AVAHO

It’s estimated that half of all people in the world are infected with Helicobacter pylori, a bacterium associated with increased risk for gastric ulcers and gastric cancer.

However, only a small percentage of people with H. pylori infection will go on to develop gastric cancer.

Now a team from Japan reports that specific mutations in genes associated with DNA repair, when combined with the common bacterial infection H. pylori, appear to significantly increase the risk for gastric cancer.

The new findings imply that the hereditary contribution to the risk of gastric cancer is more important than previously believed, say editorialists commenting on the study.

The article and accompanying editorial were published in The New England Journal of Medicine.

For this study, Yoshiaki Usui, MD, PhD, of the RIKEN Center for Integrative Medical Sciences in Yokohama, Japan, and colleagues analyzed samples from 10,426 patients with gastric cancer as well as 38,153 control samples from a Japanese biobank.

First, they looked at the association between gastric cancer and germline pathogenic variants in 27 genes known to predispose carriers to cancers.

They also looked at the combined effects of pathogenic variants and H. pylori infection and calculated the cumulative risk among 1,433 patients with gastric cancer and 5,997 control samples from a cancer-center research database.

They found that germline pathogenic variants in nine genes were associated with the risk for gastric cancer. The genes were APC, ATM, BRCA1, BRCA2, CDH1, MLH1, MSH2, MSH6, and PALB2.

The pathogenic germline (inherited) variants in these nine genes were associated with homologous recombination, which involves an exchange of nucleotide sequences between two similar or identical DNA molecules that occurs during meiosis and during repair of double-strand DNA breaks.

The investigators calculated that the cumulative risk for gastric cancer at age 85 among carriers of the variants who were infected with H. pylori was 45.5%, compared with 14.4% for control persons who were infected but were not carriers of the germline pathogenic variants.

The risk for gastric cancer was less than 5% among those without H. pylori infections, regardless of their carrier status.

“Our results suggest that in persons known to carry a pathogenic variant in a homologous-recombination gene, evaluation and eradication of H. pylori infection may be particularly important,” Dr. Usui and colleagues wrote.

“It is remarkable that pathogenic variants in homologous-recombination genes drive tumorigenesis only in the context of H. pylori infection,” Anne Müller, PhD, and Jiazhuo He, MD, of the University of Zürich, wrote in the accompanying editorial.

“This observation has numerous implications, not only for the diagnosis, prevention, and possibly treatment of the fraction of cases of gastric cancer with pathogenic gene variants that arise due to H. pylori infection but also for a better understanding of the biology of other cancers arising on a background of homologous-recombination deficiency. It is quite conceivable that other DNA-damaging environmental factors contributing to human carcinogenesis have been overlooked.” they wrote.

The study was supported by grants from the Japan Agency for Medical Research and Development; the Ministry of Education, Science, Sports, Culture, and Technology of Japan; the Ministry of Health, Labor, and Welfare of Japan; and the Australian National Health and Medical Research Council. Dr. Usui, Dr. Müller, and Dr. He have disclosed no relevant financial relationships.
 

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

It’s estimated that half of all people in the world are infected with Helicobacter pylori, a bacterium associated with increased risk for gastric ulcers and gastric cancer.

However, only a small percentage of people with H. pylori infection will go on to develop gastric cancer.

Now a team from Japan reports that specific mutations in genes associated with DNA repair, when combined with the common bacterial infection H. pylori, appear to significantly increase the risk for gastric cancer.

The new findings imply that the hereditary contribution to the risk of gastric cancer is more important than previously believed, say editorialists commenting on the study.

The article and accompanying editorial were published in The New England Journal of Medicine.

For this study, Yoshiaki Usui, MD, PhD, of the RIKEN Center for Integrative Medical Sciences in Yokohama, Japan, and colleagues analyzed samples from 10,426 patients with gastric cancer as well as 38,153 control samples from a Japanese biobank.

First, they looked at the association between gastric cancer and germline pathogenic variants in 27 genes known to predispose carriers to cancers.

They also looked at the combined effects of pathogenic variants and H. pylori infection and calculated the cumulative risk among 1,433 patients with gastric cancer and 5,997 control samples from a cancer-center research database.

They found that germline pathogenic variants in nine genes were associated with the risk for gastric cancer. The genes were APC, ATM, BRCA1, BRCA2, CDH1, MLH1, MSH2, MSH6, and PALB2.

The pathogenic germline (inherited) variants in these nine genes were associated with homologous recombination, which involves an exchange of nucleotide sequences between two similar or identical DNA molecules that occurs during meiosis and during repair of double-strand DNA breaks.

The investigators calculated that the cumulative risk for gastric cancer at age 85 among carriers of the variants who were infected with H. pylori was 45.5%, compared with 14.4% for control persons who were infected but were not carriers of the germline pathogenic variants.

The risk for gastric cancer was less than 5% among those without H. pylori infections, regardless of their carrier status.

“Our results suggest that in persons known to carry a pathogenic variant in a homologous-recombination gene, evaluation and eradication of H. pylori infection may be particularly important,” Dr. Usui and colleagues wrote.

“It is remarkable that pathogenic variants in homologous-recombination genes drive tumorigenesis only in the context of H. pylori infection,” Anne Müller, PhD, and Jiazhuo He, MD, of the University of Zürich, wrote in the accompanying editorial.

“This observation has numerous implications, not only for the diagnosis, prevention, and possibly treatment of the fraction of cases of gastric cancer with pathogenic gene variants that arise due to H. pylori infection but also for a better understanding of the biology of other cancers arising on a background of homologous-recombination deficiency. It is quite conceivable that other DNA-damaging environmental factors contributing to human carcinogenesis have been overlooked.” they wrote.

The study was supported by grants from the Japan Agency for Medical Research and Development; the Ministry of Education, Science, Sports, Culture, and Technology of Japan; the Ministry of Health, Labor, and Welfare of Japan; and the Australian National Health and Medical Research Council. Dr. Usui, Dr. Müller, and Dr. He have disclosed no relevant financial relationships.
 

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

It’s estimated that half of all people in the world are infected with Helicobacter pylori, a bacterium associated with increased risk for gastric ulcers and gastric cancer.

However, only a small percentage of people with H. pylori infection will go on to develop gastric cancer.

Now a team from Japan reports that specific mutations in genes associated with DNA repair, when combined with the common bacterial infection H. pylori, appear to significantly increase the risk for gastric cancer.

The new findings imply that the hereditary contribution to the risk of gastric cancer is more important than previously believed, say editorialists commenting on the study.

The article and accompanying editorial were published in The New England Journal of Medicine.

For this study, Yoshiaki Usui, MD, PhD, of the RIKEN Center for Integrative Medical Sciences in Yokohama, Japan, and colleagues analyzed samples from 10,426 patients with gastric cancer as well as 38,153 control samples from a Japanese biobank.

First, they looked at the association between gastric cancer and germline pathogenic variants in 27 genes known to predispose carriers to cancers.

They also looked at the combined effects of pathogenic variants and H. pylori infection and calculated the cumulative risk among 1,433 patients with gastric cancer and 5,997 control samples from a cancer-center research database.

They found that germline pathogenic variants in nine genes were associated with the risk for gastric cancer. The genes were APC, ATM, BRCA1, BRCA2, CDH1, MLH1, MSH2, MSH6, and PALB2.

The pathogenic germline (inherited) variants in these nine genes were associated with homologous recombination, which involves an exchange of nucleotide sequences between two similar or identical DNA molecules that occurs during meiosis and during repair of double-strand DNA breaks.

The investigators calculated that the cumulative risk for gastric cancer at age 85 among carriers of the variants who were infected with H. pylori was 45.5%, compared with 14.4% for control persons who were infected but were not carriers of the germline pathogenic variants.

The risk for gastric cancer was less than 5% among those without H. pylori infections, regardless of their carrier status.

“Our results suggest that in persons known to carry a pathogenic variant in a homologous-recombination gene, evaluation and eradication of H. pylori infection may be particularly important,” Dr. Usui and colleagues wrote.

“It is remarkable that pathogenic variants in homologous-recombination genes drive tumorigenesis only in the context of H. pylori infection,” Anne Müller, PhD, and Jiazhuo He, MD, of the University of Zürich, wrote in the accompanying editorial.

“This observation has numerous implications, not only for the diagnosis, prevention, and possibly treatment of the fraction of cases of gastric cancer with pathogenic gene variants that arise due to H. pylori infection but also for a better understanding of the biology of other cancers arising on a background of homologous-recombination deficiency. It is quite conceivable that other DNA-damaging environmental factors contributing to human carcinogenesis have been overlooked.” they wrote.

The study was supported by grants from the Japan Agency for Medical Research and Development; the Ministry of Education, Science, Sports, Culture, and Technology of Japan; the Ministry of Health, Labor, and Welfare of Japan; and the Australian National Health and Medical Research Council. Dr. Usui, Dr. Müller, and Dr. He have disclosed no relevant financial relationships.
 

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

BOSTON – Women with breast cancer who have several tumors in one breast do not necessarily need to have a mastectomy, as new data show a low risk of recurrence at 5 years when they are treated with breast-conserving therapy and radiation.

“[The study] proves the oncologic safety of breast conservation in women with two or three sites of disease, making this a very reasonable option for (previously reluctant) surgeons to present to patients,” first author Kari Rosenkranz, MD, an associate professor at Dartmouth Health in Norwich, Vt., said in an interview.

The findings were presented here at the International Conference on Surgical Cancer Care (SSO 2023), and were published online in the Journal of Clinical Oncology.

Commenting on the study, Hiram S. Cody III, MD, an attending surgeon and professor of surgery at Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center, in New York, said the findings provide valuable new evidence on the issue.

“This is an important study confirming that breast conservation is feasible and safe for women with multiple ipsilateral breast cancers, with excellent results comparable to those for women with unifocal (single site) disease,” he said in an interview.

Although there have been as many as seven previous randomized trials that have shown identical outcomes in survival and local control of disease with breast-conserving therapy versus mastectomy, all those studies excluded patients with more than one site of disease.

At present, many surgeons and guidelines continue to recommend mastectomy for women with multiple-site tumors, based on older data that showed higher recurrence rates.

That is why the new study is so important, Dr. Cody explained. “Here, we see in a prospective trial that breast-conserving therapy is feasible for those with more than one site of disease as well, with high survival and very low rates of local recurrence,” he emphasized.

Dr. Cody noted that “the ideal candidate would be a woman with relatively small tumor size and a breast large enough that the multiple excisions could be performed with a good cosmetic result.”

“We have followed this approach for some time and hope that with the publication of these results more surgeons will recommend this approach for suitable patients,” he said.

The new results were also highlighted in a press release from Mayo Clinic highlighting the Journal of Clinical Oncology publication. Lead author of the article, surgical oncologist Judy Boughey, MD, from the Mayo Clinic in Rochester, Minn., commented: “I am excited about these findings because it will empower patients and the multidisciplinary care teams caring for patients to be thinking about this option for women who may want to preserve their breast.”

This study showed the rate of cancer local recurrence was 3.1%, she noted. This is an excellent outcome and is similar to the local recurrence rate for patients with a single tumor in a breast who had breast-conserving therapy, Dr. Boughey said.

Historically, women with multiple tumors in one breast have been advised to have a mastectomy. Now, patients can be offered a less invasive option with faster recovery, resulting in better patient satisfaction and cosmetic outcomes, she added.


 

Study details

This study, known as the ACOSOG (Alliance) Z11102 trial, was a phase 2 trial conducted in 204 patients enrolled between 2012 and 2016 who had two or three sites of biopsy-proven breast cancer (each site less rhan 5 cm in size, with cN0 or cN1 disease).

These patients were a median age of 61 years, and 83.5% were ER-positive/HER2-negative, 11.5% were HER2-positive, 5.0% were ER-negative/HER2-negative, and 77.5% were node-negative.

All patients were treated with breast conservation surgery, including lumpectomy resected to negative margins, followed by whole breast radiation with a cavity boost to all lumpectomy beds.

With a median follow-up of 66.4 months, six patients developed local recurrence, with five of the recurrences occurring in the ipsilateral breast and one in the chest wall.

For the primary endpoint, the six recurrences represented an estimated cumulative incidence of local recurrence of 3.1% (95% CI, 1.3-6.4), well below the cutoff of 8% that was determined to be the acceptable 5-year local recurrence rate based on historic recurrence rates for unifocal disease, Dr. Rosenkranz explained.

There were no cases of synchronous local and distant recurrences, six contralateral breast cancers, and three new primary nonbreast cancers. Eight patients died, including one related to breast cancer.

There were no significant associations between risk of local recurrence and factors including patient age, number of sites of preoperative biopsy-proven breast cancer, HER2 status, and pathologic T and N category.

In terms of secondary endpoints, 14 patients (7.1%) converted to mastectomy because of positive margins, while 67.6% achieved margin-negative excision in a single operation.

Regarding cosmesis, 70.6% of patients reported good or excellent cosmetic outcomes at 2 years.

In terms of adherence, the whole breast radiation therapy protocol was feasible in most patients.

Of note, among patients without a breast preoperative MRI, the 5-year rate of local recurrence was significantly higher, at 22.6% (n = 14) at 5 years, compared with 1.7% among the 180 patients who did have a preoperative MRI (P = .002). However, Dr. Rosenkranz said these differences should be interpreted with caution.

“We may look at these data and think we should consider preoperative breast MRI in patients who do have known multiple ipsilateral breast cancer, although I think this cohort was certainly much too small to draw definitive conclusions, and this was not a planned secondary endpoint of the trial,” she said during her presentation.
 

Most prefer breast conservation, when possible

Overall, the findings are important considering the array of known benefits of breast conservation over mastectomy, Dr. Rosenkranz concluded.

“The reason this is so important is that we know that patients who undergo breast conservation report improved quality of life, self-esteem, and body image, and therefore it’s incumbent on us as surgeons to expand the indications for breast conservation where we can,” she told the audience.

Speaking with this news organization, she added that the decision-making around breast conservation versus mastectomy can be complicated, and some women do opt for mastectomy because of a variety of factors; therefore, “tailoring therapy to the individual goals and priorities in addition to the disease characteristics is critical.”

That said, she added that “the majority of patients who are eligible for breast conservation do prefer this option.”

Dr. Rosenkranz and Dr. Cody have reported no relevant financial relationships.

