MT-ND4-LHON) is the most common and is seen in approximately 75% of LHON patients in Europe and North America.

It also leads to the most severe form of the disease, in which patients experience rapid, progressive, and painless bilateral loss of vision, either simultaneously or sequentially in both eyes. Within 1 year of onset, 97% of patients have bilateral involvement.

Lenadogene nolparvovec uses an adeno-associated virus vector to deliver the wild-type ND4 gene directly to the mitochondrial membrane of the retinal ganglion cells. This compensates for the mutation and leads to protein synthesis and restoration of energy production.

Dr. La Morgia said that, so far, five clinical studies are or have been conducted with the gene therapy with patients in France, Italy, the United Kingdom, and the United States.

In the current analysis, patients who received the therapy as part of an early access program underwent unilateral or bilateral intravitreal injection at a dose of 9x10¹⁰ viral genomes per eye. Efficacy and safety data, as well as patient baseline characteristics, were collected.

Between August 2018 and March 2022, 63 patients with MT-ND4-LHON received lenadogene nolparvovec. Individual-level data were pooled and analyzed. The mean age at first injection was 33.7 years; 90.5% of participants were aged 60 years or younger. The majority (77.8%) were male; just over half (55.6%) were from France, while 28.6% were from the United States.

The average disease duration at first injection was 11.3 years. Sixty-seven percent of patients were injected in both eyes, and 81.0% had previously received idebenone, a short-chain benzoquinone, the only treatment for LHON that has marketing authorization.

At 2-year follow-up, there was a marked improvement in best-corrected visual acuity (BCVA) scores. Moreover, among all 90 treated eyes for which data were available, the mean change in BCVA from nadir at 1 year was –0.45 log of the minimum angle of resolution (LogMAR), or +22.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters on a chart.

Among 58 bilaterally treated eyes, the mean improvement was –0.49 LogMAR, or +24.5 ETDRS letters, over the same period. In 32 unilaterally treated eyes, mean improvement was –0.39 LogMAR, or +19.5 ETDRS letters.

Overall, 64.4% of treated eyes showed an improvement from nadir of ≥ 0.3 LogMAR. A clinically relevant response, defined as an improvement of ≥ 10 ETDRS letters, was achieved by 60.0% of patients.

Regarding safety, Dr. La Morgia showed that 42.9% of eyes had at least one episode of intraocular inflammation, a rate she described as “quite high.” The episodes lasted for an average of 155.8 days.

“But all of this inflammation was very easily treatable in a majority of cases without using oral steroids,” she added, “just topical steroids.”

She also noted that in most cases, the inflammation was not severe.
 

Approval status

Session cochair Gianfranco De Stefano, MD, department of human neuroscience, Sapienza University of Rome, asked Dr. La Morgia about the current approval status of lenadogene nolparvovec.

She said that it was presented to the European Medicines Agency for approval, but the application was withdrawn earlier this year. The “main criticism” was that bilateral improvement was seen even in patients who received only a unilateral injection.

This is “not easily explainable,” said Dr. La Morgia, although it was found that the viral vector was present in the uninjected eye.

There was also a question regarding the heterogeneity of the patient data, which it is hoped will be addressed in future clinical trials.

Commenting after the session, De Stefano said in an interview that the results are “very interesting” and “very promising.”

He pointed out that idebenone may be the only currently available therapy for LHON, but it is “not very effective, and it’s something you give the patient just for the sake of doing something” in light of the possibility that he or she might have “even a small improvement” in eyesight.

However, he believes that lenadogene nolparvovec is a long way from becoming available in the clinic, primarily because longer follow-up is required to determine whether just one injection is enough.

“It may be likely that this gene therapy does not have a long-lasting effect,” he explained.

Currently, the longest follow-up is just 2 years; “I don’t know if there will be a need for repeat injection,” De Stefano said.

No funding was declared. Dr. La Morgia has relationships with Chiesi Farmaceutici, GenSight Biologics, Regulatory Pharma Net, Thenewway, Santhera Pharmaceuticals, First Class srl, Biologix, Stoke Therapeutics, and Reneo.

A version of this article first appeared on Medscape.com.

The incidence of type 1 diabetes has risen during the COVID-19 pandemic, according to a recent meta-analysis.

The review compared 2 years of data from during the pandemic to data from a prepandemic period, and showed a higher incidence of type 1 diabetes in the first year (incidence rate ratio, 1.14) and second year (IRR, 1.27) of the pandemic. The investigators also found an increase in the incidence of diabetic ketoacidosis (DKA) (IRR, 1.26).

The meta-analysis included 17 studies of 38,149 children and adolescents with newly diagnosed type 1 diabetes. “Putting them all together really gave us more confidence to say this is something that we think is real,” study author Rayzel Shulman, MD, PhD, an endocrinologist at The Hospital for Sick Children in Toronto and associate professor of pediatrics at the University of Toronto, said in an interview.

The study was published in JAMA Network Open.
 

Increased incidence

The investigators reviewed 42 studies, including 17 that examined rates of type 1 diabetes incidence, 10 on type 2 diabetes, and 15 on DKA. The included studies all had a minimum observation period of 12 months during the pandemic and at least 12 months before it. Relative to the prepandemic period, the meta-analysis found higher rates of type 1 diabetes and DKA during the pandemic.

The review was conducted in response to questions about the methodology of study results suggesting an association between the COVID-19 pandemic and the incidence of diabetes, according to Dr. Shulman.

Although this is not the first review of studies on the connection between diabetes and COVID-19, it adds to the literature by extending the study period to 2 years of the pandemic. The longer time frame helps address potential seasonal differences in incidence and increases confidence in the results.

