Cancer

Approximately one-third of people between 45 and 49 years of age who undergo colonoscopies have neoplastic colorectal pathology, according to a retrospective analysis.

According to the researchers, led by Parth Trivedi, MD, of the Icahn School of Medicine at Mount Sinai, New York, there has progressively been a “disturbing” rise in early-onset colorectal cancer (CRC) in the United States, which has prompted guidelines from the American Cancer Society to the U.S. Preventive Services Task Force to recommend lowering the CRC screening starting age to 45 years old for average-risk individuals. Despite these recommendations, little research to date has fully characterized the prevalence of colorectal neoplasia in individuals younger than the currently recommended CRC onset screening age of 50 years.

Dr. Trivedi and colleagues, who published their study findings in Gastroenterology, retrospectively reviewed colonoscopy data recorded in the Gastrointestinal Quality Improvement Consortium Registry to address the current knowledge gaps on early-onset CRC. Collected data were for procedures conducted at 123 AMSURG ambulatory endoscopy centers across 29 states between January 2014 and February 2021. In total, 2,921,816 colonoscopies during the study period among patients aged 18-54 years were recorded by AMSURG-associated endoscopists; of these, 562,559 met inclusion criteria for high-quality screening or diagnostic colonoscopy procedures.

The researchers pooled a young-onset age group, including patients between the ages of 18 and 49 years old, in whom 145,998 procedures were performed, including 79,934 procedures in patients aged 45-49 years. A comparator group with 336,627 procedures in patients aged 50-54 years was also included in the study. The findings were categorized into CRC, advanced premalignant lesions (APL), and “any neoplasia,” the latter of which included all adenomas, sessile serrated polyps, and CRC.

Among patients aged 18-44 years, the most frequent indications were “diagnostic-other” (45.6%) as well as “diagnostic-bleeding” (39.4%). Among patients between 45 and 49 years of age, the most frequent indications were “screening” (41.4%) and “diagnostic-other” (30.7%). Nearly all (90%) procedures among those aged 50-54 years were for screening.

A multivariable logistic regression identified 5 variables predictive of either APL or CRC in patients between 18 and 49 years of age: increasing age (odds ratio, 1.08; 95% confidence interval, 1.07-1.08; P <0.01), male sex (OR = 1.67; 95% CI, 1.63-1.70; P <0.01), White race (vs. African American: OR = 0.76; 95% CI, 0.73-0.79, P <0.01; vs. Asian: OR = 0.89; 95% CI, 0.84-0.94, P <0.01), family history of CRC (OR = 1.21; 95% CI, 1.16-1.26; P <0.01) and polyps (OR = 1.33; 95% CI, 1.24-1.43; P <0.01), and examinations for bleeding (OR = 1.15; 95% CI, 1.12-1.18; P <0.01) or screening (OR = 1.20; 95% CI, 1.16-1.24; P <0.01).

The prevalence of neoplastic findings in the young-onset age-group increased with increasing age for the categories of any neoplasia, APLs, and CRC. Among patients aged 40-44, 26.59% had any neoplasia, 5.76% had APL, and 0.53% had CRC. In those aged 45-49 years, around 32% had any neoplasia, approximately 7.5% had APLs, and nearly 0.58% had CRC. In the 50- to 54-year-old group, the prevalences of any neoplasia, APL, and CRC were 37.72%, 9.48%, and 0.32%, respectively.

Across all age groups, a family history of CRC was associated with a higher prevalence of any neoplasia and APL. In addition, the rates of any APL and neoplasia in patients with a family history of CRC were comparable to patients who were 5 years older but had no family history of the disease. Across most young-onset age group, individuals with a positive family history had a lower CRC prevalence versus patients with no family history.

The researchers noted that their population data are derived from ambulatory endoscopy centers, which may introduce bias associated with insurance coverage or patient preference to attend specific endoscopic centers. Additionally, the investigators stated that many records on race and ethnicity were missing, further limiting the findings.

“The present analysis of neoplastic colorectal pathology among individuals younger than age 50 suggests that lowering the screening age to 45 for men and women of all races and ethnicities will likely detect important pathology rather frequently,” they concluded. In addition, the researchers noted that the study results “underscore the importance of early messaging to patients and providers in the years leading up to age 45.” Ultimately, improved “awareness of pathology prevalence in individuals younger than age 45 can help guide clinicians in the clinical management of CRC risk,” the researchers wrote.

Several of the researchers reported conflicts of interest with Exact Sciences Corp and Freenome. The study received no industry funding.

Approximately one-third of people between 45 and 49 years of age who undergo colonoscopies have neoplastic colorectal pathology, according to a retrospective analysis.

According to the researchers, led by Parth Trivedi, MD, of the Icahn School of Medicine at Mount Sinai, New York, there has progressively been a “disturbing” rise in early-onset colorectal cancer (CRC) in the United States, which has prompted guidelines from the American Cancer Society to the U.S. Preventive Services Task Force to recommend lowering the CRC screening starting age to 45 years old for average-risk individuals. Despite these recommendations, little research to date has fully characterized the prevalence of colorectal neoplasia in individuals younger than the currently recommended CRC onset screening age of 50 years.

Dr. Trivedi and colleagues, who published their study findings in Gastroenterology, retrospectively reviewed colonoscopy data recorded in the Gastrointestinal Quality Improvement Consortium Registry to address the current knowledge gaps on early-onset CRC. Collected data were for procedures conducted at 123 AMSURG ambulatory endoscopy centers across 29 states between January 2014 and February 2021. In total, 2,921,816 colonoscopies during the study period among patients aged 18-54 years were recorded by AMSURG-associated endoscopists; of these, 562,559 met inclusion criteria for high-quality screening or diagnostic colonoscopy procedures.

The researchers pooled a young-onset age group, including patients between the ages of 18 and 49 years old, in whom 145,998 procedures were performed, including 79,934 procedures in patients aged 45-49 years. A comparator group with 336,627 procedures in patients aged 50-54 years was also included in the study. The findings were categorized into CRC, advanced premalignant lesions (APL), and “any neoplasia,” the latter of which included all adenomas, sessile serrated polyps, and CRC.

Among patients aged 18-44 years, the most frequent indications were “diagnostic-other” (45.6%) as well as “diagnostic-bleeding” (39.4%). Among patients between 45 and 49 years of age, the most frequent indications were “screening” (41.4%) and “diagnostic-other” (30.7%). Nearly all (90%) procedures among those aged 50-54 years were for screening.

A multivariable logistic regression identified 5 variables predictive of either APL or CRC in patients between 18 and 49 years of age: increasing age (odds ratio, 1.08; 95% confidence interval, 1.07-1.08; P <0.01), male sex (OR = 1.67; 95% CI, 1.63-1.70; P <0.01), White race (vs. African American: OR = 0.76; 95% CI, 0.73-0.79, P <0.01; vs. Asian: OR = 0.89; 95% CI, 0.84-0.94, P <0.01), family history of CRC (OR = 1.21; 95% CI, 1.16-1.26; P <0.01) and polyps (OR = 1.33; 95% CI, 1.24-1.43; P <0.01), and examinations for bleeding (OR = 1.15; 95% CI, 1.12-1.18; P <0.01) or screening (OR = 1.20; 95% CI, 1.16-1.24; P <0.01).

The prevalence of neoplastic findings in the young-onset age-group increased with increasing age for the categories of any neoplasia, APLs, and CRC. Among patients aged 40-44, 26.59% had any neoplasia, 5.76% had APL, and 0.53% had CRC. In those aged 45-49 years, around 32% had any neoplasia, approximately 7.5% had APLs, and nearly 0.58% had CRC. In the 50- to 54-year-old group, the prevalences of any neoplasia, APL, and CRC were 37.72%, 9.48%, and 0.32%, respectively.

Across all age groups, a family history of CRC was associated with a higher prevalence of any neoplasia and APL. In addition, the rates of any APL and neoplasia in patients with a family history of CRC were comparable to patients who were 5 years older but had no family history of the disease. Across most young-onset age group, individuals with a positive family history had a lower CRC prevalence versus patients with no family history.

The researchers noted that their population data are derived from ambulatory endoscopy centers, which may introduce bias associated with insurance coverage or patient preference to attend specific endoscopic centers. Additionally, the investigators stated that many records on race and ethnicity were missing, further limiting the findings.

“The present analysis of neoplastic colorectal pathology among individuals younger than age 50 suggests that lowering the screening age to 45 for men and women of all races and ethnicities will likely detect important pathology rather frequently,” they concluded. In addition, the researchers noted that the study results “underscore the importance of early messaging to patients and providers in the years leading up to age 45.” Ultimately, improved “awareness of pathology prevalence in individuals younger than age 45 can help guide clinicians in the clinical management of CRC risk,” the researchers wrote.

Several of the researchers reported conflicts of interest with Exact Sciences Corp and Freenome. The study received no industry funding.

Approximately one-third of people between 45 and 49 years of age who undergo colonoscopies have neoplastic colorectal pathology, according to a retrospective analysis.

According to the researchers, led by Parth Trivedi, MD, of the Icahn School of Medicine at Mount Sinai, New York, there has progressively been a “disturbing” rise in early-onset colorectal cancer (CRC) in the United States, which has prompted guidelines from the American Cancer Society to the U.S. Preventive Services Task Force to recommend lowering the CRC screening starting age to 45 years old for average-risk individuals. Despite these recommendations, little research to date has fully characterized the prevalence of colorectal neoplasia in individuals younger than the currently recommended CRC onset screening age of 50 years.

Dr. Trivedi and colleagues, who published their study findings in Gastroenterology, retrospectively reviewed colonoscopy data recorded in the Gastrointestinal Quality Improvement Consortium Registry to address the current knowledge gaps on early-onset CRC. Collected data were for procedures conducted at 123 AMSURG ambulatory endoscopy centers across 29 states between January 2014 and February 2021. In total, 2,921,816 colonoscopies during the study period among patients aged 18-54 years were recorded by AMSURG-associated endoscopists; of these, 562,559 met inclusion criteria for high-quality screening or diagnostic colonoscopy procedures.

The researchers pooled a young-onset age group, including patients between the ages of 18 and 49 years old, in whom 145,998 procedures were performed, including 79,934 procedures in patients aged 45-49 years. A comparator group with 336,627 procedures in patients aged 50-54 years was also included in the study. The findings were categorized into CRC, advanced premalignant lesions (APL), and “any neoplasia,” the latter of which included all adenomas, sessile serrated polyps, and CRC.

Among patients aged 18-44 years, the most frequent indications were “diagnostic-other” (45.6%) as well as “diagnostic-bleeding” (39.4%). Among patients between 45 and 49 years of age, the most frequent indications were “screening” (41.4%) and “diagnostic-other” (30.7%). Nearly all (90%) procedures among those aged 50-54 years were for screening.

A multivariable logistic regression identified 5 variables predictive of either APL or CRC in patients between 18 and 49 years of age: increasing age (odds ratio, 1.08; 95% confidence interval, 1.07-1.08; P <0.01), male sex (OR = 1.67; 95% CI, 1.63-1.70; P <0.01), White race (vs. African American: OR = 0.76; 95% CI, 0.73-0.79, P <0.01; vs. Asian: OR = 0.89; 95% CI, 0.84-0.94, P <0.01), family history of CRC (OR = 1.21; 95% CI, 1.16-1.26; P <0.01) and polyps (OR = 1.33; 95% CI, 1.24-1.43; P <0.01), and examinations for bleeding (OR = 1.15; 95% CI, 1.12-1.18; P <0.01) or screening (OR = 1.20; 95% CI, 1.16-1.24; P <0.01).

The prevalence of neoplastic findings in the young-onset age-group increased with increasing age for the categories of any neoplasia, APLs, and CRC. Among patients aged 40-44, 26.59% had any neoplasia, 5.76% had APL, and 0.53% had CRC. In those aged 45-49 years, around 32% had any neoplasia, approximately 7.5% had APLs, and nearly 0.58% had CRC. In the 50- to 54-year-old group, the prevalences of any neoplasia, APL, and CRC were 37.72%, 9.48%, and 0.32%, respectively.

Across all age groups, a family history of CRC was associated with a higher prevalence of any neoplasia and APL. In addition, the rates of any APL and neoplasia in patients with a family history of CRC were comparable to patients who were 5 years older but had no family history of the disease. Across most young-onset age group, individuals with a positive family history had a lower CRC prevalence versus patients with no family history.

The researchers noted that their population data are derived from ambulatory endoscopy centers, which may introduce bias associated with insurance coverage or patient preference to attend specific endoscopic centers. Additionally, the investigators stated that many records on race and ethnicity were missing, further limiting the findings.

“The present analysis of neoplastic colorectal pathology among individuals younger than age 50 suggests that lowering the screening age to 45 for men and women of all races and ethnicities will likely detect important pathology rather frequently,” they concluded. In addition, the researchers noted that the study results “underscore the importance of early messaging to patients and providers in the years leading up to age 45.” Ultimately, improved “awareness of pathology prevalence in individuals younger than age 45 can help guide clinicians in the clinical management of CRC risk,” the researchers wrote.

Several of the researchers reported conflicts of interest with Exact Sciences Corp and Freenome. The study received no industry funding.

Airflow obstruction caused by a malignant tracheal tumor may be managed with a uniquely designed, 3-dimensional (3D) drug-eluting tracheal stent that, at least in animal models so far, works well and may soon be ready for human trials, Chinese investigators are reporting.

The research was published online Jan. 29 in Materials Today Chemistry.

The problems with currently available stents used to treat airflow obstruction are considerable, corresponding author Shengrong Guo, PhD, professor of pharmaceutics, Shanghai Jiao Tong University, China, and colleagues observe. “Tracheal stents physically open up stenosis, recover airway patency, and promptly relieve symptoms, but [they] cannot treat the tumor,” they explain.

“Thus, tracheal restenosis always occurs soon [after], due to progressive tumor growth after stent placement,” they add. Moreover, implanted stents cover the entire tracheal mucosa, thus preventing mucus and sputum discharge, causing airway blockage, the investigators also note. Compounding these flaws is the unalterable fact that delivery of chemotherapy to a malignant tracheal tumor is inefficient, and systemic chemotherapy is always associated with systemic side effects.

All of these issues make it very challenging to treat these tumors, Dr. Guo noted. On the other hand, if there were a means to deliver a chemotherapeutic agent more directly to the disease site – as is done with drug-eluting beads, for example, in other tumor types – then at least drug delivery would be much more efficient. “In this study, a novel tracheal stent was designed with features of a C-shaped and trilayered wall,” the researchers explain.

The gap angle of the newly developed stent is 72°; the inner diameter is 0.5 cm, and it is 2.0 cm in length. The trilayered wall consists of an inner layer of poly (ε-caprolactone) (PCL), which is a biodegradable and implantable material used alone or compounded with other ingredients to print implants. The middle layer consists of magnetic nanoparticle (MNP)–loaded PCL. The authors explain that MNPs have been approved in the U.S. as contrast agents in MRI.