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

BOSTON – Women with breast cancer who have several tumors in one breast do not necessarily need to have a mastectomy, as new data show a low risk of recurrence at 5 years when they are treated with breast-conserving therapy and radiation.

“[The study] proves the oncologic safety of breast conservation in women with two or three sites of disease, making this a very reasonable option for (previously reluctant) surgeons to present to patients,” first author Kari Rosenkranz, MD, an associate professor at Dartmouth Health in Norwich, Vt., said in an interview.

The findings were presented here at the International Conference on Surgical Cancer Care (SSO 2023), and were published online in the Journal of Clinical Oncology.

Commenting on the study, Hiram S. Cody III, MD, an attending surgeon and professor of surgery at Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center, in New York, said the findings provide valuable new evidence on the issue.

“This is an important study confirming that breast conservation is feasible and safe for women with multiple ipsilateral breast cancers, with excellent results comparable to those for women with unifocal (single site) disease,” he said in an interview.

Although there have been as many as seven previous randomized trials that have shown identical outcomes in survival and local control of disease with breast-conserving therapy versus mastectomy, all those studies excluded patients with more than one site of disease.

At present, many surgeons and guidelines continue to recommend mastectomy for women with multiple-site tumors, based on older data that showed higher recurrence rates.

That is why the new study is so important, Dr. Cody explained. “Here, we see in a prospective trial that breast-conserving therapy is feasible for those with more than one site of disease as well, with high survival and very low rates of local recurrence,” he emphasized.

Dr. Cody noted that “the ideal candidate would be a woman with relatively small tumor size and a breast large enough that the multiple excisions could be performed with a good cosmetic result.”

“We have followed this approach for some time and hope that with the publication of these results more surgeons will recommend this approach for suitable patients,” he said.

The new results were also highlighted in a press release from Mayo Clinic highlighting the Journal of Clinical Oncology publication. Lead author of the article, surgical oncologist Judy Boughey, MD, from the Mayo Clinic in Rochester, Minn., commented: “I am excited about these findings because it will empower patients and the multidisciplinary care teams caring for patients to be thinking about this option for women who may want to preserve their breast.”

This study showed the rate of cancer local recurrence was 3.1%, she noted. This is an excellent outcome and is similar to the local recurrence rate for patients with a single tumor in a breast who had breast-conserving therapy, Dr. Boughey said.

Historically, women with multiple tumors in one breast have been advised to have a mastectomy. Now, patients can be offered a less invasive option with faster recovery, resulting in better patient satisfaction and cosmetic outcomes, she added.


 

Study details

This study, known as the ACOSOG (Alliance) Z11102 trial, was a phase 2 trial conducted in 204 patients enrolled between 2012 and 2016 who had two or three sites of biopsy-proven breast cancer (each site less rhan 5 cm in size, with cN0 or cN1 disease).

These patients were a median age of 61 years, and 83.5% were ER-positive/HER2-negative, 11.5% were HER2-positive, 5.0% were ER-negative/HER2-negative, and 77.5% were node-negative.

All patients were treated with breast conservation surgery, including lumpectomy resected to negative margins, followed by whole breast radiation with a cavity boost to all lumpectomy beds.

With a median follow-up of 66.4 months, six patients developed local recurrence, with five of the recurrences occurring in the ipsilateral breast and one in the chest wall.

For the primary endpoint, the six recurrences represented an estimated cumulative incidence of local recurrence of 3.1% (95% CI, 1.3-6.4), well below the cutoff of 8% that was determined to be the acceptable 5-year local recurrence rate based on historic recurrence rates for unifocal disease, Dr. Rosenkranz explained.

There were no cases of synchronous local and distant recurrences, six contralateral breast cancers, and three new primary nonbreast cancers. Eight patients died, including one related to breast cancer.

There were no significant associations between risk of local recurrence and factors including patient age, number of sites of preoperative biopsy-proven breast cancer, HER2 status, and pathologic T and N category.

In terms of secondary endpoints, 14 patients (7.1%) converted to mastectomy because of positive margins, while 67.6% achieved margin-negative excision in a single operation.

Regarding cosmesis, 70.6% of patients reported good or excellent cosmetic outcomes at 2 years.

In terms of adherence, the whole breast radiation therapy protocol was feasible in most patients.

Of note, among patients without a breast preoperative MRI, the 5-year rate of local recurrence was significantly higher, at 22.6% (n = 14) at 5 years, compared with 1.7% among the 180 patients who did have a preoperative MRI (P = .002). However, Dr. Rosenkranz said these differences should be interpreted with caution.

“We may look at these data and think we should consider preoperative breast MRI in patients who do have known multiple ipsilateral breast cancer, although I think this cohort was certainly much too small to draw definitive conclusions, and this was not a planned secondary endpoint of the trial,” she said during her presentation.
 

Most prefer breast conservation, when possible

Overall, the findings are important considering the array of known benefits of breast conservation over mastectomy, Dr. Rosenkranz concluded.

“The reason this is so important is that we know that patients who undergo breast conservation report improved quality of life, self-esteem, and body image, and therefore it’s incumbent on us as surgeons to expand the indications for breast conservation where we can,” she told the audience.

Speaking with this news organization, she added that the decision-making around breast conservation versus mastectomy can be complicated, and some women do opt for mastectomy because of a variety of factors; therefore, “tailoring therapy to the individual goals and priorities in addition to the disease characteristics is critical.”

That said, she added that “the majority of patients who are eligible for breast conservation do prefer this option.”

Dr. Rosenkranz and Dr. Cody have reported no relevant financial relationships.

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

BOSTON – Women with breast cancer who have several tumors in one breast do not necessarily need to have a mastectomy, as new data show a low risk of recurrence at 5 years when they are treated with breast-conserving therapy and radiation.

“[The study] proves the oncologic safety of breast conservation in women with two or three sites of disease, making this a very reasonable option for (previously reluctant) surgeons to present to patients,” first author Kari Rosenkranz, MD, an associate professor at Dartmouth Health in Norwich, Vt., said in an interview.

The findings were presented here at the International Conference on Surgical Cancer Care (SSO 2023), and were published online in the Journal of Clinical Oncology.

Commenting on the study, Hiram S. Cody III, MD, an attending surgeon and professor of surgery at Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center, in New York, said the findings provide valuable new evidence on the issue.

“This is an important study confirming that breast conservation is feasible and safe for women with multiple ipsilateral breast cancers, with excellent results comparable to those for women with unifocal (single site) disease,” he said in an interview.

Although there have been as many as seven previous randomized trials that have shown identical outcomes in survival and local control of disease with breast-conserving therapy versus mastectomy, all those studies excluded patients with more than one site of disease.

At present, many surgeons and guidelines continue to recommend mastectomy for women with multiple-site tumors, based on older data that showed higher recurrence rates.

That is why the new study is so important, Dr. Cody explained. “Here, we see in a prospective trial that breast-conserving therapy is feasible for those with more than one site of disease as well, with high survival and very low rates of local recurrence,” he emphasized.

Dr. Cody noted that “the ideal candidate would be a woman with relatively small tumor size and a breast large enough that the multiple excisions could be performed with a good cosmetic result.”

“We have followed this approach for some time and hope that with the publication of these results more surgeons will recommend this approach for suitable patients,” he said.

The new results were also highlighted in a press release from Mayo Clinic highlighting the Journal of Clinical Oncology publication. Lead author of the article, surgical oncologist Judy Boughey, MD, from the Mayo Clinic in Rochester, Minn., commented: “I am excited about these findings because it will empower patients and the multidisciplinary care teams caring for patients to be thinking about this option for women who may want to preserve their breast.”

This study showed the rate of cancer local recurrence was 3.1%, she noted. This is an excellent outcome and is similar to the local recurrence rate for patients with a single tumor in a breast who had breast-conserving therapy, Dr. Boughey said.

Historically, women with multiple tumors in one breast have been advised to have a mastectomy. Now, patients can be offered a less invasive option with faster recovery, resulting in better patient satisfaction and cosmetic outcomes, she added.


 

Study details

This study, known as the ACOSOG (Alliance) Z11102 trial, was a phase 2 trial conducted in 204 patients enrolled between 2012 and 2016 who had two or three sites of biopsy-proven breast cancer (each site less rhan 5 cm in size, with cN0 or cN1 disease).

These patients were a median age of 61 years, and 83.5% were ER-positive/HER2-negative, 11.5% were HER2-positive, 5.0% were ER-negative/HER2-negative, and 77.5% were node-negative.

All patients were treated with breast conservation surgery, including lumpectomy resected to negative margins, followed by whole breast radiation with a cavity boost to all lumpectomy beds.

With a median follow-up of 66.4 months, six patients developed local recurrence, with five of the recurrences occurring in the ipsilateral breast and one in the chest wall.

For the primary endpoint, the six recurrences represented an estimated cumulative incidence of local recurrence of 3.1% (95% CI, 1.3-6.4), well below the cutoff of 8% that was determined to be the acceptable 5-year local recurrence rate based on historic recurrence rates for unifocal disease, Dr. Rosenkranz explained.

There were no cases of synchronous local and distant recurrences, six contralateral breast cancers, and three new primary nonbreast cancers. Eight patients died, including one related to breast cancer.

There were no significant associations between risk of local recurrence and factors including patient age, number of sites of preoperative biopsy-proven breast cancer, HER2 status, and pathologic T and N category.

In terms of secondary endpoints, 14 patients (7.1%) converted to mastectomy because of positive margins, while 67.6% achieved margin-negative excision in a single operation.

Regarding cosmesis, 70.6% of patients reported good or excellent cosmetic outcomes at 2 years.

In terms of adherence, the whole breast radiation therapy protocol was feasible in most patients.

Of note, among patients without a breast preoperative MRI, the 5-year rate of local recurrence was significantly higher, at 22.6% (n = 14) at 5 years, compared with 1.7% among the 180 patients who did have a preoperative MRI (P = .002). However, Dr. Rosenkranz said these differences should be interpreted with caution.

“We may look at these data and think we should consider preoperative breast MRI in patients who do have known multiple ipsilateral breast cancer, although I think this cohort was certainly much too small to draw definitive conclusions, and this was not a planned secondary endpoint of the trial,” she said during her presentation.
 

Most prefer breast conservation, when possible

Overall, the findings are important considering the array of known benefits of breast conservation over mastectomy, Dr. Rosenkranz concluded.

“The reason this is so important is that we know that patients who undergo breast conservation report improved quality of life, self-esteem, and body image, and therefore it’s incumbent on us as surgeons to expand the indications for breast conservation where we can,” she told the audience.

Speaking with this news organization, she added that the decision-making around breast conservation versus mastectomy can be complicated, and some women do opt for mastectomy because of a variety of factors; therefore, “tailoring therapy to the individual goals and priorities in addition to the disease characteristics is critical.”

That said, she added that “the majority of patients who are eligible for breast conservation do prefer this option.”

Dr. Rosenkranz and Dr. Cody have reported no relevant financial relationships.

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

Cases of acquired hypogammaglobulinemia are expected to rise, as patients live longer with such B-cell malignancies as chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma, and multiple myeloma. But there’s a striking shortage of research into the best prophylactic approaches to prevent infections, a new systematic review and meta-analysis showed.

Researchers found just 22 randomized controlled studies into prophylactic strategies, with several of them conducted prior to 2000. According to the report, published in Blood Advances, the studies together only evaluated a few thousand participants.

Reliable findings are so sparse that study coauthor Zoe McQuilten, MBBS, PhD, MD, a hematologist at Monash University, Melbourne, said “we simply don’t know” which preventive strategy is most effective. This is especially worrisome because more patients will survive their cancers and “be at risk of infection or have significant cytopenias and will experience impaired quality of life as a result,” she said in an interview.

The study authors launched the analysis to better understand the evidence regarding infection prevention and to guide the development of clinical trials, study coauthor Robert Weinkove, MBBS, PhD, a hematologist at Malaghan Institute of Medical Research, Wellington, New Zealand, said in an interview.

As he explained, targeted therapies have revolutionized the treatment of some B-cell cancers. They also have boosted the number of patients who survive the diseases yet still have profound hypogammaglobulinemia.

“Indeed, we may soon reach the point at which infection, and not tumor progression, is the leading cause of death for patients with certain B-cell cancers,” he said. “The evidence base for managing hypogammaglobulinemia is largely based on randomized trials of immunoglobulin replacement conducted in the 1980s and early 1990s, before the advent of B cell–targeted therapies. Immunoglobulin replacement is a costly intervention, and many countries are facing a shortage of immunoglobulin.”

The report authors identified 22 total randomized controlled trials, including one led by Dr. McQuilten: 8 studies into prophylactic immunoglobulin (n = 370; all but 1 study published prior to 2000), 5 into prophylactic antibiotics (n = 1,587), 7 into vaccination (n = 3,996), and 1 comparing immunoglobulin versus antibiotics (n = 60).

No evidence was found to support a lowering of risk by prophylactic antibiotics, although they caused adverse events.

Prophylactic immunoglobulin also caused adverse events, but a meta-analysis found that it reduced the risk of clinically documented infection by 28% (n = 2 trials; relative risk, 0.72; 95% confidence interval, 0.54-0.96). Three trials reported adverse events and found a higher risk overall (RR, 2.23; 95% CI, 1.67-2.99).

Varicella zoster virus vaccination reduced the risk of one or more infections by 63% (n = 5 trials, RR, 0.37; 95% CI, 0.30-0.45, n = 3,515). Prophylactic antibiotics did not reduce the risk.

No intervention reduced all-cause mortality.

“Our findings should be interpreted with caution, Dr. McQuilten said, “because of the low number of patients, high risk of bias in the included studies, and lack of contemporary data applicable to the current standard of care for such patients.”

The lack of useful data is surprising, she said, especially considering “how commonly these interventions are used in current clinical practice and the cost and supply constraints for immunoglobulin. Given the variation in international guidelines, rising global demand and cost of immunoglobulin, and concerns regarding antimicrobial resistance, more evidence is needed to inform infection prevention strategies for this patient population.”

More data is expected soon. One ongoing study is examining intravenous immunoglobulin versus placebo in patients with CLL. It’s expected to be completed in September 2023.

What should clinicians do for now? “Given the lack of a proven survival benefit in favor of prophylactic immunoglobulin replacement, one strategy is to maximize use of vaccination and to educate both patients and clinicians regarding the need for early treatment of infections,” Dr. Weinkove said. “For people who have recurrent or severe infections despite these measures, both immunoglobulin replacement and prophylactic antibiotics are clinical options. It would be reasonable to take account of patient preference, logistical considerations, and reimbursement and availability in deciding between these options.”

