VA Launches Virtual Tumor Board

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Ten sessions have been held over the past 6 months in a bid to bring better cancer care to the military medical system.

SAN DIEGO The US Department of Veterans Affairs (VA) TeleOncology program has rolled out a virtual tumor board that brings medical professionals together to offer insight and guidance about challenging hematology cases. Over the past 6 months the board has held 10 sessions and reviewed about 20 cases. A small survey found that participants think the meetings are beneficial. 

“Virtual tumor boards help to connect experts across the country to leverage the expertise within the VA,” he-matologist/oncologist Thomas Rodgers, MD, of the Duke Cancer Institute and Durham Veterans Affairs Medical Center, told Federal Practitioner in an interview. He is the lead author of a poster about the program that was pre-sented here at the annual meeting of the Association of VA Hematology/Oncology (AVAHO).

As Dr. Rodgers noted, tumor boards are already in place at some VA centers. However, “they are not available at every VA and often are not set up to cover every cancer type.”

The VA National TeleOncology program created the virtual tumor board program as part of its mission to ex-tend hematology/oncology services across the system. “Cancer care has become increasingly complex. Beyond ad-vancing therapeutics, patient care often involves multiple specialties and medical disciplines,” Dr. Rodgers said. “A tumor board offers a forum for these specialists to communicate with each other in real time, not only to help estab-lish the correct diagnosis and stage of cancer but also to form a consensus on the most fitting treatment option. Think of it as getting all of the people involved in a person’s care in the same room.”

Currently, he said, the virtual tumor boards cover patients with malignant hematology diagnoses such as leuke-mia, multiple myeloma, and lymphomas. “We welcome submissions. If a provider is interested in submitting a case, they can email us and will be provided with a short intake form. Once submitted, we will collect necessary imaging and pathology for review. The provider will then present the patient case on the day of the tumor board.”

Typically, more than 30 medical professionals participate in the virtual tumor boards, Dr. Rodgers said, repre-senting medical oncology/hematology, pathology, radiology, palliative care, pharmacy, social work, and die-tary/nutrition. 

According to the poster presented at AVAHO, 9 participants responded to a survey after 4 tumor board sessions. All found the boards to be beneficial or somewhat beneficial, and 55% reported that they were “highly applicable” to their practice. 

Pathologist Claudio A. Mosse, MD, PhD, of Vanderbilt University Medical Center and VA Tennessee Valley Healthcare System, praised the virtual tumor board program. “It’s been incredibly useful from my end as a pathologist as it shows me which diagnoses are most challenging for my colleagues,” Dr. Mosse said in an inter-view. “Reviewing and then presenting these challenging cases forces me to go into the published literature to come to a unitary diagnosis based on the patient history, radiology, various laboratory tests, and the biopsy I was asked to review.”

He added that “as a pathologist, I learn so much from the hematologists as they discuss the possible therapeutic options, and that strengthens my ability as a pathologist because I have to understand how one diagnosis versus an-other affects their therapeutic decision tree.”

What’s next for the virtual tumor board program? The next step is to expand to solid tumors, said VA Pittsburgh Healthcare System hematologist/oncologist Vida Almario Passero, MD, MBA, chief medical officer of National TeleOncology, in an interview. 

No disclosures were reported.

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Ten sessions have been held over the past 6 months in a bid to bring better cancer care to the military medical system.
Ten sessions have been held over the past 6 months in a bid to bring better cancer care to the military medical system.

SAN DIEGO The US Department of Veterans Affairs (VA) TeleOncology program has rolled out a virtual tumor board that brings medical professionals together to offer insight and guidance about challenging hematology cases. Over the past 6 months the board has held 10 sessions and reviewed about 20 cases. A small survey found that participants think the meetings are beneficial. 

“Virtual tumor boards help to connect experts across the country to leverage the expertise within the VA,” he-matologist/oncologist Thomas Rodgers, MD, of the Duke Cancer Institute and Durham Veterans Affairs Medical Center, told Federal Practitioner in an interview. He is the lead author of a poster about the program that was pre-sented here at the annual meeting of the Association of VA Hematology/Oncology (AVAHO).

As Dr. Rodgers noted, tumor boards are already in place at some VA centers. However, “they are not available at every VA and often are not set up to cover every cancer type.”

The VA National TeleOncology program created the virtual tumor board program as part of its mission to ex-tend hematology/oncology services across the system. “Cancer care has become increasingly complex. Beyond ad-vancing therapeutics, patient care often involves multiple specialties and medical disciplines,” Dr. Rodgers said. “A tumor board offers a forum for these specialists to communicate with each other in real time, not only to help estab-lish the correct diagnosis and stage of cancer but also to form a consensus on the most fitting treatment option. Think of it as getting all of the people involved in a person’s care in the same room.”

Currently, he said, the virtual tumor boards cover patients with malignant hematology diagnoses such as leuke-mia, multiple myeloma, and lymphomas. “We welcome submissions. If a provider is interested in submitting a case, they can email us and will be provided with a short intake form. Once submitted, we will collect necessary imaging and pathology for review. The provider will then present the patient case on the day of the tumor board.”

Typically, more than 30 medical professionals participate in the virtual tumor boards, Dr. Rodgers said, repre-senting medical oncology/hematology, pathology, radiology, palliative care, pharmacy, social work, and die-tary/nutrition. 

According to the poster presented at AVAHO, 9 participants responded to a survey after 4 tumor board sessions. All found the boards to be beneficial or somewhat beneficial, and 55% reported that they were “highly applicable” to their practice. 

Pathologist Claudio A. Mosse, MD, PhD, of Vanderbilt University Medical Center and VA Tennessee Valley Healthcare System, praised the virtual tumor board program. “It’s been incredibly useful from my end as a pathologist as it shows me which diagnoses are most challenging for my colleagues,” Dr. Mosse said in an inter-view. “Reviewing and then presenting these challenging cases forces me to go into the published literature to come to a unitary diagnosis based on the patient history, radiology, various laboratory tests, and the biopsy I was asked to review.”

He added that “as a pathologist, I learn so much from the hematologists as they discuss the possible therapeutic options, and that strengthens my ability as a pathologist because I have to understand how one diagnosis versus an-other affects their therapeutic decision tree.”

What’s next for the virtual tumor board program? The next step is to expand to solid tumors, said VA Pittsburgh Healthcare System hematologist/oncologist Vida Almario Passero, MD, MBA, chief medical officer of National TeleOncology, in an interview. 

No disclosures were reported.

SAN DIEGO The US Department of Veterans Affairs (VA) TeleOncology program has rolled out a virtual tumor board that brings medical professionals together to offer insight and guidance about challenging hematology cases. Over the past 6 months the board has held 10 sessions and reviewed about 20 cases. A small survey found that participants think the meetings are beneficial. 

“Virtual tumor boards help to connect experts across the country to leverage the expertise within the VA,” he-matologist/oncologist Thomas Rodgers, MD, of the Duke Cancer Institute and Durham Veterans Affairs Medical Center, told Federal Practitioner in an interview. He is the lead author of a poster about the program that was pre-sented here at the annual meeting of the Association of VA Hematology/Oncology (AVAHO).

As Dr. Rodgers noted, tumor boards are already in place at some VA centers. However, “they are not available at every VA and often are not set up to cover every cancer type.”

The VA National TeleOncology program created the virtual tumor board program as part of its mission to ex-tend hematology/oncology services across the system. “Cancer care has become increasingly complex. Beyond ad-vancing therapeutics, patient care often involves multiple specialties and medical disciplines,” Dr. Rodgers said. “A tumor board offers a forum for these specialists to communicate with each other in real time, not only to help estab-lish the correct diagnosis and stage of cancer but also to form a consensus on the most fitting treatment option. Think of it as getting all of the people involved in a person’s care in the same room.”

Currently, he said, the virtual tumor boards cover patients with malignant hematology diagnoses such as leuke-mia, multiple myeloma, and lymphomas. “We welcome submissions. If a provider is interested in submitting a case, they can email us and will be provided with a short intake form. Once submitted, we will collect necessary imaging and pathology for review. The provider will then present the patient case on the day of the tumor board.”

Typically, more than 30 medical professionals participate in the virtual tumor boards, Dr. Rodgers said, repre-senting medical oncology/hematology, pathology, radiology, palliative care, pharmacy, social work, and die-tary/nutrition. 

According to the poster presented at AVAHO, 9 participants responded to a survey after 4 tumor board sessions. All found the boards to be beneficial or somewhat beneficial, and 55% reported that they were “highly applicable” to their practice. 

Pathologist Claudio A. Mosse, MD, PhD, of Vanderbilt University Medical Center and VA Tennessee Valley Healthcare System, praised the virtual tumor board program. “It’s been incredibly useful from my end as a pathologist as it shows me which diagnoses are most challenging for my colleagues,” Dr. Mosse said in an inter-view. “Reviewing and then presenting these challenging cases forces me to go into the published literature to come to a unitary diagnosis based on the patient history, radiology, various laboratory tests, and the biopsy I was asked to review.”

He added that “as a pathologist, I learn so much from the hematologists as they discuss the possible therapeutic options, and that strengthens my ability as a pathologist because I have to understand how one diagnosis versus an-other affects their therapeutic decision tree.”

What’s next for the virtual tumor board program? The next step is to expand to solid tumors, said VA Pittsburgh Healthcare System hematologist/oncologist Vida Almario Passero, MD, MBA, chief medical officer of National TeleOncology, in an interview. 

No disclosures were reported.

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New Research Supports a Changing Approach to Peripheral Artery Disease

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Outdated ACC/AHA guidelines haven’t caught up to newer data, cardiologist tells VA oncologists at AVAHO meeting

SAN DIEGO–A cardiologist/vascular medicine specialist urged hematologist and oncologists within the US Department of Veterans Affairs system to think beyond the guidelines–at least until they’re updated–when they consider how to treat peripheral artery disease (PAD).

 

The 2016 American College of Cardiology/American Heart Association guidelines for PAD care are due for an update and don’t reflect recent positive research into the role that the blood thinner rivaroxaban can play in certain patients, said Geoffrey Barnes, MD, MSc, of the University of Michigan Health System, in a presentation here at the annual meeting of the Association of VA Hematology/Oncology (AVAHO).

Recent research has “really got us excited about the potential for this drug in this particular patient population,” Barnes said, although he cautioned that it’s most appropriate for patients at highest risk of PAD.

 

Research has found that patients with PAD are more likely to develop cancer, apparently because of common risk factors, and there’s discussion about whether they should undergo special screening. Cancer treatment may also boost the risk of PAD, according to a 2021 US study that tracked 248 patients with both breast cancer and PAD. “Of all patients, 48% were on statins and 54% were on antiplatelet therapies,” the study found, although the 2016 guidelines recommend both (statins for all patients with PAD, antiplatelets for those with symptoms).

 

In his presentation, Barnes noted that the 2016 guidelines specifically recommend aspirin (75-325 mg daily) or clopidogrel (75 mg) in patients with symptomatic PAD. Treatment is especially important, he said, because the risk of cardiovascular mortality in PAD is high. A 2020 study found that 9.1% of 13,885 patients died over a median 30-month follow-up.

 

The good news about treatment Brand said, came in a 2020 industry-funded study of patients with PAD who had undergone revascularization. Various outcomes such as amputation, heart attack, and death from cardiovascular causes—the primary efficacy outcome—were less common in subjects who took 2.5 mg twice daily of rivaroxaban plus aspirin or placebo plus aspirin (hazard ratio, 0.85, 95% CI, 0.76-0.96; P = .009). 

 

So who should go on rivaroxaban? As Brand noted, a 2019 study found that patients with no high-risk features didn’t benefit much in terms of risk of vascular events, but those with high-risk features did. In higher-risk patients, the study found, “rivaroxaban and aspirin prevented 33 serious vascular events, whereas in lower-risk patients, rivaroxaban and aspirin treatment led to the avoidance of 10 events per 1,000 patients treated for 30 months.”

 

Per the study, patients at higher risk are those with heart failure, at least 2 vascular beds affected, renal insufficiency, or diabetes.

 

Brand supports the use of rivaroxaban in these patients. However, he cautioned colleagues not to switch out the drug with apixaban, another blood thinner. “These are not interchangeable,” he said. “You do need to stick with rivaroxaban. And you do need to remember that you’re going to use 2.5 milligrams twice a day—very different than many of the other ways we are using rivaroxaban.”

 

Brand discloses consulting fees (Pfizer/Bristol-Myers Squib, Janssen, Acelis Connected Health, Boston Scientific, Abbott Vascular), grant funding (Boston Scientific) and board of directors service (Anticoagulation Forum).

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Outdated ACC/AHA guidelines haven’t caught up to newer data, cardiologist tells VA oncologists at AVAHO meeting
Outdated ACC/AHA guidelines haven’t caught up to newer data, cardiologist tells VA oncologists at AVAHO meeting

SAN DIEGO–A cardiologist/vascular medicine specialist urged hematologist and oncologists within the US Department of Veterans Affairs system to think beyond the guidelines–at least until they’re updated–when they consider how to treat peripheral artery disease (PAD).