The investigators also sought to look at the incidence of type 2 diabetes in children but found few studies that met the study criteria. Although some studies reported rates of type 2 diabetes, most lacked information about the population, specifically, the “denominator” needed for findings regarding any association with the COVID-19 pandemic.

With greater confidence in the increased incidence of type 1 diabetes, Dr. Shulman emphasized a need to ensure sufficient resources to care for newly diagnosed patients, including education and support for families.

The study’s secondary outcome was the change in incidence rate of DKA among children with newly diagnosed diabetes. Data reported in 15 studies showed a 26% increase in DKA incidence during the first year of the pandemic.

“DKA is a serious and life-threatening condition that is preventable,” said Dr. Shulman. Symptoms of type 1 diabetes include increased thirst and urination, weight loss, and fatigue. If parents or caregivers notice these signs, Dr. Shulman advises them to seek care immediately to reduce the risk of DKA.
 

Possible mechanisms

In a comment, Elizabeth Sellers, MD, an endocrinologist at the Children’s Hospital Research Institute of Manitoba and associate professor of pediatrics at the University of Manitoba, both in Winnipeg, said the study’s findings on DKA are an important reminder to be attentive to symptoms of diabetes. Dr. Sellers did not participate in the meta-analysis.

One possible explanation for the increase is a hesitancy to seek care among parents and caregivers during the pandemic. “I think we use that information and turn it into a positive,” said Dr. Sellers, by increasing recognition of the symptoms. Dr. Sellers, whose research is included in the review, is part of an initiative by the Canadian Pediatric Endocrine Group to increase diabetes awareness.

The study provides important findings, particularly the second-year results, but is not designed to answer why there has been an increase in diabetes incidence, said Dr. Sellers. “You have to identify the problem first and then you can go back and look at mechanisms.”

The meta-analysis did not seek to draw conclusions about the underlying mechanisms that would explain changes in diabetes incidence but rather indicates a need for further studies to seek a better understanding of the connection. Several theories may be considered, wrote Clemens Kamrath, MD, of the Centre of Child and Adolescent Medicine at Justus Liebig University in Giessen, Germany, and colleagues in an accompanying editorial.

Studies have suggested a direct effect of infections such as COVID-19, whereby the virus damages insulin-producing beta cells. However, the commentary notes these studies do not account for asymptomatic infections among children.

Dr. Kamrath and colleagues also considered the indirect effects of the COVID-19 pandemic, which they indicate may be more likely than direct effects. These indirect effects include autoimmunity and environmental changes that occurred during the pandemic.

Researchers will need to continue monitoring the data to see if the trend persists and continue working to determine the mechanisms, said Dr. Schulman. “I don’t think this is the end of the story.”

The study was supported in part by grant funding from the department of pediatrics at The Hospital for Sick Children. Dr. Shulman, Dr. Sellers, and Dr. Kamrath reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The incidence of type 1 diabetes has risen during the COVID-19 pandemic, according to a recent meta-analysis.

The review compared 2 years of data from during the pandemic to data from a prepandemic period, and showed a higher incidence of type 1 diabetes in the first year (incidence rate ratio, 1.14) and second year (IRR, 1.27) of the pandemic. The investigators also found an increase in the incidence of diabetic ketoacidosis (DKA) (IRR, 1.26).

The meta-analysis included 17 studies of 38,149 children and adolescents with newly diagnosed type 1 diabetes. “Putting them all together really gave us more confidence to say this is something that we think is real,” study author Rayzel Shulman, MD, PhD, an endocrinologist at The Hospital for Sick Children in Toronto and associate professor of pediatrics at the University of Toronto, said in an interview.

The study was published in JAMA Network Open.
 

Increased incidence

The investigators reviewed 42 studies, including 17 that examined rates of type 1 diabetes incidence, 10 on type 2 diabetes, and 15 on DKA. The included studies all had a minimum observation period of 12 months during the pandemic and at least 12 months before it. Relative to the prepandemic period, the meta-analysis found higher rates of type 1 diabetes and DKA during the pandemic.

The review was conducted in response to questions about the methodology of study results suggesting an association between the COVID-19 pandemic and the incidence of diabetes, according to Dr. Shulman.

Although this is not the first review of studies on the connection between diabetes and COVID-19, it adds to the literature by extending the study period to 2 years of the pandemic. The longer time frame helps address potential seasonal differences in incidence and increases confidence in the results.

The investigators also sought to look at the incidence of type 2 diabetes in children but found few studies that met the study criteria. Although some studies reported rates of type 2 diabetes, most lacked information about the population, specifically, the “denominator” needed for findings regarding any association with the COVID-19 pandemic.

With greater confidence in the increased incidence of type 1 diabetes, Dr. Shulman emphasized a need to ensure sufficient resources to care for newly diagnosed patients, including education and support for families.

The study’s secondary outcome was the change in incidence rate of DKA among children with newly diagnosed diabetes. Data reported in 15 studies showed a 26% increase in DKA incidence during the first year of the pandemic.

“DKA is a serious and life-threatening condition that is preventable,” said Dr. Shulman. Symptoms of type 1 diabetes include increased thirst and urination, weight loss, and fatigue. If parents or caregivers notice these signs, Dr. Shulman advises them to seek care immediately to reduce the risk of DKA.
 

Possible mechanisms

In a comment, Elizabeth Sellers, MD, an endocrinologist at the Children’s Hospital Research Institute of Manitoba and associate professor of pediatrics at the University of Manitoba, both in Winnipeg, said the study’s findings on DKA are an important reminder to be attentive to symptoms of diabetes. Dr. Sellers did not participate in the meta-analysis.