He added that, “for people with severe hypogammaglobulinemia who experience recurrent or severe infections despite prophylactic antibiotics, switching to immunoglobulin replacement would be appropriate. We advocate enrollment in clinical trials, if possible.”

In an interview, Juthaporn Cowan, MD, PhD, an infectious disease physician with the University of Ottawa, said many patients with B-cell lymphomas develop acquired hypogammaglobulinemia. “Patients tend to get prolonged colds, frequent sinusitis, bronchitis, or pneumonia. Some can end up with severe infection. Many patients told me that, even though their cancer is cured or in remission, quality of life is still quite poor due to these infections and fatigue.”

Dr. Cowan said the new report is somewhat useful, although “concluding that vaccination reduces infection is misleading. Vaccination reduces the infection that patients were vaccinated against. Patients who received Shingrix will have less shingles but will continue to have bronchitis and other infections.”

As for advice for clinicians, she said preventing acquired hypogammaglobulinemia is difficult since it can be caused by the malignancies, by treatment, or both. “The other item to consider is that we do not know how long we should continue [immunoglobulin] treatment in these patients. I have a patient post CAR [chimeric antigen receptor] T therapy who still does not have B-cell 5-6 years after CAR T, while I have lymphoma patients who could safely discontinue [immunoglobulin] treatment in a few years.”

Dr. Cowan added that patients on immunoglobulin treatment can still get opportunistic infections from cytomegalovirus or herpes simplex virus “because the mechanism of host defense against these infections is different. Antimicrobial prophylaxis should still be considered as vaccination is not available for every single potential opportunistic infection.”

Australia funded the research through the National Blood Authority. Dr. McQuilten and Dr. Weinkove reported no disclosures. Other report authors disclosed ties with Aegros, CSL Behring, Janssen, AbbVie, and BeiGene. Monash University has received funding for unrelated projects from CSL Behring. Dr. Cowan reports honoraria from Takeda, CSL Behring, Octapharma, GlaxoSmithKline, Merck, and AstraZeneca.

Cases of acquired hypogammaglobulinemia are expected to rise, as patients live longer with such B-cell malignancies as chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma, and multiple myeloma. But there’s a striking shortage of research into the best prophylactic approaches to prevent infections, a new systematic review and meta-analysis showed.

Researchers found just 22 randomized controlled studies into prophylactic strategies, with several of them conducted prior to 2000. According to the report, published in Blood Advances, the studies together only evaluated a few thousand participants.

Reliable findings are so sparse that study coauthor Zoe McQuilten, MBBS, PhD, MD, a hematologist at Monash University, Melbourne, said “we simply don’t know” which preventive strategy is most effective. This is especially worrisome because more patients will survive their cancers and “be at risk of infection or have significant cytopenias and will experience impaired quality of life as a result,” she said in an interview.

The study authors launched the analysis to better understand the evidence regarding infection prevention and to guide the development of clinical trials, study coauthor Robert Weinkove, MBBS, PhD, a hematologist at Malaghan Institute of Medical Research, Wellington, New Zealand, said in an interview.

As he explained, targeted therapies have revolutionized the treatment of some B-cell cancers. They also have boosted the number of patients who survive the diseases yet still have profound hypogammaglobulinemia.

“Indeed, we may soon reach the point at which infection, and not tumor progression, is the leading cause of death for patients with certain B-cell cancers,” he said. “The evidence base for managing hypogammaglobulinemia is largely based on randomized trials of immunoglobulin replacement conducted in the 1980s and early 1990s, before the advent of B cell–targeted therapies. Immunoglobulin replacement is a costly intervention, and many countries are facing a shortage of immunoglobulin.”

The report authors identified 22 total randomized controlled trials, including one led by Dr. McQuilten: 8 studies into prophylactic immunoglobulin (n = 370; all but 1 study published prior to 2000), 5 into prophylactic antibiotics (n = 1,587), 7 into vaccination (n = 3,996), and 1 comparing immunoglobulin versus antibiotics (n = 60).

No evidence was found to support a lowering of risk by prophylactic antibiotics, although they caused adverse events.

Prophylactic immunoglobulin also caused adverse events, but a meta-analysis found that it reduced the risk of clinically documented infection by 28% (n = 2 trials; relative risk, 0.72; 95% confidence interval, 0.54-0.96). Three trials reported adverse events and found a higher risk overall (RR, 2.23; 95% CI, 1.67-2.99).

Varicella zoster virus vaccination reduced the risk of one or more infections by 63% (n = 5 trials, RR, 0.37; 95% CI, 0.30-0.45, n = 3,515). Prophylactic antibiotics did not reduce the risk.

No intervention reduced all-cause mortality.

“Our findings should be interpreted with caution, Dr. McQuilten said, “because of the low number of patients, high risk of bias in the included studies, and lack of contemporary data applicable to the current standard of care for such patients.”

The lack of useful data is surprising, she said, especially considering “how commonly these interventions are used in current clinical practice and the cost and supply constraints for immunoglobulin. Given the variation in international guidelines, rising global demand and cost of immunoglobulin, and concerns regarding antimicrobial resistance, more evidence is needed to inform infection prevention strategies for this patient population.”

More data is expected soon. One ongoing study is examining intravenous immunoglobulin versus placebo in patients with CLL. It’s expected to be completed in September 2023.

What should clinicians do for now? “Given the lack of a proven survival benefit in favor of prophylactic immunoglobulin replacement, one strategy is to maximize use of vaccination and to educate both patients and clinicians regarding the need for early treatment of infections,” Dr. Weinkove said. “For people who have recurrent or severe infections despite these measures, both immunoglobulin replacement and prophylactic antibiotics are clinical options. It would be reasonable to take account of patient preference, logistical considerations, and reimbursement and availability in deciding between these options.”

He added that, “for people with severe hypogammaglobulinemia who experience recurrent or severe infections despite prophylactic antibiotics, switching to immunoglobulin replacement would be appropriate. We advocate enrollment in clinical trials, if possible.”

In an interview, Juthaporn Cowan, MD, PhD, an infectious disease physician with the University of Ottawa, said many patients with B-cell lymphomas develop acquired hypogammaglobulinemia. “Patients tend to get prolonged colds, frequent sinusitis, bronchitis, or pneumonia. Some can end up with severe infection. Many patients told me that, even though their cancer is cured or in remission, quality of life is still quite poor due to these infections and fatigue.”

Dr. Cowan said the new report is somewhat useful, although “concluding that vaccination reduces infection is misleading. Vaccination reduces the infection that patients were vaccinated against. Patients who received Shingrix will have less shingles but will continue to have bronchitis and other infections.”

As for advice for clinicians, she said preventing acquired hypogammaglobulinemia is difficult since it can be caused by the malignancies, by treatment, or both. “The other item to consider is that we do not know how long we should continue [immunoglobulin] treatment in these patients. I have a patient post CAR [chimeric antigen receptor] T therapy who still does not have B-cell 5-6 years after CAR T, while I have lymphoma patients who could safely discontinue [immunoglobulin] treatment in a few years.”

Dr. Cowan added that patients on immunoglobulin treatment can still get opportunistic infections from cytomegalovirus or herpes simplex virus “because the mechanism of host defense against these infections is different. Antimicrobial prophylaxis should still be considered as vaccination is not available for every single potential opportunistic infection.”

Australia funded the research through the National Blood Authority. Dr. McQuilten and Dr. Weinkove reported no disclosures. Other report authors disclosed ties with Aegros, CSL Behring, Janssen, AbbVie, and BeiGene. Monash University has received funding for unrelated projects from CSL Behring. Dr. Cowan reports honoraria from Takeda, CSL Behring, Octapharma, GlaxoSmithKline, Merck, and AstraZeneca.

Cases of acquired hypogammaglobulinemia are expected to rise, as patients live longer with such B-cell malignancies as chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma, and multiple myeloma. But there’s a striking shortage of research into the best prophylactic approaches to prevent infections, a new systematic review and meta-analysis showed.

Researchers found just 22 randomized controlled studies into prophylactic strategies, with several of them conducted prior to 2000. According to the report, published in Blood Advances, the studies together only evaluated a few thousand participants.

Reliable findings are so sparse that study coauthor Zoe McQuilten, MBBS, PhD, MD, a hematologist at Monash University, Melbourne, said “we simply don’t know” which preventive strategy is most effective. This is especially worrisome because more patients will survive their cancers and “be at risk of infection or have significant cytopenias and will experience impaired quality of life as a result,” she said in an interview.

The study authors launched the analysis to better understand the evidence regarding infection prevention and to guide the development of clinical trials, study coauthor Robert Weinkove, MBBS, PhD, a hematologist at Malaghan Institute of Medical Research, Wellington, New Zealand, said in an interview.

As he explained, targeted therapies have revolutionized the treatment of some B-cell cancers. They also have boosted the number of patients who survive the diseases yet still have profound hypogammaglobulinemia.

“Indeed, we may soon reach the point at which infection, and not tumor progression, is the leading cause of death for patients with certain B-cell cancers,” he said. “The evidence base for managing hypogammaglobulinemia is largely based on randomized trials of immunoglobulin replacement conducted in the 1980s and early 1990s, before the advent of B cell–targeted therapies. Immunoglobulin replacement is a costly intervention, and many countries are facing a shortage of immunoglobulin.”

The report authors identified 22 total randomized controlled trials, including one led by Dr. McQuilten: 8 studies into prophylactic immunoglobulin (n = 370; all but 1 study published prior to 2000), 5 into prophylactic antibiotics (n = 1,587), 7 into vaccination (n = 3,996), and 1 comparing immunoglobulin versus antibiotics (n = 60).

No evidence was found to support a lowering of risk by prophylactic antibiotics, although they caused adverse events.

Prophylactic immunoglobulin also caused adverse events, but a meta-analysis found that it reduced the risk of clinically documented infection by 28% (n = 2 trials; relative risk, 0.72; 95% confidence interval, 0.54-0.96). Three trials reported adverse events and found a higher risk overall (RR, 2.23; 95% CI, 1.67-2.99).

Varicella zoster virus vaccination reduced the risk of one or more infections by 63% (n = 5 trials, RR, 0.37; 95% CI, 0.30-0.45, n = 3,515). Prophylactic antibiotics did not reduce the risk.

No intervention reduced all-cause mortality.

“Our findings should be interpreted with caution, Dr. McQuilten said, “because of the low number of patients, high risk of bias in the included studies, and lack of contemporary data applicable to the current standard of care for such patients.”

The lack of useful data is surprising, she said, especially considering “how commonly these interventions are used in current clinical practice and the cost and supply constraints for immunoglobulin. Given the variation in international guidelines, rising global demand and cost of immunoglobulin, and concerns regarding antimicrobial resistance, more evidence is needed to inform infection prevention strategies for this patient population.”

More data is expected soon. One ongoing study is examining intravenous immunoglobulin versus placebo in patients with CLL. It’s expected to be completed in September 2023.

What should clinicians do for now? “Given the lack of a proven survival benefit in favor of prophylactic immunoglobulin replacement, one strategy is to maximize use of vaccination and to educate both patients and clinicians regarding the need for early treatment of infections,” Dr. Weinkove said. “For people who have recurrent or severe infections despite these measures, both immunoglobulin replacement and prophylactic antibiotics are clinical options. It would be reasonable to take account of patient preference, logistical considerations, and reimbursement and availability in deciding between these options.”

He added that, “for people with severe hypogammaglobulinemia who experience recurrent or severe infections despite prophylactic antibiotics, switching to immunoglobulin replacement would be appropriate. We advocate enrollment in clinical trials, if possible.”

In an interview, Juthaporn Cowan, MD, PhD, an infectious disease physician with the University of Ottawa, said many patients with B-cell lymphomas develop acquired hypogammaglobulinemia. “Patients tend to get prolonged colds, frequent sinusitis, bronchitis, or pneumonia. Some can end up with severe infection. Many patients told me that, even though their cancer is cured or in remission, quality of life is still quite poor due to these infections and fatigue.”

Dr. Cowan said the new report is somewhat useful, although “concluding that vaccination reduces infection is misleading. Vaccination reduces the infection that patients were vaccinated against. Patients who received Shingrix will have less shingles but will continue to have bronchitis and other infections.”

As for advice for clinicians, she said preventing acquired hypogammaglobulinemia is difficult since it can be caused by the malignancies, by treatment, or both. “The other item to consider is that we do not know how long we should continue [immunoglobulin] treatment in these patients. I have a patient post CAR [chimeric antigen receptor] T therapy who still does not have B-cell 5-6 years after CAR T, while I have lymphoma patients who could safely discontinue [immunoglobulin] treatment in a few years.”

Dr. Cowan added that patients on immunoglobulin treatment can still get opportunistic infections from cytomegalovirus or herpes simplex virus “because the mechanism of host defense against these infections is different. Antimicrobial prophylaxis should still be considered as vaccination is not available for every single potential opportunistic infection.”

Australia funded the research through the National Blood Authority. Dr. McQuilten and Dr. Weinkove reported no disclosures. Other report authors disclosed ties with Aegros, CSL Behring, Janssen, AbbVie, and BeiGene. Monash University has received funding for unrelated projects from CSL Behring. Dr. Cowan reports honoraria from Takeda, CSL Behring, Octapharma, GlaxoSmithKline, Merck, and AstraZeneca.

Targeting cancer screenings based on idiopathic inflammatory myositis (IIM) subtype, autoantibodies, and age may help to maximize cancer detection while limiting false positives.

In a retrospective, single-center study conducted at Johns Hopkins University in Baltimore, researchers found that when screening patients with IIM for cancer via CT imaging, the diagnostic yield (number of cancers detected/tests performed) was highest in patients with dermatomyositis and the autoantibody anti–TIF1-gamma. Screening patients below age 40 years was associated with lower diagnostic yields and higher false positives, regardless of subtype.

Because of the well-known association between IIM and contemporaneous cancer, newly diagnosed patients with IIM often undergo screening. Yet, there is little research on the most efficient assessment approaches, Christopher Mecoli, MD, an assistant professor of medicine at John Hopkins University School of Medicine and lead author of the study, told this news organization. “There has been a lot written about how these patients should be evaluated for cancer. Unfortunately, the majority of literature is based on eminence,” he said. This study is “one of the first pieces of real data to inform that conversation,” he added.