 

The 2016 American College of Cardiology/American Heart Association guidelines for PAD care are due for an update and don’t reflect recent positive research into the role that the blood thinner rivaroxaban can play in certain patients, said Geoffrey Barnes, MD, MSc, of the University of Michigan Health System, in a presentation here at the annual meeting of the Association of VA Hematology/Oncology (AVAHO).

Recent research has “really got us excited about the potential for this drug in this particular patient population,” Barnes said, although he cautioned that it’s most appropriate for patients at highest risk of PAD.

 

Research has found that patients with PAD are more likely to develop cancer, apparently because of common risk factors, and there’s discussion about whether they should undergo special screening. Cancer treatment may also boost the risk of PAD, according to a 2021 US study that tracked 248 patients with both breast cancer and PAD. “Of all patients, 48% were on statins and 54% were on antiplatelet therapies,” the study found, although the 2016 guidelines recommend both (statins for all patients with PAD, antiplatelets for those with symptoms).

 

In his presentation, Barnes noted that the 2016 guidelines specifically recommend aspirin (75-325 mg daily) or clopidogrel (75 mg) in patients with symptomatic PAD. Treatment is especially important, he said, because the risk of cardiovascular mortality in PAD is high. A 2020 study found that 9.1% of 13,885 patients died over a median 30-month follow-up.

 

The good news about treatment Brand said, came in a 2020 industry-funded study of patients with PAD who had undergone revascularization. Various outcomes such as amputation, heart attack, and death from cardiovascular causes—the primary efficacy outcome—were less common in subjects who took 2.5 mg twice daily of rivaroxaban plus aspirin or placebo plus aspirin (hazard ratio, 0.85, 95% CI, 0.76-0.96; P = .009). 

 

So who should go on rivaroxaban? As Brand noted, a 2019 study found that patients with no high-risk features didn’t benefit much in terms of risk of vascular events, but those with high-risk features did. In higher-risk patients, the study found, “rivaroxaban and aspirin prevented 33 serious vascular events, whereas in lower-risk patients, rivaroxaban and aspirin treatment led to the avoidance of 10 events per 1,000 patients treated for 30 months.”

 

Per the study, patients at higher risk are those with heart failure, at least 2 vascular beds affected, renal insufficiency, or diabetes.

 

Brand supports the use of rivaroxaban in these patients. However, he cautioned colleagues not to switch out the drug with apixaban, another blood thinner. “These are not interchangeable,” he said. “You do need to stick with rivaroxaban. And you do need to remember that you’re going to use 2.5 milligrams twice a day—very different than many of the other ways we are using rivaroxaban.”

 

Brand discloses consulting fees (Pfizer/Bristol-Myers Squib, Janssen, Acelis Connected Health, Boston Scientific, Abbott Vascular), grant funding (Boston Scientific) and board of directors service (Anticoagulation Forum).

SAN DIEGO–A cardiologist/vascular medicine specialist urged hematologist and oncologists within the US Department of Veterans Affairs system to think beyond the guidelines–at least until they’re updated–when they consider how to treat peripheral artery disease (PAD).

 

The 2016 American College of Cardiology/American Heart Association guidelines for PAD care are due for an update and don’t reflect recent positive research into the role that the blood thinner rivaroxaban can play in certain patients, said Geoffrey Barnes, MD, MSc, of the University of Michigan Health System, in a presentation here at the annual meeting of the Association of VA Hematology/Oncology (AVAHO).

Recent research has “really got us excited about the potential for this drug in this particular patient population,” Barnes said, although he cautioned that it’s most appropriate for patients at highest risk of PAD.

 

Research has found that patients with PAD are more likely to develop cancer, apparently because of common risk factors, and there’s discussion about whether they should undergo special screening. Cancer treatment may also boost the risk of PAD, according to a 2021 US study that tracked 248 patients with both breast cancer and PAD. “Of all patients, 48% were on statins and 54% were on antiplatelet therapies,” the study found, although the 2016 guidelines recommend both (statins for all patients with PAD, antiplatelets for those with symptoms).

 

In his presentation, Barnes noted that the 2016 guidelines specifically recommend aspirin (75-325 mg daily) or clopidogrel (75 mg) in patients with symptomatic PAD. Treatment is especially important, he said, because the risk of cardiovascular mortality in PAD is high. A 2020 study found that 9.1% of 13,885 patients died over a median 30-month follow-up.

 

The good news about treatment Brand said, came in a 2020 industry-funded study of patients with PAD who had undergone revascularization. Various outcomes such as amputation, heart attack, and death from cardiovascular causes—the primary efficacy outcome—were less common in subjects who took 2.5 mg twice daily of rivaroxaban plus aspirin or placebo plus aspirin (hazard ratio, 0.85, 95% CI, 0.76-0.96; P = .009). 

 

So who should go on rivaroxaban? As Brand noted, a 2019 study found that patients with no high-risk features didn’t benefit much in terms of risk of vascular events, but those with high-risk features did. In higher-risk patients, the study found, “rivaroxaban and aspirin prevented 33 serious vascular events, whereas in lower-risk patients, rivaroxaban and aspirin treatment led to the avoidance of 10 events per 1,000 patients treated for 30 months.”

 

Per the study, patients at higher risk are those with heart failure, at least 2 vascular beds affected, renal insufficiency, or diabetes.

 

Brand supports the use of rivaroxaban in these patients. However, he cautioned colleagues not to switch out the drug with apixaban, another blood thinner. “These are not interchangeable,” he said. “You do need to stick with rivaroxaban. And you do need to remember that you’re going to use 2.5 milligrams twice a day—very different than many of the other ways we are using rivaroxaban.”

 

Brand discloses consulting fees (Pfizer/Bristol-Myers Squib, Janssen, Acelis Connected Health, Boston Scientific, Abbott Vascular), grant funding (Boston Scientific) and board of directors service (Anticoagulation Forum).

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Time to pull back on postsurgery radiation in breast cancer?

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A new study suggests that oncologists can safely pull back on standard locoregional radiotherapy (RT) in select patients with cT1-2N1 breast cancer who are treated with primary chemotherapy prior to surgery. The key is to divide patients by risk level and treat them according to the study’s guidelines, the researchers reported.

“We think this study is a good step towards de-escalation, which should lead to equal survival chances but better quality of life,” lead study author Sabine de Wild, MD, a PhD student at Maastricht (the Netherlands) University Medical Center, said in an interview.

The study, published in The Lancet Oncology, was intended to provide insight into which breast cancer patients need adjuvant locoregional radiotherapy following postchemotherapy surgery, coauthor Liesbeth Boersma, MD, PhD, a radiation oncologist at Maastricht University Medical Center, said in an interview. “It is not yet known which of these patients would benefit from adjuvant locoregional radiotherapy and to what extent the response of the tumor to the chemotherapy should be taken into account.”

For the study, believed to be the first prospective analysis tackling this topic, researchers tracked 838 patients in The Netherlands who were treated for cT1-2N1 breast cancer with primary chemotherapy and surgery of the breast and axilla from 2011-2015. Tumors were less than 5 cm and metastases were one to three axillary nodes.

The subjects were divided into groups based on risk of locoregional recurrence, and each group underwent different therapies.

  • Low-risk group: no metastases were present in the nodes (n = 291). “We omitted regional radiotherapy, and we omitted RT of the chest wall in case of a mastectomy. After breast conserving surgery, regular RT of the breast was recommended,” Dr. de Wild said.
  • Intermediate-risk group, one to three metastases were still present (n = 370). “We omitted regional radiotherapy, but irradiated the chest wall or breast,” she said.
  • High-risk group, three metastases were present (n = 177). “We did not de-escalate, and all patients were treated with locoregional RT,” she said.

According to the study, “the 5-year locoregional recurrence rate in all patients was 2.2% (95% confidence interval, 1.4-3.4). The 5-year locoregional recurrence rate was 2.1% (95% CI, 0.9-4.3) in the low-risk group, 2.2% (95% CI, 1.0-4.1) in the intermediate-risk group, and 2.3% (95% CI, 0.8-5.5) in the high-risk group.”

In 26% of cases, patients received more radiotherapy than the study guidelines suggested. “Remarkably,” the researchers wrote, “this did not seem to affect locoregional recurrence rate, recurrence­-free interval, and overall survival in a statistically significant or clinically relevant way.”

As for limitations, the authors noted that, “in each risk group, the actual sample size treated according to the study guideline was smaller than required based on the power calculation. Nevertheless, when performing the analyses in the subset of patients treated according to the study guideline, the upper limit of 95% CI of 5­-year locoregional recurrence rate did not exceed 7.8%.”

The study authors wrote that, “in the future, the results of this study might lead to more frequent omission of locoregional radiotherapy, which could result in lower morbidity and a better quality of life for patients with breast cancer who are receiving primary chemotherapy.”

However, Dr. de Wild said randomized trials are necessary “to investigate how treatment can be individualized further, i.e., by taking into account specific tumor characteristics.” Also, most patients in the study underwent axillary lymph node dissection, “while patients in daily practice may instead undergo targeted axillary dissection. Future studies are needed to determine if less radiotherapy is also safe in patients in whom axillary lymph node dissection is omitted.”

The study was funded by the Dutch Cancer Society. One coauthor reported a pending patent plus grants from AstraZeneca, Eurocept Plaza, Roche, Genentech, Gilead Sciences, Tesaro, Novartis, Dutch Cancer Society, ZonMw, and A Sister’s Hope; as well as consulting fees and other financial support from a variety of pharmaceutical companies. The other authors had no disclosures.

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A new study suggests that oncologists can safely pull back on standard locoregional radiotherapy (RT) in select patients with cT1-2N1 breast cancer who are treated with primary chemotherapy prior to surgery. The key is to divide patients by risk level and treat them according to the study’s guidelines, the researchers reported.

“We think this study is a good step towards de-escalation, which should lead to equal survival chances but better quality of life,” lead study author Sabine de Wild, MD, a PhD student at Maastricht (the Netherlands) University Medical Center, said in an interview.

The study, published in The Lancet Oncology, was intended to provide insight into which breast cancer patients need adjuvant locoregional radiotherapy following postchemotherapy surgery, coauthor Liesbeth Boersma, MD, PhD, a radiation oncologist at Maastricht University Medical Center, said in an interview. “It is not yet known which of these patients would benefit from adjuvant locoregional radiotherapy and to what extent the response of the tumor to the chemotherapy should be taken into account.”

For the study, believed to be the first prospective analysis tackling this topic, researchers tracked 838 patients in The Netherlands who were treated for cT1-2N1 breast cancer with primary chemotherapy and surgery of the breast and axilla from 2011-2015. Tumors were less than 5 cm and metastases were one to three axillary nodes.

The subjects were divided into groups based on risk of locoregional recurrence, and each group underwent different therapies.

  • Low-risk group: no metastases were present in the nodes (n = 291). “We omitted regional radiotherapy, and we omitted RT of the chest wall in case of a mastectomy. After breast conserving surgery, regular RT of the breast was recommended,” Dr. de Wild said.
  • Intermediate-risk group, one to three metastases were still present (n = 370). “We omitted regional radiotherapy, but irradiated the chest wall or breast,” she said.
  • High-risk group, three metastases were present (n = 177). “We did not de-escalate, and all patients were treated with locoregional RT,” she said.

According to the study, “the 5-year locoregional recurrence rate in all patients was 2.2% (95% confidence interval, 1.4-3.4). The 5-year locoregional recurrence rate was 2.1% (95% CI, 0.9-4.3) in the low-risk group, 2.2% (95% CI, 1.0-4.1) in the intermediate-risk group, and 2.3% (95% CI, 0.8-5.5) in the high-risk group.”

In 26% of cases, patients received more radiotherapy than the study guidelines suggested. “Remarkably,” the researchers wrote, “this did not seem to affect locoregional recurrence rate, recurrence­-free interval, and overall survival in a statistically significant or clinically relevant way.”

As for limitations, the authors noted that, “in each risk group, the actual sample size treated according to the study guideline was smaller than required based on the power calculation. Nevertheless, when performing the analyses in the subset of patients treated according to the study guideline, the upper limit of 95% CI of 5­-year locoregional recurrence rate did not exceed 7.8%.”

The study authors wrote that, “in the future, the results of this study might lead to more frequent omission of locoregional radiotherapy, which could result in lower morbidity and a better quality of life for patients with breast cancer who are receiving primary chemotherapy.”

However, Dr. de Wild said randomized trials are necessary “to investigate how treatment can be individualized further, i.e., by taking into account specific tumor characteristics.” Also, most patients in the study underwent axillary lymph node dissection, “while patients in daily practice may instead undergo targeted axillary dissection. Future studies are needed to determine if less radiotherapy is also safe in patients in whom axillary lymph node dissection is omitted.”

