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Genes related to osteosarcoma survival identified
When they combined them into a risk score and added one additional factor – metastases at diagnosis – the model was an “excellent” predictor of 1-year survival, the team said (area under the curve, 0.947; 95% confidence interval, 0.832-0.972).
“The survival-associated” immune-related genes (IRGs) “examined in this study have potential for identifying prognosis in osteosarcoma and may be clinically useful as relevant clinical biomarkers and candidate targets for anticancer therapy,” said investigators led by Wangmi Liu, MD, of Zhejiang University in Hangzhou, China. The study was published in JAMA Network Open.
They explained that it’s often difficult to distinguish high- and low-risk patients at osteosarcoma diagnosis. To address the issue, they analyzed the genomic signatures of 84 patients in the Cancer Genome Atlas and their associated clinical information.
The team split their subjects evenly into high-risk and low-risk groups based on a score developed from their genetic signatures. A total of 26 patients in the high-risk group (61.9%) died over a median follow up of 4.1 years versus only 1 (2.4%) in the low-risk group.
The risk score also correlated positively with B-cell tumor infiltration, and negatively with infiltration of CD8 T cells and macrophages.
Overall, 16 genes were significantly up-regulated, and 187 genes were significantly down-regulated in the high-risk group, including three survival-associated IRGs: CCL2, CD79A, and FPR1.
The differentially expressed genes were most significantly associated with transmembrane signaling receptor activity and inflammatory response. The team noted that “it has been reported that inflammatory response plays a critical role in tumor initiation, promotion, malignant conversion, invasion, and metastases.”
Of the 14 survival-associated IRGs, 5 have been reported before in osteosarcoma. The other nine were deduced from computational analysis and may be potential treatment targets, including bone morphogenetic protein 8b (BMP8b). Another member of the BMP family, BMP9, has been shown to promote the proliferation of osteosarcoma cells, “which is similar to this study’s finding that BMP8b was a risk factor in osteosarcoma. Therefore, the role of BMP8b in osteosarcoma needs further research,” the team said.
“Because the database provides limited clinical information, other important factors, such as staging and grading, were not included in our analysis. Therefore, extrapolation based on the findings must be done very carefully,” they cautioned.
The work was supported by the National Natural Science Foundation of China and others. The investigators didn’t have any disclosures.
When they combined them into a risk score and added one additional factor – metastases at diagnosis – the model was an “excellent” predictor of 1-year survival, the team said (area under the curve, 0.947; 95% confidence interval, 0.832-0.972).
“The survival-associated” immune-related genes (IRGs) “examined in this study have potential for identifying prognosis in osteosarcoma and may be clinically useful as relevant clinical biomarkers and candidate targets for anticancer therapy,” said investigators led by Wangmi Liu, MD, of Zhejiang University in Hangzhou, China. The study was published in JAMA Network Open.
They explained that it’s often difficult to distinguish high- and low-risk patients at osteosarcoma diagnosis. To address the issue, they analyzed the genomic signatures of 84 patients in the Cancer Genome Atlas and their associated clinical information.
The team split their subjects evenly into high-risk and low-risk groups based on a score developed from their genetic signatures. A total of 26 patients in the high-risk group (61.9%) died over a median follow up of 4.1 years versus only 1 (2.4%) in the low-risk group.
The risk score also correlated positively with B-cell tumor infiltration, and negatively with infiltration of CD8 T cells and macrophages.
Overall, 16 genes were significantly up-regulated, and 187 genes were significantly down-regulated in the high-risk group, including three survival-associated IRGs: CCL2, CD79A, and FPR1.
The differentially expressed genes were most significantly associated with transmembrane signaling receptor activity and inflammatory response. The team noted that “it has been reported that inflammatory response plays a critical role in tumor initiation, promotion, malignant conversion, invasion, and metastases.”
Of the 14 survival-associated IRGs, 5 have been reported before in osteosarcoma. The other nine were deduced from computational analysis and may be potential treatment targets, including bone morphogenetic protein 8b (BMP8b). Another member of the BMP family, BMP9, has been shown to promote the proliferation of osteosarcoma cells, “which is similar to this study’s finding that BMP8b was a risk factor in osteosarcoma. Therefore, the role of BMP8b in osteosarcoma needs further research,” the team said.
“Because the database provides limited clinical information, other important factors, such as staging and grading, were not included in our analysis. Therefore, extrapolation based on the findings must be done very carefully,” they cautioned.
The work was supported by the National Natural Science Foundation of China and others. The investigators didn’t have any disclosures.
When they combined them into a risk score and added one additional factor – metastases at diagnosis – the model was an “excellent” predictor of 1-year survival, the team said (area under the curve, 0.947; 95% confidence interval, 0.832-0.972).
“The survival-associated” immune-related genes (IRGs) “examined in this study have potential for identifying prognosis in osteosarcoma and may be clinically useful as relevant clinical biomarkers and candidate targets for anticancer therapy,” said investigators led by Wangmi Liu, MD, of Zhejiang University in Hangzhou, China. The study was published in JAMA Network Open.
They explained that it’s often difficult to distinguish high- and low-risk patients at osteosarcoma diagnosis. To address the issue, they analyzed the genomic signatures of 84 patients in the Cancer Genome Atlas and their associated clinical information.
The team split their subjects evenly into high-risk and low-risk groups based on a score developed from their genetic signatures. A total of 26 patients in the high-risk group (61.9%) died over a median follow up of 4.1 years versus only 1 (2.4%) in the low-risk group.
The risk score also correlated positively with B-cell tumor infiltration, and negatively with infiltration of CD8 T cells and macrophages.
Overall, 16 genes were significantly up-regulated, and 187 genes were significantly down-regulated in the high-risk group, including three survival-associated IRGs: CCL2, CD79A, and FPR1.
The differentially expressed genes were most significantly associated with transmembrane signaling receptor activity and inflammatory response. The team noted that “it has been reported that inflammatory response plays a critical role in tumor initiation, promotion, malignant conversion, invasion, and metastases.”
Of the 14 survival-associated IRGs, 5 have been reported before in osteosarcoma. The other nine were deduced from computational analysis and may be potential treatment targets, including bone morphogenetic protein 8b (BMP8b). Another member of the BMP family, BMP9, has been shown to promote the proliferation of osteosarcoma cells, “which is similar to this study’s finding that BMP8b was a risk factor in osteosarcoma. Therefore, the role of BMP8b in osteosarcoma needs further research,” the team said.
“Because the database provides limited clinical information, other important factors, such as staging and grading, were not included in our analysis. Therefore, extrapolation based on the findings must be done very carefully,” they cautioned.
The work was supported by the National Natural Science Foundation of China and others. The investigators didn’t have any disclosures.
FROM JAMA NETWORK OPEN
MRI screening cost effective for women with dense breasts
Alternatively, if a woman worries that the 4-year screening interval is too long, screening mammography may be offered every 2 years, with MRI screening offered for the second 2-year interval, according to the findings. This strategy would still require the patient to undergo MRI breast cancer screening every 4 years.
“MRI is more effective not only for selected patients. It is actually more effective than mammography for all women,” editorialist Christiane Kuhl, MD, PhD, University of Aachen (Germany), said in an interview.
“But the superior diagnostic accuracy of MRI is more often needed for women who are at higher risk for breast cancer, and therefore the cost-effectiveness is easier to achieve in women who are at higher risk,” she added.
The study was published online Sept. 29 in the Journal of the National Cancer Institute.
DENSE trial
The simulation model used for the study was based on results from the Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial, which showed that additional MRI screening for women with extremely dense breast tissue led to significantly fewer interval cancers in comparison with mammography alone (P < .001). In the DENSE trial, MRI participants underwent mammography plus MRI at 2-year intervals; the control group underwent mammography alone at 2-year intervals.
In the current study, “screening strategies varied in the number of MRIs and mammograms offered to women aged 50-75 years,” explains Amarens Geuzinge, MSc, University Medical Center, Rotterdam, the Netherlands, and colleagues, “and incremental cost-effectiveness ratios (ICERs) were calculated ... with a willingness-to-pay threshold of 22,000 euros (>$25,000 U.S.),” the investigators add.
Analyses indicated that screening every 2 years with mammography alone cost the least of all strategies that were evaluated, but it also resulted in the lowest number of quality-adjusted life years (QALYs) – in other words, it delivered the least amount of benefit for patients, coauthor Eveline Heijnsdijk, PhD, University Medical Center, Rotterdam, the Netherlands, explained to this news organization.
Offering an additional MRI every 2 years resulted in the highest costs but not the highest number of QALYs and was inferior to the other screening strategies analyzed, she added. Alternating mammography with MRI breast cancer screening, each conducted every 2 years, came close to providing the same benefits to patients as the every-4-year MRI screening strategy, Dr. Heijnsdijk noted.
However, when the authors applied the National Institute for Health and Care Excellence (NICE) threshold, MRI screening every 4 years yielded the highest acceptable incremental cost-effectiveness ratio (ICER), at 15,620 euros per QALYs, whereas screening every 3 years with MRI alone yielded an ICER of 37,181 euros per QALY.
If decision-makers are willing to pay more than 22,000 euros per QALY gained, “MRI every 2 or 3 years can also become cost effective,” the authors add.
Asked how acceptable MRI screening might be if performed only once every 4 years, Dr. Heijnsdijk noted that, in another of their studies, most of the women who had undergone MRI screening for breast cancer said that they would do so again. “MRI is not a pleasant test, but mammography is also not a pleasant test,” she said.
“So many women prefer MRI above mammography, especially because the detection rate with MRI is better than mammography,” she noted. Dr. Heijnsdijk also said that the percentage of women with extremely dense breasts who would be candidates for MRI screening is small – no more than 10% of women.
At a unit cost of slightly under 300 euros for MRI screening – compared with about 100 euros for screening mammography in the Netherlands – the cost of offering 10% of women MRI instead of mammography might increase, but any additional screening costs could be offset by reductions in the need to treat late-stage breast cancer more aggressively.
‘Interval’ cancers
Commenting further on the study, Dr. Kuhl pointed out that from 25% to 45% of cancers that occur in women who have undergone screening mammography are diagnosed as “interval” cancers, even among women who participate in the best mammography programs. “For a long time, people argued that these interval cancers developed only after the last respective mammogram, but that’s not true at all, because we know that with MRI screening, we can reduce the interval cancer rate down to zero,” Dr. Kuhl emphasized.
This is partially explained by the fact that mammography is “particularly blind” when it comes to detecting rapidly growing tumors. “The fact is that mammography has a modality-inherent tendency to preferentially detect slow-growing cancers, whereas rapidly growing tumors are indistinguishable from ubiquitous benign changes like cysts. [This] is why women who undergo screening mammography are frequently not diagnosed with the cancers that we really need to find,” she said.
Although there is ample talk about overdiagnosis when it comes to screening mammography, the overwhelmingly important problem is underdiagnosis. Even in exemplary mammography screening programs, at least 20% of tumors that are diagnosed on mammography have already advanced to a stage that is too late, Dr. Kuhl noted.
This means that at least half of women do not benefit from screening mammography nearly to the extent that they – and their health care practitioners – believe they should, she added. Dr. Kuhl underscored that this does not mean that clinicians should abandon screening mammography.