The research was published online in Arthritis Care & Research.

In the study, Dr. Mecoli and colleagues looked at 1,086 patients enrolled in the center’s Myositis Research Registry from 2003 through 2020. The analysis included patients with a diagnosis of dermatomyositis, polymyositis, immune-mediated necrotizing myopathy (IMNM), and antisynthetase syndrome (ASyS). The researchers also looked at myositis-specific autoantibodies, including anti–TIF1-gamma, –Jo1, and –HMGCR. Patients were excluded from the analysis if they had a cancer diagnosis prior to their IIM onset.

Among patients included in the analysis, the average age of IIM onset was 49 years, and median follow-up duration was 5.3 years. Most patients were female (71%), 68% were white, 21% were Black, 3.6% were Asian, and 7.4% had a listed race of other or unknown. About 66% of all patients received a chest CT scan within 3 years of IIM onset, and 51% received an abdomen/pelvis CT in that same time frame. False positives were defined as the percentage of scans that led to a noncancerous biopsy.

During the study period, 62 patients had a cancer diagnosis within the first 3 years of IIM onset, with the most common cancers being breast (19%), melanoma (13%), and cervical/uterine (10%). Of 1,011 chest scans performed, 9 led to a cancer diagnosis (0.9%), compared with 12 of the 657 abdomen/pelvis (a/p) CT scans (1.8%). Patients with the dermatomyositis-specific autoantibody anti–TIF1-gamma had the highest diagnostic yield (2.9% in chest CT and 2.4% in a/p CT). Regardless of autoantibodies, dermatomyositis patients above 40 years of age had a diagnostic yield of 1.4% in chest CT and 2.7% in a/p CT. For patients under the age of 40 with polymyositis, IMNM, and ASyS, the diagnostic yield for all CT scans was 0.0%. The diagnostic yield in patients under 40 with dermatomyositis was also low (0.0% in chest CT, 0.8% in a/p CT).

The false-positive rate for all chest CT scans was 2.8%, with patients with IMNM and ASyS having the highest frequency of false positivity (both 4.4%). “Based on our data, CT chest imaging in ASyS and IMNM patients are associated with the most harm from a cancer screening perspective,” the authors write. In a/p CT, patients with dermatomyositis under 40 and patients with ASyS had the highest false-positive rates (4.9% and 3.8%, respectively).

“Age was a really big deal in terms of predicting diagnostic yield and false-positivity rate,” Dr. Mecoli said, particularly in patients with dermatomyositis. “This subgroup has historically been thought to have the biggest dissociation with cancer,” he said, but in patients under 40, “it doesn’t look like CT scans were that helpful. They were not picking up a lot of cancers, and they were leading to a lot of false-positive results.”

Still, Rohit Aggarwal, MD, of the division of rheumatology and clinical immunology at the University of Pittsburgh, Pennsylvania, noted that the diagnostic yields of 1%-2% and even 2%-4% in higher-risk populations were high. By comparison, lung cancer screening trials had a diagnostic yield of about 1%, and trials examining CT screening for colorectal cancers had diagnostic yields of 0.5%, the authors write.

“The key message for me is that we should definitely perform CT scans of the chest, abdomen, and pelvis within 3 years of diagnosis – typically at presentation – if the patient has any risk factor for increased risk of cancer, which include dermatomyositis and age above 40,” Dr. Aggarwal toldthis news organization. He was not involved with the research. There are also other clinical factors to consider that were not included in the study, he added, such as severe dysphagia, patients with refractory treatment, and male sex.

Both Dr. Aggarwal and Dr. Mecoli agreed that there are limitations to this single-center, retrospective study that make it difficult to generalize the results. Similar studies should be conducted at other institutions to see if these associations hold true, Dr. Mecoli said. A prospective study could also help control for factors such as selection bias, Dr. Aggarwal added. “I don’t think these are definitive data, but I think these data were needed at retrospective levels” to plan future research, he said.

The study was supported in part by grants from the National Institutes of Health, the Jerome L. Greene Foundation, the Donald B. and Dorothy L. Stabler Foundation, the Huayi and Siuling Zhang Discovery Fund, and Dr. Peter Buck. Dr. Mecoli and Dr. Aggarwal have disclosed no relevant financial relationships.

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

Targeting cancer screenings based on idiopathic inflammatory myositis (IIM) subtype, autoantibodies, and age may help to maximize cancer detection while limiting false positives.

In a retrospective, single-center study conducted at Johns Hopkins University in Baltimore, researchers found that when screening patients with IIM for cancer via CT imaging, the diagnostic yield (number of cancers detected/tests performed) was highest in patients with dermatomyositis and the autoantibody anti–TIF1-gamma. Screening patients below age 40 years was associated with lower diagnostic yields and higher false positives, regardless of subtype.

Because of the well-known association between IIM and contemporaneous cancer, newly diagnosed patients with IIM often undergo screening. Yet, there is little research on the most efficient assessment approaches, Christopher Mecoli, MD, an assistant professor of medicine at John Hopkins University School of Medicine and lead author of the study, told this news organization. “There has been a lot written about how these patients should be evaluated for cancer. Unfortunately, the majority of literature is based on eminence,” he said. This study is “one of the first pieces of real data to inform that conversation,” he added.

The research was published online in Arthritis Care & Research.

In the study, Dr. Mecoli and colleagues looked at 1,086 patients enrolled in the center’s Myositis Research Registry from 2003 through 2020. The analysis included patients with a diagnosis of dermatomyositis, polymyositis, immune-mediated necrotizing myopathy (IMNM), and antisynthetase syndrome (ASyS). The researchers also looked at myositis-specific autoantibodies, including anti–TIF1-gamma, –Jo1, and –HMGCR. Patients were excluded from the analysis if they had a cancer diagnosis prior to their IIM onset.

Among patients included in the analysis, the average age of IIM onset was 49 years, and median follow-up duration was 5.3 years. Most patients were female (71%), 68% were white, 21% were Black, 3.6% were Asian, and 7.4% had a listed race of other or unknown. About 66% of all patients received a chest CT scan within 3 years of IIM onset, and 51% received an abdomen/pelvis CT in that same time frame. False positives were defined as the percentage of scans that led to a noncancerous biopsy.

During the study period, 62 patients had a cancer diagnosis within the first 3 years of IIM onset, with the most common cancers being breast (19%), melanoma (13%), and cervical/uterine (10%). Of 1,011 chest scans performed, 9 led to a cancer diagnosis (0.9%), compared with 12 of the 657 abdomen/pelvis (a/p) CT scans (1.8%). Patients with the dermatomyositis-specific autoantibody anti–TIF1-gamma had the highest diagnostic yield (2.9% in chest CT and 2.4% in a/p CT). Regardless of autoantibodies, dermatomyositis patients above 40 years of age had a diagnostic yield of 1.4% in chest CT and 2.7% in a/p CT. For patients under the age of 40 with polymyositis, IMNM, and ASyS, the diagnostic yield for all CT scans was 0.0%. The diagnostic yield in patients under 40 with dermatomyositis was also low (0.0% in chest CT, 0.8% in a/p CT).

The false-positive rate for all chest CT scans was 2.8%, with patients with IMNM and ASyS having the highest frequency of false positivity (both 4.4%). “Based on our data, CT chest imaging in ASyS and IMNM patients are associated with the most harm from a cancer screening perspective,” the authors write. In a/p CT, patients with dermatomyositis under 40 and patients with ASyS had the highest false-positive rates (4.9% and 3.8%, respectively).

“Age was a really big deal in terms of predicting diagnostic yield and false-positivity rate,” Dr. Mecoli said, particularly in patients with dermatomyositis. “This subgroup has historically been thought to have the biggest dissociation with cancer,” he said, but in patients under 40, “it doesn’t look like CT scans were that helpful. They were not picking up a lot of cancers, and they were leading to a lot of false-positive results.”

Still, Rohit Aggarwal, MD, of the division of rheumatology and clinical immunology at the University of Pittsburgh, Pennsylvania, noted that the diagnostic yields of 1%-2% and even 2%-4% in higher-risk populations were high. By comparison, lung cancer screening trials had a diagnostic yield of about 1%, and trials examining CT screening for colorectal cancers had diagnostic yields of 0.5%, the authors write.

“The key message for me is that we should definitely perform CT scans of the chest, abdomen, and pelvis within 3 years of diagnosis – typically at presentation – if the patient has any risk factor for increased risk of cancer, which include dermatomyositis and age above 40,” Dr. Aggarwal toldthis news organization. He was not involved with the research. There are also other clinical factors to consider that were not included in the study, he added, such as severe dysphagia, patients with refractory treatment, and male sex.

Both Dr. Aggarwal and Dr. Mecoli agreed that there are limitations to this single-center, retrospective study that make it difficult to generalize the results. Similar studies should be conducted at other institutions to see if these associations hold true, Dr. Mecoli said. A prospective study could also help control for factors such as selection bias, Dr. Aggarwal added. “I don’t think these are definitive data, but I think these data were needed at retrospective levels” to plan future research, he said.

The study was supported in part by grants from the National Institutes of Health, the Jerome L. Greene Foundation, the Donald B. and Dorothy L. Stabler Foundation, the Huayi and Siuling Zhang Discovery Fund, and Dr. Peter Buck. Dr. Mecoli and Dr. Aggarwal have disclosed no relevant financial relationships.

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

Targeting cancer screenings based on idiopathic inflammatory myositis (IIM) subtype, autoantibodies, and age may help to maximize cancer detection while limiting false positives.

In a retrospective, single-center study conducted at Johns Hopkins University in Baltimore, researchers found that when screening patients with IIM for cancer via CT imaging, the diagnostic yield (number of cancers detected/tests performed) was highest in patients with dermatomyositis and the autoantibody anti–TIF1-gamma. Screening patients below age 40 years was associated with lower diagnostic yields and higher false positives, regardless of subtype.

Because of the well-known association between IIM and contemporaneous cancer, newly diagnosed patients with IIM often undergo screening. Yet, there is little research on the most efficient assessment approaches, Christopher Mecoli, MD, an assistant professor of medicine at John Hopkins University School of Medicine and lead author of the study, told this news organization. “There has been a lot written about how these patients should be evaluated for cancer. Unfortunately, the majority of literature is based on eminence,” he said. This study is “one of the first pieces of real data to inform that conversation,” he added.

The research was published online in Arthritis Care & Research.

In the study, Dr. Mecoli and colleagues looked at 1,086 patients enrolled in the center’s Myositis Research Registry from 2003 through 2020. The analysis included patients with a diagnosis of dermatomyositis, polymyositis, immune-mediated necrotizing myopathy (IMNM), and antisynthetase syndrome (ASyS). The researchers also looked at myositis-specific autoantibodies, including anti–TIF1-gamma, –Jo1, and –HMGCR. Patients were excluded from the analysis if they had a cancer diagnosis prior to their IIM onset.

Among patients included in the analysis, the average age of IIM onset was 49 years, and median follow-up duration was 5.3 years. Most patients were female (71%), 68% were white, 21% were Black, 3.6% were Asian, and 7.4% had a listed race of other or unknown. About 66% of all patients received a chest CT scan within 3 years of IIM onset, and 51% received an abdomen/pelvis CT in that same time frame. False positives were defined as the percentage of scans that led to a noncancerous biopsy.

During the study period, 62 patients had a cancer diagnosis within the first 3 years of IIM onset, with the most common cancers being breast (19%), melanoma (13%), and cervical/uterine (10%). Of 1,011 chest scans performed, 9 led to a cancer diagnosis (0.9%), compared with 12 of the 657 abdomen/pelvis (a/p) CT scans (1.8%). Patients with the dermatomyositis-specific autoantibody anti–TIF1-gamma had the highest diagnostic yield (2.9% in chest CT and 2.4% in a/p CT). Regardless of autoantibodies, dermatomyositis patients above 40 years of age had a diagnostic yield of 1.4% in chest CT and 2.7% in a/p CT. For patients under the age of 40 with polymyositis, IMNM, and ASyS, the diagnostic yield for all CT scans was 0.0%. The diagnostic yield in patients under 40 with dermatomyositis was also low (0.0% in chest CT, 0.8% in a/p CT).

The false-positive rate for all chest CT scans was 2.8%, with patients with IMNM and ASyS having the highest frequency of false positivity (both 4.4%). “Based on our data, CT chest imaging in ASyS and IMNM patients are associated with the most harm from a cancer screening perspective,” the authors write. In a/p CT, patients with dermatomyositis under 40 and patients with ASyS had the highest false-positive rates (4.9% and 3.8%, respectively).

“Age was a really big deal in terms of predicting diagnostic yield and false-positivity rate,” Dr. Mecoli said, particularly in patients with dermatomyositis. “This subgroup has historically been thought to have the biggest dissociation with cancer,” he said, but in patients under 40, “it doesn’t look like CT scans were that helpful. They were not picking up a lot of cancers, and they were leading to a lot of false-positive results.”

Still, Rohit Aggarwal, MD, of the division of rheumatology and clinical immunology at the University of Pittsburgh, Pennsylvania, noted that the diagnostic yields of 1%-2% and even 2%-4% in higher-risk populations were high. By comparison, lung cancer screening trials had a diagnostic yield of about 1%, and trials examining CT screening for colorectal cancers had diagnostic yields of 0.5%, the authors write.

“The key message for me is that we should definitely perform CT scans of the chest, abdomen, and pelvis within 3 years of diagnosis – typically at presentation – if the patient has any risk factor for increased risk of cancer, which include dermatomyositis and age above 40,” Dr. Aggarwal toldthis news organization. He was not involved with the research. There are also other clinical factors to consider that were not included in the study, he added, such as severe dysphagia, patients with refractory treatment, and male sex.

Both Dr. Aggarwal and Dr. Mecoli agreed that there are limitations to this single-center, retrospective study that make it difficult to generalize the results. Similar studies should be conducted at other institutions to see if these associations hold true, Dr. Mecoli said. A prospective study could also help control for factors such as selection bias, Dr. Aggarwal added. “I don’t think these are definitive data, but I think these data were needed at retrospective levels” to plan future research, he said.

The study was supported in part by grants from the National Institutes of Health, the Jerome L. Greene Foundation, the Donald B. and Dorothy L. Stabler Foundation, the Huayi and Siuling Zhang Discovery Fund, and Dr. Peter Buck. Dr. Mecoli and Dr. Aggarwal have disclosed no relevant financial relationships.