The study was funded by the Dutch Cancer Society. One coauthor reported a pending patent plus grants from AstraZeneca, Eurocept Plaza, Roche, Genentech, Gilead Sciences, Tesaro, Novartis, Dutch Cancer Society, ZonMw, and A Sister’s Hope; as well as consulting fees and other financial support from a variety of pharmaceutical companies. The other authors had no disclosures.

A new study suggests that oncologists can safely pull back on standard locoregional radiotherapy (RT) in select patients with cT1-2N1 breast cancer who are treated with primary chemotherapy prior to surgery. The key is to divide patients by risk level and treat them according to the study’s guidelines, the researchers reported.

“We think this study is a good step towards de-escalation, which should lead to equal survival chances but better quality of life,” lead study author Sabine de Wild, MD, a PhD student at Maastricht (the Netherlands) University Medical Center, said in an interview.

The study, published in The Lancet Oncology, was intended to provide insight into which breast cancer patients need adjuvant locoregional radiotherapy following postchemotherapy surgery, coauthor Liesbeth Boersma, MD, PhD, a radiation oncologist at Maastricht University Medical Center, said in an interview. “It is not yet known which of these patients would benefit from adjuvant locoregional radiotherapy and to what extent the response of the tumor to the chemotherapy should be taken into account.”

For the study, believed to be the first prospective analysis tackling this topic, researchers tracked 838 patients in The Netherlands who were treated for cT1-2N1 breast cancer with primary chemotherapy and surgery of the breast and axilla from 2011-2015. Tumors were less than 5 cm and metastases were one to three axillary nodes.

The subjects were divided into groups based on risk of locoregional recurrence, and each group underwent different therapies.

  • Low-risk group: no metastases were present in the nodes (n = 291). “We omitted regional radiotherapy, and we omitted RT of the chest wall in case of a mastectomy. After breast conserving surgery, regular RT of the breast was recommended,” Dr. de Wild said.
  • Intermediate-risk group, one to three metastases were still present (n = 370). “We omitted regional radiotherapy, but irradiated the chest wall or breast,” she said.
  • High-risk group, three metastases were present (n = 177). “We did not de-escalate, and all patients were treated with locoregional RT,” she said.

According to the study, “the 5-year locoregional recurrence rate in all patients was 2.2% (95% confidence interval, 1.4-3.4). The 5-year locoregional recurrence rate was 2.1% (95% CI, 0.9-4.3) in the low-risk group, 2.2% (95% CI, 1.0-4.1) in the intermediate-risk group, and 2.3% (95% CI, 0.8-5.5) in the high-risk group.”

In 26% of cases, patients received more radiotherapy than the study guidelines suggested. “Remarkably,” the researchers wrote, “this did not seem to affect locoregional recurrence rate, recurrence­-free interval, and overall survival in a statistically significant or clinically relevant way.”

As for limitations, the authors noted that, “in each risk group, the actual sample size treated according to the study guideline was smaller than required based on the power calculation. Nevertheless, when performing the analyses in the subset of patients treated according to the study guideline, the upper limit of 95% CI of 5­-year locoregional recurrence rate did not exceed 7.8%.”

The study authors wrote that, “in the future, the results of this study might lead to more frequent omission of locoregional radiotherapy, which could result in lower morbidity and a better quality of life for patients with breast cancer who are receiving primary chemotherapy.”

However, Dr. de Wild said randomized trials are necessary “to investigate how treatment can be individualized further, i.e., by taking into account specific tumor characteristics.” Also, most patients in the study underwent axillary lymph node dissection, “while patients in daily practice may instead undergo targeted axillary dissection. Future studies are needed to determine if less radiotherapy is also safe in patients in whom axillary lymph node dissection is omitted.”

The study was funded by the Dutch Cancer Society. One coauthor reported a pending patent plus grants from AstraZeneca, Eurocept Plaza, Roche, Genentech, Gilead Sciences, Tesaro, Novartis, Dutch Cancer Society, ZonMw, and A Sister’s Hope; as well as consulting fees and other financial support from a variety of pharmaceutical companies. The other authors had no disclosures.

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FROM THE LANCET ONCOLOGY

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Oncologists often misinterpret posttreatment HNSCC scan details

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Patient outcomes could be threatened because of misinterpretation by oncologic surgeons of free-form posttreatment radiological reports in head and neck squamous cell carcinoma (HNSCC), a new study finds.

“Clinician perception of patient response from the post-RT [radiation treament] PET/CT free-form report is unreliable and does not consistently reflect the radiologist’s intended meaning, which was strongly associated with survival,” researchers wrote in a study published Aug. 18 in JAMA Otolaryngology-Head & Neck Surgery. They found “minimal agreement between clinicians’ consensus perspective on the patient’s response status derived from free-form imaging reports and the criterion standard response category assigned by a nuclear medicine specialist after PET/CT image review.”

According to radiation oncologist Ryan T. Hughes, MD, and colleagues at Wake Forest University, Winston-Salem, N.C., it’s common for patients with HNSCC to get PET, CT, or PET/CT imaging following treatment in order to assess how patients responded. Accurate communication about the results is essential to determining next steps, they write.

However, they write, “to our knowledge there is no universally accepted standardized method for communicating results,” such as whether there’s been a complete or partial response. Discrepancies between a radiological posttreatment report and an oncologist’s perception of the findings “may contribute to unnecessary patient care complexities, including elevated patient anxiety, unnecessary follow-up testing/procedures, and failure to recognize and adequately treat residual, recurrent, or progressive disease,” the researchers write.

For the new study, the authors tracked 171 patients (26.3% women, median age 61 years, ethnicity not provided), mainly (87%) with stage III-IV disease. Most (89%) received concurrent chemotherapy, and 30% received radiotherapy following operations.

Four oncologists reviewed free-form radiologic reports and determined whether the patient had a complete, indeterminate or partial response, or progressive disease. “Next, the group conferred to assign a consensus clinician MDS [modified Deauville score] and associated response category to assess the percentage of agreement with the criterion standard nuclear medicine physician MDS response derived from PET/CT image review.”

The researchers found that “interrater reliability of clinician-perceived post-RT PET/CT response was moderate [k = 0.680; 95% confidence interval, 0.638-0.721], and there was minimal reliability and low rate of agreement between clinician perception and radiologist-intended PET/CT response [63.7%; k = 0.365; 95% CI, 0.251-0.478).”

The clinicians were more likely to perceive patients as having an indeterminate response (28.1%), compared with the radiologists (9.3%). “There were 16 instances of significant discordance: 7 patients for whom the clinician perception MDS was 1 to 2 and nuclear medicine MDS 3 to 4, and 9 patients for whom the clinician perception MDS was 3 to 4 and nuclear medicine MDS 1 to 2.”

Due to statistical limitations, the researchers were unable to link the MDS scores to prognoses. The researchers suggest it’s time to further standardize the assessment of posttreatment responses to therapy. They add that “the decision to use a standardized interpretation and reporting system rather than free-form reporting is more important than the specific system selected.”

As for next steps, the researchers report that “prospective studies of post-RT PET/CT standardized reporting among patients with HNSCC are warranted, and a prospective implementation study of this workflow is planned at our institution.”

The study was funded by the National Center for Advancing Translational Sciences and National Institutes of Health. The authors had no disclosures.

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Patient outcomes could be threatened because of misinterpretation by oncologic surgeons of free-form posttreatment radiological reports in head and neck squamous cell carcinoma (HNSCC), a new study finds.

“Clinician perception of patient response from the post-RT [radiation treament] PET/CT free-form report is unreliable and does not consistently reflect the radiologist’s intended meaning, which was strongly associated with survival,” researchers wrote in a study published Aug. 18 in JAMA Otolaryngology-Head & Neck Surgery. They found “minimal agreement between clinicians’ consensus perspective on the patient’s response status derived from free-form imaging reports and the criterion standard response category assigned by a nuclear medicine specialist after PET/CT image review.”

According to radiation oncologist Ryan T. Hughes, MD, and colleagues at Wake Forest University, Winston-Salem, N.C., it’s common for patients with HNSCC to get PET, CT, or PET/CT imaging following treatment in order to assess how patients responded. Accurate communication about the results is essential to determining next steps, they write.

However, they write, “to our knowledge there is no universally accepted standardized method for communicating results,” such as whether there’s been a complete or partial response. Discrepancies between a radiological posttreatment report and an oncologist’s perception of the findings “may contribute to unnecessary patient care complexities, including elevated patient anxiety, unnecessary follow-up testing/procedures, and failure to recognize and adequately treat residual, recurrent, or progressive disease,” the researchers write.

For the new study, the authors tracked 171 patients (26.3% women, median age 61 years, ethnicity not provided), mainly (87%) with stage III-IV disease. Most (89%) received concurrent chemotherapy, and 30% received radiotherapy following operations.

Four oncologists reviewed free-form radiologic reports and determined whether the patient had a complete, indeterminate or partial response, or progressive disease. “Next, the group conferred to assign a consensus clinician MDS [modified Deauville score] and associated response category to assess the percentage of agreement with the criterion standard nuclear medicine physician MDS response derived from PET/CT image review.”

The researchers found that “interrater reliability of clinician-perceived post-RT PET/CT response was moderate [k = 0.680; 95% confidence interval, 0.638-0.721], and there was minimal reliability and low rate of agreement between clinician perception and radiologist-intended PET/CT response [63.7%; k = 0.365; 95% CI, 0.251-0.478).”

The clinicians were more likely to perceive patients as having an indeterminate response (28.1%), compared with the radiologists (9.3%). “There were 16 instances of significant discordance: 7 patients for whom the clinician perception MDS was 1 to 2 and nuclear medicine MDS 3 to 4, and 9 patients for whom the clinician perception MDS was 3 to 4 and nuclear medicine MDS 1 to 2.”

Due to statistical limitations, the researchers were unable to link the MDS scores to prognoses. The researchers suggest it’s time to further standardize the assessment of posttreatment responses to therapy. They add that “the decision to use a standardized interpretation and reporting system rather than free-form reporting is more important than the specific system selected.”

As for next steps, the researchers report that “prospective studies of post-RT PET/CT standardized reporting among patients with HNSCC are warranted, and a prospective implementation study of this workflow is planned at our institution.”

The study was funded by the National Center for Advancing Translational Sciences and National Institutes of Health. The authors had no disclosures.

Patient outcomes could be threatened because of misinterpretation by oncologic surgeons of free-form posttreatment radiological reports in head and neck squamous cell carcinoma (HNSCC), a new study finds.

“Clinician perception of patient response from the post-RT [radiation treament] PET/CT free-form report is unreliable and does not consistently reflect the radiologist’s intended meaning, which was strongly associated with survival,” researchers wrote in a study published Aug. 18 in JAMA Otolaryngology-Head & Neck Surgery. They found “minimal agreement between clinicians’ consensus perspective on the patient’s response status derived from free-form imaging reports and the criterion standard response category assigned by a nuclear medicine specialist after PET/CT image review.”

According to radiation oncologist Ryan T. Hughes, MD, and colleagues at Wake Forest University, Winston-Salem, N.C., it’s common for patients with HNSCC to get PET, CT, or PET/CT imaging following treatment in order to assess how patients responded. Accurate communication about the results is essential to determining next steps, they write.

However, they write, “to our knowledge there is no universally accepted standardized method for communicating results,” such as whether there’s been a complete or partial response. Discrepancies between a radiological posttreatment report and an oncologist’s perception of the findings “may contribute to unnecessary patient care complexities, including elevated patient anxiety, unnecessary follow-up testing/procedures, and failure to recognize and adequately treat residual, recurrent, or progressive disease,” the researchers write.

For the new study, the authors tracked 171 patients (26.3% women, median age 61 years, ethnicity not provided), mainly (87%) with stage III-IV disease. Most (89%) received concurrent chemotherapy, and 30% received radiotherapy following operations.

Four oncologists reviewed free-form radiologic reports and determined whether the patient had a complete, indeterminate or partial response, or progressive disease. “Next, the group conferred to assign a consensus clinician MDS [modified Deauville score] and associated response category to assess the percentage of agreement with the criterion standard nuclear medicine physician MDS response derived from PET/CT image review.”

The researchers found that “interrater reliability of clinician-perceived post-RT PET/CT response was moderate [k = 0.680; 95% confidence interval, 0.638-0.721], and there was minimal reliability and low rate of agreement between clinician perception and radiologist-intended PET/CT response [63.7%; k = 0.365; 95% CI, 0.251-0.478).”

The clinicians were more likely to perceive patients as having an indeterminate response (28.1%), compared with the radiologists (9.3%). “There were 16 instances of significant discordance: 7 patients for whom the clinician perception MDS was 1 to 2 and nuclear medicine MDS 3 to 4, and 9 patients for whom the clinician perception MDS was 3 to 4 and nuclear medicine MDS 1 to 2.”