Combined with temperature-responsive materials, MNPs can serve as a source of magnetic thermotherapy as well, which can be used to control drug release and facilitate drug penetration into deeper tissues. The outer layer of the stent contains a paclitaxel-loaded ethylene-vinyl acetate copolymer layer.

“The C-shaped tracheal stents are easily fabricated on a roller by using a self-made specific three-dimensional printer,” the authors explain. They point out that the C-shaped tracheal stents do not cover the entire tracheal wall, and the uncovered gap in that wall allows for normal mucus and sputum discharge.
 

In vivo evaluation

Once the stents were printed, the researchers evaluated the biosafety and applicability of their C-shaped tracheal stents. Small rabbits weighing 2.5 to 3.0 kg were used as experimental models and were prepared for surgery. The stent was implanted in the rabbits’ tracheas through the use of a simple stent delivery device. During follow-up, the rabbits recovered well without any sign of infection or respiratory complications.

The animals were also eating well within about 5 days of the surgery, and their weight gradually increased, suggesting that the implantation of a stent with intermittent magnetic heating did not lead to any prominent systemic toxicities. “All rabbits were [euthanized] 30 days after the placement of the tracheal stents” and the stent was removed from the rabbits’ trachea, the researchers report.

Close observation of the trachea indicated that the gap left by the C-shaped stent could keep the airway patent without blocking either mucus or sputum discharge. “The stents have good biosafety in rabbits and keep airway patency for 1 month without the occurrence of mucus/sputum blockage after implantation in rabbit trachea,” Dr. Guo and colleagues conclude.

“These results provide a scientific basis for the development of novel self-expandable C-shaped tracheal stents with combinatorial tracheal support and local chemotherapy,” they affirm.
 

Pediatric airway obstruction

Thus far, the role of 3D printing seems to be most prominent in the treatment of pediatric airway obstruction, where it is used in the surgical planning stages and to create the implant itself. In a systematic review of its use for this, Joshua Stramiello, MD, University of California, San Diego, and colleagues identified 37 original articles, 11 of which discussed 3D printing for surgical planning, and 26 of which discussed 3D printing implants for interventions.

“3D printing for surgical planning not only improves preoperative assessment of surgical approach and stent customization but also helps facilitate patient/family education,” the authors observe. Most of the research so far has been focused on bioresorbable external airway splints and biological grafts, they add – “with both animal studies and human case reports showing good results in improving symptoms.” One clinical series focused on the use of a 3D-printed, patient-specific, bioresorbable airway splint in a cohort of critically ill children with severe tracheobronchomalacia. (Tracheobronchomalacia is the abnormal collapse of the windpipe).

When reported, 29 splints had been implanted in 15 children with intrathoracic tracheobronchomalacia. At a median follow-up of 8.5 months, 12 children were long-term survivors, and all but one lived at home. As recently discussed by George Cheng, MD, cofounder of restor3D, a Duke University startup that created the first 3D-printed airway stent using a compressible biocompatible material with properties similar to that of silicone, personalized airway stents have the potential for advance customization, minimize pressure points, and improve airflow dynamics to increase mucus clearance.

In fact, the U.S. Food and Drug Administration has already cleared patient-specific airway stents developed by Thomas Gildea, MD, of the Cleveland Clinic. Both the Duke University and Cleveland Clinic stents have been used in patients, with promising outcomes, Dr. Cheng noted.

The authors and Dr. Stramiello and colleagues have disclosed no relevant financial relationships. Dr. Cheng is the cofounder of restor3D.

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

Airflow obstruction caused by a malignant tracheal tumor may be managed with a uniquely designed, 3-dimensional (3D) drug-eluting tracheal stent that, at least in animal models so far, works well and may soon be ready for human trials, Chinese investigators are reporting.

The research was published online Jan. 29 in Materials Today Chemistry.

The problems with currently available stents used to treat airflow obstruction are considerable, corresponding author Shengrong Guo, PhD, professor of pharmaceutics, Shanghai Jiao Tong University, China, and colleagues observe. “Tracheal stents physically open up stenosis, recover airway patency, and promptly relieve symptoms, but [they] cannot treat the tumor,” they explain.

“Thus, tracheal restenosis always occurs soon [after], due to progressive tumor growth after stent placement,” they add. Moreover, implanted stents cover the entire tracheal mucosa, thus preventing mucus and sputum discharge, causing airway blockage, the investigators also note. Compounding these flaws is the unalterable fact that delivery of chemotherapy to a malignant tracheal tumor is inefficient, and systemic chemotherapy is always associated with systemic side effects.

All of these issues make it very challenging to treat these tumors, Dr. Guo noted. On the other hand, if there were a means to deliver a chemotherapeutic agent more directly to the disease site – as is done with drug-eluting beads, for example, in other tumor types – then at least drug delivery would be much more efficient. “In this study, a novel tracheal stent was designed with features of a C-shaped and trilayered wall,” the researchers explain.

The gap angle of the newly developed stent is 72°; the inner diameter is 0.5 cm, and it is 2.0 cm in length. The trilayered wall consists of an inner layer of poly (ε-caprolactone) (PCL), which is a biodegradable and implantable material used alone or compounded with other ingredients to print implants. The middle layer consists of magnetic nanoparticle (MNP)–loaded PCL. The authors explain that MNPs have been approved in the U.S. as contrast agents in MRI.

Combined with temperature-responsive materials, MNPs can serve as a source of magnetic thermotherapy as well, which can be used to control drug release and facilitate drug penetration into deeper tissues. The outer layer of the stent contains a paclitaxel-loaded ethylene-vinyl acetate copolymer layer.

“The C-shaped tracheal stents are easily fabricated on a roller by using a self-made specific three-dimensional printer,” the authors explain. They point out that the C-shaped tracheal stents do not cover the entire tracheal wall, and the uncovered gap in that wall allows for normal mucus and sputum discharge.
 

In vivo evaluation

Once the stents were printed, the researchers evaluated the biosafety and applicability of their C-shaped tracheal stents. Small rabbits weighing 2.5 to 3.0 kg were used as experimental models and were prepared for surgery. The stent was implanted in the rabbits’ tracheas through the use of a simple stent delivery device. During follow-up, the rabbits recovered well without any sign of infection or respiratory complications.

The animals were also eating well within about 5 days of the surgery, and their weight gradually increased, suggesting that the implantation of a stent with intermittent magnetic heating did not lead to any prominent systemic toxicities. “All rabbits were [euthanized] 30 days after the placement of the tracheal stents” and the stent was removed from the rabbits’ trachea, the researchers report.

Close observation of the trachea indicated that the gap left by the C-shaped stent could keep the airway patent without blocking either mucus or sputum discharge. “The stents have good biosafety in rabbits and keep airway patency for 1 month without the occurrence of mucus/sputum blockage after implantation in rabbit trachea,” Dr. Guo and colleagues conclude.

“These results provide a scientific basis for the development of novel self-expandable C-shaped tracheal stents with combinatorial tracheal support and local chemotherapy,” they affirm.
 

Pediatric airway obstruction

Thus far, the role of 3D printing seems to be most prominent in the treatment of pediatric airway obstruction, where it is used in the surgical planning stages and to create the implant itself. In a systematic review of its use for this, Joshua Stramiello, MD, University of California, San Diego, and colleagues identified 37 original articles, 11 of which discussed 3D printing for surgical planning, and 26 of which discussed 3D printing implants for interventions.

“3D printing for surgical planning not only improves preoperative assessment of surgical approach and stent customization but also helps facilitate patient/family education,” the authors observe. Most of the research so far has been focused on bioresorbable external airway splints and biological grafts, they add – “with both animal studies and human case reports showing good results in improving symptoms.” One clinical series focused on the use of a 3D-printed, patient-specific, bioresorbable airway splint in a cohort of critically ill children with severe tracheobronchomalacia. (Tracheobronchomalacia is the abnormal collapse of the windpipe).

When reported, 29 splints had been implanted in 15 children with intrathoracic tracheobronchomalacia. At a median follow-up of 8.5 months, 12 children were long-term survivors, and all but one lived at home. As recently discussed by George Cheng, MD, cofounder of restor3D, a Duke University startup that created the first 3D-printed airway stent using a compressible biocompatible material with properties similar to that of silicone, personalized airway stents have the potential for advance customization, minimize pressure points, and improve airflow dynamics to increase mucus clearance.

In fact, the U.S. Food and Drug Administration has already cleared patient-specific airway stents developed by Thomas Gildea, MD, of the Cleveland Clinic. Both the Duke University and Cleveland Clinic stents have been used in patients, with promising outcomes, Dr. Cheng noted.

The authors and Dr. Stramiello and colleagues have disclosed no relevant financial relationships. Dr. Cheng is the cofounder of restor3D.

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

Airflow obstruction caused by a malignant tracheal tumor may be managed with a uniquely designed, 3-dimensional (3D) drug-eluting tracheal stent that, at least in animal models so far, works well and may soon be ready for human trials, Chinese investigators are reporting.

The research was published online Jan. 29 in Materials Today Chemistry.

The problems with currently available stents used to treat airflow obstruction are considerable, corresponding author Shengrong Guo, PhD, professor of pharmaceutics, Shanghai Jiao Tong University, China, and colleagues observe. “Tracheal stents physically open up stenosis, recover airway patency, and promptly relieve symptoms, but [they] cannot treat the tumor,” they explain.

“Thus, tracheal restenosis always occurs soon [after], due to progressive tumor growth after stent placement,” they add. Moreover, implanted stents cover the entire tracheal mucosa, thus preventing mucus and sputum discharge, causing airway blockage, the investigators also note. Compounding these flaws is the unalterable fact that delivery of chemotherapy to a malignant tracheal tumor is inefficient, and systemic chemotherapy is always associated with systemic side effects.

All of these issues make it very challenging to treat these tumors, Dr. Guo noted. On the other hand, if there were a means to deliver a chemotherapeutic agent more directly to the disease site – as is done with drug-eluting beads, for example, in other tumor types – then at least drug delivery would be much more efficient. “In this study, a novel tracheal stent was designed with features of a C-shaped and trilayered wall,” the researchers explain.

The gap angle of the newly developed stent is 72°; the inner diameter is 0.5 cm, and it is 2.0 cm in length. The trilayered wall consists of an inner layer of poly (ε-caprolactone) (PCL), which is a biodegradable and implantable material used alone or compounded with other ingredients to print implants. The middle layer consists of magnetic nanoparticle (MNP)–loaded PCL. The authors explain that MNPs have been approved in the U.S. as contrast agents in MRI.

Combined with temperature-responsive materials, MNPs can serve as a source of magnetic thermotherapy as well, which can be used to control drug release and facilitate drug penetration into deeper tissues. The outer layer of the stent contains a paclitaxel-loaded ethylene-vinyl acetate copolymer layer.

“The C-shaped tracheal stents are easily fabricated on a roller by using a self-made specific three-dimensional printer,” the authors explain. They point out that the C-shaped tracheal stents do not cover the entire tracheal wall, and the uncovered gap in that wall allows for normal mucus and sputum discharge.
 

In vivo evaluation

Once the stents were printed, the researchers evaluated the biosafety and applicability of their C-shaped tracheal stents. Small rabbits weighing 2.5 to 3.0 kg were used as experimental models and were prepared for surgery. The stent was implanted in the rabbits’ tracheas through the use of a simple stent delivery device. During follow-up, the rabbits recovered well without any sign of infection or respiratory complications.

The animals were also eating well within about 5 days of the surgery, and their weight gradually increased, suggesting that the implantation of a stent with intermittent magnetic heating did not lead to any prominent systemic toxicities. “All rabbits were [euthanized] 30 days after the placement of the tracheal stents” and the stent was removed from the rabbits’ trachea, the researchers report.

Close observation of the trachea indicated that the gap left by the C-shaped stent could keep the airway patent without blocking either mucus or sputum discharge. “The stents have good biosafety in rabbits and keep airway patency for 1 month without the occurrence of mucus/sputum blockage after implantation in rabbit trachea,” Dr. Guo and colleagues conclude.

“These results provide a scientific basis for the development of novel self-expandable C-shaped tracheal stents with combinatorial tracheal support and local chemotherapy,” they affirm.
 

Pediatric airway obstruction

Thus far, the role of 3D printing seems to be most prominent in the treatment of pediatric airway obstruction, where it is used in the surgical planning stages and to create the implant itself. In a systematic review of its use for this, Joshua Stramiello, MD, University of California, San Diego, and colleagues identified 37 original articles, 11 of which discussed 3D printing for surgical planning, and 26 of which discussed 3D printing implants for interventions.

“3D printing for surgical planning not only improves preoperative assessment of surgical approach and stent customization but also helps facilitate patient/family education,” the authors observe. Most of the research so far has been focused on bioresorbable external airway splints and biological grafts, they add – “with both animal studies and human case reports showing good results in improving symptoms.” One clinical series focused on the use of a 3D-printed, patient-specific, bioresorbable airway splint in a cohort of critically ill children with severe tracheobronchomalacia. (Tracheobronchomalacia is the abnormal collapse of the windpipe).

When reported, 29 splints had been implanted in 15 children with intrathoracic tracheobronchomalacia. At a median follow-up of 8.5 months, 12 children were long-term survivors, and all but one lived at home. As recently discussed by George Cheng, MD, cofounder of restor3D, a Duke University startup that created the first 3D-printed airway stent using a compressible biocompatible material with properties similar to that of silicone, personalized airway stents have the potential for advance customization, minimize pressure points, and improve airflow dynamics to increase mucus clearance.

In fact, the U.S. Food and Drug Administration has already cleared patient-specific airway stents developed by Thomas Gildea, MD, of the Cleveland Clinic. Both the Duke University and Cleveland Clinic stents have been used in patients, with promising outcomes, Dr. Cheng noted.

The authors and Dr. Stramiello and colleagues have disclosed no relevant financial relationships. Dr. Cheng is the cofounder of restor3D.

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

Radiofrequency ablation (RFA) is effective and long lasting in preventing esophageal adenocarcinoma, new data suggest.

Researchers, led by Paul Wolfson, MBBS, from the Wellcome/EPSRC (Engineering and Physical Sciences Research Council) Centre for Interventional & Surgical Sciences, University College London also found that most treatment relapses happen early and can be re-treated successfully.

Findings were published in a final 10-year report from the United Kingdom National Halo Radiofrequency Ablation Registry and in Gastrointestinal Endoscopy. Because RFA has been used in mainstream clinical practice only since 2005, long-term data of more than 5 years has been lacking.

Multiple studies have shown that RFA is effective in preventing esophageal cancer, but data have been lacking on how long RFA is effective in preventing esophageal adenocarcinoma in patients with dysplastic Barrett’s esophagus (BE). A significant number of patients with dysplastic BE do not initially have visible lesions. For instance, the U.S. RFA Patient Registry reported an average 2.7-year follow up of 4,982 patients, but only 1,305 had dysplasia, the authors of the U.K. report note.