One possible explanation for the increase is a hesitancy to seek care among parents and caregivers during the pandemic. “I think we use that information and turn it into a positive,” said Dr. Sellers, by increasing recognition of the symptoms. Dr. Sellers, whose research is included in the review, is part of an initiative by the Canadian Pediatric Endocrine Group to increase diabetes awareness.

The study provides important findings, particularly the second-year results, but is not designed to answer why there has been an increase in diabetes incidence, said Dr. Sellers. “You have to identify the problem first and then you can go back and look at mechanisms.”

The meta-analysis did not seek to draw conclusions about the underlying mechanisms that would explain changes in diabetes incidence but rather indicates a need for further studies to seek a better understanding of the connection. Several theories may be considered, wrote Clemens Kamrath, MD, of the Centre of Child and Adolescent Medicine at Justus Liebig University in Giessen, Germany, and colleagues in an accompanying editorial.

Studies have suggested a direct effect of infections such as COVID-19, whereby the virus damages insulin-producing beta cells. However, the commentary notes these studies do not account for asymptomatic infections among children.

Dr. Kamrath and colleagues also considered the indirect effects of the COVID-19 pandemic, which they indicate may be more likely than direct effects. These indirect effects include autoimmunity and environmental changes that occurred during the pandemic.

Researchers will need to continue monitoring the data to see if the trend persists and continue working to determine the mechanisms, said Dr. Schulman. “I don’t think this is the end of the story.”

The study was supported in part by grant funding from the department of pediatrics at The Hospital for Sick Children. Dr. Shulman, Dr. Sellers, and Dr. Kamrath reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The incidence of type 1 diabetes has risen during the COVID-19 pandemic, according to a recent meta-analysis.

The review compared 2 years of data from during the pandemic to data from a prepandemic period, and showed a higher incidence of type 1 diabetes in the first year (incidence rate ratio, 1.14) and second year (IRR, 1.27) of the pandemic. The investigators also found an increase in the incidence of diabetic ketoacidosis (DKA) (IRR, 1.26).

The meta-analysis included 17 studies of 38,149 children and adolescents with newly diagnosed type 1 diabetes. “Putting them all together really gave us more confidence to say this is something that we think is real,” study author Rayzel Shulman, MD, PhD, an endocrinologist at The Hospital for Sick Children in Toronto and associate professor of pediatrics at the University of Toronto, said in an interview.

The study was published in JAMA Network Open.
 

Increased incidence

The investigators reviewed 42 studies, including 17 that examined rates of type 1 diabetes incidence, 10 on type 2 diabetes, and 15 on DKA. The included studies all had a minimum observation period of 12 months during the pandemic and at least 12 months before it. Relative to the prepandemic period, the meta-analysis found higher rates of type 1 diabetes and DKA during the pandemic.

The review was conducted in response to questions about the methodology of study results suggesting an association between the COVID-19 pandemic and the incidence of diabetes, according to Dr. Shulman.

Although this is not the first review of studies on the connection between diabetes and COVID-19, it adds to the literature by extending the study period to 2 years of the pandemic. The longer time frame helps address potential seasonal differences in incidence and increases confidence in the results.

The investigators also sought to look at the incidence of type 2 diabetes in children but found few studies that met the study criteria. Although some studies reported rates of type 2 diabetes, most lacked information about the population, specifically, the “denominator” needed for findings regarding any association with the COVID-19 pandemic.

With greater confidence in the increased incidence of type 1 diabetes, Dr. Shulman emphasized a need to ensure sufficient resources to care for newly diagnosed patients, including education and support for families.

The study’s secondary outcome was the change in incidence rate of DKA among children with newly diagnosed diabetes. Data reported in 15 studies showed a 26% increase in DKA incidence during the first year of the pandemic.

“DKA is a serious and life-threatening condition that is preventable,” said Dr. Shulman. Symptoms of type 1 diabetes include increased thirst and urination, weight loss, and fatigue. If parents or caregivers notice these signs, Dr. Shulman advises them to seek care immediately to reduce the risk of DKA.
 

Possible mechanisms

In a comment, Elizabeth Sellers, MD, an endocrinologist at the Children’s Hospital Research Institute of Manitoba and associate professor of pediatrics at the University of Manitoba, both in Winnipeg, said the study’s findings on DKA are an important reminder to be attentive to symptoms of diabetes. Dr. Sellers did not participate in the meta-analysis.

One possible explanation for the increase is a hesitancy to seek care among parents and caregivers during the pandemic. “I think we use that information and turn it into a positive,” said Dr. Sellers, by increasing recognition of the symptoms. Dr. Sellers, whose research is included in the review, is part of an initiative by the Canadian Pediatric Endocrine Group to increase diabetes awareness.

The study provides important findings, particularly the second-year results, but is not designed to answer why there has been an increase in diabetes incidence, said Dr. Sellers. “You have to identify the problem first and then you can go back and look at mechanisms.”

The meta-analysis did not seek to draw conclusions about the underlying mechanisms that would explain changes in diabetes incidence but rather indicates a need for further studies to seek a better understanding of the connection. Several theories may be considered, wrote Clemens Kamrath, MD, of the Centre of Child and Adolescent Medicine at Justus Liebig University in Giessen, Germany, and colleagues in an accompanying editorial.

Studies have suggested a direct effect of infections such as COVID-19, whereby the virus damages insulin-producing beta cells. However, the commentary notes these studies do not account for asymptomatic infections among children.

Dr. Kamrath and colleagues also considered the indirect effects of the COVID-19 pandemic, which they indicate may be more likely than direct effects. These indirect effects include autoimmunity and environmental changes that occurred during the pandemic.

Researchers will need to continue monitoring the data to see if the trend persists and continue working to determine the mechanisms, said Dr. Schulman. “I don’t think this is the end of the story.”