Due to statistical limitations, the researchers were unable to link the MDS scores to prognoses. The researchers suggest it’s time to further standardize the assessment of posttreatment responses to therapy. They add that “the decision to use a standardized interpretation and reporting system rather than free-form reporting is more important than the specific system selected.”

As for next steps, the researchers report that “prospective studies of post-RT PET/CT standardized reporting among patients with HNSCC are warranted, and a prospective implementation study of this workflow is planned at our institution.”

The study was funded by the National Center for Advancing Translational Sciences and National Institutes of Health. The authors had no disclosures.

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FROM JAMA OTOLARYNGOLOGY–HEAD & NECK SURGERY

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Thyroid autoimmunity linked to cancer, but screening not advised

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A new study provides more evidence that people with thyroid autoimmunity are more likely than are others to develop papillary thyroid cancer (odds ratio [OR] = 1.90, 95% confidence interval [CI], 1.33-2.70), although the overall risk remains very low. 
Researchers aren't recommending routine screening in all patients with thyroid autoimmunity, but they're calling for more research into whether it's a good idea in severe cases. "This is the one circumstance where screening for subclinical disease could make sense," said Donald McLeod, MPH, PhD, an epidemiologist at Royal Brisbane & Women's Hospital in Australia and lead author of the study, published in the Journal of Clinical Oncology. "However, more research is needed because our study is the first to show this result, and we need to prove that screening would make a difference to the prognosis of these patients." 
According to Dr. McLeod, "doctors and patients have been wondering about the connection between thyroid autoimmunity and thyroid cancer for many years. In fact, the first report was in 1955. While the association was plausible, all previous studies had potential for biases that could have influenced the results." 
For example, he said, multiple studies didn't control for confounders, while others didn't account for the possibility that cancer could have triggered an immune response. "Other case-control studies could have been affected by selection bias, where a diagnosis of thyroid autoimmunity leads to thyroid cancer identification and entry into the study," he said. "Finally, medical surveillance of people diagnosed with thyroid autoimmunity could lead to overdiagnosis, where small, subclinical cancers are diagnosed in those patients but not identified in people who are not under medical follow-up." 
For the new retrospective case-control study, researchers compared 451 active-duty members of the U.S. military who developed papillary thyroid cancer from the period of 1996-2014 to matched controls (61% of all subjects were men and the mean age was 36). Those with cancer had their serum collected 3-5 years and 7-10 years before the date of diagnosis - the index date for all subjects. Some of those considered to have thyroid autoimmunity had conditions such as Graves' disease and Hashimoto's thyroiditis. 
"Eighty-five percent of cases (379 of 451) had a thyroid-related diagnosis recorded ... before their index date, compared with 5% of controls," the researchers reported. "Most cases (80%) had classical papillary thyroid cancer, with the rest having the follicular variant of papillary thyroid cancer."  
After adjustment to account for various confounders, those who were positive for thyroid peroxidase antibodies 7-10 years prior to the index date were more likely to have developed thyroid cancer (OR = 1.90, 95% CI, 1.33-2.70). "The results could not be fully explained by diagnosis of thyroid autoimmunity," the researchers reported, "although when autoimmunity had been identified, thyroid cancers were diagnosed at a very early stage." 
Two groups - those with the highest thyroid antibody levels and women - faced the greatest risk, Dr. McLeod said. The results regarding women were the most surprising in the study, he said. "This is the first time this has been found. We think this result needs to be confirmed. If true, it could explain why women have a three-times-higher risk of thyroid cancer than men." 
The overall incidence of thyroid cancer in the U.S. was estimated at 13.49 per 100,000 person-years in 2018, with women (76% of cases) and Whites (81%) accounting for the majority. Rates have nearly doubled since 2000. The authors of a 2022 report that disclosed these numbers suggest the rise is due to overdiagnosis of small tumors. 
It's not clear why thyroid autoimmunity and thyroid cancer may be linked. "Chronic inflammation from thyroid autoimmunity could cause thyroid cancer, as chronic inflammation in other organs precedes cancers at those sites," Dr. McLeod said. "Alternatively, thyroid autoimmunity could appear to be associated with thyroid cancer because of biases inherent in previous studies, including previous diagnosis of autoimmunity. Thyroid cancer could also induce an immune response, which mimics thyroid autoimmunity and could bias assessment." 
As for screening of patients with thyroid autoimmunity, "the main danger is that you will commonly identify small thyroid cancers that would never become clinically apparent," he said. "This leads to unnecessary treatments that can cause complications and give people a cancer label, which can also cause harm. Diagnosis and treatment guidelines recommend against screening the general population for this reason." 
Many of those with thyroid autoimmunity developed small cancers, he said, most likely "detected from ultrasound being performed because autoimmune thyroid disease was known. If all patients with thyroid autoimmunity were screened for thyroid cancer, the likelihood is that many people's cancers would be overdiagnosed." 
The study was funded by the Walton Family Foundation. Dr. McLeod reports no disclosures. Some of the authors report various relationships with industry.

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A new study provides more evidence that people with thyroid autoimmunity are more likely than are others to develop papillary thyroid cancer (odds ratio [OR] = 1.90, 95% confidence interval [CI], 1.33-2.70), although the overall risk remains very low. 
Researchers aren't recommending routine screening in all patients with thyroid autoimmunity, but they're calling for more research into whether it's a good idea in severe cases. "This is the one circumstance where screening for subclinical disease could make sense," said Donald McLeod, MPH, PhD, an epidemiologist at Royal Brisbane & Women's Hospital in Australia and lead author of the study, published in the Journal of Clinical Oncology. "However, more research is needed because our study is the first to show this result, and we need to prove that screening would make a difference to the prognosis of these patients." 
According to Dr. McLeod, "doctors and patients have been wondering about the connection between thyroid autoimmunity and thyroid cancer for many years. In fact, the first report was in 1955. While the association was plausible, all previous studies had potential for biases that could have influenced the results." 
For example, he said, multiple studies didn't control for confounders, while others didn't account for the possibility that cancer could have triggered an immune response. "Other case-control studies could have been affected by selection bias, where a diagnosis of thyroid autoimmunity leads to thyroid cancer identification and entry into the study," he said. "Finally, medical surveillance of people diagnosed with thyroid autoimmunity could lead to overdiagnosis, where small, subclinical cancers are diagnosed in those patients but not identified in people who are not under medical follow-up." 
For the new retrospective case-control study, researchers compared 451 active-duty members of the U.S. military who developed papillary thyroid cancer from the period of 1996-2014 to matched controls (61% of all subjects were men and the mean age was 36). Those with cancer had their serum collected 3-5 years and 7-10 years before the date of diagnosis - the index date for all subjects. Some of those considered to have thyroid autoimmunity had conditions such as Graves' disease and Hashimoto's thyroiditis. 
"Eighty-five percent of cases (379 of 451) had a thyroid-related diagnosis recorded ... before their index date, compared with 5% of controls," the researchers reported. "Most cases (80%) had classical papillary thyroid cancer, with the rest having the follicular variant of papillary thyroid cancer."  
After adjustment to account for various confounders, those who were positive for thyroid peroxidase antibodies 7-10 years prior to the index date were more likely to have developed thyroid cancer (OR = 1.90, 95% CI, 1.33-2.70). "The results could not be fully explained by diagnosis of thyroid autoimmunity," the researchers reported, "although when autoimmunity had been identified, thyroid cancers were diagnosed at a very early stage." 
Two groups - those with the highest thyroid antibody levels and women - faced the greatest risk, Dr. McLeod said. The results regarding women were the most surprising in the study, he said. "This is the first time this has been found. We think this result needs to be confirmed. If true, it could explain why women have a three-times-higher risk of thyroid cancer than men." 
The overall incidence of thyroid cancer in the U.S. was estimated at 13.49 per 100,000 person-years in 2018, with women (76% of cases) and Whites (81%) accounting for the majority. Rates have nearly doubled since 2000. The authors of a 2022 report that disclosed these numbers suggest the rise is due to overdiagnosis of small tumors. 
It's not clear why thyroid autoimmunity and thyroid cancer may be linked. "Chronic inflammation from thyroid autoimmunity could cause thyroid cancer, as chronic inflammation in other organs precedes cancers at those sites," Dr. McLeod said. "Alternatively, thyroid autoimmunity could appear to be associated with thyroid cancer because of biases inherent in previous studies, including previous diagnosis of autoimmunity. Thyroid cancer could also induce an immune response, which mimics thyroid autoimmunity and could bias assessment." 
As for screening of patients with thyroid autoimmunity, "the main danger is that you will commonly identify small thyroid cancers that would never become clinically apparent," he said. "This leads to unnecessary treatments that can cause complications and give people a cancer label, which can also cause harm. Diagnosis and treatment guidelines recommend against screening the general population for this reason." 
Many of those with thyroid autoimmunity developed small cancers, he said, most likely "detected from ultrasound being performed because autoimmune thyroid disease was known. If all patients with thyroid autoimmunity were screened for thyroid cancer, the likelihood is that many people's cancers would be overdiagnosed." 
The study was funded by the Walton Family Foundation. Dr. McLeod reports no disclosures. Some of the authors report various relationships with industry.

A new study provides more evidence that people with thyroid autoimmunity are more likely than are others to develop papillary thyroid cancer (odds ratio [OR] = 1.90, 95% confidence interval [CI], 1.33-2.70), although the overall risk remains very low. 
Researchers aren't recommending routine screening in all patients with thyroid autoimmunity, but they're calling for more research into whether it's a good idea in severe cases. "This is the one circumstance where screening for subclinical disease could make sense," said Donald McLeod, MPH, PhD, an epidemiologist at Royal Brisbane & Women's Hospital in Australia and lead author of the study, published in the Journal of Clinical Oncology. "However, more research is needed because our study is the first to show this result, and we need to prove that screening would make a difference to the prognosis of these patients." 
According to Dr. McLeod, "doctors and patients have been wondering about the connection between thyroid autoimmunity and thyroid cancer for many years. In fact, the first report was in 1955. While the association was plausible, all previous studies had potential for biases that could have influenced the results." 
For example, he said, multiple studies didn't control for confounders, while others didn't account for the possibility that cancer could have triggered an immune response. "Other case-control studies could have been affected by selection bias, where a diagnosis of thyroid autoimmunity leads to thyroid cancer identification and entry into the study," he said. "Finally, medical surveillance of people diagnosed with thyroid autoimmunity could lead to overdiagnosis, where small, subclinical cancers are diagnosed in those patients but not identified in people who are not under medical follow-up." 
For the new retrospective case-control study, researchers compared 451 active-duty members of the U.S. military who developed papillary thyroid cancer from the period of 1996-2014 to matched controls (61% of all subjects were men and the mean age was 36). Those with cancer had their serum collected 3-5 years and 7-10 years before the date of diagnosis - the index date for all subjects. Some of those considered to have thyroid autoimmunity had conditions such as Graves' disease and Hashimoto's thyroiditis. 
"Eighty-five percent of cases (379 of 451) had a thyroid-related diagnosis recorded ... before their index date, compared with 5% of controls," the researchers reported. "Most cases (80%) had classical papillary thyroid cancer, with the rest having the follicular variant of papillary thyroid cancer."  
After adjustment to account for various confounders, those who were positive for thyroid peroxidase antibodies 7-10 years prior to the index date were more likely to have developed thyroid cancer (OR = 1.90, 95% CI, 1.33-2.70). "The results could not be fully explained by diagnosis of thyroid autoimmunity," the researchers reported, "although when autoimmunity had been identified, thyroid cancers were diagnosed at a very early stage." 
Two groups - those with the highest thyroid antibody levels and women - faced the greatest risk, Dr. McLeod said. The results regarding women were the most surprising in the study, he said. "This is the first time this has been found. We think this result needs to be confirmed. If true, it could explain why women have a three-times-higher risk of thyroid cancer than men." 
The overall incidence of thyroid cancer in the U.S. was estimated at 13.49 per 100,000 person-years in 2018, with women (76% of cases) and Whites (81%) accounting for the majority. Rates have nearly doubled since 2000. The authors of a 2022 report that disclosed these numbers suggest the rise is due to overdiagnosis of small tumors. 
It's not clear why thyroid autoimmunity and thyroid cancer may be linked. "Chronic inflammation from thyroid autoimmunity could cause thyroid cancer, as chronic inflammation in other organs precedes cancers at those sites," Dr. McLeod said. "Alternatively, thyroid autoimmunity could appear to be associated with thyroid cancer because of biases inherent in previous studies, including previous diagnosis of autoimmunity. Thyroid cancer could also induce an immune response, which mimics thyroid autoimmunity and could bias assessment." 
As for screening of patients with thyroid autoimmunity, "the main danger is that you will commonly identify small thyroid cancers that would never become clinically apparent," he said. "This leads to unnecessary treatments that can cause complications and give people a cancer label, which can also cause harm. Diagnosis and treatment guidelines recommend against screening the general population for this reason." 
Many of those with thyroid autoimmunity developed small cancers, he said, most likely "detected from ultrasound being performed because autoimmune thyroid disease was known. If all patients with thyroid autoimmunity were screened for thyroid cancer, the likelihood is that many people's cancers would be overdiagnosed." 
The study was funded by the Walton Family Foundation. Dr. McLeod reports no disclosures. Some of the authors report various relationships with industry.