“It is well-established that endoscopic treatment of dysplastic BE is initially successful in up to 90% of patients,” the authors wrote. “What is less well understood is how long that benefit lasts and if this contributes to a substantial reduction in progression to cancer.”

Researchers prospectively gathered data from 2,535 patients from 28 U.K. specialist centers who underwent RFA therapy for BE (average length 5.2cm, range 1-20 cm). Among the group, 20% had low-grade dysplasia, 54% had high-grade dysplasia, and 26% had intramucosal carcinoma.

They looked at rates of invasive cancer and analyzed data for 1,175 patients to assess clearance rates of dysplasia (CR-D) and intestinal metaplasia (CR-IM) within 2 years of starting RFA, then looked at relapses and rates of return to CR-D and CR-IM after more therapy.

One year after RFA therapy, the Kaplan Meier (KM) rate of invasive cancer in the 2,535 patients was 0.5%. Ten years after starting treatment, the KM cancer rate was 4.1%, with a crude incidence rate of 0.52 per 100 patient-years. After 2 years of RFA, CR-D was 88% and CR-IM was 62.6%.

At 8 years, the KM relapse rates were 5.9% from CR-D and 18.7% from CR-IM. Most relapses happened in the first 2 years.

“Our study confirms durable reversal of dysplasia and BE with RFA, which reduces cancer risk by more than 90% compared to historical control data of 6-19% per annum,” the authors wrote.

Despite advances in diagnosis and treatment for esophageal adenocarcinoma, there has been only small improvement in 5-year survival over the past 40 years, the authors note. Meanwhile, the incidence of continues to rise in the Western world.
 

Researchers look for minimally invasive solutions

Surgery removing the esophagus and lymph node clearance had been the standard for high-grade dysplasia, the authors wrote. It is still the intervention of choice for patients with locoregional disease, but it comes with high morbidity and mortality rates.

This has spurred researchers to look for a minimally invasive solution focused on organ preservation to treat early disease and avoid surgical side effects but also to deliver a cure, according to the authors.

Shria Kumar, MD, assistant professor in the Division of Digestive and Liver Diseases at University of Miami Miller School of Medicine, told this publication, “Endoscopic ablation of dysplasia or intramucosal cancer is a mainstay of Barrett’s treatment.”

She noted the importance of the 10-year time period as the initial studies that established ablation evaluated outcomes within 1-3 years, and more recent data shows 5-year favorable outcomes.

Citing a study from the New England Journal of Medicine, Dr. Kumar said, “The present study’s cohort developed cancer at rates similar to one of the earlier U.S.-based cohorts of Barrett’s patients, suggesting that we can draw some parallels.”

She pointed out notable characteristics in the U.K. cohort: “The majority of participants were male and Caucasian; 80% of had high-grade dysplasia or early cancer upon enrollment and long-segment Barrett’s.”

That difference is important when thinking about how this applies to a more diverse U.S. population, she said, or even patients who don’t have high-grade dysplasia or early cancer when they enroll.

“It’s also important to point out are that individuals with low-grade dysplasia were included in this U.K.-based study. There has been evidence that persons in Europe with low-grade dysplasia have higher rates of progression than persons in the U.S. with low-grade dysplasia.”

Dr. Kumar said this may be attributable to differences in the way pathologists practice in the two countries or in endoscopists’ treatment patterns. U.S. guidelines agree that ablation can be used in select persons with low-grade dysplasia, she said, but it’s an area that needs further study.

“Overall, though, this is a really important study of real-time data showing that ablation is impacting cancer rates in a positive way and that in select patients, we can really decrease the risk of invasive cancer by endoscopic eradication therapies,” Dr. Kumar said.

Two coauthors have received grants from Medtronic and Pentax Medical. The other authors have declared no relevant financial relationships. Dr. Kumar reports no relevant financial relationships.

Radiofrequency ablation (RFA) is effective and long lasting in preventing esophageal adenocarcinoma, new data suggest.

Researchers, led by Paul Wolfson, MBBS, from the Wellcome/EPSRC (Engineering and Physical Sciences Research Council) Centre for Interventional & Surgical Sciences, University College London also found that most treatment relapses happen early and can be re-treated successfully.

Findings were published in a final 10-year report from the United Kingdom National Halo Radiofrequency Ablation Registry and in Gastrointestinal Endoscopy. Because RFA has been used in mainstream clinical practice only since 2005, long-term data of more than 5 years has been lacking.

Multiple studies have shown that RFA is effective in preventing esophageal cancer, but data have been lacking on how long RFA is effective in preventing esophageal adenocarcinoma in patients with dysplastic Barrett’s esophagus (BE). A significant number of patients with dysplastic BE do not initially have visible lesions. For instance, the U.S. RFA Patient Registry reported an average 2.7-year follow up of 4,982 patients, but only 1,305 had dysplasia, the authors of the U.K. report note.

“It is well-established that endoscopic treatment of dysplastic BE is initially successful in up to 90% of patients,” the authors wrote. “What is less well understood is how long that benefit lasts and if this contributes to a substantial reduction in progression to cancer.”

Researchers prospectively gathered data from 2,535 patients from 28 U.K. specialist centers who underwent RFA therapy for BE (average length 5.2cm, range 1-20 cm). Among the group, 20% had low-grade dysplasia, 54% had high-grade dysplasia, and 26% had intramucosal carcinoma.

They looked at rates of invasive cancer and analyzed data for 1,175 patients to assess clearance rates of dysplasia (CR-D) and intestinal metaplasia (CR-IM) within 2 years of starting RFA, then looked at relapses and rates of return to CR-D and CR-IM after more therapy.

One year after RFA therapy, the Kaplan Meier (KM) rate of invasive cancer in the 2,535 patients was 0.5%. Ten years after starting treatment, the KM cancer rate was 4.1%, with a crude incidence rate of 0.52 per 100 patient-years. After 2 years of RFA, CR-D was 88% and CR-IM was 62.6%.

At 8 years, the KM relapse rates were 5.9% from CR-D and 18.7% from CR-IM. Most relapses happened in the first 2 years.

“Our study confirms durable reversal of dysplasia and BE with RFA, which reduces cancer risk by more than 90% compared to historical control data of 6-19% per annum,” the authors wrote.

Despite advances in diagnosis and treatment for esophageal adenocarcinoma, there has been only small improvement in 5-year survival over the past 40 years, the authors note. Meanwhile, the incidence of continues to rise in the Western world.
 

Researchers look for minimally invasive solutions

Surgery removing the esophagus and lymph node clearance had been the standard for high-grade dysplasia, the authors wrote. It is still the intervention of choice for patients with locoregional disease, but it comes with high morbidity and mortality rates.

This has spurred researchers to look for a minimally invasive solution focused on organ preservation to treat early disease and avoid surgical side effects but also to deliver a cure, according to the authors.

Shria Kumar, MD, assistant professor in the Division of Digestive and Liver Diseases at University of Miami Miller School of Medicine, told this publication, “Endoscopic ablation of dysplasia or intramucosal cancer is a mainstay of Barrett’s treatment.”

She noted the importance of the 10-year time period as the initial studies that established ablation evaluated outcomes within 1-3 years, and more recent data shows 5-year favorable outcomes.

Citing a study from the New England Journal of Medicine, Dr. Kumar said, “The present study’s cohort developed cancer at rates similar to one of the earlier U.S.-based cohorts of Barrett’s patients, suggesting that we can draw some parallels.”

She pointed out notable characteristics in the U.K. cohort: “The majority of participants were male and Caucasian; 80% of had high-grade dysplasia or early cancer upon enrollment and long-segment Barrett’s.”

That difference is important when thinking about how this applies to a more diverse U.S. population, she said, or even patients who don’t have high-grade dysplasia or early cancer when they enroll.

“It’s also important to point out are that individuals with low-grade dysplasia were included in this U.K.-based study. There has been evidence that persons in Europe with low-grade dysplasia have higher rates of progression than persons in the U.S. with low-grade dysplasia.”

Dr. Kumar said this may be attributable to differences in the way pathologists practice in the two countries or in endoscopists’ treatment patterns. U.S. guidelines agree that ablation can be used in select persons with low-grade dysplasia, she said, but it’s an area that needs further study.

“Overall, though, this is a really important study of real-time data showing that ablation is impacting cancer rates in a positive way and that in select patients, we can really decrease the risk of invasive cancer by endoscopic eradication therapies,” Dr. Kumar said.

Two coauthors have received grants from Medtronic and Pentax Medical. The other authors have declared no relevant financial relationships. Dr. Kumar reports no relevant financial relationships.

Radiofrequency ablation (RFA) is effective and long lasting in preventing esophageal adenocarcinoma, new data suggest.

Researchers, led by Paul Wolfson, MBBS, from the Wellcome/EPSRC (Engineering and Physical Sciences Research Council) Centre for Interventional & Surgical Sciences, University College London also found that most treatment relapses happen early and can be re-treated successfully.

Findings were published in a final 10-year report from the United Kingdom National Halo Radiofrequency Ablation Registry and in Gastrointestinal Endoscopy. Because RFA has been used in mainstream clinical practice only since 2005, long-term data of more than 5 years has been lacking.

Multiple studies have shown that RFA is effective in preventing esophageal cancer, but data have been lacking on how long RFA is effective in preventing esophageal adenocarcinoma in patients with dysplastic Barrett’s esophagus (BE). A significant number of patients with dysplastic BE do not initially have visible lesions. For instance, the U.S. RFA Patient Registry reported an average 2.7-year follow up of 4,982 patients, but only 1,305 had dysplasia, the authors of the U.K. report note.

“It is well-established that endoscopic treatment of dysplastic BE is initially successful in up to 90% of patients,” the authors wrote. “What is less well understood is how long that benefit lasts and if this contributes to a substantial reduction in progression to cancer.”

Researchers prospectively gathered data from 2,535 patients from 28 U.K. specialist centers who underwent RFA therapy for BE (average length 5.2cm, range 1-20 cm). Among the group, 20% had low-grade dysplasia, 54% had high-grade dysplasia, and 26% had intramucosal carcinoma.

They looked at rates of invasive cancer and analyzed data for 1,175 patients to assess clearance rates of dysplasia (CR-D) and intestinal metaplasia (CR-IM) within 2 years of starting RFA, then looked at relapses and rates of return to CR-D and CR-IM after more therapy.

One year after RFA therapy, the Kaplan Meier (KM) rate of invasive cancer in the 2,535 patients was 0.5%. Ten years after starting treatment, the KM cancer rate was 4.1%, with a crude incidence rate of 0.52 per 100 patient-years. After 2 years of RFA, CR-D was 88% and CR-IM was 62.6%.

At 8 years, the KM relapse rates were 5.9% from CR-D and 18.7% from CR-IM. Most relapses happened in the first 2 years.

“Our study confirms durable reversal of dysplasia and BE with RFA, which reduces cancer risk by more than 90% compared to historical control data of 6-19% per annum,” the authors wrote.

Despite advances in diagnosis and treatment for esophageal adenocarcinoma, there has been only small improvement in 5-year survival over the past 40 years, the authors note. Meanwhile, the incidence of continues to rise in the Western world.
 

Researchers look for minimally invasive solutions

Surgery removing the esophagus and lymph node clearance had been the standard for high-grade dysplasia, the authors wrote. It is still the intervention of choice for patients with locoregional disease, but it comes with high morbidity and mortality rates.

This has spurred researchers to look for a minimally invasive solution focused on organ preservation to treat early disease and avoid surgical side effects but also to deliver a cure, according to the authors.

Shria Kumar, MD, assistant professor in the Division of Digestive and Liver Diseases at University of Miami Miller School of Medicine, told this publication, “Endoscopic ablation of dysplasia or intramucosal cancer is a mainstay of Barrett’s treatment.”

She noted the importance of the 10-year time period as the initial studies that established ablation evaluated outcomes within 1-3 years, and more recent data shows 5-year favorable outcomes.

Citing a study from the New England Journal of Medicine, Dr. Kumar said, “The present study’s cohort developed cancer at rates similar to one of the earlier U.S.-based cohorts of Barrett’s patients, suggesting that we can draw some parallels.”

She pointed out notable characteristics in the U.K. cohort: “The majority of participants were male and Caucasian; 80% of had high-grade dysplasia or early cancer upon enrollment and long-segment Barrett’s.”

That difference is important when thinking about how this applies to a more diverse U.S. population, she said, or even patients who don’t have high-grade dysplasia or early cancer when they enroll.

“It’s also important to point out are that individuals with low-grade dysplasia were included in this U.K.-based study. There has been evidence that persons in Europe with low-grade dysplasia have higher rates of progression than persons in the U.S. with low-grade dysplasia.”

Dr. Kumar said this may be attributable to differences in the way pathologists practice in the two countries or in endoscopists’ treatment patterns. U.S. guidelines agree that ablation can be used in select persons with low-grade dysplasia, she said, but it’s an area that needs further study.

“Overall, though, this is a really important study of real-time data showing that ablation is impacting cancer rates in a positive way and that in select patients, we can really decrease the risk of invasive cancer by endoscopic eradication therapies,” Dr. Kumar said.

Two coauthors have received grants from Medtronic and Pentax Medical. The other authors have declared no relevant financial relationships. Dr. Kumar reports no relevant financial relationships.

Heavy drinking during early adulthood may raise the risk for alcohol-related cancers, even after drinking stops or decreases in middle age, according to a new study from Australia.

Although alcohol is a known risk factor for cancer, people generally do not expect their heavy drinking in early adulthood to affect their cancer risk many years later, lead author Harindra Jayasekara, MBBS, MD, PhD, with Cancer Council Victoria and University of Melbourne, said in an interview. But in this analysis, “we found evidence consistent with early initiation and chronic progression of carcinogenesis linked to alcohol and its toxic metabolites.”

Courtesy Debora Cartagena, USCDCP

Impact on cancer risk

For men, relative to lifetime abstention, heavy drinking trajectories were associated with an increased risk for alcohol-related cancer overall.

The strongest associations were for the early decreasing heavy trajectory (hazard ratio, 1.75) and the late decreasing heavy trajectory (HR, 1.94), with the increasing heavy trajectory not far behind (HR, 1.45).

The strength of these associations did not change appreciably in analyses excluding current smokers at baseline.

Among men, the early decreasing heavy and late decreasing heavy intake trajectories were similarly associated with an increased risk for colorectal cancer (HR, 1.56 for early, and HR, 1.74 for late). The corresponding HR for the increasing heavy trajectory was 1.36.

For women, compared with lifetime abstention, the alcohol intake trajectory classified as increasing moderate (30-59 g/day) was associated with a greater risk for alcohol-related cancer overall (HR, 1.25). The strength of this association weakened slightly when current smokers were excluded.

Compared with lifetime abstention, the increasing moderate trajectory in women was similarly associated with an increased risk for breast cancer (HR, 1.30) and colorectal cancer (HR, 1.23).