What it does mean is that physicians need to abandon the one-size-fits-all approach to screening mammography and start stratifying women on the basis of their individual risk of developing breast cancer by taking a family or personal history. Most women do undergo screening mammography at least once, Dr. Kuhl pointed out. From that mammogram, physicians can use information on breast density and breast architecture to better determine individual risk.
“We have good ideas about how to achieve risk stratification, but we’re not using them, because as long as mammography is the answer for everybody, there isn’t much motivation to dig deeper into the issue of how to determine risk,” Dr. Kuhl said.
“But we have to ensure the early diagnosis of aggressive cancers, and it’s exactly MRI that can do this, and we should start with women with very dense breasts because they are doubly underserved by mammography,” she said.
The study was supported by the University Medical Center Utrecht, Bayer HealthCare Medical Care, Matakina, and others. Ms. Geuzinge, Dr. Heijnsdijk, and Dr. Kuhl have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Alternatively, if a woman worries that the 4-year screening interval is too long, screening mammography may be offered every 2 years, with MRI screening offered for the second 2-year interval, according to the findings. This strategy would still require the patient to undergo MRI breast cancer screening every 4 years.
“MRI is more effective not only for selected patients. It is actually more effective than mammography for all women,” editorialist Christiane Kuhl, MD, PhD, University of Aachen (Germany), said in an interview.
“But the superior diagnostic accuracy of MRI is more often needed for women who are at higher risk for breast cancer, and therefore the cost-effectiveness is easier to achieve in women who are at higher risk,” she added.
The study was published online Sept. 29 in the Journal of the National Cancer Institute.
DENSE trial
The simulation model used for the study was based on results from the Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial, which showed that additional MRI screening for women with extremely dense breast tissue led to significantly fewer interval cancers in comparison with mammography alone (P < .001). In the DENSE trial, MRI participants underwent mammography plus MRI at 2-year intervals; the control group underwent mammography alone at 2-year intervals.
In the current study, “screening strategies varied in the number of MRIs and mammograms offered to women aged 50-75 years,” explains Amarens Geuzinge, MSc, University Medical Center, Rotterdam, the Netherlands, and colleagues, “and incremental cost-effectiveness ratios (ICERs) were calculated ... with a willingness-to-pay threshold of 22,000 euros (>$25,000 U.S.),” the investigators add.
Analyses indicated that screening every 2 years with mammography alone cost the least of all strategies that were evaluated, but it also resulted in the lowest number of quality-adjusted life years (QALYs) – in other words, it delivered the least amount of benefit for patients, coauthor Eveline Heijnsdijk, PhD, University Medical Center, Rotterdam, the Netherlands, explained to this news organization.
Offering an additional MRI every 2 years resulted in the highest costs but not the highest number of QALYs and was inferior to the other screening strategies analyzed, she added. Alternating mammography with MRI breast cancer screening, each conducted every 2 years, came close to providing the same benefits to patients as the every-4-year MRI screening strategy, Dr. Heijnsdijk noted.
However, when the authors applied the National Institute for Health and Care Excellence (NICE) threshold, MRI screening every 4 years yielded the highest acceptable incremental cost-effectiveness ratio (ICER), at 15,620 euros per QALYs, whereas screening every 3 years with MRI alone yielded an ICER of 37,181 euros per QALY.
If decision-makers are willing to pay more than 22,000 euros per QALY gained, “MRI every 2 or 3 years can also become cost effective,” the authors add.
Asked how acceptable MRI screening might be if performed only once every 4 years, Dr. Heijnsdijk noted that, in another of their studies, most of the women who had undergone MRI screening for breast cancer said that they would do so again. “MRI is not a pleasant test, but mammography is also not a pleasant test,” she said.
“So many women prefer MRI above mammography, especially because the detection rate with MRI is better than mammography,” she noted. Dr. Heijnsdijk also said that the percentage of women with extremely dense breasts who would be candidates for MRI screening is small – no more than 10% of women.
At a unit cost of slightly under 300 euros for MRI screening – compared with about 100 euros for screening mammography in the Netherlands – the cost of offering 10% of women MRI instead of mammography might increase, but any additional screening costs could be offset by reductions in the need to treat late-stage breast cancer more aggressively.
‘Interval’ cancers
Commenting further on the study, Dr. Kuhl pointed out that from 25% to 45% of cancers that occur in women who have undergone screening mammography are diagnosed as “interval” cancers, even among women who participate in the best mammography programs. “For a long time, people argued that these interval cancers developed only after the last respective mammogram, but that’s not true at all, because we know that with MRI screening, we can reduce the interval cancer rate down to zero,” Dr. Kuhl emphasized.
This is partially explained by the fact that mammography is “particularly blind” when it comes to detecting rapidly growing tumors. “The fact is that mammography has a modality-inherent tendency to preferentially detect slow-growing cancers, whereas rapidly growing tumors are indistinguishable from ubiquitous benign changes like cysts. [This] is why women who undergo screening mammography are frequently not diagnosed with the cancers that we really need to find,” she said.
Although there is ample talk about overdiagnosis when it comes to screening mammography, the overwhelmingly important problem is underdiagnosis. Even in exemplary mammography screening programs, at least 20% of tumors that are diagnosed on mammography have already advanced to a stage that is too late, Dr. Kuhl noted.
This means that at least half of women do not benefit from screening mammography nearly to the extent that they – and their health care practitioners – believe they should, she added. Dr. Kuhl underscored that this does not mean that clinicians should abandon screening mammography.
What it does mean is that physicians need to abandon the one-size-fits-all approach to screening mammography and start stratifying women on the basis of their individual risk of developing breast cancer by taking a family or personal history. Most women do undergo screening mammography at least once, Dr. Kuhl pointed out. From that mammogram, physicians can use information on breast density and breast architecture to better determine individual risk.
“We have good ideas about how to achieve risk stratification, but we’re not using them, because as long as mammography is the answer for everybody, there isn’t much motivation to dig deeper into the issue of how to determine risk,” Dr. Kuhl said.
“But we have to ensure the early diagnosis of aggressive cancers, and it’s exactly MRI that can do this, and we should start with women with very dense breasts because they are doubly underserved by mammography,” she said.
The study was supported by the University Medical Center Utrecht, Bayer HealthCare Medical Care, Matakina, and others. Ms. Geuzinge, Dr. Heijnsdijk, and Dr. Kuhl have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Alternatively, if a woman worries that the 4-year screening interval is too long, screening mammography may be offered every 2 years, with MRI screening offered for the second 2-year interval, according to the findings. This strategy would still require the patient to undergo MRI breast cancer screening every 4 years.
“MRI is more effective not only for selected patients. It is actually more effective than mammography for all women,” editorialist Christiane Kuhl, MD, PhD, University of Aachen (Germany), said in an interview.
“But the superior diagnostic accuracy of MRI is more often needed for women who are at higher risk for breast cancer, and therefore the cost-effectiveness is easier to achieve in women who are at higher risk,” she added.
The study was published online Sept. 29 in the Journal of the National Cancer Institute.
DENSE trial
The simulation model used for the study was based on results from the Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial, which showed that additional MRI screening for women with extremely dense breast tissue led to significantly fewer interval cancers in comparison with mammography alone (P < .001). In the DENSE trial, MRI participants underwent mammography plus MRI at 2-year intervals; the control group underwent mammography alone at 2-year intervals.
In the current study, “screening strategies varied in the number of MRIs and mammograms offered to women aged 50-75 years,” explains Amarens Geuzinge, MSc, University Medical Center, Rotterdam, the Netherlands, and colleagues, “and incremental cost-effectiveness ratios (ICERs) were calculated ... with a willingness-to-pay threshold of 22,000 euros (>$25,000 U.S.),” the investigators add.
Analyses indicated that screening every 2 years with mammography alone cost the least of all strategies that were evaluated, but it also resulted in the lowest number of quality-adjusted life years (QALYs) – in other words, it delivered the least amount of benefit for patients, coauthor Eveline Heijnsdijk, PhD, University Medical Center, Rotterdam, the Netherlands, explained to this news organization.
Offering an additional MRI every 2 years resulted in the highest costs but not the highest number of QALYs and was inferior to the other screening strategies analyzed, she added. Alternating mammography with MRI breast cancer screening, each conducted every 2 years, came close to providing the same benefits to patients as the every-4-year MRI screening strategy, Dr. Heijnsdijk noted.
However, when the authors applied the National Institute for Health and Care Excellence (NICE) threshold, MRI screening every 4 years yielded the highest acceptable incremental cost-effectiveness ratio (ICER), at 15,620 euros per QALYs, whereas screening every 3 years with MRI alone yielded an ICER of 37,181 euros per QALY.
If decision-makers are willing to pay more than 22,000 euros per QALY gained, “MRI every 2 or 3 years can also become cost effective,” the authors add.
Asked how acceptable MRI screening might be if performed only once every 4 years, Dr. Heijnsdijk noted that, in another of their studies, most of the women who had undergone MRI screening for breast cancer said that they would do so again. “MRI is not a pleasant test, but mammography is also not a pleasant test,” she said.
“So many women prefer MRI above mammography, especially because the detection rate with MRI is better than mammography,” she noted. Dr. Heijnsdijk also said that the percentage of women with extremely dense breasts who would be candidates for MRI screening is small – no more than 10% of women.
At a unit cost of slightly under 300 euros for MRI screening – compared with about 100 euros for screening mammography in the Netherlands – the cost of offering 10% of women MRI instead of mammography might increase, but any additional screening costs could be offset by reductions in the need to treat late-stage breast cancer more aggressively.
‘Interval’ cancers
Commenting further on the study, Dr. Kuhl pointed out that from 25% to 45% of cancers that occur in women who have undergone screening mammography are diagnosed as “interval” cancers, even among women who participate in the best mammography programs. “For a long time, people argued that these interval cancers developed only after the last respective mammogram, but that’s not true at all, because we know that with MRI screening, we can reduce the interval cancer rate down to zero,” Dr. Kuhl emphasized.
This is partially explained by the fact that mammography is “particularly blind” when it comes to detecting rapidly growing tumors. “The fact is that mammography has a modality-inherent tendency to preferentially detect slow-growing cancers, whereas rapidly growing tumors are indistinguishable from ubiquitous benign changes like cysts. [This] is why women who undergo screening mammography are frequently not diagnosed with the cancers that we really need to find,” she said.
Although there is ample talk about overdiagnosis when it comes to screening mammography, the overwhelmingly important problem is underdiagnosis. Even in exemplary mammography screening programs, at least 20% of tumors that are diagnosed on mammography have already advanced to a stage that is too late, Dr. Kuhl noted.
This means that at least half of women do not benefit from screening mammography nearly to the extent that they – and their health care practitioners – believe they should, she added. Dr. Kuhl underscored that this does not mean that clinicians should abandon screening mammography.
What it does mean is that physicians need to abandon the one-size-fits-all approach to screening mammography and start stratifying women on the basis of their individual risk of developing breast cancer by taking a family or personal history. Most women do undergo screening mammography at least once, Dr. Kuhl pointed out. From that mammogram, physicians can use information on breast density and breast architecture to better determine individual risk.
“We have good ideas about how to achieve risk stratification, but we’re not using them, because as long as mammography is the answer for everybody, there isn’t much motivation to dig deeper into the issue of how to determine risk,” Dr. Kuhl said.