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

Ascend Laboratories is recalling 10 lots of the oral anticoagulant dabigatran etexilate capsules (75 mg and 150 mg) because of unacceptable levels of a potential carcinogen.

The nationwide recall, to the consumer level, is because of the detection of the nitrosamine impurity, N-nitroso-dabigatran, which may increase the risk of cancer with prolonged exposure to levels higher than acceptable.

To date, Ascend Laboratories has not received any reports of adverse events related to this recall.

The recalled product was distributed nationwide to wholesalers, distributors, and retailers in the United States from June 2022 to October 2022.

Complete details of the recalled product, including national drug code, lot numbers, expiration dates, and configuration/counts, are provided in a company announcement that was posted on the Food and Drug Administration website.

The company is advising patients who have any dabigatran that has been recalled to continue taking their medication and to contact their physician for advice regarding an alternative treatment.

Wholesalers/distributors and pharmacies with an existing inventory of the affected lots should stop use and distribution and quarantine the product immediately. Wholesalers and distributors should also recall the distributed product.

Questions regarding this recall can call Ascend Laboratories at 877.272.7901 (24 hours, 7 days a week).

Problems with this product should be reported to the FDA through MedWatch, its adverse event reporting program.

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

Ascend Laboratories is recalling 10 lots of the oral anticoagulant dabigatran etexilate capsules (75 mg and 150 mg) because of unacceptable levels of a potential carcinogen.

The nationwide recall, to the consumer level, is because of the detection of the nitrosamine impurity, N-nitroso-dabigatran, which may increase the risk of cancer with prolonged exposure to levels higher than acceptable.

To date, Ascend Laboratories has not received any reports of adverse events related to this recall.

The recalled product was distributed nationwide to wholesalers, distributors, and retailers in the United States from June 2022 to October 2022.

Complete details of the recalled product, including national drug code, lot numbers, expiration dates, and configuration/counts, are provided in a company announcement that was posted on the Food and Drug Administration website.

The company is advising patients who have any dabigatran that has been recalled to continue taking their medication and to contact their physician for advice regarding an alternative treatment.

Wholesalers/distributors and pharmacies with an existing inventory of the affected lots should stop use and distribution and quarantine the product immediately. Wholesalers and distributors should also recall the distributed product.

Questions regarding this recall can call Ascend Laboratories at 877.272.7901 (24 hours, 7 days a week).

Problems with this product should be reported to the FDA through MedWatch, its adverse event reporting program.

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

Ascend Laboratories is recalling 10 lots of the oral anticoagulant dabigatran etexilate capsules (75 mg and 150 mg) because of unacceptable levels of a potential carcinogen.

The nationwide recall, to the consumer level, is because of the detection of the nitrosamine impurity, N-nitroso-dabigatran, which may increase the risk of cancer with prolonged exposure to levels higher than acceptable.

To date, Ascend Laboratories has not received any reports of adverse events related to this recall.

The recalled product was distributed nationwide to wholesalers, distributors, and retailers in the United States from June 2022 to October 2022.

Complete details of the recalled product, including national drug code, lot numbers, expiration dates, and configuration/counts, are provided in a company announcement that was posted on the Food and Drug Administration website.

The company is advising patients who have any dabigatran that has been recalled to continue taking their medication and to contact their physician for advice regarding an alternative treatment.

Wholesalers/distributors and pharmacies with an existing inventory of the affected lots should stop use and distribution and quarantine the product immediately. Wholesalers and distributors should also recall the distributed product.

Questions regarding this recall can call Ascend Laboratories at 877.272.7901 (24 hours, 7 days a week).

Problems with this product should be reported to the FDA through MedWatch, its adverse event reporting program.

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

In a small cohort of patients with hematologic cancer and their caregivers, the use of a financial navigator helped secure cost savings of approximately $2,500 per person. This saving was achieved by helping participants to optimize health insurance, identify different types of assistance for out-of-pocket expenses, or apply for disability or family medical leave.

Cancer patients in the United States face complex financial issues in navigating with medical insurance companies to cover their care. This “financial toxicity” has come to be regarded as a side effect of cancer treatment.

Patients with hematologic malignancies may be particularly vulnerable to financial toxicity, owing to the nature of their treatment, which often includes bone marrow transplantation, lengthy hospital stays, and prolonged intensive follow-up, as well as potential treatment-related complications, such as graft vs. host disease.

The results from this small study suggest that using an oncology financial navigator could be helpful. But not all cancer patients have access to such a person, explained lead author Jean S. Edward, PhD, RN, associate professor in the college of nursing at the University of Kentucky, Lexington.

“Unfortunately, it’s not as common as we would like, especially in underserved areas with patient and caregiver populations that need it the most,” she said. Dr. Edward is hopeful that the results from this study, even though it is small, might help to boost use of this intervention. “OFN [oncology financial navigation] is not necessarily a cutting-edge program or ‘novel’ intervention, but the lack of programs and limitations in implementing in cancer centers does make it a gap in practice,” Dr. Edward told this news organization.

“There are gaps in evidence on how to incorporate an oncology financial navigator in current workflows and sustainability of positions, but as our study has shown, the return on investment to the health care system and/or financial benefits to patients/caregivers could help cover the cost of implementing such programs,” she said.

The study was published in JCO Oncology Practice.

The intervention used in this study, Coverage and Cost-of-Care Links (CC Links), was designed specifically to address financial toxicity among patients with hematologic cancers.

The study’s primary outcomes were defined as improvements in financial distress as well as in physical and mental quality of life.

A total of 54 patients and 32 caregivers completed the intervention and pre-/postintervention surveys. More than half of participants were women. The average age was 63 years. Less than a quarter of the patients were employed (23%), about one-third had income that was below the federal poverty level, and almost all had insurance. About 59% of the caregivers were employed.

The navigators’ functions included screening for financial toxicity using FACIT-Comprehensive Score for Financial Toxicity (COST) and the National Comprehensive Cancer Network’s Distress Thermometer and Problem List. They also helped patients to estimate cost of care, assessed health insurance coverage, and connected patients/caregivers with disease-specific resources and other external assistance programs, among other things.

Participants had an average of three in-person meetings and five telephone interactions with the financial navigator. The most common concern was in regard to high out-of-pocket costs. The most frequently provided services from the navigator were helping with financial assistance programs and grant applications. Overall, the navigator was able to obtain $124,600 in financial benefits for 48 participants, as well as money for travel ($24,000), urgent needs ($16,000), patient financial assistance ($9,100), and copay assistance grants ($75,500).

With regard to scores on the screening tools, the only significant change from pre- to postintervention was in the psychological response score, or COST. It decreased by an average of 2.30 points (P = .019; Hedges’ g = 0.33). For caregivers, there was a significant improvement in COST (average decrease, 2.97 points; P = .021; g = 0.43), material condition scores (average decrease, 0.63 points; P = .031; g = 0.39), and total financial toxicity scores (average decrease, 0.13 points; P = .041; g = 0.37).

Most of the participants gave the intervention high ratings for acceptability (89%) and appropriateness (88%).

“Standardized screening for financial toxicity in cancer care settings is essential to support early identification of financial needs that serve as barriers to care,” the authors conclude. “Close collaboration and coordination with existing services and workflows are essential for the seamless integration of OFN interventions within health systems and to help facilitate contact and communication with participants.”

The study was supported by the National Cancer Institute; the University of Kentucky’s Markey Cancer Center; the Research Communications Office of the Patient Oriented and Population Science Shared Resource Facilities; Joan Scales, LCSW, and the Psych-Oncology Program at the University of Kentucky Markey Cancer Center; and UK HealthCare’s Patient Financial Services. Dr. Edward has disclosed no relevant financial relationships.
 

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

In a small cohort of patients with hematologic cancer and their caregivers, the use of a financial navigator helped secure cost savings of approximately $2,500 per person. This saving was achieved by helping participants to optimize health insurance, identify different types of assistance for out-of-pocket expenses, or apply for disability or family medical leave.

Cancer patients in the United States face complex financial issues in navigating with medical insurance companies to cover their care. This “financial toxicity” has come to be regarded as a side effect of cancer treatment.

Patients with hematologic malignancies may be particularly vulnerable to financial toxicity, owing to the nature of their treatment, which often includes bone marrow transplantation, lengthy hospital stays, and prolonged intensive follow-up, as well as potential treatment-related complications, such as graft vs. host disease.

The results from this small study suggest that using an oncology financial navigator could be helpful. But not all cancer patients have access to such a person, explained lead author Jean S. Edward, PhD, RN, associate professor in the college of nursing at the University of Kentucky, Lexington.

“Unfortunately, it’s not as common as we would like, especially in underserved areas with patient and caregiver populations that need it the most,” she said. Dr. Edward is hopeful that the results from this study, even though it is small, might help to boost use of this intervention. “OFN [oncology financial navigation] is not necessarily a cutting-edge program or ‘novel’ intervention, but the lack of programs and limitations in implementing in cancer centers does make it a gap in practice,” Dr. Edward told this news organization.

“There are gaps in evidence on how to incorporate an oncology financial navigator in current workflows and sustainability of positions, but as our study has shown, the return on investment to the health care system and/or financial benefits to patients/caregivers could help cover the cost of implementing such programs,” she said.

The study was published in JCO Oncology Practice.

The intervention used in this study, Coverage and Cost-of-Care Links (CC Links), was designed specifically to address financial toxicity among patients with hematologic cancers.

The study’s primary outcomes were defined as improvements in financial distress as well as in physical and mental quality of life.

A total of 54 patients and 32 caregivers completed the intervention and pre-/postintervention surveys. More than half of participants were women. The average age was 63 years. Less than a quarter of the patients were employed (23%), about one-third had income that was below the federal poverty level, and almost all had insurance. About 59% of the caregivers were employed.

The navigators’ functions included screening for financial toxicity using FACIT-Comprehensive Score for Financial Toxicity (COST) and the National Comprehensive Cancer Network’s Distress Thermometer and Problem List. They also helped patients to estimate cost of care, assessed health insurance coverage, and connected patients/caregivers with disease-specific resources and other external assistance programs, among other things.

Participants had an average of three in-person meetings and five telephone interactions with the financial navigator. The most common concern was in regard to high out-of-pocket costs. The most frequently provided services from the navigator were helping with financial assistance programs and grant applications. Overall, the navigator was able to obtain $124,600 in financial benefits for 48 participants, as well as money for travel ($24,000), urgent needs ($16,000), patient financial assistance ($9,100), and copay assistance grants ($75,500).

With regard to scores on the screening tools, the only significant change from pre- to postintervention was in the psychological response score, or COST. It decreased by an average of 2.30 points (P = .019; Hedges’ g = 0.33). For caregivers, there was a significant improvement in COST (average decrease, 2.97 points; P = .021; g = 0.43), material condition scores (average decrease, 0.63 points; P = .031; g = 0.39), and total financial toxicity scores (average decrease, 0.13 points; P = .041; g = 0.37).

Most of the participants gave the intervention high ratings for acceptability (89%) and appropriateness (88%).

“Standardized screening for financial toxicity in cancer care settings is essential to support early identification of financial needs that serve as barriers to care,” the authors conclude. “Close collaboration and coordination with existing services and workflows are essential for the seamless integration of OFN interventions within health systems and to help facilitate contact and communication with participants.”

The study was supported by the National Cancer Institute; the University of Kentucky’s Markey Cancer Center; the Research Communications Office of the Patient Oriented and Population Science Shared Resource Facilities; Joan Scales, LCSW, and the Psych-Oncology Program at the University of Kentucky Markey Cancer Center; and UK HealthCare’s Patient Financial Services. Dr. Edward has disclosed no relevant financial relationships.
 

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

In a small cohort of patients with hematologic cancer and their caregivers, the use of a financial navigator helped secure cost savings of approximately $2,500 per person. This saving was achieved by helping participants to optimize health insurance, identify different types of assistance for out-of-pocket expenses, or apply for disability or family medical leave.

Cancer patients in the United States face complex financial issues in navigating with medical insurance companies to cover their care. This “financial toxicity” has come to be regarded as a side effect of cancer treatment.

Patients with hematologic malignancies may be particularly vulnerable to financial toxicity, owing to the nature of their treatment, which often includes bone marrow transplantation, lengthy hospital stays, and prolonged intensive follow-up, as well as potential treatment-related complications, such as graft vs. host disease.

The results from this small study suggest that using an oncology financial navigator could be helpful. But not all cancer patients have access to such a person, explained lead author Jean S. Edward, PhD, RN, associate professor in the college of nursing at the University of Kentucky, Lexington.

“Unfortunately, it’s not as common as we would like, especially in underserved areas with patient and caregiver populations that need it the most,” she said. Dr. Edward is hopeful that the results from this study, even though it is small, might help to boost use of this intervention. “OFN [oncology financial navigation] is not necessarily a cutting-edge program or ‘novel’ intervention, but the lack of programs and limitations in implementing in cancer centers does make it a gap in practice,” Dr. Edward told this news organization.

“There are gaps in evidence on how to incorporate an oncology financial navigator in current workflows and sustainability of positions, but as our study has shown, the return on investment to the health care system and/or financial benefits to patients/caregivers could help cover the cost of implementing such programs,” she said.

The study was published in JCO Oncology Practice.

The intervention used in this study, Coverage and Cost-of-Care Links (CC Links), was designed specifically to address financial toxicity among patients with hematologic cancers.

The study’s primary outcomes were defined as improvements in financial distress as well as in physical and mental quality of life.

A total of 54 patients and 32 caregivers completed the intervention and pre-/postintervention surveys. More than half of participants were women. The average age was 63 years. Less than a quarter of the patients were employed (23%), about one-third had income that was below the federal poverty level, and almost all had insurance. About 59% of the caregivers were employed.

The navigators’ functions included screening for financial toxicity using FACIT-Comprehensive Score for Financial Toxicity (COST) and the National Comprehensive Cancer Network’s Distress Thermometer and Problem List. They also helped patients to estimate cost of care, assessed health insurance coverage, and connected patients/caregivers with disease-specific resources and other external assistance programs, among other things.

Participants had an average of three in-person meetings and five telephone interactions with the financial navigator. The most common concern was in regard to high out-of-pocket costs. The most frequently provided services from the navigator were helping with financial assistance programs and grant applications. Overall, the navigator was able to obtain $124,600 in financial benefits for 48 participants, as well as money for travel ($24,000), urgent needs ($16,000), patient financial assistance ($9,100), and copay assistance grants ($75,500).