The 2018 World Cancer Research Fund and American Institute for Cancer Research global cancer prevention recommendation on alcohol is to “avoid any alcohol,” study investigator Julie Bassett, PhD, MSc, with Cancer Council Victoria, said in an interview. “As much as it is important to limit alcohol intake during middle age to prevent cancer, we have shown that limiting intake during early adulthood is also important.”
 

‘Striking’ findings

Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services at the Addiction Institute of Mount Sinai in New York, said it is “striking” that heavy drinking in early adulthood led to an increased risk for alcohol-related cancers, even among people who drank much less in middle age.

“We’ve known for decades that alcohol is not harmless, but this data adds to the growing body of literature regarding the significant dangers of heavy drinking during early adulthood,” said Dr. Brennan, who wasn’t involved in the study.

Dr. Brennan cautioned, however, that the authors studied alcohol-related cancers, and “there are likely many other [cancer] risk factors that were not analyzed in this dataset.”

Nevertheless, this evidence helps counter the “troubling narrative” that “it is somehow normal and safe to drink excessively in young adulthood.”

“It is most certainly not safe,” Dr. Brennan told this news organization . “We see in this study that drinking excessively in young adulthood can raise the risk of cancer much later in life.”

The study had no commercial funding. Dr. Bassett, Dr. Jayasekara, and Dr. Brennan have disclosed no relevant financial relationships.

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

Heavy drinking during early adulthood may raise the risk for alcohol-related cancers, even after drinking stops or decreases in middle age, according to a new study from Australia.

Although alcohol is a known risk factor for cancer, people generally do not expect their heavy drinking in early adulthood to affect their cancer risk many years later, lead author Harindra Jayasekara, MBBS, MD, PhD, with Cancer Council Victoria and University of Melbourne, said in an interview. But in this analysis, “we found evidence consistent with early initiation and chronic progression of carcinogenesis linked to alcohol and its toxic metabolites.”

Courtesy Debora Cartagena, USCDCP

Impact on cancer risk

For men, relative to lifetime abstention, heavy drinking trajectories were associated with an increased risk for alcohol-related cancer overall.

The strongest associations were for the early decreasing heavy trajectory (hazard ratio, 1.75) and the late decreasing heavy trajectory (HR, 1.94), with the increasing heavy trajectory not far behind (HR, 1.45).

The strength of these associations did not change appreciably in analyses excluding current smokers at baseline.

Among men, the early decreasing heavy and late decreasing heavy intake trajectories were similarly associated with an increased risk for colorectal cancer (HR, 1.56 for early, and HR, 1.74 for late). The corresponding HR for the increasing heavy trajectory was 1.36.

For women, compared with lifetime abstention, the alcohol intake trajectory classified as increasing moderate (30-59 g/day) was associated with a greater risk for alcohol-related cancer overall (HR, 1.25). The strength of this association weakened slightly when current smokers were excluded.

Compared with lifetime abstention, the increasing moderate trajectory in women was similarly associated with an increased risk for breast cancer (HR, 1.30) and colorectal cancer (HR, 1.23).

The 2018 World Cancer Research Fund and American Institute for Cancer Research global cancer prevention recommendation on alcohol is to “avoid any alcohol,” study investigator Julie Bassett, PhD, MSc, with Cancer Council Victoria, said in an interview. “As much as it is important to limit alcohol intake during middle age to prevent cancer, we have shown that limiting intake during early adulthood is also important.”
 

‘Striking’ findings

Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services at the Addiction Institute of Mount Sinai in New York, said it is “striking” that heavy drinking in early adulthood led to an increased risk for alcohol-related cancers, even among people who drank much less in middle age.

“We’ve known for decades that alcohol is not harmless, but this data adds to the growing body of literature regarding the significant dangers of heavy drinking during early adulthood,” said Dr. Brennan, who wasn’t involved in the study.

Dr. Brennan cautioned, however, that the authors studied alcohol-related cancers, and “there are likely many other [cancer] risk factors that were not analyzed in this dataset.”

Nevertheless, this evidence helps counter the “troubling narrative” that “it is somehow normal and safe to drink excessively in young adulthood.”

“It is most certainly not safe,” Dr. Brennan told this news organization . “We see in this study that drinking excessively in young adulthood can raise the risk of cancer much later in life.”

The study had no commercial funding. Dr. Bassett, Dr. Jayasekara, and Dr. Brennan have disclosed no relevant financial relationships.

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

Heavy drinking during early adulthood may raise the risk for alcohol-related cancers, even after drinking stops or decreases in middle age, according to a new study from Australia.

Although alcohol is a known risk factor for cancer, people generally do not expect their heavy drinking in early adulthood to affect their cancer risk many years later, lead author Harindra Jayasekara, MBBS, MD, PhD, with Cancer Council Victoria and University of Melbourne, said in an interview. But in this analysis, “we found evidence consistent with early initiation and chronic progression of carcinogenesis linked to alcohol and its toxic metabolites.”

Courtesy Debora Cartagena, USCDCP

Impact on cancer risk

For men, relative to lifetime abstention, heavy drinking trajectories were associated with an increased risk for alcohol-related cancer overall.

The strongest associations were for the early decreasing heavy trajectory (hazard ratio, 1.75) and the late decreasing heavy trajectory (HR, 1.94), with the increasing heavy trajectory not far behind (HR, 1.45).

The strength of these associations did not change appreciably in analyses excluding current smokers at baseline.

Among men, the early decreasing heavy and late decreasing heavy intake trajectories were similarly associated with an increased risk for colorectal cancer (HR, 1.56 for early, and HR, 1.74 for late). The corresponding HR for the increasing heavy trajectory was 1.36.

For women, compared with lifetime abstention, the alcohol intake trajectory classified as increasing moderate (30-59 g/day) was associated with a greater risk for alcohol-related cancer overall (HR, 1.25). The strength of this association weakened slightly when current smokers were excluded.

Compared with lifetime abstention, the increasing moderate trajectory in women was similarly associated with an increased risk for breast cancer (HR, 1.30) and colorectal cancer (HR, 1.23).

The 2018 World Cancer Research Fund and American Institute for Cancer Research global cancer prevention recommendation on alcohol is to “avoid any alcohol,” study investigator Julie Bassett, PhD, MSc, with Cancer Council Victoria, said in an interview. “As much as it is important to limit alcohol intake during middle age to prevent cancer, we have shown that limiting intake during early adulthood is also important.”
 

‘Striking’ findings

Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services at the Addiction Institute of Mount Sinai in New York, said it is “striking” that heavy drinking in early adulthood led to an increased risk for alcohol-related cancers, even among people who drank much less in middle age.

“We’ve known for decades that alcohol is not harmless, but this data adds to the growing body of literature regarding the significant dangers of heavy drinking during early adulthood,” said Dr. Brennan, who wasn’t involved in the study.

Dr. Brennan cautioned, however, that the authors studied alcohol-related cancers, and “there are likely many other [cancer] risk factors that were not analyzed in this dataset.”

Nevertheless, this evidence helps counter the “troubling narrative” that “it is somehow normal and safe to drink excessively in young adulthood.”

“It is most certainly not safe,” Dr. Brennan told this news organization . “We see in this study that drinking excessively in young adulthood can raise the risk of cancer much later in life.”

The study had no commercial funding. Dr. Bassett, Dr. Jayasekara, and Dr. Brennan have disclosed no relevant financial relationships.

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

Patients with low-risk differentiated thyroid cancer (DTC) undergoing thyroidectomy show no improvements in outcomes with the use of postoperative radioiodine ablation compared to those who do not receive this therapy, suggesting these patients can be spared the previously common treatment.

The study’s take-home message for clinicians should be to “stop systematic radioiodine ablation administration in low-risk thyroid cancer patients,” lead author Sophie Leboulleux, MD, PhD, said in an interview.

The results were first reported at ENDO 2021 and have now been published in the New England Journal of Medicine by Dr. Leboulleux, of the department of nuclear medicine and endocrine oncology, Gustave Roussy Cancer Institute, Villejuif, France, and colleagues.

While American Thyroid Association (ATA) guidelines already indicate that radioiodine ablation is not routinely recommended after thyroidectomy for patients with low-risk thyroid cancer, the guidance is only a “weak recommendation,” supported by “low-quality evidence.”  

However, the new findings should give that level of evidence a much-needed boost, said one expert. “I think the main contribution of this paper is to change the evidence level to ‘high quality,’ therefore making the recommendation ‘strong,’ rather than ‘weak,’ ” David S. Cooper, MD, said in an interview.

Dr. Cooper, professor of medicine and radiology at Johns Hopkins University, Baltimore, wrote an editorial that accompanies Dr. Leboulleux’s study.

The ability to safely spare patients the radioiodine ablation step after thyroidectomy has important benefits in terms of cost and convenience, Dr. Cooper stressed.
 

ESTIMABL2 trial

The new findings are from the prospective, randomized, phase 3 Essai Stimulation Ablation 2 (ESTIMABL2) trial, in which 730 patients at 35 centers in France with low-risk DTC scheduled to undergo thyroidectomy were enrolled between May 2013 and March 2017.

Patients were randomized to receive either postoperative radioiodine ablation (1.1 GBq) after injections of recombinant human thyrotropin (n = 363) or no postoperative radioiodine (n = 367).

Patients were a mean age of 52 years and 83% were women. About 96% had papillary tumors, and pathological tumor node (pTN) stages were mostly pT1b thyroid with a nodal status of N0 or Nx (81.1%). It is these patients in particular in whom retrospective studies of the use of radioiodine ablation have yielded inconsistent results, Dr. Leboulleux and colleagues noted. Hence, their decision to look at this prospectively.

Outcomes were based on the groups’ rates of events, defined as the presence of abnormal foci of radioiodine uptake on whole-body scanning that required treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or increased levels of thyroglobulin or thyroglobulin antibodies.

After a 3-year follow-up, the rates of having no events in both groups were very high – and nearly identical – at 95.6% among those receiving no radioiodine ablation and 95.9% in the radioiodine group, for a between-group difference of –0.3 percentage points, which met the criteria for noninferiority for the no-radioiodine group.

Likewise, the events that did occur were nearly equally split between the no-radioiodine group (16 events, 4.4%) and the radioiodine group (15 events, 4.1%).

Among patients who had events, subsequent treatments, including surgery, radioiodine administration, or both, were necessary for four patients in the no-radioiodine group and 10 in the radioiodine group, and additional treatments were not necessary for the other patients who experienced events.

There were no differences between those who did and did not experience events in terms of molecular alterations, and 50 of the tumors had BRAF mutations, with no significant differences between groups.

Of the adverse events that occurred in 30 patients, none were determined to be related to treatment, and there were no thyroid-related deaths.

The recurrence rates align with the rates observed overall with low-risk thyroid cancer, the authors noted. 

“We observed that less than 5% of the patients in the two groups had events that included abnormal findings on whole-body scanning or neck ultrasonography or elevated levels of thyroglobulin or thyroglobulin antibodies during the first 3 years of follow-up,” they reported.

“This rate is concordant with the definition of low-risk thyroid cancer, and our trial showed that the risk of events was not higher in the absence of postoperative administration of radioiodine.”
 

Patients spared costs, work losses

Dr. Cooper elaborated on the advantages, for patients, of avoiding radioiodine ablation.

For one thing, the recombinant human TSH that is necessary to prepare for radioiodine therapy is very expensive, ranging from $2,000 to $3,000, with patients often having a copay, he explained.

“Patients usually have to take time off work, which is also an expense to society and to them if they don’t get paid for days that they don’t work,” Dr. Cooper added.

A possible study limitation is the question of whether 3 years is an ample follow-up period to detect events. However, Dr. Cooper said he considers the period to be sufficient.

“As the authors point out, most recurrences of thyroid cancer are detected within the first 3-5 years of initial treatment, so ... the 3-year window is still clinically relevant,” he said.

Regarding the study’s inclusion of centers only in France, Dr. Cooper added, “I do not think that this is a study limitation. There is nothing specific about the French population that would lead me to conclude that the results were not generalizable to all populations with low-risk papillary thyroid cancer.”
 

Some continue radioiodine use, but lobectomies add to decline

Despite the mounting evidence of the lack of benefit of radioiodine ablation in low-risk patients, some centers, particularly in Europe, continue the practice, which was standard in the treatment of DTC until relatively recently.

“[While] U.S. guidelines changed in 2015 in favor of no radioiodine in low-risk differentiated thyroid cancer patients, this study should help to change European guidelines,” Dr. Leboulleux said. “The results will help to change practice both in the U.S. and in Europe.”

In addition to awareness of guidelines and new evidence, another reason for the decline in radioiodine ablation for low-risk DTC is the increasing use of thyroid lobectomy, which does not involve the use of radioiodine ablation, rather than total thyroidectomy, Dr. Cooper noted.

“The [new] NEJM paper will hopefully decrease the inappropriate use of radioiodine in low-risk patients even further,” he concluded.

The study received support from the French Ministry of Health through a grant from the National Cancer Institute. The authors have reported no relevant financial relationships.

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

Patients with low-risk differentiated thyroid cancer (DTC) undergoing thyroidectomy show no improvements in outcomes with the use of postoperative radioiodine ablation compared to those who do not receive this therapy, suggesting these patients can be spared the previously common treatment.

The study’s take-home message for clinicians should be to “stop systematic radioiodine ablation administration in low-risk thyroid cancer patients,” lead author Sophie Leboulleux, MD, PhD, said in an interview.

The results were first reported at ENDO 2021 and have now been published in the New England Journal of Medicine by Dr. Leboulleux, of the department of nuclear medicine and endocrine oncology, Gustave Roussy Cancer Institute, Villejuif, France, and colleagues.

While American Thyroid Association (ATA) guidelines already indicate that radioiodine ablation is not routinely recommended after thyroidectomy for patients with low-risk thyroid cancer, the guidance is only a “weak recommendation,” supported by “low-quality evidence.”  

However, the new findings should give that level of evidence a much-needed boost, said one expert. “I think the main contribution of this paper is to change the evidence level to ‘high quality,’ therefore making the recommendation ‘strong,’ rather than ‘weak,’ ” David S. Cooper, MD, said in an interview.

Dr. Cooper, professor of medicine and radiology at Johns Hopkins University, Baltimore, wrote an editorial that accompanies Dr. Leboulleux’s study.

The ability to safely spare patients the radioiodine ablation step after thyroidectomy has important benefits in terms of cost and convenience, Dr. Cooper stressed.
 

ESTIMABL2 trial

The new findings are from the prospective, randomized, phase 3 Essai Stimulation Ablation 2 (ESTIMABL2) trial, in which 730 patients at 35 centers in France with low-risk DTC scheduled to undergo thyroidectomy were enrolled between May 2013 and March 2017.

Patients were randomized to receive either postoperative radioiodine ablation (1.1 GBq) after injections of recombinant human thyrotropin (n = 363) or no postoperative radioiodine (n = 367).