“But we have to ensure the early diagnosis of aggressive cancers, and it’s exactly MRI that can do this, and we should start with women with very dense breasts because they are doubly underserved by mammography,” she said.
The study was supported by the University Medical Center Utrecht, Bayer HealthCare Medical Care, Matakina, and others. Ms. Geuzinge, Dr. Heijnsdijk, and Dr. Kuhl have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Opioid prescriptions following Mohs surgery dropped over the last decade
by 26.3% between 2009 and 2020, according to a cross-sectional analysis of national insurance claims data.
The findings suggest that dermatologic surgeons generally understood opioid prescription risks and public health warnings about the opioid epidemic, corresponding study author Surya A. Veerabagu said in an interview.
“The frequency of opioid prescriptions after Mohs surgery went up a little bit from 2009 to 2011, but then it subsequently decreased,” said Ms. Veerabagu, a 4th-year student at Tulane University, New Orleans. “It very much correlates with the overarching opioid trends of the time. From 2010 to 2015, research questioning the safety of opioids increased and in 2012, national prescriptions claims for opioids began to decrease. More media outlets voiced concerns over the growing opioid epidemic, as well.”
As she and her associates noted in their study, published online Sept. 22 in JAMA Dermatology, sales of opioids skyrocketed, increasing by 400% from 1999 to 2011, while prescription opioid–related deaths exceeded deaths caused by heroin and cocaine combined.
“In 2016, the U.S. Department of Health and Human Services declared the opioid epidemic a public health emergency, and the Centers for Disease Control and Prevention released guidelines to curtail unnecessary opioid prescriptions,” they wrote. “Unfortunately, overdose deaths involving prescription opioids continued to increase even after these measures.”
The researchers drew from Optum Clinformatics Data Mart (Optum CDM), a nationally representative insurance claims database, and limited the analysis to 358,012 adults who underwent Mohs surgery and obtained an opioid prescription within 2 days of surgery in the United States from Jan. 1, 2009, to June 1, 2020. They found that 34.6% of patients underwent Mohs surgery with opioid claims in 2009. This rose to a peak of 39.6% in 2011, then decreased annually to a rate of 11.7% in 2020.
The four opioids obtained most during the study period were hydrocodone (55%), codeine (16.3%), oxycodone (12%), and tramadol (11.6%). However, over time, the proportion of patients who obtained hydrocodone fell 21.7% from a peak of 67.1% in 2011 to 45.4% in 2020, while the proportion of patients who obtained tramadol – generally recognized as a safer option – increased 26.3% from a low of 1.6% in 2009 to 27.9% in 2020.
“The switch from very addictive opioids like hydrocodone and oxycodone to weaker opioids like tramadol was fascinating to see,” said Ms. Veerabagu, who conducted the study during her research fellowship in the department of dermatology at the University of Pennsylvania, Philadelphia. “I remember at first thinking I had coded the data wrong. I reviewed the results with the team to ensure it was correct. We noticed that propoxyphene prescriptions suddenly dropped to 0% in 2011.” She found that the FDA warning in 2010 and recall regarding the use of propoxyphene because of cardiotoxicity correlated with her data, which, “in addition to the thorough review, convinced me that my coding was correct.” Prior to 2011, propoxyphene constituted 28% of prescriptions in 2009 and 24% of prescriptions in 2010.
In an interview, Maryam M. Asgari, MD, professor of dermatology at Harvard Medical School, Boston, said that the findings support recent opioid prescription recommendations following Mohs and other dermatologic procedures from professional societies including those from the American College of Mohs Surgery.
“More awareness has been raised in the past decade regarding the opioid epidemic and the rise of opioid abuse and deaths,” she said. “There has been increased scrutiny on procedures and prescribing of opioids post procedures.”
State-led efforts to lower the number of opioid prescriptions also play a role. For example, in 2016, Massachusetts launched the Massachusetts Prescription Awareness Tool (MassPAT), which imposes a 7-day limit on first-time prescriptions of opioids to patients and mandates that all prescribers check the prescription drug monitoring program before prescribing schedule II or III substances.
“The MassPAT system also gives you quarterly data on how your opioid prescriptions compare with those of your peers within your specialty and subspecialty,” Dr. Asgari said. “If you’re an outlier, I think that quickly leads you to change your prescribing patterns.”
Dr. Asgari noted that most opioids prescribed in the study by Ms. Veerabagu and colleagues were for cancers that arose on the head and neck. “There is still a perception among providers that cancers that arise in those anatomic sites can potentially cause more discomfort for the patient,” she said. “So, knowing more about the degree of pain among the head and neck cases would be an area of knowledge that would help provider behavior down the line.”
Ms. Veerabagu acknowledged certain limitations of the study, including the fact that unfilled prescriptions could not be accounted for, nor could opioids not taken or those obtained without a prescription. “We cannot survey patients in insurance claims database studies, so we have no way of knowing if everyone’s pain was adequately controlled from 2009 to 2020,” she said.
“The main takeaway message is to make sure doctors and patients share an open dialogue,” she added. “Informing patients of the major pros and cons of the appropriate postoperative pain management options available, including opioids’ addiction potential, is crucial. We hope our study adds to the larger continuing conversation of opioid usage within dermatology.”
The study’s senior author was Cerrene N. Giordano, MD, of the department of dermatology at the Hospital of the University of Pennsylvania, Philadelphia. Coauthor Jeremy R. Etzkorn, MD, is supported by a Dermatology Foundation Career Development Award in Dermatologic Surgery; coauthor Megan H. Noe, MD, MPH, reported receiving grants from Boehringer Ingelheim outside the submitted work. Another coauthor, Thuzar M. Shin, MD, PhD, reported receiving grants from Regeneron outside the submitted work. Dr. Asgari disclosed that she has received support from the Melanoma Research Alliance. She also contributes a chapter on skin cancer to UpToDate, for which she receives royalties.
by 26.3% between 2009 and 2020, according to a cross-sectional analysis of national insurance claims data.
The findings suggest that dermatologic surgeons generally understood opioid prescription risks and public health warnings about the opioid epidemic, corresponding study author Surya A. Veerabagu said in an interview.
“The frequency of opioid prescriptions after Mohs surgery went up a little bit from 2009 to 2011, but then it subsequently decreased,” said Ms. Veerabagu, a 4th-year student at Tulane University, New Orleans. “It very much correlates with the overarching opioid trends of the time. From 2010 to 2015, research questioning the safety of opioids increased and in 2012, national prescriptions claims for opioids began to decrease. More media outlets voiced concerns over the growing opioid epidemic, as well.”
As she and her associates noted in their study, published online Sept. 22 in JAMA Dermatology, sales of opioids skyrocketed, increasing by 400% from 1999 to 2011, while prescription opioid–related deaths exceeded deaths caused by heroin and cocaine combined.
“In 2016, the U.S. Department of Health and Human Services declared the opioid epidemic a public health emergency, and the Centers for Disease Control and Prevention released guidelines to curtail unnecessary opioid prescriptions,” they wrote. “Unfortunately, overdose deaths involving prescription opioids continued to increase even after these measures.”
The researchers drew from Optum Clinformatics Data Mart (Optum CDM), a nationally representative insurance claims database, and limited the analysis to 358,012 adults who underwent Mohs surgery and obtained an opioid prescription within 2 days of surgery in the United States from Jan. 1, 2009, to June 1, 2020. They found that 34.6% of patients underwent Mohs surgery with opioid claims in 2009. This rose to a peak of 39.6% in 2011, then decreased annually to a rate of 11.7% in 2020.
The four opioids obtained most during the study period were hydrocodone (55%), codeine (16.3%), oxycodone (12%), and tramadol (11.6%). However, over time, the proportion of patients who obtained hydrocodone fell 21.7% from a peak of 67.1% in 2011 to 45.4% in 2020, while the proportion of patients who obtained tramadol – generally recognized as a safer option – increased 26.3% from a low of 1.6% in 2009 to 27.9% in 2020.
“The switch from very addictive opioids like hydrocodone and oxycodone to weaker opioids like tramadol was fascinating to see,” said Ms. Veerabagu, who conducted the study during her research fellowship in the department of dermatology at the University of Pennsylvania, Philadelphia. “I remember at first thinking I had coded the data wrong. I reviewed the results with the team to ensure it was correct. We noticed that propoxyphene prescriptions suddenly dropped to 0% in 2011.” She found that the FDA warning in 2010 and recall regarding the use of propoxyphene because of cardiotoxicity correlated with her data, which, “in addition to the thorough review, convinced me that my coding was correct.” Prior to 2011, propoxyphene constituted 28% of prescriptions in 2009 and 24% of prescriptions in 2010.
In an interview, Maryam M. Asgari, MD, professor of dermatology at Harvard Medical School, Boston, said that the findings support recent opioid prescription recommendations following Mohs and other dermatologic procedures from professional societies including those from the American College of Mohs Surgery.
“More awareness has been raised in the past decade regarding the opioid epidemic and the rise of opioid abuse and deaths,” she said. “There has been increased scrutiny on procedures and prescribing of opioids post procedures.”
State-led efforts to lower the number of opioid prescriptions also play a role. For example, in 2016, Massachusetts launched the Massachusetts Prescription Awareness Tool (MassPAT), which imposes a 7-day limit on first-time prescriptions of opioids to patients and mandates that all prescribers check the prescription drug monitoring program before prescribing schedule II or III substances.
“The MassPAT system also gives you quarterly data on how your opioid prescriptions compare with those of your peers within your specialty and subspecialty,” Dr. Asgari said. “If you’re an outlier, I think that quickly leads you to change your prescribing patterns.”
Dr. Asgari noted that most opioids prescribed in the study by Ms. Veerabagu and colleagues were for cancers that arose on the head and neck. “There is still a perception among providers that cancers that arise in those anatomic sites can potentially cause more discomfort for the patient,” she said. “So, knowing more about the degree of pain among the head and neck cases would be an area of knowledge that would help provider behavior down the line.”
Ms. Veerabagu acknowledged certain limitations of the study, including the fact that unfilled prescriptions could not be accounted for, nor could opioids not taken or those obtained without a prescription. “We cannot survey patients in insurance claims database studies, so we have no way of knowing if everyone’s pain was adequately controlled from 2009 to 2020,” she said.
“The main takeaway message is to make sure doctors and patients share an open dialogue,” she added. “Informing patients of the major pros and cons of the appropriate postoperative pain management options available, including opioids’ addiction potential, is crucial. We hope our study adds to the larger continuing conversation of opioid usage within dermatology.”
The study’s senior author was Cerrene N. Giordano, MD, of the department of dermatology at the Hospital of the University of Pennsylvania, Philadelphia. Coauthor Jeremy R. Etzkorn, MD, is supported by a Dermatology Foundation Career Development Award in Dermatologic Surgery; coauthor Megan H. Noe, MD, MPH, reported receiving grants from Boehringer Ingelheim outside the submitted work. Another coauthor, Thuzar M. Shin, MD, PhD, reported receiving grants from Regeneron outside the submitted work. Dr. Asgari disclosed that she has received support from the Melanoma Research Alliance. She also contributes a chapter on skin cancer to UpToDate, for which she receives royalties.
by 26.3% between 2009 and 2020, according to a cross-sectional analysis of national insurance claims data.