With regard to scores on the screening tools, the only significant change from pre- to postintervention was in the psychological response score, or COST. It decreased by an average of 2.30 points (P = .019; Hedges’ g = 0.33). For caregivers, there was a significant improvement in COST (average decrease, 2.97 points; P = .021; g = 0.43), material condition scores (average decrease, 0.63 points; P = .031; g = 0.39), and total financial toxicity scores (average decrease, 0.13 points; P = .041; g = 0.37).

Most of the participants gave the intervention high ratings for acceptability (89%) and appropriateness (88%).

“Standardized screening for financial toxicity in cancer care settings is essential to support early identification of financial needs that serve as barriers to care,” the authors conclude. “Close collaboration and coordination with existing services and workflows are essential for the seamless integration of OFN interventions within health systems and to help facilitate contact and communication with participants.”

The study was supported by the National Cancer Institute; the University of Kentucky’s Markey Cancer Center; the Research Communications Office of the Patient Oriented and Population Science Shared Resource Facilities; Joan Scales, LCSW, and the Psych-Oncology Program at the University of Kentucky Markey Cancer Center; and UK HealthCare’s Patient Financial Services. Dr. Edward has disclosed no relevant financial relationships.
 

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

For women who are overdue for cervical cancer screening, mailing self-sampling kits for high-risk human papillomavirus (HPV) is a cost-effective means of increasing screening uptake, reveals an analysis of a large U.S. trial.

The finding comes from a randomized trial in almost 20,000 women, which compared women who received a mailed HPV testing kit with those who did not. The results show that mailing was most cost-effective in women aged 50-64 years and in those who were only recently overdue for cervical screening.

The study was published by JAMA Network Open.

“These results support mailing HPV kits as an efficient outreach strategy for increasing screening rates in U.S. health care systems,” say the authors, led by Rachel L. Winer, PhD, MPH, department of epidemiology, University of Washington, Seattle.

They note that their results are consistent with those from previous studies in other health care contexts, but their analysis “benefited from the randomized clinical trial design and a large sample size,” they write.

However, they point out that the trial was conducted “before the beginning of the COVID-19 pandemic,” and it is “well established” that cancer screening rates “decreased substantially during the pandemic.”

They suggest that mailed HPV self-sampling kits could nevertheless be a “means of overcoming screening barriers among underscreened women,” which may have been exacerbated by the “societal consequences of the pandemic.”


 

Reducing barriers to screening

Cervical screening is associated with “substantial global reductions” in the incidence and mortality of cervical cancer, the authors point out. Because most cases of the disease are consequently preventable, it now occurs “predominantly in individuals who have never or rarely received screening.”

Home-based HPV-only testing reduces the need for office visits and reduces barriers to screening, such as discomfort, embarrassment, and difficulties with scheduling or attending appointments.

Previous studies have shown that the direct mailing of home-based HPV self-collection kits is associated with increased uptake of screening among underscreened women and is cost-effective, although the researchers point out that these previous studies were conducted in countries with “organized national screening programs.”

For their own study, they focused on home-based HPV screening among underscreened individuals in the United States. The team examined data from the Home-based Options to Make cervical cancer screening Easy trial, which has previously showed that mailing kits to women increased screening uptake, compared with usual care alone.

For the current analysis, they conducted an economic evaluation of data on 19,851 trial participants, who were randomized to receive home-based screening or usual care between February 2014 and August 2016 and were followed up to February 2018.

All of the women were aged 30-64 years and had been enrolled in a health plan from Kaiser Permanente Washington (KPW) for at least 3 years and 5 months. They were also required not have undergone a hysterectomy.

Participant-level economic data were collected between June 2019 and March 2021, with intervention delivery costs calculated from the perspective of both the KPW and Medicare health systems and based on the cost of either a wellness visit or Papanicolaou (Pap) test–only visit.

The mean age of the participants was 50.1 years, and the majority (76.7%) were White; 9.7% were Asian and 4.7% were Black or African American.

There were no significant differences in baseline characteristics between the group assigned to usual care, which comprised patient reminders and ad hoc screening outreach, and those in the intervention group, who received usual care and a mailed HPV self-sampling kit.

The researchers report that 1,206 women in the intervention group sent back a mailed HPV kit, with 1,178 (97.7%) meeting the criteria for completed screening uptake.

Overall, screening uptake was higher in the intervention group than in control participants, at 26.3% vs. 17.4%, respectively (relative risk, 1.51).

Intervention participants were also more likely than controls to have a positive test result (relative risk, 1.49) and to receive treatment (relative risk, 1.70).

The incremental cost-effectiveness ratio for increased screening uptake, defined as the incremental difference in cost between the study groups divided by the difference in the number of participants completing screening within 6 months, ranged from $85.84 per additional completed screening to $146.29, depending on the health system and test considered.

In terms of willingness-to-pay (WTP) thresholds for each additional completed screening, the team found that home-based screening achieved a 90% probability of cost-effectiveness, at a WTP of just $148 if the participant’s last Pap test was between 3.4 and 5.0 years before randomization.

A 90% probability of cost-effectiveness was also achieved at a WTP of $198 among participants aged 50-64 years, a threshold that was lower than that among other age groups.

At a WTP threshold of over $350, the intervention was considered to have 100% probability of being cost-effective in all age groups.

The study was supported by a grant from the National Cancer Institute of the National Institutes of Health. Dr. Winer reports a relationship with the National Cancer Institute outside of the submitted work, as do several other authors.

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

For women who are overdue for cervical cancer screening, mailing self-sampling kits for high-risk human papillomavirus (HPV) is a cost-effective means of increasing screening uptake, reveals an analysis of a large U.S. trial.

The finding comes from a randomized trial in almost 20,000 women, which compared women who received a mailed HPV testing kit with those who did not. The results show that mailing was most cost-effective in women aged 50-64 years and in those who were only recently overdue for cervical screening.

The study was published by JAMA Network Open.

“These results support mailing HPV kits as an efficient outreach strategy for increasing screening rates in U.S. health care systems,” say the authors, led by Rachel L. Winer, PhD, MPH, department of epidemiology, University of Washington, Seattle.

They note that their results are consistent with those from previous studies in other health care contexts, but their analysis “benefited from the randomized clinical trial design and a large sample size,” they write.

However, they point out that the trial was conducted “before the beginning of the COVID-19 pandemic,” and it is “well established” that cancer screening rates “decreased substantially during the pandemic.”

They suggest that mailed HPV self-sampling kits could nevertheless be a “means of overcoming screening barriers among underscreened women,” which may have been exacerbated by the “societal consequences of the pandemic.”


 

Reducing barriers to screening

Cervical screening is associated with “substantial global reductions” in the incidence and mortality of cervical cancer, the authors point out. Because most cases of the disease are consequently preventable, it now occurs “predominantly in individuals who have never or rarely received screening.”

Home-based HPV-only testing reduces the need for office visits and reduces barriers to screening, such as discomfort, embarrassment, and difficulties with scheduling or attending appointments.

Previous studies have shown that the direct mailing of home-based HPV self-collection kits is associated with increased uptake of screening among underscreened women and is cost-effective, although the researchers point out that these previous studies were conducted in countries with “organized national screening programs.”

For their own study, they focused on home-based HPV screening among underscreened individuals in the United States. The team examined data from the Home-based Options to Make cervical cancer screening Easy trial, which has previously showed that mailing kits to women increased screening uptake, compared with usual care alone.

For the current analysis, they conducted an economic evaluation of data on 19,851 trial participants, who were randomized to receive home-based screening or usual care between February 2014 and August 2016 and were followed up to February 2018.

All of the women were aged 30-64 years and had been enrolled in a health plan from Kaiser Permanente Washington (KPW) for at least 3 years and 5 months. They were also required not have undergone a hysterectomy.

Participant-level economic data were collected between June 2019 and March 2021, with intervention delivery costs calculated from the perspective of both the KPW and Medicare health systems and based on the cost of either a wellness visit or Papanicolaou (Pap) test–only visit.

The mean age of the participants was 50.1 years, and the majority (76.7%) were White; 9.7% were Asian and 4.7% were Black or African American.

There were no significant differences in baseline characteristics between the group assigned to usual care, which comprised patient reminders and ad hoc screening outreach, and those in the intervention group, who received usual care and a mailed HPV self-sampling kit.

The researchers report that 1,206 women in the intervention group sent back a mailed HPV kit, with 1,178 (97.7%) meeting the criteria for completed screening uptake.

Overall, screening uptake was higher in the intervention group than in control participants, at 26.3% vs. 17.4%, respectively (relative risk, 1.51).

Intervention participants were also more likely than controls to have a positive test result (relative risk, 1.49) and to receive treatment (relative risk, 1.70).

The incremental cost-effectiveness ratio for increased screening uptake, defined as the incremental difference in cost between the study groups divided by the difference in the number of participants completing screening within 6 months, ranged from $85.84 per additional completed screening to $146.29, depending on the health system and test considered.

In terms of willingness-to-pay (WTP) thresholds for each additional completed screening, the team found that home-based screening achieved a 90% probability of cost-effectiveness, at a WTP of just $148 if the participant’s last Pap test was between 3.4 and 5.0 years before randomization.

A 90% probability of cost-effectiveness was also achieved at a WTP of $198 among participants aged 50-64 years, a threshold that was lower than that among other age groups.

At a WTP threshold of over $350, the intervention was considered to have 100% probability of being cost-effective in all age groups.

The study was supported by a grant from the National Cancer Institute of the National Institutes of Health. Dr. Winer reports a relationship with the National Cancer Institute outside of the submitted work, as do several other authors.

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

For women who are overdue for cervical cancer screening, mailing self-sampling kits for high-risk human papillomavirus (HPV) is a cost-effective means of increasing screening uptake, reveals an analysis of a large U.S. trial.

The finding comes from a randomized trial in almost 20,000 women, which compared women who received a mailed HPV testing kit with those who did not. The results show that mailing was most cost-effective in women aged 50-64 years and in those who were only recently overdue for cervical screening.

The study was published by JAMA Network Open.

“These results support mailing HPV kits as an efficient outreach strategy for increasing screening rates in U.S. health care systems,” say the authors, led by Rachel L. Winer, PhD, MPH, department of epidemiology, University of Washington, Seattle.

They note that their results are consistent with those from previous studies in other health care contexts, but their analysis “benefited from the randomized clinical trial design and a large sample size,” they write.

However, they point out that the trial was conducted “before the beginning of the COVID-19 pandemic,” and it is “well established” that cancer screening rates “decreased substantially during the pandemic.”

They suggest that mailed HPV self-sampling kits could nevertheless be a “means of overcoming screening barriers among underscreened women,” which may have been exacerbated by the “societal consequences of the pandemic.”


 

Reducing barriers to screening

Cervical screening is associated with “substantial global reductions” in the incidence and mortality of cervical cancer, the authors point out. Because most cases of the disease are consequently preventable, it now occurs “predominantly in individuals who have never or rarely received screening.”

Home-based HPV-only testing reduces the need for office visits and reduces barriers to screening, such as discomfort, embarrassment, and difficulties with scheduling or attending appointments.

Previous studies have shown that the direct mailing of home-based HPV self-collection kits is associated with increased uptake of screening among underscreened women and is cost-effective, although the researchers point out that these previous studies were conducted in countries with “organized national screening programs.”

For their own study, they focused on home-based HPV screening among underscreened individuals in the United States. The team examined data from the Home-based Options to Make cervical cancer screening Easy trial, which has previously showed that mailing kits to women increased screening uptake, compared with usual care alone.

For the current analysis, they conducted an economic evaluation of data on 19,851 trial participants, who were randomized to receive home-based screening or usual care between February 2014 and August 2016 and were followed up to February 2018.

All of the women were aged 30-64 years and had been enrolled in a health plan from Kaiser Permanente Washington (KPW) for at least 3 years and 5 months. They were also required not have undergone a hysterectomy.

Participant-level economic data were collected between June 2019 and March 2021, with intervention delivery costs calculated from the perspective of both the KPW and Medicare health systems and based on the cost of either a wellness visit or Papanicolaou (Pap) test–only visit.

The mean age of the participants was 50.1 years, and the majority (76.7%) were White; 9.7% were Asian and 4.7% were Black or African American.

There were no significant differences in baseline characteristics between the group assigned to usual care, which comprised patient reminders and ad hoc screening outreach, and those in the intervention group, who received usual care and a mailed HPV self-sampling kit.

The researchers report that 1,206 women in the intervention group sent back a mailed HPV kit, with 1,178 (97.7%) meeting the criteria for completed screening uptake.

Overall, screening uptake was higher in the intervention group than in control participants, at 26.3% vs. 17.4%, respectively (relative risk, 1.51).

Intervention participants were also more likely than controls to have a positive test result (relative risk, 1.49) and to receive treatment (relative risk, 1.70).

The incremental cost-effectiveness ratio for increased screening uptake, defined as the incremental difference in cost between the study groups divided by the difference in the number of participants completing screening within 6 months, ranged from $85.84 per additional completed screening to $146.29, depending on the health system and test considered.

In terms of willingness-to-pay (WTP) thresholds for each additional completed screening, the team found that home-based screening achieved a 90% probability of cost-effectiveness, at a WTP of just $148 if the participant’s last Pap test was between 3.4 and 5.0 years before randomization.

A 90% probability of cost-effectiveness was also achieved at a WTP of $198 among participants aged 50-64 years, a threshold that was lower than that among other age groups.

At a WTP threshold of over $350, the intervention was considered to have 100% probability of being cost-effective in all age groups.

The study was supported by a grant from the National Cancer Institute of the National Institutes of Health. Dr. Winer reports a relationship with the National Cancer Institute outside of the submitted work, as do several other authors.

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

Researchers are homing in on a new connection between colon cancer and Clostridioides difficile.

C. diff. is a bacterium that infects the large intestine, causing difficult GI symptoms like frequent diarrhea. C. diff. is a widespread infection among patients who have been hospitalized, estimated at almost a half-million cases per year. It’s extremely contagious. 

C. diff. has been known to lead to dangerous problems like sepsis if left untreated. Previous research has found there is a higher amount of C. diff. in cancerous lesions than in healthy body tissue, but a recent study published in Cancer Discovery by Johns Hopkins and Vanderbilt University has expanded upon the link between C. diff. and colon cancer. This study, which was conducted in mice, found that C. diff. bacteria may change normal cells to cancer cells. 