The study was supported in part by grant funding from the department of pediatrics at The Hospital for Sick Children. Dr. Shulman, Dr. Sellers, and Dr. Kamrath reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Nearly 9 out of every 100 U.S. children are now diagnosed with a developmental disability, according to updated figures from the CDC. 

Developmental disabilities include autism, intellectual disabilities such as Down syndrome, and a range of other diagnoses related to missing developmental milestones in how a child plays, learns, or speaks.

The newly reported increase amounts to just over 1 percentage point from 2019 to 2021. In 2019, the rate of developmental disability diagnoses was about 7 in 100 children. The latest figures are from 2021 data, published this week after the CDC finished analyzing responses to the National Health Survey.

Among children ages 3-17 years old in 2021, the survey showed that:

• 1.7% had an intellectual disability.
• 3.1% had autism spectrum disorder.
• 6.1% had a diagnosis of “other developmental delay.”

No significant change was seen from 2019 to 2021 in how common it was for survey respondents to report children having autism or an intellectual disability. The overall increase was driven by a jump in reports from parents that a doctor or health professional told them their child had “any other developmental delay,” excluding autism spectrum disorder or an intellectual disability.

“A lot of times developmental delays might be temporary diagnoses that evolve into something like autism, potentially, or intellectual disability. But also a lot of times children do age out of those,” lead report author and CDC statistician Benjamin Zablotsky, PhD, told CBS News.

The CDC offers an app called Milestone Tracker to help parents watch for signs of developmental delays, in addition to operating a public health education program called “Learn the Signs. Act Early.”

The new report showed that boys were nearly twice as likely as girls to have any developmental delay, a pattern that was magnified when looking specifically at autism diagnoses. Boys were more than three times as likely as girls to be diagnosed with autism spectrum disorder. The rate of autism among boys was 4.7%, compared with 1.5% among girls.

While these latest survey results showed consistent rates of autism from 2019 to 2021, a different CDC report earlier this year showed an alarming jump in the rate of autism spectrum disorder among 8-year-olds. That report, which compared data from 2008 to 2020, showed the rate of autism among 8-year-olds rose during those 12 years from 1 in 88 kids to 1 in 36 kids.

The two analyses also differed in their findings regarding prevalence of autism when looking at children by race and ethnicity. The report from earlier this year showed that Black and Hispanic children were more likely to be diagnosed with autism, compared with White children. This latest report did not find any differences in the prevalence of autism based on a child’s race or ethnicity.

A version of this article appeared on WebMD.com.

Nearly 9 out of every 100 U.S. children are now diagnosed with a developmental disability, according to updated figures from the CDC. 

Developmental disabilities include autism, intellectual disabilities such as Down syndrome, and a range of other diagnoses related to missing developmental milestones in how a child plays, learns, or speaks.

The newly reported increase amounts to just over 1 percentage point from 2019 to 2021. In 2019, the rate of developmental disability diagnoses was about 7 in 100 children. The latest figures are from 2021 data, published this week after the CDC finished analyzing responses to the National Health Survey.

Among children ages 3-17 years old in 2021, the survey showed that:

• 1.7% had an intellectual disability.
• 3.1% had autism spectrum disorder.
• 6.1% had a diagnosis of “other developmental delay.”

No significant change was seen from 2019 to 2021 in how common it was for survey respondents to report children having autism or an intellectual disability. The overall increase was driven by a jump in reports from parents that a doctor or health professional told them their child had “any other developmental delay,” excluding autism spectrum disorder or an intellectual disability.

“A lot of times developmental delays might be temporary diagnoses that evolve into something like autism, potentially, or intellectual disability. But also a lot of times children do age out of those,” lead report author and CDC statistician Benjamin Zablotsky, PhD, told CBS News.

The CDC offers an app called Milestone Tracker to help parents watch for signs of developmental delays, in addition to operating a public health education program called “Learn the Signs. Act Early.”

The new report showed that boys were nearly twice as likely as girls to have any developmental delay, a pattern that was magnified when looking specifically at autism diagnoses. Boys were more than three times as likely as girls to be diagnosed with autism spectrum disorder. The rate of autism among boys was 4.7%, compared with 1.5% among girls.

While these latest survey results showed consistent rates of autism from 2019 to 2021, a different CDC report earlier this year showed an alarming jump in the rate of autism spectrum disorder among 8-year-olds. That report, which compared data from 2008 to 2020, showed the rate of autism among 8-year-olds rose during those 12 years from 1 in 88 kids to 1 in 36 kids.

The two analyses also differed in their findings regarding prevalence of autism when looking at children by race and ethnicity. The report from earlier this year showed that Black and Hispanic children were more likely to be diagnosed with autism, compared with White children. This latest report did not find any differences in the prevalence of autism based on a child’s race or ethnicity.

A version of this article appeared on WebMD.com.

Nearly 9 out of every 100 U.S. children are now diagnosed with a developmental disability, according to updated figures from the CDC. 

Developmental disabilities include autism, intellectual disabilities such as Down syndrome, and a range of other diagnoses related to missing developmental milestones in how a child plays, learns, or speaks.

The newly reported increase amounts to just over 1 percentage point from 2019 to 2021. In 2019, the rate of developmental disability diagnoses was about 7 in 100 children. The latest figures are from 2021 data, published this week after the CDC finished analyzing responses to the National Health Survey.

Among children ages 3-17 years old in 2021, the survey showed that:

• 1.7% had an intellectual disability.
• 3.1% had autism spectrum disorder.
• 6.1% had a diagnosis of “other developmental delay.”