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FROM THE JOURNAL OF CLINICAL ONCOLOGY

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‘Molecular map’ of CLL yields fresh genetic insights

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An international team of researchers have developed a “molecular map” of chronic lymphocytic leukemia (CLL) and used it to refine genetic subtypes and variations that appear to be linked to clinical outcomes.

Released in a report in Nature Genetics, the map has doubled the number of genetic traits linked the disease from around 100 to 202, lead author Binyamin A. Knisbacher, PhD, a postdoctoral fellow at the Broad Institute of MIT and Harvard Medical Schoo, Boston, said in an interview.

“It also delineated the molecular landscape of the two immunoglobulin gene (IGHV) subtypes, refined CLL subtyping, and built richer genetic prognostic models,” he said.

According to Dr. Knisbacher, CLL “has been at the forefront of genomic discovery,” and research has shown that there’s a wide variety of somatic mutations that drive CLL initiation across the patient population. However, as many as 10% of cases don’t appear to be driven by any known genetic variation, he said, and there’s a need to identify more subtypes and “build richer prognostic models of patient survival” based on genetics and multiomics such as genomics, transcriptomics, and epigenomics.

For the new study, researchers analyzed RNA and DNA from 1,095 patients with CLL and 54 patients with monoclonal B cell lymphocytosis and built what they say is the largest CLL dataset in existence. It’s twice the size of previous datasets, Dr. Knisbacher said.

“We found that RNA expression data was extremely informative for characterizing CLL,” Dr. Knisbacher said. “The RNA expression subtypes refined the ‘classic’ two IGHV subtypes. It is well documented that patients with U-CLL (IGHV-unmutated CLL) have substantially worse clinical outcome in comparison to M-CLL patients (IGHV-mutated CLLs). We found that M-CLLs that have RNA expression profiles similar to U-CLLs have worse survival than M-CLLs with a typical expression profile. Failure-free survival was 50% shorter – 5.3 versus 10.7 years median failure-free survival.”

In addition, he said, “U-CLLs with expression similar to M-CLLs had better survival than U-CLLs with an RNA expression profile typical to U-CLLs.”

The researchers have made their molecular map publicly available at https://cllmap.org/. Researchers can use it “to discover more about each subtype of CLL, and these future studies can help to improve clinical prognosis for the benefit of the patient,” Dr. Knisbacher said.

The study authors added that “this molecular foundation may allow for better prediction of response to therapy or provide the basis for rational combination of novel agents.”

Lee Greenberger, PhD, chief science officer of the Leukemia & Lymphoma Society, said in an interview that the study “provides foundational data further subtyping CLL patients and outcomes. It identifies new targets for therapy or diagnostic predictions in the future. This type of foundational work has proven invaluable in the development of new medicines for cancer in general.”

While there are many medications that have improved therapeutic outcomes in CLL, he added, “cures – or life-long disease control –remain elusive for many patients. Therefore, new molecular insights are needed that could personalize therapies or even lead to entirely new therapies.”

In addition, he said, although prevention of CLL still remains elusive, “it is conceivable that some of the mutations found in this paper occur early in the CLL trajectory, perhaps even before the disease is presented clinically.”

The study was funded by the National Institutes of Health and the Broad/IBM Cancer Resistance Research Project. Dr. Knisbacher and several other authors disclose that they are inventors on a patent related to CLL. Several authors report various relationships with industry. Dr. Greenberger has no disclosures.
 

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An international team of researchers have developed a “molecular map” of chronic lymphocytic leukemia (CLL) and used it to refine genetic subtypes and variations that appear to be linked to clinical outcomes.

Released in a report in Nature Genetics, the map has doubled the number of genetic traits linked the disease from around 100 to 202, lead author Binyamin A. Knisbacher, PhD, a postdoctoral fellow at the Broad Institute of MIT and Harvard Medical Schoo, Boston, said in an interview.

“It also delineated the molecular landscape of the two immunoglobulin gene (IGHV) subtypes, refined CLL subtyping, and built richer genetic prognostic models,” he said.

According to Dr. Knisbacher, CLL “has been at the forefront of genomic discovery,” and research has shown that there’s a wide variety of somatic mutations that drive CLL initiation across the patient population. However, as many as 10% of cases don’t appear to be driven by any known genetic variation, he said, and there’s a need to identify more subtypes and “build richer prognostic models of patient survival” based on genetics and multiomics such as genomics, transcriptomics, and epigenomics.

For the new study, researchers analyzed RNA and DNA from 1,095 patients with CLL and 54 patients with monoclonal B cell lymphocytosis and built what they say is the largest CLL dataset in existence. It’s twice the size of previous datasets, Dr. Knisbacher said.

“We found that RNA expression data was extremely informative for characterizing CLL,” Dr. Knisbacher said. “The RNA expression subtypes refined the ‘classic’ two IGHV subtypes. It is well documented that patients with U-CLL (IGHV-unmutated CLL) have substantially worse clinical outcome in comparison to M-CLL patients (IGHV-mutated CLLs). We found that M-CLLs that have RNA expression profiles similar to U-CLLs have worse survival than M-CLLs with a typical expression profile. Failure-free survival was 50% shorter – 5.3 versus 10.7 years median failure-free survival.”

In addition, he said, “U-CLLs with expression similar to M-CLLs had better survival than U-CLLs with an RNA expression profile typical to U-CLLs.”

The researchers have made their molecular map publicly available at https://cllmap.org/. Researchers can use it “to discover more about each subtype of CLL, and these future studies can help to improve clinical prognosis for the benefit of the patient,” Dr. Knisbacher said.

The study authors added that “this molecular foundation may allow for better prediction of response to therapy or provide the basis for rational combination of novel agents.”

Lee Greenberger, PhD, chief science officer of the Leukemia & Lymphoma Society, said in an interview that the study “provides foundational data further subtyping CLL patients and outcomes. It identifies new targets for therapy or diagnostic predictions in the future. This type of foundational work has proven invaluable in the development of new medicines for cancer in general.”

While there are many medications that have improved therapeutic outcomes in CLL, he added, “cures – or life-long disease control –remain elusive for many patients. Therefore, new molecular insights are needed that could personalize therapies or even lead to entirely new therapies.”

In addition, he said, although prevention of CLL still remains elusive, “it is conceivable that some of the mutations found in this paper occur early in the CLL trajectory, perhaps even before the disease is presented clinically.”

The study was funded by the National Institutes of Health and the Broad/IBM Cancer Resistance Research Project. Dr. Knisbacher and several other authors disclose that they are inventors on a patent related to CLL. Several authors report various relationships with industry. Dr. Greenberger has no disclosures.
 

An international team of researchers have developed a “molecular map” of chronic lymphocytic leukemia (CLL) and used it to refine genetic subtypes and variations that appear to be linked to clinical outcomes.

Released in a report in Nature Genetics, the map has doubled the number of genetic traits linked the disease from around 100 to 202, lead author Binyamin A. Knisbacher, PhD, a postdoctoral fellow at the Broad Institute of MIT and Harvard Medical Schoo, Boston, said in an interview.

“It also delineated the molecular landscape of the two immunoglobulin gene (IGHV) subtypes, refined CLL subtyping, and built richer genetic prognostic models,” he said.

According to Dr. Knisbacher, CLL “has been at the forefront of genomic discovery,” and research has shown that there’s a wide variety of somatic mutations that drive CLL initiation across the patient population. However, as many as 10% of cases don’t appear to be driven by any known genetic variation, he said, and there’s a need to identify more subtypes and “build richer prognostic models of patient survival” based on genetics and multiomics such as genomics, transcriptomics, and epigenomics.

For the new study, researchers analyzed RNA and DNA from 1,095 patients with CLL and 54 patients with monoclonal B cell lymphocytosis and built what they say is the largest CLL dataset in existence. It’s twice the size of previous datasets, Dr. Knisbacher said.

“We found that RNA expression data was extremely informative for characterizing CLL,” Dr. Knisbacher said. “The RNA expression subtypes refined the ‘classic’ two IGHV subtypes. It is well documented that patients with U-CLL (IGHV-unmutated CLL) have substantially worse clinical outcome in comparison to M-CLL patients (IGHV-mutated CLLs). We found that M-CLLs that have RNA expression profiles similar to U-CLLs have worse survival than M-CLLs with a typical expression profile. Failure-free survival was 50% shorter – 5.3 versus 10.7 years median failure-free survival.”

In addition, he said, “U-CLLs with expression similar to M-CLLs had better survival than U-CLLs with an RNA expression profile typical to U-CLLs.”

The researchers have made their molecular map publicly available at https://cllmap.org/. Researchers can use it “to discover more about each subtype of CLL, and these future studies can help to improve clinical prognosis for the benefit of the patient,” Dr. Knisbacher said.

The study authors added that “this molecular foundation may allow for better prediction of response to therapy or provide the basis for rational combination of novel agents.”

Lee Greenberger, PhD, chief science officer of the Leukemia & Lymphoma Society, said in an interview that the study “provides foundational data further subtyping CLL patients and outcomes. It identifies new targets for therapy or diagnostic predictions in the future. This type of foundational work has proven invaluable in the development of new medicines for cancer in general.”

While there are many medications that have improved therapeutic outcomes in CLL, he added, “cures – or life-long disease control –remain elusive for many patients. Therefore, new molecular insights are needed that could personalize therapies or even lead to entirely new therapies.”

In addition, he said, although prevention of CLL still remains elusive, “it is conceivable that some of the mutations found in this paper occur early in the CLL trajectory, perhaps even before the disease is presented clinically.”

The study was funded by the National Institutes of Health and the Broad/IBM Cancer Resistance Research Project. Dr. Knisbacher and several other authors disclose that they are inventors on a patent related to CLL. Several authors report various relationships with industry. Dr. Greenberger has no disclosures.
 

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Young children with leukemia are outliving teens

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Two new studies offer insights into leukemia survival rates in the United States. From 2000 to 2014, a drop in mortality among children spurred a rise in 5-year leukemia survival rates among patients aged 0-24. But adolescents and young adults who survive 5 years after diagnosis face an ongoing higher risk of death, recent research revealed, and their long-term survival is lower compared to that of the general population.

“Outcomes are improving. However, additional efforts, support, and resources are needed to further improve short- and long-term survival for acute leukemia survivors. Targeted efforts focused on populations that face greater disparities in their survival are needed to move the needle faster,” Michael Roth, MD, codirector of the Adolescent and Young Adult Oncology Program at the University of Texas M.D. Anderson Cancer Center, said in an interview.

In one study, released in The Lancet Child & Adolescent Health, an international team of researchers tracked survival outcomes from various types of leukemia in 61 nations. The study focused on the years 2000-2014 and followed patients aged 0-24.

“Age-standardized 5-year net survival in children, adolescents, and young adults for all leukemias combined during 2010-14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia,” the researchers wrote. “Throughout 2000-14, survival from all leukemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries.”

The U.S. data came from 41 states that cover 86% of the nation’s population, lead author Naomi Ssenyonga, a research fellow at London School of Hygiene & Tropical Medicine, said in an interview.

The 5-year survival rate for acute lymphoid leukemia (ALL) rose from 80% during 2000-2004 to 86% during 2010-2014. Survival in patients with acute myeloid leukemia (AML) was lower than for other subtypes: 66% in 2010-2014 vs. 57% in 2000-2004.

In regard to all leukemias, “we noted a steady increase in the U.S. of 6 percentage points in 5-year survival, up from 77% for patients diagnosed during 2000-2004 to 83% for those diagnosed during 2010-2014,” Ms. Ssenyonga said. “The gains were largely driven by the improvements seen among children.”

Why haven’t adolescents and young adults gained as much ground in survival?

“They often have unique clinical needs,” Ms. Ssenyonga said. “Over the past few years, adolescents and young adults with leukemia in some parts of the world, including the U.S., have increasingly been treated under pediatric protocols. This has led to higher survival. However, this approach has not been adopted consistently, and survival for adolescents and young adults with leukemia is still generally lower than survival for children.”

Gwen Nichols, MD, chief medical officer of the Leukemia & Lymphoma Society, agreed that pediatric treatment protocols hold promise as treatments for young adults. However, “because we arbitrarily set an age cutoff for being an adult, many of these patients are treated by an adult [nonpediatric] hematologist/oncologist, and some patients in the 20-39 age group do not receive the more intensive treatment regimens given to children,” she said in an interview.