In colon cancer, the surface of the colon tends to be covered in biofilms – or dense amounts of bacteria. In this study, researchers found that C. diff. was capable of producing colorectal tumors in a cascade.

“Big picture, we’re working to learn what the exact mechanism for this is,” said Julia L. Drewes, PhD, assistant professor of medicine at Johns Hopkins University, Baltimore, and a coauthor of the study.

Anyone can get C. diff., but certain people are more susceptible. 

“People who are over 65, have weakened immune systems, live in nursing homes, or work in health care settings are most at risk for C. diff.,” said Lilian Chen, MD, a colon and rectal surgeon at Tufts Medical Centerand assistant professor of surgery at Tufts University, both in Boston. “People with C. diff. can also get it again. One in six patients will end up with recurrent infections.”

Another risk factor: taking antibiotics. “Trillions of microbes are normally found in and on our body, including both good and bad bacteria,” said Caroline Um, PhD, MPH, principal scientist in epidemiology research for the American Cancer Society. “Normally, good bacteria help us fight against bad bacteria such as C. diff. However, you may have a greater chance of C. diff. infection after taking antibiotics, since they usually wipe out both good and bad bacteria in our gut.”

C. diff. is transmitted through stool, often if someone doesn’t wash their hands after using the bathroom. If you touch that person’s skin or a surface that person touched, your body can be “colonized” with the bacteria. 

“Once someone is colonized with C. diff., you find it everywhere in their environment. In fact, C. diff. is all around all of us,” said Aasma Shaukat, MD, MPH, a gastroenterologist at the NYU Langone Medical Center and director of GI outcomes research at New York University. “In a healthy person, this kind of exposure doesn’t matter because C. diff. will not make them sick. It’s when someone has a compromised immune system that C. diff. becomes a concern.”

C. diff. may kickstart the process of how cancer begins to form through inflammation

“There are two types of toxins present in C. diff.: toxin A and toxin B,” said Dr. Drewes. “We need to do more work in order to determine an exact mechanism, but toxin B, or TcdB, which is found in a majority of C. diff. infections, appears to drive inflammation in the body. This inflammation contributes to cell damage in the colon, which may then be connected to a mutation that can cause cancer.” 

The findings could help researchers understand why so many people under the age of 50 are now being diagnosed with colon cancer. 

“We need a better understanding of the potential role of C. diff. in colorectal cancer before we can determine whether this changes current colorectal cancer screening guidelines,” said Dr. Um. “However, it’s a good idea to talk with your health care professional about colorectal cancer screening, regardless of whether you have had C. diff.. Various factors like smoking, poor diet, being overweight, or having a family history of colorectal cancer can affect an individual’s risk.”

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

Researchers are homing in on a new connection between colon cancer and Clostridioides difficile.

C. diff. is a bacterium that infects the large intestine, causing difficult GI symptoms like frequent diarrhea. C. diff. is a widespread infection among patients who have been hospitalized, estimated at almost a half-million cases per year. It’s extremely contagious. 

C. diff. has been known to lead to dangerous problems like sepsis if left untreated. Previous research has found there is a higher amount of C. diff. in cancerous lesions than in healthy body tissue, but a recent study published in Cancer Discovery by Johns Hopkins and Vanderbilt University has expanded upon the link between C. diff. and colon cancer. This study, which was conducted in mice, found that C. diff. bacteria may change normal cells to cancer cells. 

In colon cancer, the surface of the colon tends to be covered in biofilms – or dense amounts of bacteria. In this study, researchers found that C. diff. was capable of producing colorectal tumors in a cascade.

“Big picture, we’re working to learn what the exact mechanism for this is,” said Julia L. Drewes, PhD, assistant professor of medicine at Johns Hopkins University, Baltimore, and a coauthor of the study.

Anyone can get C. diff., but certain people are more susceptible. 

“People who are over 65, have weakened immune systems, live in nursing homes, or work in health care settings are most at risk for C. diff.,” said Lilian Chen, MD, a colon and rectal surgeon at Tufts Medical Centerand assistant professor of surgery at Tufts University, both in Boston. “People with C. diff. can also get it again. One in six patients will end up with recurrent infections.”

Another risk factor: taking antibiotics. “Trillions of microbes are normally found in and on our body, including both good and bad bacteria,” said Caroline Um, PhD, MPH, principal scientist in epidemiology research for the American Cancer Society. “Normally, good bacteria help us fight against bad bacteria such as C. diff. However, you may have a greater chance of C. diff. infection after taking antibiotics, since they usually wipe out both good and bad bacteria in our gut.”

C. diff. is transmitted through stool, often if someone doesn’t wash their hands after using the bathroom. If you touch that person’s skin or a surface that person touched, your body can be “colonized” with the bacteria. 

“Once someone is colonized with C. diff., you find it everywhere in their environment. In fact, C. diff. is all around all of us,” said Aasma Shaukat, MD, MPH, a gastroenterologist at the NYU Langone Medical Center and director of GI outcomes research at New York University. “In a healthy person, this kind of exposure doesn’t matter because C. diff. will not make them sick. It’s when someone has a compromised immune system that C. diff. becomes a concern.”

C. diff. may kickstart the process of how cancer begins to form through inflammation

“There are two types of toxins present in C. diff.: toxin A and toxin B,” said Dr. Drewes. “We need to do more work in order to determine an exact mechanism, but toxin B, or TcdB, which is found in a majority of C. diff. infections, appears to drive inflammation in the body. This inflammation contributes to cell damage in the colon, which may then be connected to a mutation that can cause cancer.” 

The findings could help researchers understand why so many people under the age of 50 are now being diagnosed with colon cancer. 

“We need a better understanding of the potential role of C. diff. in colorectal cancer before we can determine whether this changes current colorectal cancer screening guidelines,” said Dr. Um. “However, it’s a good idea to talk with your health care professional about colorectal cancer screening, regardless of whether you have had C. diff.. Various factors like smoking, poor diet, being overweight, or having a family history of colorectal cancer can affect an individual’s risk.”

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

Researchers are homing in on a new connection between colon cancer and Clostridioides difficile.

C. diff. is a bacterium that infects the large intestine, causing difficult GI symptoms like frequent diarrhea. C. diff. is a widespread infection among patients who have been hospitalized, estimated at almost a half-million cases per year. It’s extremely contagious. 

C. diff. has been known to lead to dangerous problems like sepsis if left untreated. Previous research has found there is a higher amount of C. diff. in cancerous lesions than in healthy body tissue, but a recent study published in Cancer Discovery by Johns Hopkins and Vanderbilt University has expanded upon the link between C. diff. and colon cancer. This study, which was conducted in mice, found that C. diff. bacteria may change normal cells to cancer cells. 

In colon cancer, the surface of the colon tends to be covered in biofilms – or dense amounts of bacteria. In this study, researchers found that C. diff. was capable of producing colorectal tumors in a cascade.

“Big picture, we’re working to learn what the exact mechanism for this is,” said Julia L. Drewes, PhD, assistant professor of medicine at Johns Hopkins University, Baltimore, and a coauthor of the study.

Anyone can get C. diff., but certain people are more susceptible. 

“People who are over 65, have weakened immune systems, live in nursing homes, or work in health care settings are most at risk for C. diff.,” said Lilian Chen, MD, a colon and rectal surgeon at Tufts Medical Centerand assistant professor of surgery at Tufts University, both in Boston. “People with C. diff. can also get it again. One in six patients will end up with recurrent infections.”

Another risk factor: taking antibiotics. “Trillions of microbes are normally found in and on our body, including both good and bad bacteria,” said Caroline Um, PhD, MPH, principal scientist in epidemiology research for the American Cancer Society. “Normally, good bacteria help us fight against bad bacteria such as C. diff. However, you may have a greater chance of C. diff. infection after taking antibiotics, since they usually wipe out both good and bad bacteria in our gut.”

C. diff. is transmitted through stool, often if someone doesn’t wash their hands after using the bathroom. If you touch that person’s skin or a surface that person touched, your body can be “colonized” with the bacteria. 

“Once someone is colonized with C. diff., you find it everywhere in their environment. In fact, C. diff. is all around all of us,” said Aasma Shaukat, MD, MPH, a gastroenterologist at the NYU Langone Medical Center and director of GI outcomes research at New York University. “In a healthy person, this kind of exposure doesn’t matter because C. diff. will not make them sick. It’s when someone has a compromised immune system that C. diff. becomes a concern.”

C. diff. may kickstart the process of how cancer begins to form through inflammation

“There are two types of toxins present in C. diff.: toxin A and toxin B,” said Dr. Drewes. “We need to do more work in order to determine an exact mechanism, but toxin B, or TcdB, which is found in a majority of C. diff. infections, appears to drive inflammation in the body. This inflammation contributes to cell damage in the colon, which may then be connected to a mutation that can cause cancer.” 

The findings could help researchers understand why so many people under the age of 50 are now being diagnosed with colon cancer. 

“We need a better understanding of the potential role of C. diff. in colorectal cancer before we can determine whether this changes current colorectal cancer screening guidelines,” said Dr. Um. “However, it’s a good idea to talk with your health care professional about colorectal cancer screening, regardless of whether you have had C. diff.. Various factors like smoking, poor diet, being overweight, or having a family history of colorectal cancer can affect an individual’s risk.”

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

Even after endorsement in updated guidelines, hydroxyurea is substantially underused in youth with sickle cell anemia (SCA), new research indicates.

SCA can lead to pain crises, stroke, and early death. Hydroxyurea, an oral disease-modifying medication, can reduce the complications.

In 2014, the National Heart, Lung, and Blood Institute published revised guidelines that hydroxyurea should be offered as the primary therapy to all patients who were at least 9 months old and living with SCA, regardless of disease severity.
 

Low uptake even after guideline revision

Yet, a research team led by Sarah L. Reeves, PhD, MPH, with the Child Health Evaluation and Research Center at University of Michigan, Ann Arbor, found in their study of use in two sample states – Michigan and New York – that hydroxyurea use was low in children and adolescents enrolled in Medicaid and increased only slightly in Michigan and not at all in New York after the guideline revision.

After the guidelines were updated, the researchers observed that, on average, children and adolescents were getting the medication less than a third of the days in a year (32% maximum in the year with the highest uptake). The data were gathered from a study population that included 4,302 youths aged 1-17 years with SCA.

Findings were published online in JAMA Network Open.
 

‘A national issue’

Russell Ware, MD, PhD, chair of hematology translational research at Cincinnati Children’s Hospital, who was not part of the research, says that though data were gathered from Michigan and New York, “this is a national issue.”

Dr. Ware says the main problem is the way the health system describes the importance of hydroxyurea.

“There needs to be a realization that hydroxyurea is the standard of care for children with sickle cell anemia. It’s not just something they should take when they’re sick,” Dr. Ware said.

He added, “If you have diabetes, should you only take insulin if you’re really sick and hospitalized with a diabetic coma? Of course not.”

He said often providers aren’t giving a clear and consistent message to families.

“They’re not all sure they want to recommend it. They might offer it,” Dr. Ware said, which jeopardizes uptake. “Providers need to be more committed to it. They need to know how to dose it.”
 

Bad rap from past indications

Dr. Ware says hydroxyurea also gets a bad rap from use decades ago as a chemotherapeutic agent for cancer and then as an anti-HIV medication.

Now it’s used in a completely different way with SCA, but the fear of the association lingers.

“This label as a chemotherapeutic agent has really dogged hydroxyurea,” he said. “It’s a completely different mechanism. It’s a different dose. It’s a different purpose.”

The message to families should be more direct, he says: “Your child has sickle cell anemia and needs to be on disease-modifying therapy because this is a life-threatening disease.”

The underuse of this drug is particularly ironic, he says, as each capsule, taken daily, “costs about fifty cents.”
 

Medicaid support critical

Authors conclude that multifaceted interventions may be necessary to increase the number of filled prescriptions and use. They also point out that the interventions rely on states’ Medicaid support regarding hydroxyurea use. From 70% to 90% of young people with SCA are covered by Medicaid at some point, the researchers write.

“Variation may exist across states, as well as within states, in the coverage of hydroxyurea, outpatient visits, and associated lab monitoring,” they note.

The authors point to interventions in clinical trials that have had some success in hydroxyurea use.

Creary et al., for example, found that electronic directly observed therapy was associated with high adherence. That involved sending daily texts to patients to take hydroxyurea and patients recording and sending daily videos that show they took the medication.

The authors add that incorporating clinical pharmacists into the care team to provide education and support for families has been shown to be associated with successful outcomes for other chronic conditions – this approach may be particularly well suited to hydroxyurea given that this medication requires significant dosage monitoring.

Dr. Ware, however, says that solutions should focus on the health system more clearly communicating that hydroxyurea is the standard of care for all kids with SCA.

“We need to dispel these myths and these labels that are unfairly attributed to it. Then we’d probably do a lot better,” he said.

He added that children with SCA, “are a marginalized, neglected population of patients historically,” and addressing social determinants of health is also important in getting better uptake.

“Our pharmacy, for example, ships the drug to the families if they’re just getting a refill rather than making them drive all the way in,” Dr. Ware says.

Dr. Ware said given the interruption in doctor/patient relationships in the pandemic, the poor uptake of hydroxyurea could be even worse now.

The work was funded by the Agency for Healthcare Research and Quality and National Heart, Lung, and Blood Institute. Coauthor Dr. Green was the principal investigator of an NIH-funded trial of hydroxyurea in Uganda with a study drug provided by Siklos. No other author disclosures were reported. In addition to receiving research funding from the National Institutes of Health, Dr. Ware receives research donations from Bristol Myers Squibb, Addmedica, and Hemex Health. He is a medical adviser for Nova Laboratories and Octapharma, and serves on Data Safety Monitoring Boards for Novartis and Editas.
 

Even after endorsement in updated guidelines, hydroxyurea is substantially underused in youth with sickle cell anemia (SCA), new research indicates.

SCA can lead to pain crises, stroke, and early death. Hydroxyurea, an oral disease-modifying medication, can reduce the complications.

In 2014, the National Heart, Lung, and Blood Institute published revised guidelines that hydroxyurea should be offered as the primary therapy to all patients who were at least 9 months old and living with SCA, regardless of disease severity.
 