No significant change was seen from 2019 to 2021 in how common it was for survey respondents to report children having autism or an intellectual disability. The overall increase was driven by a jump in reports from parents that a doctor or health professional told them their child had “any other developmental delay,” excluding autism spectrum disorder or an intellectual disability.

“A lot of times developmental delays might be temporary diagnoses that evolve into something like autism, potentially, or intellectual disability. But also a lot of times children do age out of those,” lead report author and CDC statistician Benjamin Zablotsky, PhD, told CBS News.

The CDC offers an app called Milestone Tracker to help parents watch for signs of developmental delays, in addition to operating a public health education program called “Learn the Signs. Act Early.”

The new report showed that boys were nearly twice as likely as girls to have any developmental delay, a pattern that was magnified when looking specifically at autism diagnoses. Boys were more than three times as likely as girls to be diagnosed with autism spectrum disorder. The rate of autism among boys was 4.7%, compared with 1.5% among girls.

While these latest survey results showed consistent rates of autism from 2019 to 2021, a different CDC report earlier this year showed an alarming jump in the rate of autism spectrum disorder among 8-year-olds. That report, which compared data from 2008 to 2020, showed the rate of autism among 8-year-olds rose during those 12 years from 1 in 88 kids to 1 in 36 kids.

The two analyses also differed in their findings regarding prevalence of autism when looking at children by race and ethnicity. The report from earlier this year showed that Black and Hispanic children were more likely to be diagnosed with autism, compared with White children. This latest report did not find any differences in the prevalence of autism based on a child’s race or ethnicity.

A version of this article appeared on WebMD.com.

Feelings of inadequacy, in terms of skills and expectations in an ever-changing system, are common emotions that many doctors have experienced since the start of the pandemic.

COVID-19 imposed challenges on health care professionals and systems by forcing changes in how doctors organize themselves professionally as well as in their relationships with patients and in their expectations (realistic or not) of their roles. The situation was bound to generate high rates of frustration and discomfort among younger and older physicians. It was compounded by a generational transition of the profession, which was accelerated by the virus. It was not managed by the decision-makers and was painful for doctors and patients.

Impostor syndrome (IS) is a psychological construct characterized by the persistent belief that one’s success is undeserved, rather than stemming from personal effort, skill, and ability. The phenomenon is common among medics for various reasons, including professional burnout. Recent studies have helped to better define the extent and characteristic features of the syndrome, as well as efforts to combat it.
 

Doctors and burnout

Although occupational burnout among physicians is a systemic issue primarily attributable to problems in the practice environment, professional norms and aspects of medical culture often contribute to the distress that individual physicians experience.

These dimensions have been well characterized and include suggestions that physicians should be impervious to normal human limitations (that is, superhuman), that work should always come first, and that seeking help is a sign of weakness. In aggregate, these attitudes lead many physicians to engage in unhealthy levels of self-sacrifice, manifested by excessive work hours, anxiety about missing something that would benefit their patients, and prioritizing work over personal health. These factors are familiar to many hospital-based and family physicians.
 

The impostor phenomenon

The impostor phenomenon (IP) is a psychological experience of intellectual and professional fraud. Individuals who suffer from it believe that others have inflated perceptions of the individual’s abilities and fear being judged. This fear persists despite continual proof of the individual’s successes. These people ignore praise, are highly self-critical, and attribute their successes to external factors, such as luck, hard work, or receiving help from others, rather than to qualities such as skill, intelligence, or ability.

IP is common among men and women. Some studies suggest it may be more prevalent among women. Studies across industries suggest that the phenomenon is associated with personal consequences (for example, low emotional well-being, problems with work-life integration, anxiety, depression, suicide) and professional consequences (for example, impaired job performance, occupational burnout). Studies involving U.S. medical students have revealed that more than one in four medical students experience IP and that those who experience it are at higher risk for burnout.
 

Surveying IS

IS, which is not a formal psychiatric diagnosis, is defined as having feelings of uncertainty, inadequacy, and being undeserving of one’s achievements despite evidence to the contrary. There are five subtypes of IS:

• Perfectionist: insecurity related to self-imposed, unachievable goals
• Expert: feeling inadequate from lacking sufficient knowledge
• Superperson: assuming excessive workloads just to feel okay among peers
• Natural genius: experiencing shame when it takes effort to develop a skill
• Soloist: believing that requesting help is a sign of weakness

Risk factors

Studies suggest that IS is a problem early in the physician training process. There is limited information on IS among physicians in practice.

Because transitions represent a risk factor for IP, the frequent rotation between clerkships and being a “perpetual novice” during medical school training may contribute to the high prevalence. Qualitative studies suggest that, once in practice, other professional experiences (for example, unfavorable patient outcomes, patient complaints, rejection of grants or manuscripts, and poor teaching evaluations or patient satisfaction scores) may contribute to IP.
 

Impact on doctors

Several methods have been used to classify how much the phenomenon interferes with a person’s life. The Clance Impostor Phenomenon Scale is a 20-item scale that asks respondents to indicate how well each item characterizes their experience on a 5-point scale. Options range from “not at all” to “very true.” The sum of responses to the individual items is used to create an aggregate score (IP score). The higher the score, the more frequently and seriously IP interferes with a person’s life.

A simplified version of the IP score was used in a study of 3,237 U.S. doctors that investigated the association between IS and burnout among doctors and to compare their rates of IS with those of other professionals.

Mean IP scores were higher for female physicians than for male physicians (mean, 10.91 vs. 9.12; P < .001). Scores decreased with age and were lower among those who were married or widowed.

With respect to professional characteristics, IP scores were greater among those in academic practice or who worked in the Veterans Affairs medical system and decreased with years in practice.