The findings suggest that dermatologic surgeons generally understood opioid prescription risks and public health warnings about the opioid epidemic, corresponding study author Surya A. Veerabagu said in an interview.
“The frequency of opioid prescriptions after Mohs surgery went up a little bit from 2009 to 2011, but then it subsequently decreased,” said Ms. Veerabagu, a 4th-year student at Tulane University, New Orleans. “It very much correlates with the overarching opioid trends of the time. From 2010 to 2015, research questioning the safety of opioids increased and in 2012, national prescriptions claims for opioids began to decrease. More media outlets voiced concerns over the growing opioid epidemic, as well.”
As she and her associates noted in their study, published online Sept. 22 in JAMA Dermatology, sales of opioids skyrocketed, increasing by 400% from 1999 to 2011, while prescription opioid–related deaths exceeded deaths caused by heroin and cocaine combined.
“In 2016, the U.S. Department of Health and Human Services declared the opioid epidemic a public health emergency, and the Centers for Disease Control and Prevention released guidelines to curtail unnecessary opioid prescriptions,” they wrote. “Unfortunately, overdose deaths involving prescription opioids continued to increase even after these measures.”
The researchers drew from Optum Clinformatics Data Mart (Optum CDM), a nationally representative insurance claims database, and limited the analysis to 358,012 adults who underwent Mohs surgery and obtained an opioid prescription within 2 days of surgery in the United States from Jan. 1, 2009, to June 1, 2020. They found that 34.6% of patients underwent Mohs surgery with opioid claims in 2009. This rose to a peak of 39.6% in 2011, then decreased annually to a rate of 11.7% in 2020.
The four opioids obtained most during the study period were hydrocodone (55%), codeine (16.3%), oxycodone (12%), and tramadol (11.6%). However, over time, the proportion of patients who obtained hydrocodone fell 21.7% from a peak of 67.1% in 2011 to 45.4% in 2020, while the proportion of patients who obtained tramadol – generally recognized as a safer option – increased 26.3% from a low of 1.6% in 2009 to 27.9% in 2020.
“The switch from very addictive opioids like hydrocodone and oxycodone to weaker opioids like tramadol was fascinating to see,” said Ms. Veerabagu, who conducted the study during her research fellowship in the department of dermatology at the University of Pennsylvania, Philadelphia. “I remember at first thinking I had coded the data wrong. I reviewed the results with the team to ensure it was correct. We noticed that propoxyphene prescriptions suddenly dropped to 0% in 2011.” She found that the FDA warning in 2010 and recall regarding the use of propoxyphene because of cardiotoxicity correlated with her data, which, “in addition to the thorough review, convinced me that my coding was correct.” Prior to 2011, propoxyphene constituted 28% of prescriptions in 2009 and 24% of prescriptions in 2010.
In an interview, Maryam M. Asgari, MD, professor of dermatology at Harvard Medical School, Boston, said that the findings support recent opioid prescription recommendations following Mohs and other dermatologic procedures from professional societies including those from the American College of Mohs Surgery.
“More awareness has been raised in the past decade regarding the opioid epidemic and the rise of opioid abuse and deaths,” she said. “There has been increased scrutiny on procedures and prescribing of opioids post procedures.”
State-led efforts to lower the number of opioid prescriptions also play a role. For example, in 2016, Massachusetts launched the Massachusetts Prescription Awareness Tool (MassPAT), which imposes a 7-day limit on first-time prescriptions of opioids to patients and mandates that all prescribers check the prescription drug monitoring program before prescribing schedule II or III substances.
“The MassPAT system also gives you quarterly data on how your opioid prescriptions compare with those of your peers within your specialty and subspecialty,” Dr. Asgari said. “If you’re an outlier, I think that quickly leads you to change your prescribing patterns.”
Dr. Asgari noted that most opioids prescribed in the study by Ms. Veerabagu and colleagues were for cancers that arose on the head and neck. “There is still a perception among providers that cancers that arise in those anatomic sites can potentially cause more discomfort for the patient,” she said. “So, knowing more about the degree of pain among the head and neck cases would be an area of knowledge that would help provider behavior down the line.”
Ms. Veerabagu acknowledged certain limitations of the study, including the fact that unfilled prescriptions could not be accounted for, nor could opioids not taken or those obtained without a prescription. “We cannot survey patients in insurance claims database studies, so we have no way of knowing if everyone’s pain was adequately controlled from 2009 to 2020,” she said.
“The main takeaway message is to make sure doctors and patients share an open dialogue,” she added. “Informing patients of the major pros and cons of the appropriate postoperative pain management options available, including opioids’ addiction potential, is crucial. We hope our study adds to the larger continuing conversation of opioid usage within dermatology.”
The study’s senior author was Cerrene N. Giordano, MD, of the department of dermatology at the Hospital of the University of Pennsylvania, Philadelphia. Coauthor Jeremy R. Etzkorn, MD, is supported by a Dermatology Foundation Career Development Award in Dermatologic Surgery; coauthor Megan H. Noe, MD, MPH, reported receiving grants from Boehringer Ingelheim outside the submitted work. Another coauthor, Thuzar M. Shin, MD, PhD, reported receiving grants from Regeneron outside the submitted work. Dr. Asgari disclosed that she has received support from the Melanoma Research Alliance. She also contributes a chapter on skin cancer to UpToDate, for which she receives royalties.
FROM JAMA DERMATOLOGY
Evaluating the Impact of a Simulated Hypersensitivity Reaction Case Study for New Fellows and Chemotherapy Nurses in an Outpatient Infusion Clinic
Background
All chemotherapeutic agents have potential to cause infusion reactions. Our primary objective was to develop a project to assist in appropriate training of nursing staff and incoming fellows for clinic efficiency and patient safety.
Methods
A multi-disciplinary team, including physicians, nurses, and a pharmacist met and following a pre-assessment, a pareto chart was created to determine where to focus our efforts. The results revealed the following areas of concern from most important to least important: utilization of an infusion reaction “kit,” team discussion with staff, infusion reaction simulation, a competency checklist for reactions and “other.” Other responses included: reaction orders in the chart, hands on scenarios, and continued reinforcements. The team resolved to conduct an infusion reaction simulation program to provide an environment to meet many needs of the team, new and experienced. Set in the outpatient infusion center, the program included: a patient/actor, a facilitator, infusion nursing staff, and physicians/fellows. Physicians were invited to participate in the training, but infusion staff were unaware of the program to provide another real life aspect to the simulation; however, both were blinded to the scenario. The pharmacist facilitated the event where the patient actor proceeded to start with a minor infusion reaction that progressed to full anaphylaxis.
Results
Using a Likert scale, a post simulation assessment included 6 questions: 90% of participants felt strongly the exercise increased awareness of the infusion reaction e-kit, 80% felt strongly the exercise was meaningful to their practice, 90% strongly agreed or agreed the scenario simulated a real life situation, also 90% strongly agreed or agreed the program helped them think critically. Finally, 100% of participants strongly agreed or agreed they felt confident in their ability to intervene in the event of a hypersensitivity reaction. Our objectives were achieved: identify the signs and symptoms of a hypersensitivity reaction, utilize the proper intervention in the event of a hypersensitivity reaction. Other outcomes include an updated chemotherapy order consult complete with standing reaction orders in the medical record.
Conclusion
Ultimately, our interdisciplinary simulation concluded with increased awareness, improved confidence, and strengthened collaboration, communication and accountability among our infusion staff and oncology providers
Background
All chemotherapeutic agents have potential to cause infusion reactions. Our primary objective was to develop a project to assist in appropriate training of nursing staff and incoming fellows for clinic efficiency and patient safety.
Methods
A multi-disciplinary team, including physicians, nurses, and a pharmacist met and following a pre-assessment, a pareto chart was created to determine where to focus our efforts. The results revealed the following areas of concern from most important to least important: utilization of an infusion reaction “kit,” team discussion with staff, infusion reaction simulation, a competency checklist for reactions and “other.” Other responses included: reaction orders in the chart, hands on scenarios, and continued reinforcements. The team resolved to conduct an infusion reaction simulation program to provide an environment to meet many needs of the team, new and experienced. Set in the outpatient infusion center, the program included: a patient/actor, a facilitator, infusion nursing staff, and physicians/fellows. Physicians were invited to participate in the training, but infusion staff were unaware of the program to provide another real life aspect to the simulation; however, both were blinded to the scenario. The pharmacist facilitated the event where the patient actor proceeded to start with a minor infusion reaction that progressed to full anaphylaxis.
Results
Using a Likert scale, a post simulation assessment included 6 questions: 90% of participants felt strongly the exercise increased awareness of the infusion reaction e-kit, 80% felt strongly the exercise was meaningful to their practice, 90% strongly agreed or agreed the scenario simulated a real life situation, also 90% strongly agreed or agreed the program helped them think critically. Finally, 100% of participants strongly agreed or agreed they felt confident in their ability to intervene in the event of a hypersensitivity reaction. Our objectives were achieved: identify the signs and symptoms of a hypersensitivity reaction, utilize the proper intervention in the event of a hypersensitivity reaction. Other outcomes include an updated chemotherapy order consult complete with standing reaction orders in the medical record.
Conclusion
Ultimately, our interdisciplinary simulation concluded with increased awareness, improved confidence, and strengthened collaboration, communication and accountability among our infusion staff and oncology providers
Background
All chemotherapeutic agents have potential to cause infusion reactions. Our primary objective was to develop a project to assist in appropriate training of nursing staff and incoming fellows for clinic efficiency and patient safety.
Methods
A multi-disciplinary team, including physicians, nurses, and a pharmacist met and following a pre-assessment, a pareto chart was created to determine where to focus our efforts. The results revealed the following areas of concern from most important to least important: utilization of an infusion reaction “kit,” team discussion with staff, infusion reaction simulation, a competency checklist for reactions and “other.” Other responses included: reaction orders in the chart, hands on scenarios, and continued reinforcements. The team resolved to conduct an infusion reaction simulation program to provide an environment to meet many needs of the team, new and experienced. Set in the outpatient infusion center, the program included: a patient/actor, a facilitator, infusion nursing staff, and physicians/fellows. Physicians were invited to participate in the training, but infusion staff were unaware of the program to provide another real life aspect to the simulation; however, both were blinded to the scenario. The pharmacist facilitated the event where the patient actor proceeded to start with a minor infusion reaction that progressed to full anaphylaxis.
Results
Using a Likert scale, a post simulation assessment included 6 questions: 90% of participants felt strongly the exercise increased awareness of the infusion reaction e-kit, 80% felt strongly the exercise was meaningful to their practice, 90% strongly agreed or agreed the scenario simulated a real life situation, also 90% strongly agreed or agreed the program helped them think critically. Finally, 100% of participants strongly agreed or agreed they felt confident in their ability to intervene in the event of a hypersensitivity reaction. Our objectives were achieved: identify the signs and symptoms of a hypersensitivity reaction, utilize the proper intervention in the event of a hypersensitivity reaction. Other outcomes include an updated chemotherapy order consult complete with standing reaction orders in the medical record.