In another study, published in Cancer Epidemiology, Biomarkers, & Prevention, M.D. Anderson Cancer Center’s Dr. Roth and colleagues tracked 1,938 patients with ALL and 2,350 with AML who were diagnosed at ages 15-39 from 1980 to 2009. All lived at least 5 years after diagnosis. In both groups, about 58% were White, and most of the rest were Hispanic. The median age of diagnosis for ALL was 23 (range: 15-39) and 28 years for AML (range: 15-39).

“For ALL, 10-year survival for those diagnosed in the 1980s, 1990s, and 2000s was 83%, 88%, and 88%, respectively,” the researchers reported. “Ten-year survival for AML was 82%, 90%, and 90% for those diagnosed in the 1980s, 1990s, and 2000s, respectively.”

“Early mortality within 10 years of diagnosis was mostly secondary to leukemia progressing or recurring. We believe that later mortality is secondary to the development of late side effects from their cancer treatment,” Dr. Roth said.

He noted that many adolescents and young adults with ALL or AML receive stem-cell transplants. “This treatment approach is effective. However, it is associated with short- and long-term toxicity that impacts patients’ health for many years after treatment.”

Indeed, up to 80% of acute leukemia survivors have significant health complications after therapy, said the Leukemia & Lymphoma Society’s Dr. Nichols, who wasn’t surprised by the findings. According to the society, “even when treatments are effective, more than 70% of childhood cancer survivors have a chronic health condition and 42% have a severe, disabling or life-threatening condition 30 years after diagnosis.”

“It would be interesting to understand the male predominance better,” she added, noting that the study found that male patients had worse long-term survival than females (survival time ratio: 0.61, 95% confidence interval, 0.45-0.82). “While it is tempting to suggest it is due to difference in cardiac disease, I am not aware of data to support why there is this survival difference.”

What’s next? “In ALL, we now have a number of new modalities to treat high-risk and relapsed disease such as antibodies and CAR-T,” Dr. Nichols said. “We anticipate that 5-year survival can improve utilizing these modalities due to getting more patients into remission, hopefully while reducing chemotherapeutic toxicity.”

Dr. Nichol’s also highlighted the society’s new genomic-led Pediatric Acute Leukemia (PedAL) Master Clinical Trial, which began enrolling children with acute leukemia in the United States and Canada this year, in an effort to transform medicine’s traditional high-level chemotherapy strategy to their care. The project was launched in collaboration with the National Cancer Institute, Children’s Oncology Group, and the European Pediatric Acute Leukemia Foundation.

As part of the screening process, the biology of each child’s cancer will be identified, and families will be encouraged to enroll them in appropriate targeted therapy trials.

“Until we are able to decrease the toxicity of leukemia regimens, we won’t see a dramatic shift in late effects and thus in morbidity and mortality,” Dr. Nichols said. “The trial is an effort to test newer, less toxic regimens to begin to change that cycle.”

The 5-year survival study was funded by Children with Cancer UK, Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, National Cancer Institute, and the American Cancer Society. One author reports a grant from Macmillan Cancer Support, consultancy fees from Pfizer, and unsolicited small gifts from Moondance Cancer Initiative for philanthropic work. The other authors report no disclosures.

The long-term survival study was funded by the National Cancer Institute, the Archer Foundation and LyondellBasell Industries. Dr. Roth reports no disclosures; other authors report various disclosures. Dr. Nichols reports no disclosures.

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Two new studies offer insights into leukemia survival rates in the United States. From 2000 to 2014, a drop in mortality among children spurred a rise in 5-year leukemia survival rates among patients aged 0-24. But adolescents and young adults who survive 5 years after diagnosis face an ongoing higher risk of death, recent research revealed, and their long-term survival is lower compared to that of the general population.

“Outcomes are improving. However, additional efforts, support, and resources are needed to further improve short- and long-term survival for acute leukemia survivors. Targeted efforts focused on populations that face greater disparities in their survival are needed to move the needle faster,” Michael Roth, MD, codirector of the Adolescent and Young Adult Oncology Program at the University of Texas M.D. Anderson Cancer Center, said in an interview.

In one study, released in The Lancet Child & Adolescent Health, an international team of researchers tracked survival outcomes from various types of leukemia in 61 nations. The study focused on the years 2000-2014 and followed patients aged 0-24.

“Age-standardized 5-year net survival in children, adolescents, and young adults for all leukemias combined during 2010-14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia,” the researchers wrote. “Throughout 2000-14, survival from all leukemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries.”

The U.S. data came from 41 states that cover 86% of the nation’s population, lead author Naomi Ssenyonga, a research fellow at London School of Hygiene & Tropical Medicine, said in an interview.

The 5-year survival rate for acute lymphoid leukemia (ALL) rose from 80% during 2000-2004 to 86% during 2010-2014. Survival in patients with acute myeloid leukemia (AML) was lower than for other subtypes: 66% in 2010-2014 vs. 57% in 2000-2004.

In regard to all leukemias, “we noted a steady increase in the U.S. of 6 percentage points in 5-year survival, up from 77% for patients diagnosed during 2000-2004 to 83% for those diagnosed during 2010-2014,” Ms. Ssenyonga said. “The gains were largely driven by the improvements seen among children.”

Why haven’t adolescents and young adults gained as much ground in survival?

“They often have unique clinical needs,” Ms. Ssenyonga said. “Over the past few years, adolescents and young adults with leukemia in some parts of the world, including the U.S., have increasingly been treated under pediatric protocols. This has led to higher survival. However, this approach has not been adopted consistently, and survival for adolescents and young adults with leukemia is still generally lower than survival for children.”

Gwen Nichols, MD, chief medical officer of the Leukemia & Lymphoma Society, agreed that pediatric treatment protocols hold promise as treatments for young adults. However, “because we arbitrarily set an age cutoff for being an adult, many of these patients are treated by an adult [nonpediatric] hematologist/oncologist, and some patients in the 20-39 age group do not receive the more intensive treatment regimens given to children,” she said in an interview.

In another study, published in Cancer Epidemiology, Biomarkers, & Prevention, M.D. Anderson Cancer Center’s Dr. Roth and colleagues tracked 1,938 patients with ALL and 2,350 with AML who were diagnosed at ages 15-39 from 1980 to 2009. All lived at least 5 years after diagnosis. In both groups, about 58% were White, and most of the rest were Hispanic. The median age of diagnosis for ALL was 23 (range: 15-39) and 28 years for AML (range: 15-39).

“For ALL, 10-year survival for those diagnosed in the 1980s, 1990s, and 2000s was 83%, 88%, and 88%, respectively,” the researchers reported. “Ten-year survival for AML was 82%, 90%, and 90% for those diagnosed in the 1980s, 1990s, and 2000s, respectively.”

“Early mortality within 10 years of diagnosis was mostly secondary to leukemia progressing or recurring. We believe that later mortality is secondary to the development of late side effects from their cancer treatment,” Dr. Roth said.

He noted that many adolescents and young adults with ALL or AML receive stem-cell transplants. “This treatment approach is effective. However, it is associated with short- and long-term toxicity that impacts patients’ health for many years after treatment.”

Indeed, up to 80% of acute leukemia survivors have significant health complications after therapy, said the Leukemia & Lymphoma Society’s Dr. Nichols, who wasn’t surprised by the findings. According to the society, “even when treatments are effective, more than 70% of childhood cancer survivors have a chronic health condition and 42% have a severe, disabling or life-threatening condition 30 years after diagnosis.”

“It would be interesting to understand the male predominance better,” she added, noting that the study found that male patients had worse long-term survival than females (survival time ratio: 0.61, 95% confidence interval, 0.45-0.82). “While it is tempting to suggest it is due to difference in cardiac disease, I am not aware of data to support why there is this survival difference.”

What’s next? “In ALL, we now have a number of new modalities to treat high-risk and relapsed disease such as antibodies and CAR-T,” Dr. Nichols said. “We anticipate that 5-year survival can improve utilizing these modalities due to getting more patients into remission, hopefully while reducing chemotherapeutic toxicity.”

Dr. Nichol’s also highlighted the society’s new genomic-led Pediatric Acute Leukemia (PedAL) Master Clinical Trial, which began enrolling children with acute leukemia in the United States and Canada this year, in an effort to transform medicine’s traditional high-level chemotherapy strategy to their care. The project was launched in collaboration with the National Cancer Institute, Children’s Oncology Group, and the European Pediatric Acute Leukemia Foundation.

As part of the screening process, the biology of each child’s cancer will be identified, and families will be encouraged to enroll them in appropriate targeted therapy trials.

“Until we are able to decrease the toxicity of leukemia regimens, we won’t see a dramatic shift in late effects and thus in morbidity and mortality,” Dr. Nichols said. “The trial is an effort to test newer, less toxic regimens to begin to change that cycle.”

The 5-year survival study was funded by Children with Cancer UK, Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, National Cancer Institute, and the American Cancer Society. One author reports a grant from Macmillan Cancer Support, consultancy fees from Pfizer, and unsolicited small gifts from Moondance Cancer Initiative for philanthropic work. The other authors report no disclosures.

The long-term survival study was funded by the National Cancer Institute, the Archer Foundation and LyondellBasell Industries. Dr. Roth reports no disclosures; other authors report various disclosures. Dr. Nichols reports no disclosures.

Two new studies offer insights into leukemia survival rates in the United States. From 2000 to 2014, a drop in mortality among children spurred a rise in 5-year leukemia survival rates among patients aged 0-24. But adolescents and young adults who survive 5 years after diagnosis face an ongoing higher risk of death, recent research revealed, and their long-term survival is lower compared to that of the general population.

“Outcomes are improving. However, additional efforts, support, and resources are needed to further improve short- and long-term survival for acute leukemia survivors. Targeted efforts focused on populations that face greater disparities in their survival are needed to move the needle faster,” Michael Roth, MD, codirector of the Adolescent and Young Adult Oncology Program at the University of Texas M.D. Anderson Cancer Center, said in an interview.

In one study, released in The Lancet Child & Adolescent Health, an international team of researchers tracked survival outcomes from various types of leukemia in 61 nations. The study focused on the years 2000-2014 and followed patients aged 0-24.

“Age-standardized 5-year net survival in children, adolescents, and young adults for all leukemias combined during 2010-14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia,” the researchers wrote. “Throughout 2000-14, survival from all leukemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries.”

The U.S. data came from 41 states that cover 86% of the nation’s population, lead author Naomi Ssenyonga, a research fellow at London School of Hygiene & Tropical Medicine, said in an interview.

The 5-year survival rate for acute lymphoid leukemia (ALL) rose from 80% during 2000-2004 to 86% during 2010-2014. Survival in patients with acute myeloid leukemia (AML) was lower than for other subtypes: 66% in 2010-2014 vs. 57% in 2000-2004.

In regard to all leukemias, “we noted a steady increase in the U.S. of 6 percentage points in 5-year survival, up from 77% for patients diagnosed during 2000-2004 to 83% for those diagnosed during 2010-2014,” Ms. Ssenyonga said. “The gains were largely driven by the improvements seen among children.”

Why haven’t adolescents and young adults gained as much ground in survival?

“They often have unique clinical needs,” Ms. Ssenyonga said. “Over the past few years, adolescents and young adults with leukemia in some parts of the world, including the U.S., have increasingly been treated under pediatric protocols. This has led to higher survival. However, this approach has not been adopted consistently, and survival for adolescents and young adults with leukemia is still generally lower than survival for children.”

Gwen Nichols, MD, chief medical officer of the Leukemia & Lymphoma Society, agreed that pediatric treatment protocols hold promise as treatments for young adults. However, “because we arbitrarily set an age cutoff for being an adult, many of these patients are treated by an adult [nonpediatric] hematologist/oncologist, and some patients in the 20-39 age group do not receive the more intensive treatment regimens given to children,” she said in an interview.

In another study, published in Cancer Epidemiology, Biomarkers, & Prevention, M.D. Anderson Cancer Center’s Dr. Roth and colleagues tracked 1,938 patients with ALL and 2,350 with AML who were diagnosed at ages 15-39 from 1980 to 2009. All lived at least 5 years after diagnosis. In both groups, about 58% were White, and most of the rest were Hispanic. The median age of diagnosis for ALL was 23 (range: 15-39) and 28 years for AML (range: 15-39).

“For ALL, 10-year survival for those diagnosed in the 1980s, 1990s, and 2000s was 83%, 88%, and 88%, respectively,” the researchers reported. “Ten-year survival for AML was 82%, 90%, and 90% for those diagnosed in the 1980s, 1990s, and 2000s, respectively.”

“Early mortality within 10 years of diagnosis was mostly secondary to leukemia progressing or recurring. We believe that later mortality is secondary to the development of late side effects from their cancer treatment,” Dr. Roth said.

He noted that many adolescents and young adults with ALL or AML receive stem-cell transplants. “This treatment approach is effective. However, it is associated with short- and long-term toxicity that impacts patients’ health for many years after treatment.”