The highest IP scores were among pediatric subspecialists, general pediatricians, and emergency medicine physicians. Scores were lowest among ophthalmologists, radiologists, and orthopedic surgeons. IP has been independently associated with the risk of burnout and low professional fulfillment.
 

Lessening the impact

An article commenting on the study highlighted the following expert practice strategies that doctors can use to reduce the impact of IS in their professional life.

• Review and celebrate feats that have led to your professional role.
• Share concerns with trusted colleagues who can validate your accomplishments and normalize your feelings by reporting their own struggles with IS.
• Combat perfectionism by accepting that it is okay to be good enough when meeting the challenges of a demanding profession.
• Exercise self-compassion as an alternative to relying on an external locus of self-worth.
• Understand that IS may be common, especially during transitions, such as when entering medical school, graduate medical training, or starting a new career.

This article was translated from Univadis Italy. A version appeared on Medscape.com.

Feelings of inadequacy, in terms of skills and expectations in an ever-changing system, are common emotions that many doctors have experienced since the start of the pandemic.

COVID-19 imposed challenges on health care professionals and systems by forcing changes in how doctors organize themselves professionally as well as in their relationships with patients and in their expectations (realistic or not) of their roles. The situation was bound to generate high rates of frustration and discomfort among younger and older physicians. It was compounded by a generational transition of the profession, which was accelerated by the virus. It was not managed by the decision-makers and was painful for doctors and patients.

Impostor syndrome (IS) is a psychological construct characterized by the persistent belief that one’s success is undeserved, rather than stemming from personal effort, skill, and ability. The phenomenon is common among medics for various reasons, including professional burnout. Recent studies have helped to better define the extent and characteristic features of the syndrome, as well as efforts to combat it.
 

Doctors and burnout

Although occupational burnout among physicians is a systemic issue primarily attributable to problems in the practice environment, professional norms and aspects of medical culture often contribute to the distress that individual physicians experience.

These dimensions have been well characterized and include suggestions that physicians should be impervious to normal human limitations (that is, superhuman), that work should always come first, and that seeking help is a sign of weakness. In aggregate, these attitudes lead many physicians to engage in unhealthy levels of self-sacrifice, manifested by excessive work hours, anxiety about missing something that would benefit their patients, and prioritizing work over personal health. These factors are familiar to many hospital-based and family physicians.
 

The impostor phenomenon

The impostor phenomenon (IP) is a psychological experience of intellectual and professional fraud. Individuals who suffer from it believe that others have inflated perceptions of the individual’s abilities and fear being judged. This fear persists despite continual proof of the individual’s successes. These people ignore praise, are highly self-critical, and attribute their successes to external factors, such as luck, hard work, or receiving help from others, rather than to qualities such as skill, intelligence, or ability.

IP is common among men and women. Some studies suggest it may be more prevalent among women. Studies across industries suggest that the phenomenon is associated with personal consequences (for example, low emotional well-being, problems with work-life integration, anxiety, depression, suicide) and professional consequences (for example, impaired job performance, occupational burnout). Studies involving U.S. medical students have revealed that more than one in four medical students experience IP and that those who experience it are at higher risk for burnout.
 

Surveying IS

IS, which is not a formal psychiatric diagnosis, is defined as having feelings of uncertainty, inadequacy, and being undeserving of one’s achievements despite evidence to the contrary. There are five subtypes of IS:

• Perfectionist: insecurity related to self-imposed, unachievable goals
• Expert: feeling inadequate from lacking sufficient knowledge
• Superperson: assuming excessive workloads just to feel okay among peers
• Natural genius: experiencing shame when it takes effort to develop a skill
• Soloist: believing that requesting help is a sign of weakness

Risk factors

Studies suggest that IS is a problem early in the physician training process. There is limited information on IS among physicians in practice.

Because transitions represent a risk factor for IP, the frequent rotation between clerkships and being a “perpetual novice” during medical school training may contribute to the high prevalence. Qualitative studies suggest that, once in practice, other professional experiences (for example, unfavorable patient outcomes, patient complaints, rejection of grants or manuscripts, and poor teaching evaluations or patient satisfaction scores) may contribute to IP.
 

Impact on doctors

Several methods have been used to classify how much the phenomenon interferes with a person’s life. The Clance Impostor Phenomenon Scale is a 20-item scale that asks respondents to indicate how well each item characterizes their experience on a 5-point scale. Options range from “not at all” to “very true.” The sum of responses to the individual items is used to create an aggregate score (IP score). The higher the score, the more frequently and seriously IP interferes with a person’s life.

A simplified version of the IP score was used in a study of 3,237 U.S. doctors that investigated the association between IS and burnout among doctors and to compare their rates of IS with those of other professionals.

Mean IP scores were higher for female physicians than for male physicians (mean, 10.91 vs. 9.12; P < .001). Scores decreased with age and were lower among those who were married or widowed.

With respect to professional characteristics, IP scores were greater among those in academic practice or who worked in the Veterans Affairs medical system and decreased with years in practice.

The highest IP scores were among pediatric subspecialists, general pediatricians, and emergency medicine physicians. Scores were lowest among ophthalmologists, radiologists, and orthopedic surgeons. IP has been independently associated with the risk of burnout and low professional fulfillment.
 

Lessening the impact

An article commenting on the study highlighted the following expert practice strategies that doctors can use to reduce the impact of IS in their professional life.

• Review and celebrate feats that have led to your professional role.
• Share concerns with trusted colleagues who can validate your accomplishments and normalize your feelings by reporting their own struggles with IS.
• Combat perfectionism by accepting that it is okay to be good enough when meeting the challenges of a demanding profession.
• Exercise self-compassion as an alternative to relying on an external locus of self-worth.
• Understand that IS may be common, especially during transitions, such as when entering medical school, graduate medical training, or starting a new career.