Conclusion
Ultimately, our interdisciplinary simulation concluded with increased awareness, improved confidence, and strengthened collaboration, communication and accountability among our infusion staff and oncology providers
Extending Maintenance Flush Intervals for Implanted Ports at VA Northeast Ohio Healthcare System (VANEOHS)
At the beginning of the COVID-19 pandemic, the Hematology Oncology Department at VANEOHS looked for ways to continue safe oncologic care delivery while limiting unnecessary in-person visits for our Veterans. The Hematology Oncology team considered extending the interval between maintenance flushes for implanted ports, however wanted to confirm the change aligned with safe practice recommendations. A literature review supported changing the medical center’s current practice of maintenance flushing from every four to six weeks to every twelve weeks. The literature review suggested that this change was safe and effective. Our goal was to ensure this change in practice did not cause an increase in alteplase usage or an increase in port related complications such as infection. A pre-intervention data review from August 1, 2019 to February 2, 2020 (n = 217) showed that 8 orders (4%) were placed for alteplase for oncology patients receiving maintenance port flushes and there were no implanted port infections reported during that timeframe. Interventions included: updating the implanted port order set in Computerized Patient Record System (CPRS) and providing education to Veterans and nurses regarding the change. A post-intervention data review from August 1, 2020 to February 28, 2021 (n = 94) demonstrated that 2 orders (2%) were placed for alteplase for oncology patients receiving maintenance port flushes and there were no implanted port infections reported during that timeframe. This trial confirmed that an implanted port flush maintenance schedule of up to twelve weeks aligned with safe practice recommendations and did not increase port related complications. Due to the positive outcome of implementing an extended interval between maintenance port flushes the medic
At the beginning of the COVID-19 pandemic, the Hematology Oncology Department at VANEOHS looked for ways to continue safe oncologic care delivery while limiting unnecessary in-person visits for our Veterans. The Hematology Oncology team considered extending the interval between maintenance flushes for implanted ports, however wanted to confirm the change aligned with safe practice recommendations. A literature review supported changing the medical center’s current practice of maintenance flushing from every four to six weeks to every twelve weeks. The literature review suggested that this change was safe and effective. Our goal was to ensure this change in practice did not cause an increase in alteplase usage or an increase in port related complications such as infection. A pre-intervention data review from August 1, 2019 to February 2, 2020 (n = 217) showed that 8 orders (4%) were placed for alteplase for oncology patients receiving maintenance port flushes and there were no implanted port infections reported during that timeframe. Interventions included: updating the implanted port order set in Computerized Patient Record System (CPRS) and providing education to Veterans and nurses regarding the change. A post-intervention data review from August 1, 2020 to February 28, 2021 (n = 94) demonstrated that 2 orders (2%) were placed for alteplase for oncology patients receiving maintenance port flushes and there were no implanted port infections reported during that timeframe. This trial confirmed that an implanted port flush maintenance schedule of up to twelve weeks aligned with safe practice recommendations and did not increase port related complications. Due to the positive outcome of implementing an extended interval between maintenance port flushes the medic
At the beginning of the COVID-19 pandemic, the Hematology Oncology Department at VANEOHS looked for ways to continue safe oncologic care delivery while limiting unnecessary in-person visits for our Veterans. The Hematology Oncology team considered extending the interval between maintenance flushes for implanted ports, however wanted to confirm the change aligned with safe practice recommendations. A literature review supported changing the medical center’s current practice of maintenance flushing from every four to six weeks to every twelve weeks. The literature review suggested that this change was safe and effective. Our goal was to ensure this change in practice did not cause an increase in alteplase usage or an increase in port related complications such as infection. A pre-intervention data review from August 1, 2019 to February 2, 2020 (n = 217) showed that 8 orders (4%) were placed for alteplase for oncology patients receiving maintenance port flushes and there were no implanted port infections reported during that timeframe. Interventions included: updating the implanted port order set in Computerized Patient Record System (CPRS) and providing education to Veterans and nurses regarding the change. A post-intervention data review from August 1, 2020 to February 28, 2021 (n = 94) demonstrated that 2 orders (2%) were placed for alteplase for oncology patients receiving maintenance port flushes and there were no implanted port infections reported during that timeframe. This trial confirmed that an implanted port flush maintenance schedule of up to twelve weeks aligned with safe practice recommendations and did not increase port related complications. Due to the positive outcome of implementing an extended interval between maintenance port flushes the medic
Pembrolizumab Dose Conversion Adoption and Immune-Mediated Adverse Events
Background/Purpose
On April 28, 2020, the Food and Drug Administration approved pembrolizumab 400mg intravenous (IV) every 6 weeks. This dosing update was rapidly adopted by VA Northeast Ohio Healthcare System (VANEOHS) hematology/oncology providers to minimize infusion appointments, for patient convenience and COVID precautions. On May 1, 2020, pembrolizumab order set templates were updated to reflect the extended interval dosing, however providers are still able to change orders to 200mg IV every 3 weeks if needed. Due to administration of higher pembrolizumab doses, there could be increased development of immune-mediated adverse events (IrAEs). This review quantified the clinic visits saved at VANEOHS by adoption of pembrolizumab 400mg dosing and report adverse events that resulted in pembrolizumab dose reduction.
Methods
A report of all pembrolizumab orders from May 1, 2020 to May 1, 2021 was obtained. All pembrolizumab 200mg orders were reviewed to evaluate reasoning for the use of the 200mg dose. A retrospective chart review was performed for patients who required a pembrolizumab dose reduction to evaluate safety. Descriptive statistics were used.
Results
There was a total of 277 pembrolizumab orders from May 1, 2020 to May 1, 2021. Of these orders, 211 (76%) were converted to pembrolizumab 400mg IV every 6 weeks, while 66 (24%) orders remained at pembrolizumab 200mg IV every 3 weeks. It is estimated that there were 211 infusion appointments avoided due to the conversion to pembrolizumab 400mg IV every 6-week dosing. The 277 pembrolizumab orders were used to treat 77 unique patients. Eighteen patients continued to receive pembrolizumab 200mg following the conversion. Sixteen of these patients were maintained on pembrolizumab 200mg due to concomitant chemotherapy schedules. One patient was receiving pembrolizumab 200mg based on clinical trial dosing. One patient returned to pembrolizumab 200mg due to an increase in drainage from pleurx catheter while receiving 400mg dose.
Implications
The conversion from pembrolizumab 200mg every 3 weeks to pembrolizumab 400mg every 6 weeks avoided approximately 200 infusion appointments without an increase in safety concerns. This supporting data may aid in supporting extended interval dosing of other immunotherapy agents.
Background/Purpose
On April 28, 2020, the Food and Drug Administration approved pembrolizumab 400mg intravenous (IV) every 6 weeks. This dosing update was rapidly adopted by VA Northeast Ohio Healthcare System (VANEOHS) hematology/oncology providers to minimize infusion appointments, for patient convenience and COVID precautions. On May 1, 2020, pembrolizumab order set templates were updated to reflect the extended interval dosing, however providers are still able to change orders to 200mg IV every 3 weeks if needed. Due to administration of higher pembrolizumab doses, there could be increased development of immune-mediated adverse events (IrAEs). This review quantified the clinic visits saved at VANEOHS by adoption of pembrolizumab 400mg dosing and report adverse events that resulted in pembrolizumab dose reduction.
Methods
A report of all pembrolizumab orders from May 1, 2020 to May 1, 2021 was obtained. All pembrolizumab 200mg orders were reviewed to evaluate reasoning for the use of the 200mg dose. A retrospective chart review was performed for patients who required a pembrolizumab dose reduction to evaluate safety. Descriptive statistics were used.
Results
There was a total of 277 pembrolizumab orders from May 1, 2020 to May 1, 2021. Of these orders, 211 (76%) were converted to pembrolizumab 400mg IV every 6 weeks, while 66 (24%) orders remained at pembrolizumab 200mg IV every 3 weeks. It is estimated that there were 211 infusion appointments avoided due to the conversion to pembrolizumab 400mg IV every 6-week dosing. The 277 pembrolizumab orders were used to treat 77 unique patients. Eighteen patients continued to receive pembrolizumab 200mg following the conversion. Sixteen of these patients were maintained on pembrolizumab 200mg due to concomitant chemotherapy schedules. One patient was receiving pembrolizumab 200mg based on clinical trial dosing. One patient returned to pembrolizumab 200mg due to an increase in drainage from pleurx catheter while receiving 400mg dose.
Implications
The conversion from pembrolizumab 200mg every 3 weeks to pembrolizumab 400mg every 6 weeks avoided approximately 200 infusion appointments without an increase in safety concerns. This supporting data may aid in supporting extended interval dosing of other immunotherapy agents.
Background/Purpose
On April 28, 2020, the Food and Drug Administration approved pembrolizumab 400mg intravenous (IV) every 6 weeks. This dosing update was rapidly adopted by VA Northeast Ohio Healthcare System (VANEOHS) hematology/oncology providers to minimize infusion appointments, for patient convenience and COVID precautions. On May 1, 2020, pembrolizumab order set templates were updated to reflect the extended interval dosing, however providers are still able to change orders to 200mg IV every 3 weeks if needed. Due to administration of higher pembrolizumab doses, there could be increased development of immune-mediated adverse events (IrAEs). This review quantified the clinic visits saved at VANEOHS by adoption of pembrolizumab 400mg dosing and report adverse events that resulted in pembrolizumab dose reduction.
Methods
A report of all pembrolizumab orders from May 1, 2020 to May 1, 2021 was obtained. All pembrolizumab 200mg orders were reviewed to evaluate reasoning for the use of the 200mg dose. A retrospective chart review was performed for patients who required a pembrolizumab dose reduction to evaluate safety. Descriptive statistics were used.
Results
There was a total of 277 pembrolizumab orders from May 1, 2020 to May 1, 2021. Of these orders, 211 (76%) were converted to pembrolizumab 400mg IV every 6 weeks, while 66 (24%) orders remained at pembrolizumab 200mg IV every 3 weeks. It is estimated that there were 211 infusion appointments avoided due to the conversion to pembrolizumab 400mg IV every 6-week dosing. The 277 pembrolizumab orders were used to treat 77 unique patients. Eighteen patients continued to receive pembrolizumab 200mg following the conversion. Sixteen of these patients were maintained on pembrolizumab 200mg due to concomitant chemotherapy schedules. One patient was receiving pembrolizumab 200mg based on clinical trial dosing. One patient returned to pembrolizumab 200mg due to an increase in drainage from pleurx catheter while receiving 400mg dose.
Implications
The conversion from pembrolizumab 200mg every 3 weeks to pembrolizumab 400mg every 6 weeks avoided approximately 200 infusion appointments without an increase in safety concerns. This supporting data may aid in supporting extended interval dosing of other immunotherapy agents.
Novel and Alternative Strategies for Management of Panitumumab-Induced Hypomagnesemia
Background
Panitumumab is an epidermal growth factor receptor (EGFR) inhibiting monoclonal antibody approved for the treatment of RAS wild-type metastatic colorectal cancer (mCRC), which has an incidence of hypomagnesemia of approximately 35%. Grade 3 or 4 hypomagnesemia occurs in roughly 7% of patients, which can lead to serious complications such as seizures and arrhythmias. In one study, hypomagnesemia led to discontinuation of targeted therapy in 3% of patients. Currently, there is no standardized prophylactic strategy or treatment protocol for panitumumab-induced hypomagnesemia. In cases of refractory hypomagnesemia, it is recommended to discontinue panitumumab, even if the patient is deriving clinical benefit.