Indeed, up to 80% of acute leukemia survivors have significant health complications after therapy, said the Leukemia & Lymphoma Society’s Dr. Nichols, who wasn’t surprised by the findings. According to the society, “even when treatments are effective, more than 70% of childhood cancer survivors have a chronic health condition and 42% have a severe, disabling or life-threatening condition 30 years after diagnosis.”

“It would be interesting to understand the male predominance better,” she added, noting that the study found that male patients had worse long-term survival than females (survival time ratio: 0.61, 95% confidence interval, 0.45-0.82). “While it is tempting to suggest it is due to difference in cardiac disease, I am not aware of data to support why there is this survival difference.”

What’s next? “In ALL, we now have a number of new modalities to treat high-risk and relapsed disease such as antibodies and CAR-T,” Dr. Nichols said. “We anticipate that 5-year survival can improve utilizing these modalities due to getting more patients into remission, hopefully while reducing chemotherapeutic toxicity.”

Dr. Nichol’s also highlighted the society’s new genomic-led Pediatric Acute Leukemia (PedAL) Master Clinical Trial, which began enrolling children with acute leukemia in the United States and Canada this year, in an effort to transform medicine’s traditional high-level chemotherapy strategy to their care. The project was launched in collaboration with the National Cancer Institute, Children’s Oncology Group, and the European Pediatric Acute Leukemia Foundation.

As part of the screening process, the biology of each child’s cancer will be identified, and families will be encouraged to enroll them in appropriate targeted therapy trials.

“Until we are able to decrease the toxicity of leukemia regimens, we won’t see a dramatic shift in late effects and thus in morbidity and mortality,” Dr. Nichols said. “The trial is an effort to test newer, less toxic regimens to begin to change that cycle.”

The 5-year survival study was funded by Children with Cancer UK, Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, National Cancer Institute, and the American Cancer Society. One author reports a grant from Macmillan Cancer Support, consultancy fees from Pfizer, and unsolicited small gifts from Moondance Cancer Initiative for philanthropic work. The other authors report no disclosures.

The long-term survival study was funded by the National Cancer Institute, the Archer Foundation and LyondellBasell Industries. Dr. Roth reports no disclosures; other authors report various disclosures. Dr. Nichols reports no disclosures.

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New international dermatology registry tracks monkeypox cases

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The American Academy of Dermatology and the International League of Dermatological Societies (ILDS) have created a new registry that now accepts reports from health care providers worldwide about monkeypox cases and monkeypox vaccine reactions.

Patient data such as names and dates of birth will not be collected.



“As with our joint COVID-19 registry, we will be doing real-time data analysis during the outbreak,” dermatologist Esther Freeman, MD, PhD, director of MGH Global Health Dermatology at Massachusetts General Hospital, Boston, and a member of the AAD’s monkeypox task force, said in an interview. “We will to try to feed information back to our front line in terms of clinical characteristics of cases, morphology, and any unexpected findings.”

NIAID

According to Dr. Freeman, the principal investigator for the COVID-19 registry, this registry has allowed the quick gathering of information about dermatologic findings of COVID-19 from over 53 countries. “We have published over 15 papers, and we share data with outside investigators wishing to do their own analysis of registry-related data,” she said. “Our most-cited paper on COVID vaccine skin reactions has been cited almost 500 times since 2021. It has been used to educate the public on vaccine side effects and to combat vaccine hesitancy.”

Dr. Esther Freeman

The monkeypox registry “doesn’t belong to any one group or person,” Dr. Freeman said. “The idea with rapid data analysis is to be able to give back to the dermatologic community what is hard for us to see with any single case: Patterns and new findings that can be helpful to share with dermatologists and other physicians worldwide, all working together to stop an outbreak.”

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The American Academy of Dermatology and the International League of Dermatological Societies (ILDS) have created a new registry that now accepts reports from health care providers worldwide about monkeypox cases and monkeypox vaccine reactions.

Patient data such as names and dates of birth will not be collected.



“As with our joint COVID-19 registry, we will be doing real-time data analysis during the outbreak,” dermatologist Esther Freeman, MD, PhD, director of MGH Global Health Dermatology at Massachusetts General Hospital, Boston, and a member of the AAD’s monkeypox task force, said in an interview. “We will to try to feed information back to our front line in terms of clinical characteristics of cases, morphology, and any unexpected findings.”

NIAID

According to Dr. Freeman, the principal investigator for the COVID-19 registry, this registry has allowed the quick gathering of information about dermatologic findings of COVID-19 from over 53 countries. “We have published over 15 papers, and we share data with outside investigators wishing to do their own analysis of registry-related data,” she said. “Our most-cited paper on COVID vaccine skin reactions has been cited almost 500 times since 2021. It has been used to educate the public on vaccine side effects and to combat vaccine hesitancy.”

Dr. Esther Freeman

The monkeypox registry “doesn’t belong to any one group or person,” Dr. Freeman said. “The idea with rapid data analysis is to be able to give back to the dermatologic community what is hard for us to see with any single case: Patterns and new findings that can be helpful to share with dermatologists and other physicians worldwide, all working together to stop an outbreak.”

The American Academy of Dermatology and the International League of Dermatological Societies (ILDS) have created a new registry that now accepts reports from health care providers worldwide about monkeypox cases and monkeypox vaccine reactions.

Patient data such as names and dates of birth will not be collected.



“As with our joint COVID-19 registry, we will be doing real-time data analysis during the outbreak,” dermatologist Esther Freeman, MD, PhD, director of MGH Global Health Dermatology at Massachusetts General Hospital, Boston, and a member of the AAD’s monkeypox task force, said in an interview. “We will to try to feed information back to our front line in terms of clinical characteristics of cases, morphology, and any unexpected findings.”

NIAID

According to Dr. Freeman, the principal investigator for the COVID-19 registry, this registry has allowed the quick gathering of information about dermatologic findings of COVID-19 from over 53 countries. “We have published over 15 papers, and we share data with outside investigators wishing to do their own analysis of registry-related data,” she said. “Our most-cited paper on COVID vaccine skin reactions has been cited almost 500 times since 2021. It has been used to educate the public on vaccine side effects and to combat vaccine hesitancy.”

Dr. Esther Freeman

The monkeypox registry “doesn’t belong to any one group or person,” Dr. Freeman said. “The idea with rapid data analysis is to be able to give back to the dermatologic community what is hard for us to see with any single case: Patterns and new findings that can be helpful to share with dermatologists and other physicians worldwide, all working together to stop an outbreak.”

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Dermatology and monkeypox: What you need to know

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Dermatologists are urging colleagues to be on the lookout for monkeypox and cautioning them to not miss cases that might appear to be something else.

Dr. Misha Rosenbach

Diagnosing cases “can be hard and folks should keep a very open mind and consider monkeypox virus,” said Misha Rosenbach, MD, a University of Pennsylvania dermatologist and member of the American Academy of Dermatology’s ad hoc task force to develop monkeypox content.
 

Although it’s named after a primate, it turns out that monkeypox is quite the copycat. As dermatologists have learned, its lesions can look like those caused by a long list of other diseases including herpes, varicella, and syphilis. In small numbers, they can even appear to be insect bites.

To make things more complicated, a patient can have one or two lesions – or dozens. They often cluster in the anogenital area, likely reflecting transmission via sexual intercourse, unlike previous outbreaks in which lesions appeared all over the body. “We have to let go of some of our conceptions about what monkeypox might look like,” said dermatologist Esther Freeman, MD, PhD, associate professor of dermatology, Harvard University, Boston, and a member of the AAD task force.

Dr. Esther Freeman


To make things even more complicated, “the spectrum of illness that we are seeing has ranged from limited, subtle lesions to dramatic, widespread, ulcerative/necrotic lesions,” said Dr. Rosenbach, associate professor of dermatology at the University of Pennsylvania, Philadelphia.

But monkeypox has unique traits that can set it apart and pave the way toward a diagnosis, dermatologists say. And important patient data can help dermatologists gauge the likelihood of a case: Almost 99% of cases with data available have been in men, and among men with available information, 94% reported male-to-male sexual or close intimate contact during the 3 weeks before developing symptoms, according to a CDC report tracking cases from May through late July. So far, cases in women and children are extremely rare, although there have been some reported in the United States.

Are dermatologists likely to see monkeypox in the clinic? It’s unclear so far. Of four dermatologists interviewed for this article, only one has seen patients with monkeypox in person. But others say they’ve been sought for consultations. “I have been asked by infectious disease colleagues for advice remotely but have not seen it,” said dermatologist Howa Yeung, MD, MSc, assistant professor of dermatology, Emory University, Atlanta. “Most of the time, they’re catching all the symptomatic cases before any need for dermatology in-person referrals.”

Dr. Howa Yeung

Still, the rapid rate of growth of the outbreak – up from 3,487 in the United States on July 25 to 12,689 as of Aug.16 – suggests that more dermatologists will see cases, and consultations may become more common too.
 

Know your lesions

Lesions are the telltale signs of symptomatic monkeypox. According to a recent New England Journal of Medicine study of 528 monkeypox cases from 16 nations, diagnosed between April 27 and June 24, 2022, 95% had skin lesions (58% were vesiculopustular), most commonly in the anogenital area (73%), and on the trunk/arms/or legs (55%) and face (25%), and the palms/soles (10%).

However, “the current monkeypox outbreak often presents differently from the multiple classic vesiculopustules on the skin we see in textbooks,” Dr. Yeung said. “Sometimes people can present with throat pain or rectal pain, with isolated pharyngitis or proctitis. Sometimes there are so few lesions on the skin that it can be easily confused with a bug bite, folliculitis, herpes, dyshidrotic eczema, or other skin problems. This is where dermatologists will get consulted to clarify the diagnosis while the monkeypox PCR test is pending.”

Dr. Rosenbach, who has provided consultation services to other physicians about cases, said the lesions often appear to be vesicles or pustules, “but if you go to ‘pop’ it – e.g., for testing – it’s firm and without fluid. This is likely due to pox virus inclusion, similar to other diseases such as molluscum,” caused by another pox virus, he said. Molluscum lesions are “characteristically umbilicated, with a dimple in the center, and monkeypox lesions seem to be showing a roughly similar morphology with many bowl- or caldera-shaped lesions that are donut-like in appearance,” he added.

Over time, Dr. Rosenbach said, “lesions tend to evolve slowly from smaller flesh-colored or vaguely white firm papules to broader more umbilicated/donut-shaped lesions which may erode, ulcerate, develop a crust or scab, and then heal. The amount of scarring is not yet clear, but we anticipate it to be significant, especially in patients with more widespread or severe disease.”

Jon Peebles, MD, a dermatologist at Kaiser Permanente in Largo, Md., who has treated a few in-person monkeypox cases, said the lesions can be “exquisitely painful,” although he’s also seen patients with asymptomatic lesions. “Lesions are showing a predilection for the anogenital skin, though they can occur anywhere and not uncommonly involve the oral mucosa,” said Dr. Peebles, also a member of the AAD monkeypox task force.

Dr. Jon Klint Peebles


Dr. Yeung said it’s important to ask patients about their sexual orientation, gender identity, and sexual behaviors. “That is the only way to know who your patients are and the only way to understand who else may be at risks and can benefit from contact tracing and additional prevention measures, such as vaccination for asymptomatic sex partners.” (The Jynneos smallpox vaccine is Food and Drug Administration–approved to prevent monkeypox, although its efficacy is not entirely clear, and there’s controversy over expanding its limited availability by administering the vaccine intradermally.)

It’s also important to keep in mind that sexually transmitted infections (STIs) are common in gay and bisexual men. “Just because the patient is diagnosed with gonorrhea or syphilis does not mean the patient cannot also have monkeypox,” Dr. Rosenbach said. Indeed, the NEJM study reported that of 377 patients screened, 29% had an STI other than HIV, mostly syphilis (9%) and gonorrhea (8%). Of all 528 patients in the study (all male or transgender/nonbinary), 41% were HIV-positive, and the median number of sex partners in the last 3 months was 5 (range, 3-15).


 
 

 

Testing is crucial to rule monkeypox in – or out

While monkeypox lesions can be confused for other diseases, Dr. Rosenbach said that a diagnosis can be confirmed through various tests. Varicella zoster virus (VZV) and herpes simplex virus (HSV) have distinct findings on Tzanck smears (nuclear molding, multinucleated cells), and have widely available fairly rapid tests (PCR, or in some places, DFA). “Staph and bacterial folliculitis can usually be cultured quickly,” he said. “If you have someone with no risk factors/exposure, and you test for VZV, HSV, folliculitis, and it’s negative – you should know within 24 hours in most places – then you can broaden your differential diagnosis and consider alternate explanations, including monkeypox.”

Quest Diagnostics and Labcorp, two of the largest commercial labs in the United States, are now offering monkeypox tests. Labcorp says its test has a 2- to 3-day turnaround time.