This article was translated from Univadis Italy. A version appeared on Medscape.com.

Feelings of inadequacy, in terms of skills and expectations in an ever-changing system, are common emotions that many doctors have experienced since the start of the pandemic.

COVID-19 imposed challenges on health care professionals and systems by forcing changes in how doctors organize themselves professionally as well as in their relationships with patients and in their expectations (realistic or not) of their roles. The situation was bound to generate high rates of frustration and discomfort among younger and older physicians. It was compounded by a generational transition of the profession, which was accelerated by the virus. It was not managed by the decision-makers and was painful for doctors and patients.

Impostor syndrome (IS) is a psychological construct characterized by the persistent belief that one’s success is undeserved, rather than stemming from personal effort, skill, and ability. The phenomenon is common among medics for various reasons, including professional burnout. Recent studies have helped to better define the extent and characteristic features of the syndrome, as well as efforts to combat it.
 

Doctors and burnout

Although occupational burnout among physicians is a systemic issue primarily attributable to problems in the practice environment, professional norms and aspects of medical culture often contribute to the distress that individual physicians experience.

These dimensions have been well characterized and include suggestions that physicians should be impervious to normal human limitations (that is, superhuman), that work should always come first, and that seeking help is a sign of weakness. In aggregate, these attitudes lead many physicians to engage in unhealthy levels of self-sacrifice, manifested by excessive work hours, anxiety about missing something that would benefit their patients, and prioritizing work over personal health. These factors are familiar to many hospital-based and family physicians.
 

The impostor phenomenon

The impostor phenomenon (IP) is a psychological experience of intellectual and professional fraud. Individuals who suffer from it believe that others have inflated perceptions of the individual’s abilities and fear being judged. This fear persists despite continual proof of the individual’s successes. These people ignore praise, are highly self-critical, and attribute their successes to external factors, such as luck, hard work, or receiving help from others, rather than to qualities such as skill, intelligence, or ability.

IP is common among men and women. Some studies suggest it may be more prevalent among women. Studies across industries suggest that the phenomenon is associated with personal consequences (for example, low emotional well-being, problems with work-life integration, anxiety, depression, suicide) and professional consequences (for example, impaired job performance, occupational burnout). Studies involving U.S. medical students have revealed that more than one in four medical students experience IP and that those who experience it are at higher risk for burnout.
 

Surveying IS

IS, which is not a formal psychiatric diagnosis, is defined as having feelings of uncertainty, inadequacy, and being undeserving of one’s achievements despite evidence to the contrary. There are five subtypes of IS:

• Perfectionist: insecurity related to self-imposed, unachievable goals
• Expert: feeling inadequate from lacking sufficient knowledge
• Superperson: assuming excessive workloads just to feel okay among peers
• Natural genius: experiencing shame when it takes effort to develop a skill
• Soloist: believing that requesting help is a sign of weakness

Risk factors

Studies suggest that IS is a problem early in the physician training process. There is limited information on IS among physicians in practice.

Because transitions represent a risk factor for IP, the frequent rotation between clerkships and being a “perpetual novice” during medical school training may contribute to the high prevalence. Qualitative studies suggest that, once in practice, other professional experiences (for example, unfavorable patient outcomes, patient complaints, rejection of grants or manuscripts, and poor teaching evaluations or patient satisfaction scores) may contribute to IP.
 

Impact on doctors

Several methods have been used to classify how much the phenomenon interferes with a person’s life. The Clance Impostor Phenomenon Scale is a 20-item scale that asks respondents to indicate how well each item characterizes their experience on a 5-point scale. Options range from “not at all” to “very true.” The sum of responses to the individual items is used to create an aggregate score (IP score). The higher the score, the more frequently and seriously IP interferes with a person’s life.

A simplified version of the IP score was used in a study of 3,237 U.S. doctors that investigated the association between IS and burnout among doctors and to compare their rates of IS with those of other professionals.

Mean IP scores were higher for female physicians than for male physicians (mean, 10.91 vs. 9.12; P < .001). Scores decreased with age and were lower among those who were married or widowed.

With respect to professional characteristics, IP scores were greater among those in academic practice or who worked in the Veterans Affairs medical system and decreased with years in practice.

The highest IP scores were among pediatric subspecialists, general pediatricians, and emergency medicine physicians. Scores were lowest among ophthalmologists, radiologists, and orthopedic surgeons. IP has been independently associated with the risk of burnout and low professional fulfillment.
 

Lessening the impact

An article commenting on the study highlighted the following expert practice strategies that doctors can use to reduce the impact of IS in their professional life.

• Review and celebrate feats that have led to your professional role.
• Share concerns with trusted colleagues who can validate your accomplishments and normalize your feelings by reporting their own struggles with IS.
• Combat perfectionism by accepting that it is okay to be good enough when meeting the challenges of a demanding profession.
• Exercise self-compassion as an alternative to relying on an external locus of self-worth.
• Understand that IS may be common, especially during transitions, such as when entering medical school, graduate medical training, or starting a new career.

This article was translated from Univadis Italy. A version appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Maurie Markman, MD, from Cancer Treatment Centers of America in Philadelphia. I wanted to discuss a highly provocative paper that I think deserves attention. It was published in the Journal of Clinical Oncology, titled Physical Activity in Stage III Colon Cancer: CALGB/SWOG 80702 (Alliance).

This is an incredibly important paper that highlights something that has not been emphasized enough in oncology practice. What are the things that we can recommend to our patients that are not expensive, but which they can do for themselves to impact a potential for adding to a positive outcome? In this case, we’re talking about physical activity.