Low uptake even after guideline revision

Yet, a research team led by Sarah L. Reeves, PhD, MPH, with the Child Health Evaluation and Research Center at University of Michigan, Ann Arbor, found in their study of use in two sample states – Michigan and New York – that hydroxyurea use was low in children and adolescents enrolled in Medicaid and increased only slightly in Michigan and not at all in New York after the guideline revision.

After the guidelines were updated, the researchers observed that, on average, children and adolescents were getting the medication less than a third of the days in a year (32% maximum in the year with the highest uptake). The data were gathered from a study population that included 4,302 youths aged 1-17 years with SCA.

Findings were published online in JAMA Network Open.
 

‘A national issue’

Russell Ware, MD, PhD, chair of hematology translational research at Cincinnati Children’s Hospital, who was not part of the research, says that though data were gathered from Michigan and New York, “this is a national issue.”

Dr. Ware says the main problem is the way the health system describes the importance of hydroxyurea.

“There needs to be a realization that hydroxyurea is the standard of care for children with sickle cell anemia. It’s not just something they should take when they’re sick,” Dr. Ware said.

He added, “If you have diabetes, should you only take insulin if you’re really sick and hospitalized with a diabetic coma? Of course not.”

He said often providers aren’t giving a clear and consistent message to families.

“They’re not all sure they want to recommend it. They might offer it,” Dr. Ware said, which jeopardizes uptake. “Providers need to be more committed to it. They need to know how to dose it.”
 

Bad rap from past indications

Dr. Ware says hydroxyurea also gets a bad rap from use decades ago as a chemotherapeutic agent for cancer and then as an anti-HIV medication.

Now it’s used in a completely different way with SCA, but the fear of the association lingers.

“This label as a chemotherapeutic agent has really dogged hydroxyurea,” he said. “It’s a completely different mechanism. It’s a different dose. It’s a different purpose.”

The message to families should be more direct, he says: “Your child has sickle cell anemia and needs to be on disease-modifying therapy because this is a life-threatening disease.”

The underuse of this drug is particularly ironic, he says, as each capsule, taken daily, “costs about fifty cents.”
 

Medicaid support critical

Authors conclude that multifaceted interventions may be necessary to increase the number of filled prescriptions and use. They also point out that the interventions rely on states’ Medicaid support regarding hydroxyurea use. From 70% to 90% of young people with SCA are covered by Medicaid at some point, the researchers write.

“Variation may exist across states, as well as within states, in the coverage of hydroxyurea, outpatient visits, and associated lab monitoring,” they note.

The authors point to interventions in clinical trials that have had some success in hydroxyurea use.

Creary et al., for example, found that electronic directly observed therapy was associated with high adherence. That involved sending daily texts to patients to take hydroxyurea and patients recording and sending daily videos that show they took the medication.

The authors add that incorporating clinical pharmacists into the care team to provide education and support for families has been shown to be associated with successful outcomes for other chronic conditions – this approach may be particularly well suited to hydroxyurea given that this medication requires significant dosage monitoring.

Dr. Ware, however, says that solutions should focus on the health system more clearly communicating that hydroxyurea is the standard of care for all kids with SCA.

“We need to dispel these myths and these labels that are unfairly attributed to it. Then we’d probably do a lot better,” he said.

He added that children with SCA, “are a marginalized, neglected population of patients historically,” and addressing social determinants of health is also important in getting better uptake.

“Our pharmacy, for example, ships the drug to the families if they’re just getting a refill rather than making them drive all the way in,” Dr. Ware says.

Dr. Ware said given the interruption in doctor/patient relationships in the pandemic, the poor uptake of hydroxyurea could be even worse now.

The work was funded by the Agency for Healthcare Research and Quality and National Heart, Lung, and Blood Institute. Coauthor Dr. Green was the principal investigator of an NIH-funded trial of hydroxyurea in Uganda with a study drug provided by Siklos. No other author disclosures were reported. In addition to receiving research funding from the National Institutes of Health, Dr. Ware receives research donations from Bristol Myers Squibb, Addmedica, and Hemex Health. He is a medical adviser for Nova Laboratories and Octapharma, and serves on Data Safety Monitoring Boards for Novartis and Editas.
 

Even after endorsement in updated guidelines, hydroxyurea is substantially underused in youth with sickle cell anemia (SCA), new research indicates.

SCA can lead to pain crises, stroke, and early death. Hydroxyurea, an oral disease-modifying medication, can reduce the complications.

In 2014, the National Heart, Lung, and Blood Institute published revised guidelines that hydroxyurea should be offered as the primary therapy to all patients who were at least 9 months old and living with SCA, regardless of disease severity.
 

Low uptake even after guideline revision

Yet, a research team led by Sarah L. Reeves, PhD, MPH, with the Child Health Evaluation and Research Center at University of Michigan, Ann Arbor, found in their study of use in two sample states – Michigan and New York – that hydroxyurea use was low in children and adolescents enrolled in Medicaid and increased only slightly in Michigan and not at all in New York after the guideline revision.

After the guidelines were updated, the researchers observed that, on average, children and adolescents were getting the medication less than a third of the days in a year (32% maximum in the year with the highest uptake). The data were gathered from a study population that included 4,302 youths aged 1-17 years with SCA.

Findings were published online in JAMA Network Open.
 

‘A national issue’

Russell Ware, MD, PhD, chair of hematology translational research at Cincinnati Children’s Hospital, who was not part of the research, says that though data were gathered from Michigan and New York, “this is a national issue.”

Dr. Ware says the main problem is the way the health system describes the importance of hydroxyurea.

“There needs to be a realization that hydroxyurea is the standard of care for children with sickle cell anemia. It’s not just something they should take when they’re sick,” Dr. Ware said.

He added, “If you have diabetes, should you only take insulin if you’re really sick and hospitalized with a diabetic coma? Of course not.”

He said often providers aren’t giving a clear and consistent message to families.

“They’re not all sure they want to recommend it. They might offer it,” Dr. Ware said, which jeopardizes uptake. “Providers need to be more committed to it. They need to know how to dose it.”
 

Bad rap from past indications

Dr. Ware says hydroxyurea also gets a bad rap from use decades ago as a chemotherapeutic agent for cancer and then as an anti-HIV medication.

Now it’s used in a completely different way with SCA, but the fear of the association lingers.

“This label as a chemotherapeutic agent has really dogged hydroxyurea,” he said. “It’s a completely different mechanism. It’s a different dose. It’s a different purpose.”

The message to families should be more direct, he says: “Your child has sickle cell anemia and needs to be on disease-modifying therapy because this is a life-threatening disease.”

The underuse of this drug is particularly ironic, he says, as each capsule, taken daily, “costs about fifty cents.”
 

Medicaid support critical

Authors conclude that multifaceted interventions may be necessary to increase the number of filled prescriptions and use. They also point out that the interventions rely on states’ Medicaid support regarding hydroxyurea use. From 70% to 90% of young people with SCA are covered by Medicaid at some point, the researchers write.

“Variation may exist across states, as well as within states, in the coverage of hydroxyurea, outpatient visits, and associated lab monitoring,” they note.

The authors point to interventions in clinical trials that have had some success in hydroxyurea use.

Creary et al., for example, found that electronic directly observed therapy was associated with high adherence. That involved sending daily texts to patients to take hydroxyurea and patients recording and sending daily videos that show they took the medication.

The authors add that incorporating clinical pharmacists into the care team to provide education and support for families has been shown to be associated with successful outcomes for other chronic conditions – this approach may be particularly well suited to hydroxyurea given that this medication requires significant dosage monitoring.

Dr. Ware, however, says that solutions should focus on the health system more clearly communicating that hydroxyurea is the standard of care for all kids with SCA.

“We need to dispel these myths and these labels that are unfairly attributed to it. Then we’d probably do a lot better,” he said.

He added that children with SCA, “are a marginalized, neglected population of patients historically,” and addressing social determinants of health is also important in getting better uptake.

“Our pharmacy, for example, ships the drug to the families if they’re just getting a refill rather than making them drive all the way in,” Dr. Ware says.

Dr. Ware said given the interruption in doctor/patient relationships in the pandemic, the poor uptake of hydroxyurea could be even worse now.

The work was funded by the Agency for Healthcare Research and Quality and National Heart, Lung, and Blood Institute. Coauthor Dr. Green was the principal investigator of an NIH-funded trial of hydroxyurea in Uganda with a study drug provided by Siklos. No other author disclosures were reported. In addition to receiving research funding from the National Institutes of Health, Dr. Ware receives research donations from Bristol Myers Squibb, Addmedica, and Hemex Health. He is a medical adviser for Nova Laboratories and Octapharma, and serves on Data Safety Monitoring Boards for Novartis and Editas.
 

The Food and Drug Administration has approved retifanlimab-dlwr (Zynyz), an intravenous programmed death–1 (PD-1) inhibitor, for the treatment of adults with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC), the agency announced.

This marks the first regulatory approval for the PD-1 inhibitor. The FDA granted accelerated approval for the drug on the basis of tumor response rate and duration of response from the POD1UM-201 trial. Drugmaker Incyte said that “continued approval of Zynyz for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.”

MCC is a rare and aggressive skin cancer with a high rate of metastatic disease and an estimated 5-year overall survival of just 14% among those who present with metastatic disease. Incidence is rapidly increasing in the United States, particularly among adults older than 65 years, Incyte noted.

“More than a third of patients with MCC present with regional or distant metastases, which are associated with high rates of mortality,” principal author Shailender Bhatia, MD, of the University of Washington and Fred Hutchinson Cancer Center, both in Seattle, said in a news release. “The approval of Zynyz offers health care providers another first-line treatment option against MCC that can result in durable responses in patients with metastatic disease.”

POD1UM-201 was an open-label, single-arm, phase 2 study that evaluated the agent in 65 systemic treatment–naive adults with metastatic or recurrent locally advanced MCC.

Overall, 52% of patients had an objective response rate. A complete response was observed in 12 patients (18%), and a partial response was observed in 22 patients (34%).

Duration of response ranged from 1.1 to 24.9 months; 76% of responders experienced responses of 6 months or longer, and 62% experienced responses of 12 months or longer.

Study participants received a 500-mg dose of retifanlimab every 4 weeks for up to 24 weeks or until disease progression or unacceptable toxicity. Serious adverse events occurred in 22% of patients and most often included fatigue, arrhythmia, and pneumonitis; 11% of patients discontinued treatment because of serious adverse events.

Retifanlimab may cause a severe or life-threatening immune response during treatment or after discontinuation. Patients should be advised to immediately report any new or worsening signs or symptoms to their health care provider. Side effects can also be reported to the FDA.

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

The Food and Drug Administration has approved retifanlimab-dlwr (Zynyz), an intravenous programmed death–1 (PD-1) inhibitor, for the treatment of adults with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC), the agency announced.

This marks the first regulatory approval for the PD-1 inhibitor. The FDA granted accelerated approval for the drug on the basis of tumor response rate and duration of response from the POD1UM-201 trial. Drugmaker Incyte said that “continued approval of Zynyz for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.”

MCC is a rare and aggressive skin cancer with a high rate of metastatic disease and an estimated 5-year overall survival of just 14% among those who present with metastatic disease. Incidence is rapidly increasing in the United States, particularly among adults older than 65 years, Incyte noted.

“More than a third of patients with MCC present with regional or distant metastases, which are associated with high rates of mortality,” principal author Shailender Bhatia, MD, of the University of Washington and Fred Hutchinson Cancer Center, both in Seattle, said in a news release. “The approval of Zynyz offers health care providers another first-line treatment option against MCC that can result in durable responses in patients with metastatic disease.”

POD1UM-201 was an open-label, single-arm, phase 2 study that evaluated the agent in 65 systemic treatment–naive adults with metastatic or recurrent locally advanced MCC.

Overall, 52% of patients had an objective response rate. A complete response was observed in 12 patients (18%), and a partial response was observed in 22 patients (34%).

Duration of response ranged from 1.1 to 24.9 months; 76% of responders experienced responses of 6 months or longer, and 62% experienced responses of 12 months or longer.

Study participants received a 500-mg dose of retifanlimab every 4 weeks for up to 24 weeks or until disease progression or unacceptable toxicity. Serious adverse events occurred in 22% of patients and most often included fatigue, arrhythmia, and pneumonitis; 11% of patients discontinued treatment because of serious adverse events.

Retifanlimab may cause a severe or life-threatening immune response during treatment or after discontinuation. Patients should be advised to immediately report any new or worsening signs or symptoms to their health care provider. Side effects can also be reported to the FDA.

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

The Food and Drug Administration has approved retifanlimab-dlwr (Zynyz), an intravenous programmed death–1 (PD-1) inhibitor, for the treatment of adults with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC), the agency announced.

This marks the first regulatory approval for the PD-1 inhibitor. The FDA granted accelerated approval for the drug on the basis of tumor response rate and duration of response from the POD1UM-201 trial. Drugmaker Incyte said that “continued approval of Zynyz for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.”

MCC is a rare and aggressive skin cancer with a high rate of metastatic disease and an estimated 5-year overall survival of just 14% among those who present with metastatic disease. Incidence is rapidly increasing in the United States, particularly among adults older than 65 years, Incyte noted.

“More than a third of patients with MCC present with regional or distant metastases, which are associated with high rates of mortality,” principal author Shailender Bhatia, MD, of the University of Washington and Fred Hutchinson Cancer Center, both in Seattle, said in a news release. “The approval of Zynyz offers health care providers another first-line treatment option against MCC that can result in durable responses in patients with metastatic disease.”

POD1UM-201 was an open-label, single-arm, phase 2 study that evaluated the agent in 65 systemic treatment–naive adults with metastatic or recurrent locally advanced MCC.

Overall, 52% of patients had an objective response rate. A complete response was observed in 12 patients (18%), and a partial response was observed in 22 patients (34%).

Duration of response ranged from 1.1 to 24.9 months; 76% of responders experienced responses of 6 months or longer, and 62% experienced responses of 12 months or longer.

Study participants received a 500-mg dose of retifanlimab every 4 weeks for up to 24 weeks or until disease progression or unacceptable toxicity. Serious adverse events occurred in 22% of patients and most often included fatigue, arrhythmia, and pneumonitis; 11% of patients discontinued treatment because of serious adverse events.

Retifanlimab may cause a severe or life-threatening immune response during treatment or after discontinuation. Patients should be advised to immediately report any new or worsening signs or symptoms to their health care provider. Side effects can also be reported to the FDA.

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