Patients were a mean age of 52 years and 83% were women. About 96% had papillary tumors, and pathological tumor node (pTN) stages were mostly pT1b thyroid with a nodal status of N0 or Nx (81.1%). It is these patients in particular in whom retrospective studies of the use of radioiodine ablation have yielded inconsistent results, Dr. Leboulleux and colleagues noted. Hence, their decision to look at this prospectively.

Outcomes were based on the groups’ rates of events, defined as the presence of abnormal foci of radioiodine uptake on whole-body scanning that required treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or increased levels of thyroglobulin or thyroglobulin antibodies.

After a 3-year follow-up, the rates of having no events in both groups were very high – and nearly identical – at 95.6% among those receiving no radioiodine ablation and 95.9% in the radioiodine group, for a between-group difference of –0.3 percentage points, which met the criteria for noninferiority for the no-radioiodine group.

Likewise, the events that did occur were nearly equally split between the no-radioiodine group (16 events, 4.4%) and the radioiodine group (15 events, 4.1%).

Among patients who had events, subsequent treatments, including surgery, radioiodine administration, or both, were necessary for four patients in the no-radioiodine group and 10 in the radioiodine group, and additional treatments were not necessary for the other patients who experienced events.

There were no differences between those who did and did not experience events in terms of molecular alterations, and 50 of the tumors had BRAF mutations, with no significant differences between groups.

Of the adverse events that occurred in 30 patients, none were determined to be related to treatment, and there were no thyroid-related deaths.

The recurrence rates align with the rates observed overall with low-risk thyroid cancer, the authors noted. 

“We observed that less than 5% of the patients in the two groups had events that included abnormal findings on whole-body scanning or neck ultrasonography or elevated levels of thyroglobulin or thyroglobulin antibodies during the first 3 years of follow-up,” they reported.

“This rate is concordant with the definition of low-risk thyroid cancer, and our trial showed that the risk of events was not higher in the absence of postoperative administration of radioiodine.”
 

Patients spared costs, work losses

Dr. Cooper elaborated on the advantages, for patients, of avoiding radioiodine ablation.

For one thing, the recombinant human TSH that is necessary to prepare for radioiodine therapy is very expensive, ranging from $2,000 to $3,000, with patients often having a copay, he explained.

“Patients usually have to take time off work, which is also an expense to society and to them if they don’t get paid for days that they don’t work,” Dr. Cooper added.

A possible study limitation is the question of whether 3 years is an ample follow-up period to detect events. However, Dr. Cooper said he considers the period to be sufficient.

“As the authors point out, most recurrences of thyroid cancer are detected within the first 3-5 years of initial treatment, so ... the 3-year window is still clinically relevant,” he said.

Regarding the study’s inclusion of centers only in France, Dr. Cooper added, “I do not think that this is a study limitation. There is nothing specific about the French population that would lead me to conclude that the results were not generalizable to all populations with low-risk papillary thyroid cancer.”
 

Some continue radioiodine use, but lobectomies add to decline

Despite the mounting evidence of the lack of benefit of radioiodine ablation in low-risk patients, some centers, particularly in Europe, continue the practice, which was standard in the treatment of DTC until relatively recently.

“[While] U.S. guidelines changed in 2015 in favor of no radioiodine in low-risk differentiated thyroid cancer patients, this study should help to change European guidelines,” Dr. Leboulleux said. “The results will help to change practice both in the U.S. and in Europe.”

In addition to awareness of guidelines and new evidence, another reason for the decline in radioiodine ablation for low-risk DTC is the increasing use of thyroid lobectomy, which does not involve the use of radioiodine ablation, rather than total thyroidectomy, Dr. Cooper noted.

“The [new] NEJM paper will hopefully decrease the inappropriate use of radioiodine in low-risk patients even further,” he concluded.

The study received support from the French Ministry of Health through a grant from the National Cancer Institute. The authors have reported no relevant financial relationships.

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

Patients with low-risk differentiated thyroid cancer (DTC) undergoing thyroidectomy show no improvements in outcomes with the use of postoperative radioiodine ablation compared to those who do not receive this therapy, suggesting these patients can be spared the previously common treatment.

The study’s take-home message for clinicians should be to “stop systematic radioiodine ablation administration in low-risk thyroid cancer patients,” lead author Sophie Leboulleux, MD, PhD, said in an interview.

The results were first reported at ENDO 2021 and have now been published in the New England Journal of Medicine by Dr. Leboulleux, of the department of nuclear medicine and endocrine oncology, Gustave Roussy Cancer Institute, Villejuif, France, and colleagues.

While American Thyroid Association (ATA) guidelines already indicate that radioiodine ablation is not routinely recommended after thyroidectomy for patients with low-risk thyroid cancer, the guidance is only a “weak recommendation,” supported by “low-quality evidence.”  

However, the new findings should give that level of evidence a much-needed boost, said one expert. “I think the main contribution of this paper is to change the evidence level to ‘high quality,’ therefore making the recommendation ‘strong,’ rather than ‘weak,’ ” David S. Cooper, MD, said in an interview.

Dr. Cooper, professor of medicine and radiology at Johns Hopkins University, Baltimore, wrote an editorial that accompanies Dr. Leboulleux’s study.

The ability to safely spare patients the radioiodine ablation step after thyroidectomy has important benefits in terms of cost and convenience, Dr. Cooper stressed.
 

ESTIMABL2 trial

The new findings are from the prospective, randomized, phase 3 Essai Stimulation Ablation 2 (ESTIMABL2) trial, in which 730 patients at 35 centers in France with low-risk DTC scheduled to undergo thyroidectomy were enrolled between May 2013 and March 2017.

Patients were randomized to receive either postoperative radioiodine ablation (1.1 GBq) after injections of recombinant human thyrotropin (n = 363) or no postoperative radioiodine (n = 367).

Patients were a mean age of 52 years and 83% were women. About 96% had papillary tumors, and pathological tumor node (pTN) stages were mostly pT1b thyroid with a nodal status of N0 or Nx (81.1%). It is these patients in particular in whom retrospective studies of the use of radioiodine ablation have yielded inconsistent results, Dr. Leboulleux and colleagues noted. Hence, their decision to look at this prospectively.

Outcomes were based on the groups’ rates of events, defined as the presence of abnormal foci of radioiodine uptake on whole-body scanning that required treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or increased levels of thyroglobulin or thyroglobulin antibodies.

After a 3-year follow-up, the rates of having no events in both groups were very high – and nearly identical – at 95.6% among those receiving no radioiodine ablation and 95.9% in the radioiodine group, for a between-group difference of –0.3 percentage points, which met the criteria for noninferiority for the no-radioiodine group.

Likewise, the events that did occur were nearly equally split between the no-radioiodine group (16 events, 4.4%) and the radioiodine group (15 events, 4.1%).

Among patients who had events, subsequent treatments, including surgery, radioiodine administration, or both, were necessary for four patients in the no-radioiodine group and 10 in the radioiodine group, and additional treatments were not necessary for the other patients who experienced events.

There were no differences between those who did and did not experience events in terms of molecular alterations, and 50 of the tumors had BRAF mutations, with no significant differences between groups.

Of the adverse events that occurred in 30 patients, none were determined to be related to treatment, and there were no thyroid-related deaths.

The recurrence rates align with the rates observed overall with low-risk thyroid cancer, the authors noted. 

“We observed that less than 5% of the patients in the two groups had events that included abnormal findings on whole-body scanning or neck ultrasonography or elevated levels of thyroglobulin or thyroglobulin antibodies during the first 3 years of follow-up,” they reported.

“This rate is concordant with the definition of low-risk thyroid cancer, and our trial showed that the risk of events was not higher in the absence of postoperative administration of radioiodine.”
 

Patients spared costs, work losses

Dr. Cooper elaborated on the advantages, for patients, of avoiding radioiodine ablation.

For one thing, the recombinant human TSH that is necessary to prepare for radioiodine therapy is very expensive, ranging from $2,000 to $3,000, with patients often having a copay, he explained.

“Patients usually have to take time off work, which is also an expense to society and to them if they don’t get paid for days that they don’t work,” Dr. Cooper added.

A possible study limitation is the question of whether 3 years is an ample follow-up period to detect events. However, Dr. Cooper said he considers the period to be sufficient.

“As the authors point out, most recurrences of thyroid cancer are detected within the first 3-5 years of initial treatment, so ... the 3-year window is still clinically relevant,” he said.

Regarding the study’s inclusion of centers only in France, Dr. Cooper added, “I do not think that this is a study limitation. There is nothing specific about the French population that would lead me to conclude that the results were not generalizable to all populations with low-risk papillary thyroid cancer.”
 

Some continue radioiodine use, but lobectomies add to decline

Despite the mounting evidence of the lack of benefit of radioiodine ablation in low-risk patients, some centers, particularly in Europe, continue the practice, which was standard in the treatment of DTC until relatively recently.

“[While] U.S. guidelines changed in 2015 in favor of no radioiodine in low-risk differentiated thyroid cancer patients, this study should help to change European guidelines,” Dr. Leboulleux said. “The results will help to change practice both in the U.S. and in Europe.”

In addition to awareness of guidelines and new evidence, another reason for the decline in radioiodine ablation for low-risk DTC is the increasing use of thyroid lobectomy, which does not involve the use of radioiodine ablation, rather than total thyroidectomy, Dr. Cooper noted.

“The [new] NEJM paper will hopefully decrease the inappropriate use of radioiodine in low-risk patients even further,” he concluded.

The study received support from the French Ministry of Health through a grant from the National Cancer Institute. The authors have reported no relevant financial relationships.

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

LAS VEGAS – Is the relationship between major depressive disorder and the development of cancer, cardiovascular disease, and other medical conditions a coincidence, or is there more at play?

According to Charles B. Nemeroff, MD, PhD, a host of circumstances potentially underlies this association, including treatment of the medical disorder itself.

Courtesy University of Texas, Austin

“The best example of that is probably the use of interferon-alpha for the treatment of malignant melanoma,” Dr. Nemeroff, professor and chair of the department of psychiatry and behavioral sciences at the University of Texas at Austin, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “Many patients treated with interferon-alpha ended up with very severe depression, including several documented suicides. Another possibility of the relationship between depression and medical disorders is that treating a patient for depression could result in a medical disorder. The best example of this is the use of 20 mg of olanzapine to augment the effects of an antidepressant, resulting in a 50-pound weight gain and the development of type 2 diabetes and metabolic syndrome. Both of those scenarios are well understood.”

Then there’s the behavioral aspects of the relationship, he continued, in which patients adopt the mindset that “I’m depressed. I don’t want to exercise. I’m a couch potato. I have been gaining a lot of weight. It’s bad for my heart.”

Converging biology is another possibility. “Is it possible that the biology of depression is linked to the biology of other disorders?” asked Dr. Nemeroff, who directs the university’s Institute for Early Life Adversity Research. “We can talk about this in relation to thyroid disease, a well known cause of depression, but we can also talk about the relationship to other disorders. There’s amazing epidemiologic evidence that patients with PTSD are much more likely to develop Alzheimer’s disease than patients without PTSD.”

Psychosocial issues also play a role. He recalled seeing patient in a clinic for the underserved who had underlying severe ulcerative colitis and anemia and couldn’t afford medical treatment. “The patient had a low hemoglobin, so it was impossible to distinguish between that and whether they had a primary depressive disorder or not,” he said.

In a study that explored the relationship between major depression and cancer, Dr. Nemeroff and colleagues found that the prevalence was highest in those with pancreatic cancer (50%), followed by oropharyngeal (40%), colon (13-25%), breast (18-25%), and gynecologic (23%), and Hodgkin’s lymphoma (17%) (Arch Gen Psychiatry 1995;52[2]:89-99). “Not all cancers have the same rate of depression,” he said. “One of the central questions is, not so much is the cancer patient depressed, but is depression a risk factor for developing cancer? The answer is a resounding yes. But what we don’t know is if you treat the depression aggressively, can you reduce that risk of either developing cancer or the progression of cancer?”

Dr. Nemeroff spotlighted several studies largely from the oncology literature, including a prospective survival analysis of 578 women with early-stage breast cancer (Lancet 1999;354:1331-6). After 5 years, 395 were alive and without relapse, 50 were alive with relapse, and 133 had died. The researchers found a significantly increased risk of death from all causes by 5 years in women with a high depression score (HR 3.59). There was a significantly increased risk of relapse or death at 5 years in women with high scores on helplessness and hopelessness measures.

In an analysis of the association between breast cancer and traumatic events, women who had severe stress or a traumatic event had lower rates of disease-free intervals (J Psychosomatic Res 2007;63:233-9). Another study by the same investigators found that a decrease in depression symptoms is associated with longer survival in patients with metastatic breast cancer (J Clin Oncol 2010;29:413-20). The median survival was 53.6 months for women with decreasing depression scores over 1 year and 25.1 months for women with increasing depression scores.

A more recent study of cervical cancer patients found that those exposed to psychological stress had an increased risk of cancer-specific mortality (HR 1.33) (Cancer Res 2019;79:3965-72). The association was mainly driven by distress experienced within 1 year before or after diagnosis (HR 1.30) but not afterward (HR 1.12). In addition, data from the large longitudinal Nurses’ Health Study II found that women with high PTSD symptoms had a twofold greater risk of ovarian cancer compared with women who had no trauma exposure (Cancer Res 2019;79:5113-20).

Authors of a separate study analyzed data from the Women’s Health Initiative to examine if depression precedes the development of a cancer diagnosis. They found that depression 3 years before a diagnosis of breast cancer was associated with all-cause mortality (HR 1.35) (Cancer 2017;123[16]:3107-15). Meanwhile, among women with late-stage breast cancer, newly developed depression at year 3 was significantly associated with all-cause mortality (HR 2.0) and breast cancer-specific mortality (HR 2.42). “That’s a pretty amazing finding,” Dr. Nemeroff said. “We have to think about depression as a systemic illness. What is depression doing that’s creating a fertile environment for cancer or worsening of cancer?”

He then discussed the risk of suicide in patients who are newly diagnosed with cancer. “No one ever talks about this, and I can’t get anybody to support research in this area,” he said. In one of the first studies on the topic, researchers conducted a case-control study of Medicare patients and determined risk of suicide among those with cancer was 2.3-fold higher compared with controls, even after adjustment for psychiatric illness and the risk of dying within a year (J Clin Oncol 2008;26[29]:4720-4). More recently, authors of a large population-based study in England found that the overall standardized mortality ratio for suicide was 1.20 (JAMA Psychiatry 2019;76[1]51-60). The risk was highest among patients with mesothelioma, with a 4.51-fold risk, followed by pancreatic (3.89-fold), esophageal (2.65-fold), lung (2.57-fold), and stomach cancer (2.20-fold). “They reported that the first 6 months after the diagnosis is associated with an increased risk of suicide – unrelated to prognosis,” Dr. Nemeroff said.