This was an extremely well-conducted study. It was a prospective cohort study that was built into an ongoing phase 3 randomized, multicenter study looking at adjuvant therapy of stage III colon cancer. The median follow-up in this population was almost 6 years. We’re talking about 1,696 patients.

The investigators did a survey, asking patients when they started treatment and then a short time after that, and measured the level of recreational physical activity. They didn’t do a design. They asked the individuals how much activity they had.

There were a number of analyses done in terms of looking at this that were reported in the paper. I want to highlight one because it’s so simple. The investigators looked at brisk walking. For brisk walking, the 3-year disease-free survival was 81.7% for individuals who had less than 1 hour per week of brisk walking versus 88.4% for individuals who walked briskly more than 3 hours per week.

Walking an additional 2 hours or more per week, prospectively viewed in individuals who had the same baseline characteristics otherwise, impacted disease-free survival in stage III colon cancer. There is no additional expense. It’s walking. There were other activities that were looked at here, including aerobic activities.

The bottom line is that physical activity is positive, is not expensive, and focuses on what the individual patient can do for themselves. It’s something I believe that, in the oncology community, we need to emphasize more.

I encourage you to review this paper and use your own opinion as to what you want to do with this information, but I strongly urge you to look at this – and other types of activities – that we can recommend that individuals do themselves to impact their outcomes related to cancer.

Dr. Markman is a clinical professor of medicine at Drexel University, Philadelphia. He reported conflicts of interest with Genentech, AstraZeneca, Celgene, Clovis, and Amgen.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Maurie Markman, MD, from Cancer Treatment Centers of America in Philadelphia. I wanted to discuss a highly provocative paper that I think deserves attention. It was published in the Journal of Clinical Oncology, titled Physical Activity in Stage III Colon Cancer: CALGB/SWOG 80702 (Alliance).

This is an incredibly important paper that highlights something that has not been emphasized enough in oncology practice. What are the things that we can recommend to our patients that are not expensive, but which they can do for themselves to impact a potential for adding to a positive outcome? In this case, we’re talking about physical activity.

This was an extremely well-conducted study. It was a prospective cohort study that was built into an ongoing phase 3 randomized, multicenter study looking at adjuvant therapy of stage III colon cancer. The median follow-up in this population was almost 6 years. We’re talking about 1,696 patients.

The investigators did a survey, asking patients when they started treatment and then a short time after that, and measured the level of recreational physical activity. They didn’t do a design. They asked the individuals how much activity they had.

There were a number of analyses done in terms of looking at this that were reported in the paper. I want to highlight one because it’s so simple. The investigators looked at brisk walking. For brisk walking, the 3-year disease-free survival was 81.7% for individuals who had less than 1 hour per week of brisk walking versus 88.4% for individuals who walked briskly more than 3 hours per week.

Walking an additional 2 hours or more per week, prospectively viewed in individuals who had the same baseline characteristics otherwise, impacted disease-free survival in stage III colon cancer. There is no additional expense. It’s walking. There were other activities that were looked at here, including aerobic activities.

The bottom line is that physical activity is positive, is not expensive, and focuses on what the individual patient can do for themselves. It’s something I believe that, in the oncology community, we need to emphasize more.

I encourage you to review this paper and use your own opinion as to what you want to do with this information, but I strongly urge you to look at this – and other types of activities – that we can recommend that individuals do themselves to impact their outcomes related to cancer.

Dr. Markman is a clinical professor of medicine at Drexel University, Philadelphia. He reported conflicts of interest with Genentech, AstraZeneca, Celgene, Clovis, and Amgen.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’m Maurie Markman, MD, from Cancer Treatment Centers of America in Philadelphia. I wanted to discuss a highly provocative paper that I think deserves attention. It was published in the Journal of Clinical Oncology, titled Physical Activity in Stage III Colon Cancer: CALGB/SWOG 80702 (Alliance).

This is an incredibly important paper that highlights something that has not been emphasized enough in oncology practice. What are the things that we can recommend to our patients that are not expensive, but which they can do for themselves to impact a potential for adding to a positive outcome? In this case, we’re talking about physical activity.

This was an extremely well-conducted study. It was a prospective cohort study that was built into an ongoing phase 3 randomized, multicenter study looking at adjuvant therapy of stage III colon cancer. The median follow-up in this population was almost 6 years. We’re talking about 1,696 patients.

The investigators did a survey, asking patients when they started treatment and then a short time after that, and measured the level of recreational physical activity. They didn’t do a design. They asked the individuals how much activity they had.

There were a number of analyses done in terms of looking at this that were reported in the paper. I want to highlight one because it’s so simple. The investigators looked at brisk walking. For brisk walking, the 3-year disease-free survival was 81.7% for individuals who had less than 1 hour per week of brisk walking versus 88.4% for individuals who walked briskly more than 3 hours per week.

Walking an additional 2 hours or more per week, prospectively viewed in individuals who had the same baseline characteristics otherwise, impacted disease-free survival in stage III colon cancer. There is no additional expense. It’s walking. There were other activities that were looked at here, including aerobic activities.

The bottom line is that physical activity is positive, is not expensive, and focuses on what the individual patient can do for themselves. It’s something I believe that, in the oncology community, we need to emphasize more.

I encourage you to review this paper and use your own opinion as to what you want to do with this information, but I strongly urge you to look at this – and other types of activities – that we can recommend that individuals do themselves to impact their outcomes related to cancer.

Dr. Markman is a clinical professor of medicine at Drexel University, Philadelphia. He reported conflicts of interest with Genentech, AstraZeneca, Celgene, Clovis, and Amgen.

A version of this article first appeared on Medscape.com.