Case Report
This 59-year-old male was diagnosed with RAS wild-type mCRC and had already progressed through multiple lines of treatment. Panitumumab was initiated with good response; however, the drug was discontinued due to grade 4 hypomagnesemia, despite intravenous and oral supplementation. As the patient progressed through further lines of treatment, the decision was made to retry panitumumab. Grade 2-3 hypomagnesemia persisted throughout treatment, requiring frequent magnesium infusions. Innovative and alternative treatment options were investigated in an effort to improve his quality of life. In addition to oral and intravenous magnesium replacement, an ambulatory elastomeric pump, traditionally used for fluorouracil administration, was repurposed to deliver between 6 and 24 grams of magnesium sulfate over 24 to 72 hours. The pump was generally well tolerated with the exception of mild skin irritation around the port site, which prevented a transition to longer infusion times. The ambulatory elastomeric pump decreased the frequency of healthcare visits and improved the hypomagnesemia sufficiently to continue treatment with panitumumab, although levels did not fully normalize. A two-week trial of amiloride was also attempted to decrease renal magnesium wasting. Amiloride normalized magnesium levels but had to be discontinued due to asymptomatic hyperkalemia. This case report suggests that amiloride and magnesium replacement via ambulatory elastomeric pumps may be safe and effective treatment options for panitumumab-induced refractory hypomagnesemia in mCRC, potentially improving quality of life and allowing beneficial anti-cancer treatments to continue. Future studies should further evaluate optimization of amiloride and intravenous magnesium replacement via ambulatory elastomeric pump.
Background
Panitumumab is an epidermal growth factor receptor (EGFR) inhibiting monoclonal antibody approved for the treatment of RAS wild-type metastatic colorectal cancer (mCRC), which has an incidence of hypomagnesemia of approximately 35%. Grade 3 or 4 hypomagnesemia occurs in roughly 7% of patients, which can lead to serious complications such as seizures and arrhythmias. In one study, hypomagnesemia led to discontinuation of targeted therapy in 3% of patients. Currently, there is no standardized prophylactic strategy or treatment protocol for panitumumab-induced hypomagnesemia. In cases of refractory hypomagnesemia, it is recommended to discontinue panitumumab, even if the patient is deriving clinical benefit.
Case Report
This 59-year-old male was diagnosed with RAS wild-type mCRC and had already progressed through multiple lines of treatment. Panitumumab was initiated with good response; however, the drug was discontinued due to grade 4 hypomagnesemia, despite intravenous and oral supplementation. As the patient progressed through further lines of treatment, the decision was made to retry panitumumab. Grade 2-3 hypomagnesemia persisted throughout treatment, requiring frequent magnesium infusions. Innovative and alternative treatment options were investigated in an effort to improve his quality of life. In addition to oral and intravenous magnesium replacement, an ambulatory elastomeric pump, traditionally used for fluorouracil administration, was repurposed to deliver between 6 and 24 grams of magnesium sulfate over 24 to 72 hours. The pump was generally well tolerated with the exception of mild skin irritation around the port site, which prevented a transition to longer infusion times. The ambulatory elastomeric pump decreased the frequency of healthcare visits and improved the hypomagnesemia sufficiently to continue treatment with panitumumab, although levels did not fully normalize. A two-week trial of amiloride was also attempted to decrease renal magnesium wasting. Amiloride normalized magnesium levels but had to be discontinued due to asymptomatic hyperkalemia. This case report suggests that amiloride and magnesium replacement via ambulatory elastomeric pumps may be safe and effective treatment options for panitumumab-induced refractory hypomagnesemia in mCRC, potentially improving quality of life and allowing beneficial anti-cancer treatments to continue. Future studies should further evaluate optimization of amiloride and intravenous magnesium replacement via ambulatory elastomeric pump.
Background
Panitumumab is an epidermal growth factor receptor (EGFR) inhibiting monoclonal antibody approved for the treatment of RAS wild-type metastatic colorectal cancer (mCRC), which has an incidence of hypomagnesemia of approximately 35%. Grade 3 or 4 hypomagnesemia occurs in roughly 7% of patients, which can lead to serious complications such as seizures and arrhythmias. In one study, hypomagnesemia led to discontinuation of targeted therapy in 3% of patients. Currently, there is no standardized prophylactic strategy or treatment protocol for panitumumab-induced hypomagnesemia. In cases of refractory hypomagnesemia, it is recommended to discontinue panitumumab, even if the patient is deriving clinical benefit.
Case Report
This 59-year-old male was diagnosed with RAS wild-type mCRC and had already progressed through multiple lines of treatment. Panitumumab was initiated with good response; however, the drug was discontinued due to grade 4 hypomagnesemia, despite intravenous and oral supplementation. As the patient progressed through further lines of treatment, the decision was made to retry panitumumab. Grade 2-3 hypomagnesemia persisted throughout treatment, requiring frequent magnesium infusions. Innovative and alternative treatment options were investigated in an effort to improve his quality of life. In addition to oral and intravenous magnesium replacement, an ambulatory elastomeric pump, traditionally used for fluorouracil administration, was repurposed to deliver between 6 and 24 grams of magnesium sulfate over 24 to 72 hours. The pump was generally well tolerated with the exception of mild skin irritation around the port site, which prevented a transition to longer infusion times. The ambulatory elastomeric pump decreased the frequency of healthcare visits and improved the hypomagnesemia sufficiently to continue treatment with panitumumab, although levels did not fully normalize. A two-week trial of amiloride was also attempted to decrease renal magnesium wasting. Amiloride normalized magnesium levels but had to be discontinued due to asymptomatic hyperkalemia. This case report suggests that amiloride and magnesium replacement via ambulatory elastomeric pumps may be safe and effective treatment options for panitumumab-induced refractory hypomagnesemia in mCRC, potentially improving quality of life and allowing beneficial anti-cancer treatments to continue. Future studies should further evaluate optimization of amiloride and intravenous magnesium replacement via ambulatory elastomeric pump.
A Single-Center Experience of Cardiac-related Adverse Events from Immune Checkpoint Inhibitors
Introduction
There have been incident reports of cardiac-related adverse events (CrAE) from immune checkpoint inhibitors (ICPI); however, the true incidence and subsequent management of these potential side effects have not been defined. It is therefore important to study ICPI related cardiac dysfunction to assist in monitoring and surveillance of these patients.
Methods
63 patients who received nivolumab and pembrolizumab at Stratton VAMC Albany between January 2015 to December 2018 were studied. Retrospective chart review was done to identify the CrAE up to two-year post-therapy completion or discontinuation. Naranjo score was used to assess drug-related side effect. IRB approval was obtained.
Results
CrAE were defined as new onset arrythmia identified on electrocardiogram, evidence of cardiomyopathy on echocardiogram, an acute coronary event, and hospitalizations from primary cardiac disorder following ICPI administration. Of the 63 patients, 6 patients developed CrAE. Our review showed 3 patients developed new arrythmias including 1 with atrial fibrillation, and 2 with atrial flutter. There was 1 case each of new heart failure with reduced ejection fraction and pericarditis with pericardial tamponade. 1 patient developed acute coronary syndrome in addition to complete heart block. Of the 6 patients, 2 had elevated brain natriuretic peptide (BNP) prior to onset of CrAE. Elevated markers including BNP and troponin-I were also seen in 13 patients with preexisting heart conditions without CrAE. Duration of therapy was variable for all patients with CrAE. Therapy was continued for 3 patients without recurrence of CrAE. Therapy was permanently discontinued in the patient who developed pericardial effusion (grade IV toxicity). The remaining 2 patients had additional concurrent immune-related toxicities that required discontinuation of therapy. Our analysis showed 25/63 patients with pre-existing cardiac conditions (including arrhythmia, heart failure or coronary artery disease) who did not develop new CrAE; however 6 of these patients required hospitalization for exacerbation related to these pre-existing conditions.
Conclusions
CrAE can occur with ICPIs, and vigilance is required in high-risk patient including those with pre-existing cardiac comorbidity. Further studies are required to establish if baseline screening EKG and echocardiogram should be obtained for all patients starting ICPI.
Introduction
There have been incident reports of cardiac-related adverse events (CrAE) from immune checkpoint inhibitors (ICPI); however, the true incidence and subsequent management of these potential side effects have not been defined. It is therefore important to study ICPI related cardiac dysfunction to assist in monitoring and surveillance of these patients.
Methods
63 patients who received nivolumab and pembrolizumab at Stratton VAMC Albany between January 2015 to December 2018 were studied. Retrospective chart review was done to identify the CrAE up to two-year post-therapy completion or discontinuation. Naranjo score was used to assess drug-related side effect. IRB approval was obtained.
Results
CrAE were defined as new onset arrythmia identified on electrocardiogram, evidence of cardiomyopathy on echocardiogram, an acute coronary event, and hospitalizations from primary cardiac disorder following ICPI administration. Of the 63 patients, 6 patients developed CrAE. Our review showed 3 patients developed new arrythmias including 1 with atrial fibrillation, and 2 with atrial flutter. There was 1 case each of new heart failure with reduced ejection fraction and pericarditis with pericardial tamponade. 1 patient developed acute coronary syndrome in addition to complete heart block. Of the 6 patients, 2 had elevated brain natriuretic peptide (BNP) prior to onset of CrAE. Elevated markers including BNP and troponin-I were also seen in 13 patients with preexisting heart conditions without CrAE. Duration of therapy was variable for all patients with CrAE. Therapy was continued for 3 patients without recurrence of CrAE. Therapy was permanently discontinued in the patient who developed pericardial effusion (grade IV toxicity). The remaining 2 patients had additional concurrent immune-related toxicities that required discontinuation of therapy. Our analysis showed 25/63 patients with pre-existing cardiac conditions (including arrhythmia, heart failure or coronary artery disease) who did not develop new CrAE; however 6 of these patients required hospitalization for exacerbation related to these pre-existing conditions.
Conclusions
CrAE can occur with ICPIs, and vigilance is required in high-risk patient including those with pre-existing cardiac comorbidity. Further studies are required to establish if baseline screening EKG and echocardiogram should be obtained for all patients starting ICPI.
Introduction
There have been incident reports of cardiac-related adverse events (CrAE) from immune checkpoint inhibitors (ICPI); however, the true incidence and subsequent management of these potential side effects have not been defined. It is therefore important to study ICPI related cardiac dysfunction to assist in monitoring and surveillance of these patients.
Methods
63 patients who received nivolumab and pembrolizumab at Stratton VAMC Albany between January 2015 to December 2018 were studied. Retrospective chart review was done to identify the CrAE up to two-year post-therapy completion or discontinuation. Naranjo score was used to assess drug-related side effect. IRB approval was obtained.