A separate analysis of SEER data from 1973-2014 and comprising more than 8.6 million cancer patients found that newly diagnosed cancer patients are 4.4 times more likely to die from suicide than patients in the same age group without cancer (Nat Commun 2019;10[1]:207). The highest risk was in lung cancer, followed by head and neck, testes, bladder, and Hodgkin’s lymphoma.

According to Dr. Nemeroff, the association between depression and the risk of certain forms of cancer or with a poor cancer prognosis “may have to do with immune function. Depression is associated with a change in inflammatory markers that very likely control the microenvironment of the tumor.” For example, he said, if the depressed environment is associated with a marked increase in tumor necrosis factor, interleukin 6, and other inflammatory markers, “that probably contributes to the body’s ability to fight disease. Ironically, depression is associated with an increase in inflammation but a decreased in T cell function. Remember, there are two fundamental types of immunity: the antibody response and the cellular response. What’s odd about depression is that there’s an increase in inflammatory markers but a decrease in the ability of T cells to function in terms of cellular immunity.”

Dr. Nemeroff disclosed that he has served as a consultant and/or scientific adviser for numerous pharmaceutical companies. He has received research and grant support from the National Institutes of Health.

LAS VEGAS – Is the relationship between major depressive disorder and the development of cancer, cardiovascular disease, and other medical conditions a coincidence, or is there more at play?

According to Charles B. Nemeroff, MD, PhD, a host of circumstances potentially underlies this association, including treatment of the medical disorder itself.

Courtesy University of Texas, Austin

“The best example of that is probably the use of interferon-alpha for the treatment of malignant melanoma,” Dr. Nemeroff, professor and chair of the department of psychiatry and behavioral sciences at the University of Texas at Austin, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “Many patients treated with interferon-alpha ended up with very severe depression, including several documented suicides. Another possibility of the relationship between depression and medical disorders is that treating a patient for depression could result in a medical disorder. The best example of this is the use of 20 mg of olanzapine to augment the effects of an antidepressant, resulting in a 50-pound weight gain and the development of type 2 diabetes and metabolic syndrome. Both of those scenarios are well understood.”

Then there’s the behavioral aspects of the relationship, he continued, in which patients adopt the mindset that “I’m depressed. I don’t want to exercise. I’m a couch potato. I have been gaining a lot of weight. It’s bad for my heart.”

Converging biology is another possibility. “Is it possible that the biology of depression is linked to the biology of other disorders?” asked Dr. Nemeroff, who directs the university’s Institute for Early Life Adversity Research. “We can talk about this in relation to thyroid disease, a well known cause of depression, but we can also talk about the relationship to other disorders. There’s amazing epidemiologic evidence that patients with PTSD are much more likely to develop Alzheimer’s disease than patients without PTSD.”

Psychosocial issues also play a role. He recalled seeing patient in a clinic for the underserved who had underlying severe ulcerative colitis and anemia and couldn’t afford medical treatment. “The patient had a low hemoglobin, so it was impossible to distinguish between that and whether they had a primary depressive disorder or not,” he said.

In a study that explored the relationship between major depression and cancer, Dr. Nemeroff and colleagues found that the prevalence was highest in those with pancreatic cancer (50%), followed by oropharyngeal (40%), colon (13-25%), breast (18-25%), and gynecologic (23%), and Hodgkin’s lymphoma (17%) (Arch Gen Psychiatry 1995;52[2]:89-99). “Not all cancers have the same rate of depression,” he said. “One of the central questions is, not so much is the cancer patient depressed, but is depression a risk factor for developing cancer? The answer is a resounding yes. But what we don’t know is if you treat the depression aggressively, can you reduce that risk of either developing cancer or the progression of cancer?”

Dr. Nemeroff spotlighted several studies largely from the oncology literature, including a prospective survival analysis of 578 women with early-stage breast cancer (Lancet 1999;354:1331-6). After 5 years, 395 were alive and without relapse, 50 were alive with relapse, and 133 had died. The researchers found a significantly increased risk of death from all causes by 5 years in women with a high depression score (HR 3.59). There was a significantly increased risk of relapse or death at 5 years in women with high scores on helplessness and hopelessness measures.

In an analysis of the association between breast cancer and traumatic events, women who had severe stress or a traumatic event had lower rates of disease-free intervals (J Psychosomatic Res 2007;63:233-9). Another study by the same investigators found that a decrease in depression symptoms is associated with longer survival in patients with metastatic breast cancer (J Clin Oncol 2010;29:413-20). The median survival was 53.6 months for women with decreasing depression scores over 1 year and 25.1 months for women with increasing depression scores.

A more recent study of cervical cancer patients found that those exposed to psychological stress had an increased risk of cancer-specific mortality (HR 1.33) (Cancer Res 2019;79:3965-72). The association was mainly driven by distress experienced within 1 year before or after diagnosis (HR 1.30) but not afterward (HR 1.12). In addition, data from the large longitudinal Nurses’ Health Study II found that women with high PTSD symptoms had a twofold greater risk of ovarian cancer compared with women who had no trauma exposure (Cancer Res 2019;79:5113-20).

Authors of a separate study analyzed data from the Women’s Health Initiative to examine if depression precedes the development of a cancer diagnosis. They found that depression 3 years before a diagnosis of breast cancer was associated with all-cause mortality (HR 1.35) (Cancer 2017;123[16]:3107-15). Meanwhile, among women with late-stage breast cancer, newly developed depression at year 3 was significantly associated with all-cause mortality (HR 2.0) and breast cancer-specific mortality (HR 2.42). “That’s a pretty amazing finding,” Dr. Nemeroff said. “We have to think about depression as a systemic illness. What is depression doing that’s creating a fertile environment for cancer or worsening of cancer?”

He then discussed the risk of suicide in patients who are newly diagnosed with cancer. “No one ever talks about this, and I can’t get anybody to support research in this area,” he said. In one of the first studies on the topic, researchers conducted a case-control study of Medicare patients and determined risk of suicide among those with cancer was 2.3-fold higher compared with controls, even after adjustment for psychiatric illness and the risk of dying within a year (J Clin Oncol 2008;26[29]:4720-4). More recently, authors of a large population-based study in England found that the overall standardized mortality ratio for suicide was 1.20 (JAMA Psychiatry 2019;76[1]51-60). The risk was highest among patients with mesothelioma, with a 4.51-fold risk, followed by pancreatic (3.89-fold), esophageal (2.65-fold), lung (2.57-fold), and stomach cancer (2.20-fold). “They reported that the first 6 months after the diagnosis is associated with an increased risk of suicide – unrelated to prognosis,” Dr. Nemeroff said.

A separate analysis of SEER data from 1973-2014 and comprising more than 8.6 million cancer patients found that newly diagnosed cancer patients are 4.4 times more likely to die from suicide than patients in the same age group without cancer (Nat Commun 2019;10[1]:207). The highest risk was in lung cancer, followed by head and neck, testes, bladder, and Hodgkin’s lymphoma.

According to Dr. Nemeroff, the association between depression and the risk of certain forms of cancer or with a poor cancer prognosis “may have to do with immune function. Depression is associated with a change in inflammatory markers that very likely control the microenvironment of the tumor.” For example, he said, if the depressed environment is associated with a marked increase in tumor necrosis factor, interleukin 6, and other inflammatory markers, “that probably contributes to the body’s ability to fight disease. Ironically, depression is associated with an increase in inflammation but a decreased in T cell function. Remember, there are two fundamental types of immunity: the antibody response and the cellular response. What’s odd about depression is that there’s an increase in inflammatory markers but a decrease in the ability of T cells to function in terms of cellular immunity.”

Dr. Nemeroff disclosed that he has served as a consultant and/or scientific adviser for numerous pharmaceutical companies. He has received research and grant support from the National Institutes of Health.

LAS VEGAS – Is the relationship between major depressive disorder and the development of cancer, cardiovascular disease, and other medical conditions a coincidence, or is there more at play?

According to Charles B. Nemeroff, MD, PhD, a host of circumstances potentially underlies this association, including treatment of the medical disorder itself.

Courtesy University of Texas, Austin

“The best example of that is probably the use of interferon-alpha for the treatment of malignant melanoma,” Dr. Nemeroff, professor and chair of the department of psychiatry and behavioral sciences at the University of Texas at Austin, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “Many patients treated with interferon-alpha ended up with very severe depression, including several documented suicides. Another possibility of the relationship between depression and medical disorders is that treating a patient for depression could result in a medical disorder. The best example of this is the use of 20 mg of olanzapine to augment the effects of an antidepressant, resulting in a 50-pound weight gain and the development of type 2 diabetes and metabolic syndrome. Both of those scenarios are well understood.”

Then there’s the behavioral aspects of the relationship, he continued, in which patients adopt the mindset that “I’m depressed. I don’t want to exercise. I’m a couch potato. I have been gaining a lot of weight. It’s bad for my heart.”

Converging biology is another possibility. “Is it possible that the biology of depression is linked to the biology of other disorders?” asked Dr. Nemeroff, who directs the university’s Institute for Early Life Adversity Research. “We can talk about this in relation to thyroid disease, a well known cause of depression, but we can also talk about the relationship to other disorders. There’s amazing epidemiologic evidence that patients with PTSD are much more likely to develop Alzheimer’s disease than patients without PTSD.”

Psychosocial issues also play a role. He recalled seeing patient in a clinic for the underserved who had underlying severe ulcerative colitis and anemia and couldn’t afford medical treatment. “The patient had a low hemoglobin, so it was impossible to distinguish between that and whether they had a primary depressive disorder or not,” he said.

In a study that explored the relationship between major depression and cancer, Dr. Nemeroff and colleagues found that the prevalence was highest in those with pancreatic cancer (50%), followed by oropharyngeal (40%), colon (13-25%), breast (18-25%), and gynecologic (23%), and Hodgkin’s lymphoma (17%) (Arch Gen Psychiatry 1995;52[2]:89-99). “Not all cancers have the same rate of depression,” he said. “One of the central questions is, not so much is the cancer patient depressed, but is depression a risk factor for developing cancer? The answer is a resounding yes. But what we don’t know is if you treat the depression aggressively, can you reduce that risk of either developing cancer or the progression of cancer?”

Dr. Nemeroff spotlighted several studies largely from the oncology literature, including a prospective survival analysis of 578 women with early-stage breast cancer (Lancet 1999;354:1331-6). After 5 years, 395 were alive and without relapse, 50 were alive with relapse, and 133 had died. The researchers found a significantly increased risk of death from all causes by 5 years in women with a high depression score (HR 3.59). There was a significantly increased risk of relapse or death at 5 years in women with high scores on helplessness and hopelessness measures.

In an analysis of the association between breast cancer and traumatic events, women who had severe stress or a traumatic event had lower rates of disease-free intervals (J Psychosomatic Res 2007;63:233-9). Another study by the same investigators found that a decrease in depression symptoms is associated with longer survival in patients with metastatic breast cancer (J Clin Oncol 2010;29:413-20). The median survival was 53.6 months for women with decreasing depression scores over 1 year and 25.1 months for women with increasing depression scores.

A more recent study of cervical cancer patients found that those exposed to psychological stress had an increased risk of cancer-specific mortality (HR 1.33) (Cancer Res 2019;79:3965-72). The association was mainly driven by distress experienced within 1 year before or after diagnosis (HR 1.30) but not afterward (HR 1.12). In addition, data from the large longitudinal Nurses’ Health Study II found that women with high PTSD symptoms had a twofold greater risk of ovarian cancer compared with women who had no trauma exposure (Cancer Res 2019;79:5113-20).

Authors of a separate study analyzed data from the Women’s Health Initiative to examine if depression precedes the development of a cancer diagnosis. They found that depression 3 years before a diagnosis of breast cancer was associated with all-cause mortality (HR 1.35) (Cancer 2017;123[16]:3107-15). Meanwhile, among women with late-stage breast cancer, newly developed depression at year 3 was significantly associated with all-cause mortality (HR 2.0) and breast cancer-specific mortality (HR 2.42). “That’s a pretty amazing finding,” Dr. Nemeroff said. “We have to think about depression as a systemic illness. What is depression doing that’s creating a fertile environment for cancer or worsening of cancer?”

He then discussed the risk of suicide in patients who are newly diagnosed with cancer. “No one ever talks about this, and I can’t get anybody to support research in this area,” he said. In one of the first studies on the topic, researchers conducted a case-control study of Medicare patients and determined risk of suicide among those with cancer was 2.3-fold higher compared with controls, even after adjustment for psychiatric illness and the risk of dying within a year (J Clin Oncol 2008;26[29]:4720-4). More recently, authors of a large population-based study in England found that the overall standardized mortality ratio for suicide was 1.20 (JAMA Psychiatry 2019;76[1]51-60). The risk was highest among patients with mesothelioma, with a 4.51-fold risk, followed by pancreatic (3.89-fold), esophageal (2.65-fold), lung (2.57-fold), and stomach cancer (2.20-fold). “They reported that the first 6 months after the diagnosis is associated with an increased risk of suicide – unrelated to prognosis,” Dr. Nemeroff said.

A separate analysis of SEER data from 1973-2014 and comprising more than 8.6 million cancer patients found that newly diagnosed cancer patients are 4.4 times more likely to die from suicide than patients in the same age group without cancer (Nat Commun 2019;10[1]:207). The highest risk was in lung cancer, followed by head and neck, testes, bladder, and Hodgkin’s lymphoma.

According to Dr. Nemeroff, the association between depression and the risk of certain forms of cancer or with a poor cancer prognosis “may have to do with immune function. Depression is associated with a change in inflammatory markers that very likely control the microenvironment of the tumor.” For example, he said, if the depressed environment is associated with a marked increase in tumor necrosis factor, interleukin 6, and other inflammatory markers, “that probably contributes to the body’s ability to fight disease. Ironically, depression is associated with an increase in inflammation but a decreased in T cell function. Remember, there are two fundamental types of immunity: the antibody response and the cellular response. What’s odd about depression is that there’s an increase in inflammatory markers but a decrease in the ability of T cells to function in terms of cellular immunity.”

Dr. Nemeroff disclosed that he has served as a consultant and/or scientific adviser for numerous pharmaceutical companies. He has received research and grant support from the National Institutes of Health.

A new meta-analysis provides more evidence that taller people may be more likely than their shorter peers to develop colorectal cancer (CRC) or colon polyps.

“There are well-known modifiable dietary associations for colorectal cancer, such as processed red meats and smoking, but guidelines currently are fixated on family history, and height is clinically neglected when it comes to risk screening,” study investigator Gerard Mullin, MD, with Johns Hopkins University, Baltimore, said in a news release. This large study “builds on evidence that taller height is an overlooked risk factor and should be considered when evaluating and recommending patients for colorectal cancer screenings.”

The study was published online March 1 in Cancer Epidemiology, Biomarkers & Prevention.
 

The evidence: Height and cancer risk

Height has been actively studied as a potential nonmodifiable risk factor for a range of cancers, including CRC.

In one large prospective study of postmenopausal women, researchers found a modest but statistically significant positive association between height and risk for any cancer and for melanoma, multiple myeloma, and cancers of the thyroid, ovary, colorectum, and endometrium. 

A separate study found that tall men, especially those who are long-legged, may be at increased risk for prostate cancer, including high-grade tumors, relative to men of more modest stature.

However, the study authors point out, past studies have also produced mixed results, used inconsistent measures of height, and failed to include the risk of adenomas.  

In the current meta-analysis, the investigators included 47 international, observational studies involving 280,644 adults with CRC and 14,139 cases of colorectal adenoma.

Because the definition of tallness differs around the world, the researchers compared the highest versus the lowest height percentile of various study groups. The findings were adjusted for demographic, socioeconomic, behavioral, and other known risk factors for CRC.

Overall, the investigators found that the tallest individuals within the highest percentile of height had a 24% higher risk of developing CRC compared to the shortest individuals within the lowest percentile (hazard ratio [HR], 1.24; P < .001).

In addition, they found that every 10-cm increase (about 4 inches) in height was associated with a 14% increased risk of developing CRC (HR, 1.14; P < .001) and a 6% increased likelihood of adenomas (odds ratio [OR], 1.06; P = .03).

In the United States, the average height for men is 5 feet, 9 inches, and for women it is 5 feet, 4 inches, which means men who are 6 feet, 1 inch and women who are 5 feet, 8 inches or taller have a 14% increased risk of CRC and a 6% increased risk of adenomas, the researchers explained.

According to co–first author Elinor Zhou, MD, also with Johns Hopkins University, a potential explanation for this link “is that adult height correlates with body organ size. More active proliferation in organs of taller people could increase the possibility of mutations leading to malignant transformation.”

The study authors said more research is needed to identify particular subgroups of tall people at risk for CRC.

“For instance, tall athletes and individuals with inherited tallness, such as those with Marfan syndrome, could be screened earlier and the impact of height further explored,” Dr. Zhou said.

Plus, Dr. Zhou added, more studies are needed to “definitively say at what height you would need earlier colorectal cancer screening.”

The current study was supported by grants from Bloomberg Philanthropies, intramural funds, and the Johns Hopkins Cancer Center Support Grant. The authors declared no conflicts of interest.

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

A new meta-analysis provides more evidence that taller people may be more likely than their shorter peers to develop colorectal cancer (CRC) or colon polyps.

“There are well-known modifiable dietary associations for colorectal cancer, such as processed red meats and smoking, but guidelines currently are fixated on family history, and height is clinically neglected when it comes to risk screening,” study investigator Gerard Mullin, MD, with Johns Hopkins University, Baltimore, said in a news release. This large study “builds on evidence that taller height is an overlooked risk factor and should be considered when evaluating and recommending patients for colorectal cancer screenings.”

The study was published online March 1 in Cancer Epidemiology, Biomarkers & Prevention.
 

The evidence: Height and cancer risk

Height has been actively studied as a potential nonmodifiable risk factor for a range of cancers, including CRC.

In one large prospective study of postmenopausal women, researchers found a modest but statistically significant positive association between height and risk for any cancer and for melanoma, multiple myeloma, and cancers of the thyroid, ovary, colorectum, and endometrium. 

A separate study found that tall men, especially those who are long-legged, may be at increased risk for prostate cancer, including high-grade tumors, relative to men of more modest stature.

However, the study authors point out, past studies have also produced mixed results, used inconsistent measures of height, and failed to include the risk of adenomas.  

In the current meta-analysis, the investigators included 47 international, observational studies involving 280,644 adults with CRC and 14,139 cases of colorectal adenoma.

Because the definition of tallness differs around the world, the researchers compared the highest versus the lowest height percentile of various study groups. The findings were adjusted for demographic, socioeconomic, behavioral, and other known risk factors for CRC.

Overall, the investigators found that the tallest individuals within the highest percentile of height had a 24% higher risk of developing CRC compared to the shortest individuals within the lowest percentile (hazard ratio [HR], 1.24; P < .001).

In addition, they found that every 10-cm increase (about 4 inches) in height was associated with a 14% increased risk of developing CRC (HR, 1.14; P < .001) and a 6% increased likelihood of adenomas (odds ratio [OR], 1.06; P = .03).

In the United States, the average height for men is 5 feet, 9 inches, and for women it is 5 feet, 4 inches, which means men who are 6 feet, 1 inch and women who are 5 feet, 8 inches or taller have a 14% increased risk of CRC and a 6% increased risk of adenomas, the researchers explained.

According to co–first author Elinor Zhou, MD, also with Johns Hopkins University, a potential explanation for this link “is that adult height correlates with body organ size. More active proliferation in organs of taller people could increase the possibility of mutations leading to malignant transformation.”

The study authors said more research is needed to identify particular subgroups of tall people at risk for CRC.

“For instance, tall athletes and individuals with inherited tallness, such as those with Marfan syndrome, could be screened earlier and the impact of height further explored,” Dr. Zhou said.

Plus, Dr. Zhou added, more studies are needed to “definitively say at what height you would need earlier colorectal cancer screening.”

The current study was supported by grants from Bloomberg Philanthropies, intramural funds, and the Johns Hopkins Cancer Center Support Grant. The authors declared no conflicts of interest.

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

A new meta-analysis provides more evidence that taller people may be more likely than their shorter peers to develop colorectal cancer (CRC) or colon polyps.

“There are well-known modifiable dietary associations for colorectal cancer, such as processed red meats and smoking, but guidelines currently are fixated on family history, and height is clinically neglected when it comes to risk screening,” study investigator Gerard Mullin, MD, with Johns Hopkins University, Baltimore, said in a news release. This large study “builds on evidence that taller height is an overlooked risk factor and should be considered when evaluating and recommending patients for colorectal cancer screenings.”

The study was published online March 1 in Cancer Epidemiology, Biomarkers & Prevention.
 

The evidence: Height and cancer risk

Height has been actively studied as a potential nonmodifiable risk factor for a range of cancers, including CRC.

In one large prospective study of postmenopausal women, researchers found a modest but statistically significant positive association between height and risk for any cancer and for melanoma, multiple myeloma, and cancers of the thyroid, ovary, colorectum, and endometrium. 

A separate study found that tall men, especially those who are long-legged, may be at increased risk for prostate cancer, including high-grade tumors, relative to men of more modest stature.

However, the study authors point out, past studies have also produced mixed results, used inconsistent measures of height, and failed to include the risk of adenomas.  

In the current meta-analysis, the investigators included 47 international, observational studies involving 280,644 adults with CRC and 14,139 cases of colorectal adenoma.

Because the definition of tallness differs around the world, the researchers compared the highest versus the lowest height percentile of various study groups. The findings were adjusted for demographic, socioeconomic, behavioral, and other known risk factors for CRC.

Overall, the investigators found that the tallest individuals within the highest percentile of height had a 24% higher risk of developing CRC compared to the shortest individuals within the lowest percentile (hazard ratio [HR], 1.24; P < .001).

In addition, they found that every 10-cm increase (about 4 inches) in height was associated with a 14% increased risk of developing CRC (HR, 1.14; P < .001) and a 6% increased likelihood of adenomas (odds ratio [OR], 1.06; P = .03).

In the United States, the average height for men is 5 feet, 9 inches, and for women it is 5 feet, 4 inches, which means men who are 6 feet, 1 inch and women who are 5 feet, 8 inches or taller have a 14% increased risk of CRC and a 6% increased risk of adenomas, the researchers explained.

According to co–first author Elinor Zhou, MD, also with Johns Hopkins University, a potential explanation for this link “is that adult height correlates with body organ size. More active proliferation in organs of taller people could increase the possibility of mutations leading to malignant transformation.”

The study authors said more research is needed to identify particular subgroups of tall people at risk for CRC.

“For instance, tall athletes and individuals with inherited tallness, such as those with Marfan syndrome, could be screened earlier and the impact of height further explored,” Dr. Zhou said.

Plus, Dr. Zhou added, more studies are needed to “definitively say at what height you would need earlier colorectal cancer screening.”

The current study was supported by grants from Bloomberg Philanthropies, intramural funds, and the Johns Hopkins Cancer Center Support Grant. The authors declared no conflicts of interest.

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

All 15 members of Wake Forest Baptist Comprehensive Cancer Center’s external advisory board (EAB) resigned on February 18 and withdrew their endorsement for renewal of the center’s National Cancer Institute comprehensive cancer center support grant.

The move was prompted by the abrupt firing of center director Boris Pasche, MD, PhD, on February 10, one day after NCI renewed a multimillion dollar grant.

The Cancer Letter broke the story and published the resignation letter from the EAB. It was signed by board chair Gerold Bepler, MD, PhD, CEO and director of the Karmanos Cancer Institute, Detroit, on behalf of the board.

The mass resignation of an EAB, a panel of outside experts that help shepherd cancer centers through the NCI grant process, is “highly unusual,” according to The Cancer Letter. It also raises concerns about the “immediate future” of Wake Forest’s cancer center, the publication added.

Numerous people involved with the situation did not respond or declined to comment when this news organization requested additional information and updates, including questions about the reason for Dr. Pasche’s termination; whether or not withdrawal of the endorsement puts Wake’s NCI designation in jeopardy; and if the EAB is being reconstituted.

A written statement from Wake Forest simply said that “the situation involving Dr. Pasche is an administrative decision. Various administrative changes occur regularly in organizations across the country. Dr. Pasche remains employed by Atrium Health Wake Forest Baptist. We are very grateful to Dr. Pasche for his years of service and many contributions to the mission and vision of our NCI-designated Comprehensive Cancer Center in Winston-Salem.”

Wake’s cancer center is in the process of combining with the Atrium Health Levine Cancer Center, which is not NCI-designated, following Atrium Health system’s recent acquisition of the Wake Forest Baptist Medical Center.

The NCI renewal notice, dated February 9, states that Dr. Pasche “and his leadership team have built a robust, transdisciplinary center that includes 140 scientists.”

Dr. Pasche was fired a day later.

The EAB resignation letter states that during Wake Forest’s recent NCI review process, “leadership gave their glowing endorsement of Dr. Pasche...This endorsement included unequivocal statements of support for Dr. Pasche’s oversight of the combined Atrium-Wake Forest cancer program.”

“What followed was his rapid dismissal after the...notice of award was issued, following a period during which the approach to integration was apparently being revisited,” Dr. Bepler said on behalf of the board.

“It is with sadness and dismay that we witnessed the change in approach by the institutional leadership towards” the merger, he wrote.

The Cancer Letter quotes an unnamed board member as saying, “EABs for cancer centers can only provide value to the center when there is openness and transparency in the process. In the absence of such, I believe the members felt that there was no further utility in providing guidance to the organization.”

The resignation letter was sent to the interim director of Wake’s cancer center, radiation oncologist William Blackstock, Jr, MD, and also copied to Atrium-Wake and NCI leadership.

The resignation letter endorsed Dr. Blackstock’s qualifications to run the center, and noted that as the board is reconstituted, “some of us would be honored to discuss participation...if there is unequivocal evidence from the health system’s senior management for support of a single, academically driven, comprehensive, and integrated cancer center.”

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

All 15 members of Wake Forest Baptist Comprehensive Cancer Center’s external advisory board (EAB) resigned on February 18 and withdrew their endorsement for renewal of the center’s National Cancer Institute comprehensive cancer center support grant.

The move was prompted by the abrupt firing of center director Boris Pasche, MD, PhD, on February 10, one day after NCI renewed a multimillion dollar grant.

The Cancer Letter broke the story and published the resignation letter from the EAB. It was signed by board chair Gerold Bepler, MD, PhD, CEO and director of the Karmanos Cancer Institute, Detroit, on behalf of the board.

The mass resignation of an EAB, a panel of outside experts that help shepherd cancer centers through the NCI grant process, is “highly unusual,” according to The Cancer Letter. It also raises concerns about the “immediate future” of Wake Forest’s cancer center, the publication added.

Numerous people involved with the situation did not respond or declined to comment when this news organization requested additional information and updates, including questions about the reason for Dr. Pasche’s termination; whether or not withdrawal of the endorsement puts Wake’s NCI designation in jeopardy; and if the EAB is being reconstituted.

A written statement from Wake Forest simply said that “the situation involving Dr. Pasche is an administrative decision. Various administrative changes occur regularly in organizations across the country. Dr. Pasche remains employed by Atrium Health Wake Forest Baptist. We are very grateful to Dr. Pasche for his years of service and many contributions to the mission and vision of our NCI-designated Comprehensive Cancer Center in Winston-Salem.”

Wake’s cancer center is in the process of combining with the Atrium Health Levine Cancer Center, which is not NCI-designated, following Atrium Health system’s recent acquisition of the Wake Forest Baptist Medical Center.

The NCI renewal notice, dated February 9, states that Dr. Pasche “and his leadership team have built a robust, transdisciplinary center that includes 140 scientists.”

Dr. Pasche was fired a day later.

The EAB resignation letter states that during Wake Forest’s recent NCI review process, “leadership gave their glowing endorsement of Dr. Pasche...This endorsement included unequivocal statements of support for Dr. Pasche’s oversight of the combined Atrium-Wake Forest cancer program.”

“What followed was his rapid dismissal after the...notice of award was issued, following a period during which the approach to integration was apparently being revisited,” Dr. Bepler said on behalf of the board.

“It is with sadness and dismay that we witnessed the change in approach by the institutional leadership towards” the merger, he wrote.

The Cancer Letter quotes an unnamed board member as saying, “EABs for cancer centers can only provide value to the center when there is openness and transparency in the process. In the absence of such, I believe the members felt that there was no further utility in providing guidance to the organization.”

The resignation letter was sent to the interim director of Wake’s cancer center, radiation oncologist William Blackstock, Jr, MD, and also copied to Atrium-Wake and NCI leadership.

The resignation letter endorsed Dr. Blackstock’s qualifications to run the center, and noted that as the board is reconstituted, “some of us would be honored to discuss participation...if there is unequivocal evidence from the health system’s senior management for support of a single, academically driven, comprehensive, and integrated cancer center.”

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

All 15 members of Wake Forest Baptist Comprehensive Cancer Center’s external advisory board (EAB) resigned on February 18 and withdrew their endorsement for renewal of the center’s National Cancer Institute comprehensive cancer center support grant.

The move was prompted by the abrupt firing of center director Boris Pasche, MD, PhD, on February 10, one day after NCI renewed a multimillion dollar grant.

The Cancer Letter broke the story and published the resignation letter from the EAB. It was signed by board chair Gerold Bepler, MD, PhD, CEO and director of the Karmanos Cancer Institute, Detroit, on behalf of the board.