Results
CrAE were defined as new onset arrythmia identified on electrocardiogram, evidence of cardiomyopathy on echocardiogram, an acute coronary event, and hospitalizations from primary cardiac disorder following ICPI administration. Of the 63 patients, 6 patients developed CrAE. Our review showed 3 patients developed new arrythmias including 1 with atrial fibrillation, and 2 with atrial flutter. There was 1 case each of new heart failure with reduced ejection fraction and pericarditis with pericardial tamponade. 1 patient developed acute coronary syndrome in addition to complete heart block. Of the 6 patients, 2 had elevated brain natriuretic peptide (BNP) prior to onset of CrAE. Elevated markers including BNP and troponin-I were also seen in 13 patients with preexisting heart conditions without CrAE. Duration of therapy was variable for all patients with CrAE. Therapy was continued for 3 patients without recurrence of CrAE. Therapy was permanently discontinued in the patient who developed pericardial effusion (grade IV toxicity). The remaining 2 patients had additional concurrent immune-related toxicities that required discontinuation of therapy. Our analysis showed 25/63 patients with pre-existing cardiac conditions (including arrhythmia, heart failure or coronary artery disease) who did not develop new CrAE; however 6 of these patients required hospitalization for exacerbation related to these pre-existing conditions.
Conclusions
CrAE can occur with ICPIs, and vigilance is required in high-risk patient including those with pre-existing cardiac comorbidity. Further studies are required to establish if baseline screening EKG and echocardiogram should be obtained for all patients starting ICPI.
VA Turns to Telehealth to Address Delays in Genetic Counseling
The U.S. Department of Veteran Affairs (VA) has been unable to provide genetic counseling to veterans at the same level as the civilian community, and other gaps exist, a genetic counselor told oncologist and hematologist colleagues. The good news is that telemedicine is turning out to be a valuable and proven way to reach veterans who need this kind of care, she said, although certain patients are being left behind.
“To me, telehealth is no doubt the way to go. But it is really important that we continue to look into these disparities, what's causing them, and how we can find a path forward,” said
Deborah Hartzfeld, MS, CGC, of the Genomic Medicine Service based in Salt Lake City, Utah. She spoke in a presentation at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) that was held virtually and in person in Denver, Colorado, from September 24 to September 26, 2021.
As Harzfeld explained, the genetic counselor workforce is expanding along with the number of indications for genetic testing, especially in cancer, “where the need for germline genetic testing for inherited cancer genes becomes broader every year.”
Genetic counselors are a homogenous group, she said, as revealed by a 2021 survey of most of the nation’s 5,629 certified generic counselors. The North American survey, by the National Society of Genetic Counselors, found that 94% of respondents identified themselves as female, and 90% were white/non-Hispanic.
The survey report also noted that “the genetic counseling profession has grown by over 100% in the last 10 years and is expected to grow another 100% over the next 10 years. By 2025 there should be nearly 7,500 certified genetic counselors, and by 2030 there are likely to be over 10,000.”
Genetic counseling within the VA has also grown rapidly. In 2010, Harzfeld said, about 737 veterans were referred for the service. In 2020, the number was about 10,000, with about half referred for personal or family history of cancer.
The VA has 18 genetic counselors, not all of whom are actively seeing patients or working full time, she said. “Per the National Society of Genetic Counselors, there's one clinical genetic counselor per 100,000 people in the general population,” she said. “It's one for about 474,000 in the VA.”
Wait times for genetic counseling within the VA exceed Mission Act standards outside of urgent referrals in matters such as surgical or medical management, she said. “We usually see those patients within a week, but other folks have to wait or are referred into the community. It remains unclear how many of our patients could access care easily in the community or what the wait times at any individual VA will be.”
Fortunately, she said, telemedicine has increased access to genetic counseling within the general population and the VA, Harzfeld said. “A recent systematic evidence review found providing genetic counseling via video or telephone is comparable to in-person care, it increases access and it's likely feasible and acceptable to major stakeholders. It's worth noting that the data in this evidence review was collected prior to COVID-19 when fewer programs were using telehealth.”
Genetic counseling works especially well via telehealth because counselors don’t perform physical examinations, she said. “Prior to COVID, service probably saw maybe 4 VVC [VA Video Connect] appointments per month for genetic counseling. Now, VVC makes up about 70% of our new patient encounters. About 25% are telephone and about 5% are clinical video telehealth where the veteran goes into their clinic to be seated in front of the machine.”
Research has suggested that non-White patients are 40 to 50% less likely to be referred to telehealth for genetic counseling vs. in-person encounters, she said, although women in general (including black women) are more likely to be referred.
Harzfeld highlighted several challenges facing genetic counseling in the VA. She notes that contracted laboratories aren’t “really set up to be experts in germline genetic testing, so they’re not as nimble, and their test catalogs are not most likely going to be as comprehensive enough for what is needed.” Also, she said, “test ordering can be quite burdensome.”
“We need to continue working with various partners to increase access and the ease of ordering genetic testing,” she said.
Hartzfeld reports no disclosures.
The U.S. Department of Veteran Affairs (VA) has been unable to provide genetic counseling to veterans at the same level as the civilian community, and other gaps exist, a genetic counselor told oncologist and hematologist colleagues. The good news is that telemedicine is turning out to be a valuable and proven way to reach veterans who need this kind of care, she said, although certain patients are being left behind.
“To me, telehealth is no doubt the way to go. But it is really important that we continue to look into these disparities, what's causing them, and how we can find a path forward,” said
Deborah Hartzfeld, MS, CGC, of the Genomic Medicine Service based in Salt Lake City, Utah. She spoke in a presentation at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) that was held virtually and in person in Denver, Colorado, from September 24 to September 26, 2021.
As Harzfeld explained, the genetic counselor workforce is expanding along with the number of indications for genetic testing, especially in cancer, “where the need for germline genetic testing for inherited cancer genes becomes broader every year.”
Genetic counselors are a homogenous group, she said, as revealed by a 2021 survey of most of the nation’s 5,629 certified generic counselors. The North American survey, by the National Society of Genetic Counselors, found that 94% of respondents identified themselves as female, and 90% were white/non-Hispanic.
The survey report also noted that “the genetic counseling profession has grown by over 100% in the last 10 years and is expected to grow another 100% over the next 10 years. By 2025 there should be nearly 7,500 certified genetic counselors, and by 2030 there are likely to be over 10,000.”
Genetic counseling within the VA has also grown rapidly. In 2010, Harzfeld said, about 737 veterans were referred for the service. In 2020, the number was about 10,000, with about half referred for personal or family history of cancer.
The VA has 18 genetic counselors, not all of whom are actively seeing patients or working full time, she said. “Per the National Society of Genetic Counselors, there's one clinical genetic counselor per 100,000 people in the general population,” she said. “It's one for about 474,000 in the VA.”
Wait times for genetic counseling within the VA exceed Mission Act standards outside of urgent referrals in matters such as surgical or medical management, she said. “We usually see those patients within a week, but other folks have to wait or are referred into the community. It remains unclear how many of our patients could access care easily in the community or what the wait times at any individual VA will be.”
Fortunately, she said, telemedicine has increased access to genetic counseling within the general population and the VA, Harzfeld said. “A recent systematic evidence review found providing genetic counseling via video or telephone is comparable to in-person care, it increases access and it's likely feasible and acceptable to major stakeholders. It's worth noting that the data in this evidence review was collected prior to COVID-19 when fewer programs were using telehealth.”
Genetic counseling works especially well via telehealth because counselors don’t perform physical examinations, she said. “Prior to COVID, service probably saw maybe 4 VVC [VA Video Connect] appointments per month for genetic counseling. Now, VVC makes up about 70% of our new patient encounters. About 25% are telephone and about 5% are clinical video telehealth where the veteran goes into their clinic to be seated in front of the machine.”
Research has suggested that non-White patients are 40 to 50% less likely to be referred to telehealth for genetic counseling vs. in-person encounters, she said, although women in general (including black women) are more likely to be referred.
Harzfeld highlighted several challenges facing genetic counseling in the VA. She notes that contracted laboratories aren’t “really set up to be experts in germline genetic testing, so they’re not as nimble, and their test catalogs are not most likely going to be as comprehensive enough for what is needed.” Also, she said, “test ordering can be quite burdensome.”
“We need to continue working with various partners to increase access and the ease of ordering genetic testing,” she said.
Hartzfeld reports no disclosures.
The U.S. Department of Veteran Affairs (VA) has been unable to provide genetic counseling to veterans at the same level as the civilian community, and other gaps exist, a genetic counselor told oncologist and hematologist colleagues. The good news is that telemedicine is turning out to be a valuable and proven way to reach veterans who need this kind of care, she said, although certain patients are being left behind.
“To me, telehealth is no doubt the way to go. But it is really important that we continue to look into these disparities, what's causing them, and how we can find a path forward,” said
Deborah Hartzfeld, MS, CGC, of the Genomic Medicine Service based in Salt Lake City, Utah. She spoke in a presentation at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) that was held virtually and in person in Denver, Colorado, from September 24 to September 26, 2021.
As Harzfeld explained, the genetic counselor workforce is expanding along with the number of indications for genetic testing, especially in cancer, “where the need for germline genetic testing for inherited cancer genes becomes broader every year.”
Genetic counselors are a homogenous group, she said, as revealed by a 2021 survey of most of the nation’s 5,629 certified generic counselors. The North American survey, by the National Society of Genetic Counselors, found that 94% of respondents identified themselves as female, and 90% were white/non-Hispanic.
The survey report also noted that “the genetic counseling profession has grown by over 100% in the last 10 years and is expected to grow another 100% over the next 10 years. By 2025 there should be nearly 7,500 certified genetic counselors, and by 2030 there are likely to be over 10,000.”
Genetic counseling within the VA has also grown rapidly. In 2010, Harzfeld said, about 737 veterans were referred for the service. In 2020, the number was about 10,000, with about half referred for personal or family history of cancer.
The VA has 18 genetic counselors, not all of whom are actively seeing patients or working full time, she said. “Per the National Society of Genetic Counselors, there's one clinical genetic counselor per 100,000 people in the general population,” she said. “It's one for about 474,000 in the VA.”
Wait times for genetic counseling within the VA exceed Mission Act standards outside of urgent referrals in matters such as surgical or medical management, she said. “We usually see those patients within a week, but other folks have to wait or are referred into the community. It remains unclear how many of our patients could access care easily in the community or what the wait times at any individual VA will be.”
Fortunately, she said, telemedicine has increased access to genetic counseling within the general population and the VA, Harzfeld said. “A recent systematic evidence review found providing genetic counseling via video or telephone is comparable to in-person care, it increases access and it's likely feasible and acceptable to major stakeholders. It's worth noting that the data in this evidence review was collected prior to COVID-19 when fewer programs were using telehealth.”
Genetic counseling works especially well via telehealth because counselors don’t perform physical examinations, she said. “Prior to COVID, service probably saw maybe 4 VVC [VA Video Connect] appointments per month for genetic counseling. Now, VVC makes up about 70% of our new patient encounters. About 25% are telephone and about 5% are clinical video telehealth where the veteran goes into their clinic to be seated in front of the machine.”
Research has suggested that non-White patients are 40 to 50% less likely to be referred to telehealth for genetic counseling vs. in-person encounters, she said, although women in general (including black women) are more likely to be referred.
Harzfeld highlighted several challenges facing genetic counseling in the VA. She notes that contracted laboratories aren’t “really set up to be experts in germline genetic testing, so they’re not as nimble, and their test catalogs are not most likely going to be as comprehensive enough for what is needed.” Also, she said, “test ordering can be quite burdensome.”
“We need to continue working with various partners to increase access and the ease of ordering genetic testing,” she said.
Hartzfeld reports no disclosures.
FDA okays new oral CGRP antagonist for migraine prevention
the manufacturer announced in a release.
The once-daily medication will be available in doses of 10 mg, 30 mg, and 60 mg.
“Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients,” coinvestigator Peter J. Goadsby, MD, PhD, DSc, neurologist and professor at the University of California, Los Angeles, and King’s College London, said in the release.
Approval was based partly on the findings from the phase 3 ADVANCE trial, in which patients with episodic migraine were randomly assigned to receive placebo or a 10-mg, 30-mg, or 60-mg daily dose of atogepant for 12 weeks.
As reported by this news organization, all three doses of atogepant reduced the number of mean monthly migraine days.
With this approval, neurologists will be able to choose from four monoclonal antibodies and two gepants for the preventive treatment of migraine.
“Having another gepant that can also be given preventively is a good idea, because one may be better than the other for a patient,” Alan M. Rapoport, MD, past president of the International Headache Society and founder and director emeritus of the New England Center for Headache, Stamford, Conn., told this news organization.
“Once we have a year or so of experience with atogepant, we’ll have a pretty good idea of which one works better preventively,” said Dr. Rapoport, who was not involved with the research.
Practice changing?
In the ADVANCE trial, there was a reduction of 3.69 migraine days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose. Placebo was associated with a reduction of 2.48 migraine days.
In addition, more than half of patients in each atogepant arm achieved a reduction in mean monthly migraine days of 50% or greater. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group. Approximately 29% patients who received placebo achieved this outcome.
The data indicated that atogepant has a favorable safety profile. The most common adverse events associated with treatment were constipation, nausea, and upper respiratory tract infection.
Dr. Rapoport, who is also a clinical professor of neurology at UCLA, noted that he was impressed with the efficacy.
“I’m not as impressed with the adverse events, but they’re not serious, and they don’t necessarily last,” he said.
Although being able to prescribe a single drug for acute and preventive treatment may be an advantage, it remains to be seen whether the tolerability and price of atogepant will be barriers for patients, Dr. Rapoport added.
How the approval will affect clinical practice is also unclear, he noted.
“If you’re going to start someone on a preventive, especially if it’s a woman of childbearing potential, you might just consider one of the two gepants. Doctors will decide once they see how they work,” said Dr. Rapoport.
Not a ‘breakthrough’ treatment
Also commenting ahead of the approval, Elizabeth W. Loder, MD, vice chair for academic affairs in the department of neurology at Brigham and Women’s Hospital, Boston, noted that the “safety of these CGRP medications in pregnancy is uncertain, and there are theoretical reasons to be concerned about it.”
Unlike injectable CGRP medications, atogepant is eliminated from the body relatively quickly after the patient stops taking it, said Dr. Loder, who is also professor of neurology at Harvard Medical School, Boston. However, atogepant may not otherwise differ greatly from other medications of its type.
“I don’t see a reason to think that one of these oral CGRP medicines is much more effective than another one,” said Dr. Loder.
“In my mind, as a clinician who will be prescribing these for patients, it will be cost and the ease of getting it covered that makes the difference,” she added.
These questions may raise concerns. “Those of us who treat patients who do not have private insurance find it very difficult to get these medications for them, even in situations where they have exhausted other alternatives,” said Dr. Loder.
Patients insured by Medicare or Medicaid “usually have no avenue to get some of these new, expensive treatments,” she said.
The approval of atogepant for acute and preventive treatment shows that the distinction between these indications may be artificial, Dr. Loder noted. The approval “will, I hope, help people think more flexibly about the way in which we use medications.”
It is a positive that atogepant has emerged as another option for preventive therapy, but the treatment cannot be considered a breakthrough, Dr. Loder added. The efficacy of atogepant, like that of other preventive treatments for migraine, is modest.
“It would be so nice if we could find things that were more effective than the treatments we currently have,” said Dr. Loder.
A version of this article first appeared on Medscape.com.
the manufacturer announced in a release.
The once-daily medication will be available in doses of 10 mg, 30 mg, and 60 mg.
“Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients,” coinvestigator Peter J. Goadsby, MD, PhD, DSc, neurologist and professor at the University of California, Los Angeles, and King’s College London, said in the release.
Approval was based partly on the findings from the phase 3 ADVANCE trial, in which patients with episodic migraine were randomly assigned to receive placebo or a 10-mg, 30-mg, or 60-mg daily dose of atogepant for 12 weeks.
As reported by this news organization, all three doses of atogepant reduced the number of mean monthly migraine days.
With this approval, neurologists will be able to choose from four monoclonal antibodies and two gepants for the preventive treatment of migraine.
“Having another gepant that can also be given preventively is a good idea, because one may be better than the other for a patient,” Alan M. Rapoport, MD, past president of the International Headache Society and founder and director emeritus of the New England Center for Headache, Stamford, Conn., told this news organization.
“Once we have a year or so of experience with atogepant, we’ll have a pretty good idea of which one works better preventively,” said Dr. Rapoport, who was not involved with the research.
Practice changing?
In the ADVANCE trial, there was a reduction of 3.69 migraine days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose. Placebo was associated with a reduction of 2.48 migraine days.
In addition, more than half of patients in each atogepant arm achieved a reduction in mean monthly migraine days of 50% or greater. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group. Approximately 29% patients who received placebo achieved this outcome.
The data indicated that atogepant has a favorable safety profile. The most common adverse events associated with treatment were constipation, nausea, and upper respiratory tract infection.
Dr. Rapoport, who is also a clinical professor of neurology at UCLA, noted that he was impressed with the efficacy.
“I’m not as impressed with the adverse events, but they’re not serious, and they don’t necessarily last,” he said.
Although being able to prescribe a single drug for acute and preventive treatment may be an advantage, it remains to be seen whether the tolerability and price of atogepant will be barriers for patients, Dr. Rapoport added.
How the approval will affect clinical practice is also unclear, he noted.
“If you’re going to start someone on a preventive, especially if it’s a woman of childbearing potential, you might just consider one of the two gepants. Doctors will decide once they see how they work,” said Dr. Rapoport.
Not a ‘breakthrough’ treatment
Also commenting ahead of the approval, Elizabeth W. Loder, MD, vice chair for academic affairs in the department of neurology at Brigham and Women’s Hospital, Boston, noted that the “safety of these CGRP medications in pregnancy is uncertain, and there are theoretical reasons to be concerned about it.”
Unlike injectable CGRP medications, atogepant is eliminated from the body relatively quickly after the patient stops taking it, said Dr. Loder, who is also professor of neurology at Harvard Medical School, Boston. However, atogepant may not otherwise differ greatly from other medications of its type.
“I don’t see a reason to think that one of these oral CGRP medicines is much more effective than another one,” said Dr. Loder.
“In my mind, as a clinician who will be prescribing these for patients, it will be cost and the ease of getting it covered that makes the difference,” she added.
These questions may raise concerns. “Those of us who treat patients who do not have private insurance find it very difficult to get these medications for them, even in situations where they have exhausted other alternatives,” said Dr. Loder.
Patients insured by Medicare or Medicaid “usually have no avenue to get some of these new, expensive treatments,” she said.
The approval of atogepant for acute and preventive treatment shows that the distinction between these indications may be artificial, Dr. Loder noted. The approval “will, I hope, help people think more flexibly about the way in which we use medications.”
It is a positive that atogepant has emerged as another option for preventive therapy, but the treatment cannot be considered a breakthrough, Dr. Loder added. The efficacy of atogepant, like that of other preventive treatments for migraine, is modest.
“It would be so nice if we could find things that were more effective than the treatments we currently have,” said Dr. Loder.
A version of this article first appeared on Medscape.com.
the manufacturer announced in a release.
The once-daily medication will be available in doses of 10 mg, 30 mg, and 60 mg.
“Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients,” coinvestigator Peter J. Goadsby, MD, PhD, DSc, neurologist and professor at the University of California, Los Angeles, and King’s College London, said in the release.
Approval was based partly on the findings from the phase 3 ADVANCE trial, in which patients with episodic migraine were randomly assigned to receive placebo or a 10-mg, 30-mg, or 60-mg daily dose of atogepant for 12 weeks.
As reported by this news organization, all three doses of atogepant reduced the number of mean monthly migraine days.
With this approval, neurologists will be able to choose from four monoclonal antibodies and two gepants for the preventive treatment of migraine.
“Having another gepant that can also be given preventively is a good idea, because one may be better than the other for a patient,” Alan M. Rapoport, MD, past president of the International Headache Society and founder and director emeritus of the New England Center for Headache, Stamford, Conn., told this news organization.
“Once we have a year or so of experience with atogepant, we’ll have a pretty good idea of which one works better preventively,” said Dr. Rapoport, who was not involved with the research.
Practice changing?
In the ADVANCE trial, there was a reduction of 3.69 migraine days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose. Placebo was associated with a reduction of 2.48 migraine days.
In addition, more than half of patients in each atogepant arm achieved a reduction in mean monthly migraine days of 50% or greater. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group. Approximately 29% patients who received placebo achieved this outcome.
The data indicated that atogepant has a favorable safety profile. The most common adverse events associated with treatment were constipation, nausea, and upper respiratory tract infection.
Dr. Rapoport, who is also a clinical professor of neurology at UCLA, noted that he was impressed with the efficacy.
“I’m not as impressed with the adverse events, but they’re not serious, and they don’t necessarily last,” he said.
Although being able to prescribe a single drug for acute and preventive treatment may be an advantage, it remains to be seen whether the tolerability and price of atogepant will be barriers for patients, Dr. Rapoport added.
How the approval will affect clinical practice is also unclear, he noted.
“If you’re going to start someone on a preventive, especially if it’s a woman of childbearing potential, you might just consider one of the two gepants. Doctors will decide once they see how they work,” said Dr. Rapoport.
Not a ‘breakthrough’ treatment
Also commenting ahead of the approval, Elizabeth W. Loder, MD, vice chair for academic affairs in the department of neurology at Brigham and Women’s Hospital, Boston, noted that the “safety of these CGRP medications in pregnancy is uncertain, and there are theoretical reasons to be concerned about it.”
Unlike injectable CGRP medications, atogepant is eliminated from the body relatively quickly after the patient stops taking it, said Dr. Loder, who is also professor of neurology at Harvard Medical School, Boston. However, atogepant may not otherwise differ greatly from other medications of its type.
“I don’t see a reason to think that one of these oral CGRP medicines is much more effective than another one,” said Dr. Loder.
“In my mind, as a clinician who will be prescribing these for patients, it will be cost and the ease of getting it covered that makes the difference,” she added.
These questions may raise concerns. “Those of us who treat patients who do not have private insurance find it very difficult to get these medications for them, even in situations where they have exhausted other alternatives,” said Dr. Loder.
Patients insured by Medicare or Medicaid “usually have no avenue to get some of these new, expensive treatments,” she said.
The approval of atogepant for acute and preventive treatment shows that the distinction between these indications may be artificial, Dr. Loder noted. The approval “will, I hope, help people think more flexibly about the way in which we use medications.”
It is a positive that atogepant has emerged as another option for preventive therapy, but the treatment cannot be considered a breakthrough, Dr. Loder added. The efficacy of atogepant, like that of other preventive treatments for migraine, is modest.
“It would be so nice if we could find things that were more effective than the treatments we currently have,” said Dr. Loder.
A version of this article first appeared on Medscape.com.