The mass resignation of an EAB, a panel of outside experts that help shepherd cancer centers through the NCI grant process, is “highly unusual,” according to The Cancer Letter. It also raises concerns about the “immediate future” of Wake Forest’s cancer center, the publication added.

Numerous people involved with the situation did not respond or declined to comment when this news organization requested additional information and updates, including questions about the reason for Dr. Pasche’s termination; whether or not withdrawal of the endorsement puts Wake’s NCI designation in jeopardy; and if the EAB is being reconstituted.

A written statement from Wake Forest simply said that “the situation involving Dr. Pasche is an administrative decision. Various administrative changes occur regularly in organizations across the country. Dr. Pasche remains employed by Atrium Health Wake Forest Baptist. We are very grateful to Dr. Pasche for his years of service and many contributions to the mission and vision of our NCI-designated Comprehensive Cancer Center in Winston-Salem.”

Wake’s cancer center is in the process of combining with the Atrium Health Levine Cancer Center, which is not NCI-designated, following Atrium Health system’s recent acquisition of the Wake Forest Baptist Medical Center.

The NCI renewal notice, dated February 9, states that Dr. Pasche “and his leadership team have built a robust, transdisciplinary center that includes 140 scientists.”

Dr. Pasche was fired a day later.

The EAB resignation letter states that during Wake Forest’s recent NCI review process, “leadership gave their glowing endorsement of Dr. Pasche...This endorsement included unequivocal statements of support for Dr. Pasche’s oversight of the combined Atrium-Wake Forest cancer program.”

“What followed was his rapid dismissal after the...notice of award was issued, following a period during which the approach to integration was apparently being revisited,” Dr. Bepler said on behalf of the board.

“It is with sadness and dismay that we witnessed the change in approach by the institutional leadership towards” the merger, he wrote.

The Cancer Letter quotes an unnamed board member as saying, “EABs for cancer centers can only provide value to the center when there is openness and transparency in the process. In the absence of such, I believe the members felt that there was no further utility in providing guidance to the organization.”

The resignation letter was sent to the interim director of Wake’s cancer center, radiation oncologist William Blackstock, Jr, MD, and also copied to Atrium-Wake and NCI leadership.

The resignation letter endorsed Dr. Blackstock’s qualifications to run the center, and noted that as the board is reconstituted, “some of us would be honored to discuss participation...if there is unequivocal evidence from the health system’s senior management for support of a single, academically driven, comprehensive, and integrated cancer center.”

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

Among women with ATM, CHEK2, or PALB2 pathogenic variants, annual MRI screening beginning at age 30 or 35, followed by concomitant MRI and mammography at age 40, could significantly reduce breast cancer mortality, according to a new model.

Adjunct screening with MRI is already recommended among women with the BRCA1 or BRCA2 mutations. ATM, CHEK2, and PALB2 are the most common of a more recently discovered group of pathogenic variants that confer a moderate to high risk of breast cancer.

In a study published online Feb. 17, 2022, in JAMA Oncology, researchers used two simulation models and risk estimates from the Cancer Risk Estimates Related to Susceptibility Consortium to predict that MRI screening at age 35 would produce a 54.4%-57.6% reduction in breast cancer mortality, with an estimated 4,661-5,001 false positive screenings and 1,280-1,368 benign biopsies per 1,000 women. At age 30, the model predicted 55.4-59.5% reduction in risk, 5,075-5,415 false positives, and 1,439-1,528 benign biopsies. Annual mammography at age 40 alone could reduce risk by 36%-39%.

The false positives and benign biopsies represent cumulative lifetime results.

“We’ve known for a long time that mammography is less sensitive in younger women than in older women and, of course, when women have a genetic predisposition, we’re very concerned about early-onset cancer. We’ve also known that when you do MRI at the same time as mammography, you find a lot more cancers. [There are] more false positives, but there is clearly a greater yield of cancer in that setting, and the cancers are found earlier,” senior author Mark Robson, MD, said in an interview.

The model showed that mammography screening in women under 40 added no survival benefit, and led to additional false positives and benign biopsies.

“We know that MRI’s detection rate for cancers in a head-to-head comparison with mammography is extremely high, and so I’m not surprised that there was such a difference from a mammography strategy. What I was excited by is just how impactful the MRI screen was in terms of projected reduction in the risk of death. I thought that great,” said Dr. Robson, who is chief of the breast medicine service at Memorial Sloan Kettering Cancer Center, New York.

The balance of mortality reduction versus false positives and benign biopsies will need to be weighed by others. “We didn’t feel like we could make those judgments, but what we were presenting was for people who do make these kinds of policies. The reason that we said 30-35 years (for MRI initiation) is because at that point, the false positive versus life-years gained curve starts to plateau. For instance, when we look at strategies of starting MRI at 25, you we don’t get significantly more life years gained, but we do get more false positives,” Dr. Robson said.

The researchers did not conduct a former cost-benefit analysis for initiating MRI screening at age 30-35.

The study “reinforces the value of MRI for women with these variants that are really just entering the clinical consciousness, and affirms that we need to be doing that in young women to help prevent death from breast cancer. I also think that we need to look at really what mammogram is adding in young women and consider whether or not we really need it at the policy level,” he said.

The study was funded by the National Cancer Institute and the Breast Cancer Research Foundation. Dr. Robson has conducted clinical trials with AstraZeneca, Merck, and Pfizer.

Among women with ATM, CHEK2, or PALB2 pathogenic variants, annual MRI screening beginning at age 30 or 35, followed by concomitant MRI and mammography at age 40, could significantly reduce breast cancer mortality, according to a new model.

Adjunct screening with MRI is already recommended among women with the BRCA1 or BRCA2 mutations. ATM, CHEK2, and PALB2 are the most common of a more recently discovered group of pathogenic variants that confer a moderate to high risk of breast cancer.

In a study published online Feb. 17, 2022, in JAMA Oncology, researchers used two simulation models and risk estimates from the Cancer Risk Estimates Related to Susceptibility Consortium to predict that MRI screening at age 35 would produce a 54.4%-57.6% reduction in breast cancer mortality, with an estimated 4,661-5,001 false positive screenings and 1,280-1,368 benign biopsies per 1,000 women. At age 30, the model predicted 55.4-59.5% reduction in risk, 5,075-5,415 false positives, and 1,439-1,528 benign biopsies. Annual mammography at age 40 alone could reduce risk by 36%-39%.

The false positives and benign biopsies represent cumulative lifetime results.

“We’ve known for a long time that mammography is less sensitive in younger women than in older women and, of course, when women have a genetic predisposition, we’re very concerned about early-onset cancer. We’ve also known that when you do MRI at the same time as mammography, you find a lot more cancers. [There are] more false positives, but there is clearly a greater yield of cancer in that setting, and the cancers are found earlier,” senior author Mark Robson, MD, said in an interview.

The model showed that mammography screening in women under 40 added no survival benefit, and led to additional false positives and benign biopsies.

“We know that MRI’s detection rate for cancers in a head-to-head comparison with mammography is extremely high, and so I’m not surprised that there was such a difference from a mammography strategy. What I was excited by is just how impactful the MRI screen was in terms of projected reduction in the risk of death. I thought that great,” said Dr. Robson, who is chief of the breast medicine service at Memorial Sloan Kettering Cancer Center, New York.

The balance of mortality reduction versus false positives and benign biopsies will need to be weighed by others. “We didn’t feel like we could make those judgments, but what we were presenting was for people who do make these kinds of policies. The reason that we said 30-35 years (for MRI initiation) is because at that point, the false positive versus life-years gained curve starts to plateau. For instance, when we look at strategies of starting MRI at 25, you we don’t get significantly more life years gained, but we do get more false positives,” Dr. Robson said.

The researchers did not conduct a former cost-benefit analysis for initiating MRI screening at age 30-35.

The study “reinforces the value of MRI for women with these variants that are really just entering the clinical consciousness, and affirms that we need to be doing that in young women to help prevent death from breast cancer. I also think that we need to look at really what mammogram is adding in young women and consider whether or not we really need it at the policy level,” he said.

The study was funded by the National Cancer Institute and the Breast Cancer Research Foundation. Dr. Robson has conducted clinical trials with AstraZeneca, Merck, and Pfizer.

Among women with ATM, CHEK2, or PALB2 pathogenic variants, annual MRI screening beginning at age 30 or 35, followed by concomitant MRI and mammography at age 40, could significantly reduce breast cancer mortality, according to a new model.

Adjunct screening with MRI is already recommended among women with the BRCA1 or BRCA2 mutations. ATM, CHEK2, and PALB2 are the most common of a more recently discovered group of pathogenic variants that confer a moderate to high risk of breast cancer.

In a study published online Feb. 17, 2022, in JAMA Oncology, researchers used two simulation models and risk estimates from the Cancer Risk Estimates Related to Susceptibility Consortium to predict that MRI screening at age 35 would produce a 54.4%-57.6% reduction in breast cancer mortality, with an estimated 4,661-5,001 false positive screenings and 1,280-1,368 benign biopsies per 1,000 women. At age 30, the model predicted 55.4-59.5% reduction in risk, 5,075-5,415 false positives, and 1,439-1,528 benign biopsies. Annual mammography at age 40 alone could reduce risk by 36%-39%.

The false positives and benign biopsies represent cumulative lifetime results.

“We’ve known for a long time that mammography is less sensitive in younger women than in older women and, of course, when women have a genetic predisposition, we’re very concerned about early-onset cancer. We’ve also known that when you do MRI at the same time as mammography, you find a lot more cancers. [There are] more false positives, but there is clearly a greater yield of cancer in that setting, and the cancers are found earlier,” senior author Mark Robson, MD, said in an interview.

The model showed that mammography screening in women under 40 added no survival benefit, and led to additional false positives and benign biopsies.

“We know that MRI’s detection rate for cancers in a head-to-head comparison with mammography is extremely high, and so I’m not surprised that there was such a difference from a mammography strategy. What I was excited by is just how impactful the MRI screen was in terms of projected reduction in the risk of death. I thought that great,” said Dr. Robson, who is chief of the breast medicine service at Memorial Sloan Kettering Cancer Center, New York.

The balance of mortality reduction versus false positives and benign biopsies will need to be weighed by others. “We didn’t feel like we could make those judgments, but what we were presenting was for people who do make these kinds of policies. The reason that we said 30-35 years (for MRI initiation) is because at that point, the false positive versus life-years gained curve starts to plateau. For instance, when we look at strategies of starting MRI at 25, you we don’t get significantly more life years gained, but we do get more false positives,” Dr. Robson said.

The researchers did not conduct a former cost-benefit analysis for initiating MRI screening at age 30-35.

The study “reinforces the value of MRI for women with these variants that are really just entering the clinical consciousness, and affirms that we need to be doing that in young women to help prevent death from breast cancer. I also think that we need to look at really what mammogram is adding in young women and consider whether or not we really need it at the policy level,” he said.

The study was funded by the National Cancer Institute and the Breast Cancer Research Foundation. Dr. Robson has conducted clinical trials with AstraZeneca, Merck, and Pfizer.

A study of testicular cancer mortality finds worse outcomes among Hispanic men, but better outcomes among Black men.

The findings were reported at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

Incidence rates for testicular cancer in the United States have increased slowly in recent decades, said Anushka Ghosh, a clinical research coordinatory with Massachusetts General Hospital, Boston. Her analysis found mortality increases from 1999 to 2019 to be significantly greater among Hispanic men. The increase was 0.0019 per 100,000, compared with a 0.0003 per 100,000 decrease among non-Hispanic men (comparison P = .010).

Among Black men, testicular cancer–specific mortality rates declined by 0.0007 per 100,000, compared with a marginally significant increase of 0.0006 per 100,000 among White men (P =.049).

“Given that testicular cancer generally has a favorable prognosis, it is concerning that the mortality rate for this disease is increasing,” said Sophia C. Kamran, MD, the study’s lead author and a radiation oncologist at Massachusetts General Hospital.

Dr. Kamran urged new efforts to understand these trends and to make testicular cancer care more accessible for all patients.

Ms. Ghosh said that other researchers have identified the same disparity among Hispanic men with prostate cancer. “Even though testicular cancer is a rare, our finding warrants further investigation to find the basis of these disparities to better serve the Hispanic community.”

Other studies have shown higher likelihood of later stage diagnosis and worse survival outcomes among Black patients.

No funding sources were reported for this study.

A study of testicular cancer mortality finds worse outcomes among Hispanic men, but better outcomes among Black men.

The findings were reported at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

Incidence rates for testicular cancer in the United States have increased slowly in recent decades, said Anushka Ghosh, a clinical research coordinatory with Massachusetts General Hospital, Boston. Her analysis found mortality increases from 1999 to 2019 to be significantly greater among Hispanic men. The increase was 0.0019 per 100,000, compared with a 0.0003 per 100,000 decrease among non-Hispanic men (comparison P = .010).

Among Black men, testicular cancer–specific mortality rates declined by 0.0007 per 100,000, compared with a marginally significant increase of 0.0006 per 100,000 among White men (P =.049).

“Given that testicular cancer generally has a favorable prognosis, it is concerning that the mortality rate for this disease is increasing,” said Sophia C. Kamran, MD, the study’s lead author and a radiation oncologist at Massachusetts General Hospital.

Dr. Kamran urged new efforts to understand these trends and to make testicular cancer care more accessible for all patients.

Ms. Ghosh said that other researchers have identified the same disparity among Hispanic men with prostate cancer. “Even though testicular cancer is a rare, our finding warrants further investigation to find the basis of these disparities to better serve the Hispanic community.”

Other studies have shown higher likelihood of later stage diagnosis and worse survival outcomes among Black patients.

No funding sources were reported for this study.

A study of testicular cancer mortality finds worse outcomes among Hispanic men, but better outcomes among Black men.

The findings were reported at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

Incidence rates for testicular cancer in the United States have increased slowly in recent decades, said Anushka Ghosh, a clinical research coordinatory with Massachusetts General Hospital, Boston. Her analysis found mortality increases from 1999 to 2019 to be significantly greater among Hispanic men. The increase was 0.0019 per 100,000, compared with a 0.0003 per 100,000 decrease among non-Hispanic men (comparison P = .010).

Among Black men, testicular cancer–specific mortality rates declined by 0.0007 per 100,000, compared with a marginally significant increase of 0.0006 per 100,000 among White men (P =.049).

“Given that testicular cancer generally has a favorable prognosis, it is concerning that the mortality rate for this disease is increasing,” said Sophia C. Kamran, MD, the study’s lead author and a radiation oncologist at Massachusetts General Hospital.

Dr. Kamran urged new efforts to understand these trends and to make testicular cancer care more accessible for all patients.

Ms. Ghosh said that other researchers have identified the same disparity among Hispanic men with prostate cancer. “Even though testicular cancer is a rare, our finding warrants further investigation to find the basis of these disparities to better serve the Hispanic community.”

Other studies have shown higher likelihood of later stage diagnosis and worse survival outcomes among Black patients.

No funding sources were reported for this study.