As for treatment, some physicians are prescribing off-label use of tecovirimat (also known as TPOXX or ST-246), a smallpox antiviral treatment. The CDC offers guidelines about its use. “It seems to work very fast, with patients improving in 24-72 hours,” Dr. Rosenbach said. However, “it is still very challenging to give and get. There’s a cumbersome system to prescribe it, and it needs to be shipped from the national stockpile. Dermatologists should be working with their state health department, infection control, and infectious disease doctors.”

It’s likely that dermatologists are not comfortable with the process to access the drug, he said, “but if we do not act quickly to control the current outbreak, we will all – unfortunately – need to learn to be comfortable prescribing it.”

In regard to pain control, an over-the-counter painkiller approach may be appropriate depending on comorbidities, Dr. Rosenbach said. “Some patients with very severe disease, such as perianal involvement and proctitis, have such severe pain they need to be hospitalized. This is less common.”

Recommendations pending on scarring prevention

There’s limited high-quality evidence about the prevention of scarring in diseases like monkeypox, Dr. Rosenbach noted. “Any recommendations are usually based on very small, limited, uncontrolled studies. In the case of monkeypox, truly we are off the edge of the map.”

He advises cleaning lesions with gentle soap and water – keeping in mind that contaminated towels may spread disease – and potentially using a topical ointment-based dressing such as a Vaseline/nonstick dressing or Vaseline-impregnated gauze. If there’s concern about superinfection, as can occur with staph infections, topical antibiotics such as mupirocin 2% ointment may be appropriate, he said.

“Some folks like to try silica gel sheets to prevent scarring,” Dr. Rosenbach said. “There’s not a lot of evidence to support that, but they’re unlikely to be harmful. I would personally consider them, but it really depends on the extent of disease, anatomic sites involved, and access to care.”

Emory University’s Dr. Yeung also suggested using silicone gel or sheets to optimize the scar appearance once the lesions have crusted over. “People have used lasers, microneedling, etc., to improve smallpox scar appearance,” he added, “and I’m sure dermatologists will be the ones to study what works best for treating monkeypox scars.”

As for the big picture, Dr. Yeung said that dermatologists are critical in the fight to control monkeypox: “We can help our colleagues and patients manage symptoms and wound care, advocate for vaccination and treatment, treat long-term scarring sequelae, and destigmatize LGBTQ health care.”

The dermatologists interviewed for this article report no disclosures.

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Dermatologists are urging colleagues to be on the lookout for monkeypox and cautioning them to not miss cases that might appear to be something else.

Dr. Misha Rosenbach

Diagnosing cases “can be hard and folks should keep a very open mind and consider monkeypox virus,” said Misha Rosenbach, MD, a University of Pennsylvania dermatologist and member of the American Academy of Dermatology’s ad hoc task force to develop monkeypox content.
 

Although it’s named after a primate, it turns out that monkeypox is quite the copycat. As dermatologists have learned, its lesions can look like those caused by a long list of other diseases including herpes, varicella, and syphilis. In small numbers, they can even appear to be insect bites.

To make things more complicated, a patient can have one or two lesions – or dozens. They often cluster in the anogenital area, likely reflecting transmission via sexual intercourse, unlike previous outbreaks in which lesions appeared all over the body. “We have to let go of some of our conceptions about what monkeypox might look like,” said dermatologist Esther Freeman, MD, PhD, associate professor of dermatology, Harvard University, Boston, and a member of the AAD task force.

Dr. Esther Freeman


To make things even more complicated, “the spectrum of illness that we are seeing has ranged from limited, subtle lesions to dramatic, widespread, ulcerative/necrotic lesions,” said Dr. Rosenbach, associate professor of dermatology at the University of Pennsylvania, Philadelphia.

But monkeypox has unique traits that can set it apart and pave the way toward a diagnosis, dermatologists say. And important patient data can help dermatologists gauge the likelihood of a case: Almost 99% of cases with data available have been in men, and among men with available information, 94% reported male-to-male sexual or close intimate contact during the 3 weeks before developing symptoms, according to a CDC report tracking cases from May through late July. So far, cases in women and children are extremely rare, although there have been some reported in the United States.

Are dermatologists likely to see monkeypox in the clinic? It’s unclear so far. Of four dermatologists interviewed for this article, only one has seen patients with monkeypox in person. But others say they’ve been sought for consultations. “I have been asked by infectious disease colleagues for advice remotely but have not seen it,” said dermatologist Howa Yeung, MD, MSc, assistant professor of dermatology, Emory University, Atlanta. “Most of the time, they’re catching all the symptomatic cases before any need for dermatology in-person referrals.”

Dr. Howa Yeung

Still, the rapid rate of growth of the outbreak – up from 3,487 in the United States on July 25 to 12,689 as of Aug.16 – suggests that more dermatologists will see cases, and consultations may become more common too.
 

Know your lesions

Lesions are the telltale signs of symptomatic monkeypox. According to a recent New England Journal of Medicine study of 528 monkeypox cases from 16 nations, diagnosed between April 27 and June 24, 2022, 95% had skin lesions (58% were vesiculopustular), most commonly in the anogenital area (73%), and on the trunk/arms/or legs (55%) and face (25%), and the palms/soles (10%).

However, “the current monkeypox outbreak often presents differently from the multiple classic vesiculopustules on the skin we see in textbooks,” Dr. Yeung said. “Sometimes people can present with throat pain or rectal pain, with isolated pharyngitis or proctitis. Sometimes there are so few lesions on the skin that it can be easily confused with a bug bite, folliculitis, herpes, dyshidrotic eczema, or other skin problems. This is where dermatologists will get consulted to clarify the diagnosis while the monkeypox PCR test is pending.”

Dr. Rosenbach, who has provided consultation services to other physicians about cases, said the lesions often appear to be vesicles or pustules, “but if you go to ‘pop’ it – e.g., for testing – it’s firm and without fluid. This is likely due to pox virus inclusion, similar to other diseases such as molluscum,” caused by another pox virus, he said. Molluscum lesions are “characteristically umbilicated, with a dimple in the center, and monkeypox lesions seem to be showing a roughly similar morphology with many bowl- or caldera-shaped lesions that are donut-like in appearance,” he added.

Over time, Dr. Rosenbach said, “lesions tend to evolve slowly from smaller flesh-colored or vaguely white firm papules to broader more umbilicated/donut-shaped lesions which may erode, ulcerate, develop a crust or scab, and then heal. The amount of scarring is not yet clear, but we anticipate it to be significant, especially in patients with more widespread or severe disease.”

Jon Peebles, MD, a dermatologist at Kaiser Permanente in Largo, Md., who has treated a few in-person monkeypox cases, said the lesions can be “exquisitely painful,” although he’s also seen patients with asymptomatic lesions. “Lesions are showing a predilection for the anogenital skin, though they can occur anywhere and not uncommonly involve the oral mucosa,” said Dr. Peebles, also a member of the AAD monkeypox task force.

Dr. Jon Klint Peebles


Dr. Yeung said it’s important to ask patients about their sexual orientation, gender identity, and sexual behaviors. “That is the only way to know who your patients are and the only way to understand who else may be at risks and can benefit from contact tracing and additional prevention measures, such as vaccination for asymptomatic sex partners.” (The Jynneos smallpox vaccine is Food and Drug Administration–approved to prevent monkeypox, although its efficacy is not entirely clear, and there’s controversy over expanding its limited availability by administering the vaccine intradermally.)

It’s also important to keep in mind that sexually transmitted infections (STIs) are common in gay and bisexual men. “Just because the patient is diagnosed with gonorrhea or syphilis does not mean the patient cannot also have monkeypox,” Dr. Rosenbach said. Indeed, the NEJM study reported that of 377 patients screened, 29% had an STI other than HIV, mostly syphilis (9%) and gonorrhea (8%). Of all 528 patients in the study (all male or transgender/nonbinary), 41% were HIV-positive, and the median number of sex partners in the last 3 months was 5 (range, 3-15).


 
 

 

Testing is crucial to rule monkeypox in – or out

While monkeypox lesions can be confused for other diseases, Dr. Rosenbach said that a diagnosis can be confirmed through various tests. Varicella zoster virus (VZV) and herpes simplex virus (HSV) have distinct findings on Tzanck smears (nuclear molding, multinucleated cells), and have widely available fairly rapid tests (PCR, or in some places, DFA). “Staph and bacterial folliculitis can usually be cultured quickly,” he said. “If you have someone with no risk factors/exposure, and you test for VZV, HSV, folliculitis, and it’s negative – you should know within 24 hours in most places – then you can broaden your differential diagnosis and consider alternate explanations, including monkeypox.”

Quest Diagnostics and Labcorp, two of the largest commercial labs in the United States, are now offering monkeypox tests. Labcorp says its test has a 2- to 3-day turnaround time.

As for treatment, some physicians are prescribing off-label use of tecovirimat (also known as TPOXX or ST-246), a smallpox antiviral treatment. The CDC offers guidelines about its use. “It seems to work very fast, with patients improving in 24-72 hours,” Dr. Rosenbach said. However, “it is still very challenging to give and get. There’s a cumbersome system to prescribe it, and it needs to be shipped from the national stockpile. Dermatologists should be working with their state health department, infection control, and infectious disease doctors.”

It’s likely that dermatologists are not comfortable with the process to access the drug, he said, “but if we do not act quickly to control the current outbreak, we will all – unfortunately – need to learn to be comfortable prescribing it.”

In regard to pain control, an over-the-counter painkiller approach may be appropriate depending on comorbidities, Dr. Rosenbach said. “Some patients with very severe disease, such as perianal involvement and proctitis, have such severe pain they need to be hospitalized. This is less common.”

Recommendations pending on scarring prevention

There’s limited high-quality evidence about the prevention of scarring in diseases like monkeypox, Dr. Rosenbach noted. “Any recommendations are usually based on very small, limited, uncontrolled studies. In the case of monkeypox, truly we are off the edge of the map.”

He advises cleaning lesions with gentle soap and water – keeping in mind that contaminated towels may spread disease – and potentially using a topical ointment-based dressing such as a Vaseline/nonstick dressing or Vaseline-impregnated gauze. If there’s concern about superinfection, as can occur with staph infections, topical antibiotics such as mupirocin 2% ointment may be appropriate, he said.

“Some folks like to try silica gel sheets to prevent scarring,” Dr. Rosenbach said. “There’s not a lot of evidence to support that, but they’re unlikely to be harmful. I would personally consider them, but it really depends on the extent of disease, anatomic sites involved, and access to care.”

Emory University’s Dr. Yeung also suggested using silicone gel or sheets to optimize the scar appearance once the lesions have crusted over. “People have used lasers, microneedling, etc., to improve smallpox scar appearance,” he added, “and I’m sure dermatologists will be the ones to study what works best for treating monkeypox scars.”

As for the big picture, Dr. Yeung said that dermatologists are critical in the fight to control monkeypox: “We can help our colleagues and patients manage symptoms and wound care, advocate for vaccination and treatment, treat long-term scarring sequelae, and destigmatize LGBTQ health care.”

The dermatologists interviewed for this article report no disclosures.

Dermatologists are urging colleagues to be on the lookout for monkeypox and cautioning them to not miss cases that might appear to be something else.

Dr. Misha Rosenbach

Diagnosing cases “can be hard and folks should keep a very open mind and consider monkeypox virus,” said Misha Rosenbach, MD, a University of Pennsylvania dermatologist and member of the American Academy of Dermatology’s ad hoc task force to develop monkeypox content.
 

Although it’s named after a primate, it turns out that monkeypox is quite the copycat. As dermatologists have learned, its lesions can look like those caused by a long list of other diseases including herpes, varicella, and syphilis. In small numbers, they can even appear to be insect bites.

To make things more complicated, a patient can have one or two lesions – or dozens. They often cluster in the anogenital area, likely reflecting transmission via sexual intercourse, unlike previous outbreaks in which lesions appeared all over the body. “We have to let go of some of our conceptions about what monkeypox might look like,” said dermatologist Esther Freeman, MD, PhD, associate professor of dermatology, Harvard University, Boston, and a member of the AAD task force.

Dr. Esther Freeman


To make things even more complicated, “the spectrum of illness that we are seeing has ranged from limited, subtle lesions to dramatic, widespread, ulcerative/necrotic lesions,” said Dr. Rosenbach, associate professor of dermatology at the University of Pennsylvania, Philadelphia.

But monkeypox has unique traits that can set it apart and pave the way toward a diagnosis, dermatologists say. And important patient data can help dermatologists gauge the likelihood of a case: Almost 99% of cases with data available have been in men, and among men with available information, 94% reported male-to-male sexual or close intimate contact during the 3 weeks before developing symptoms, according to a CDC report tracking cases from May through late July. So far, cases in women and children are extremely rare, although there have been some reported in the United States.

Are dermatologists likely to see monkeypox in the clinic? It’s unclear so far. Of four dermatologists interviewed for this article, only one has seen patients with monkeypox in person. But others say they’ve been sought for consultations. “I have been asked by infectious disease colleagues for advice remotely but have not seen it,” said dermatologist Howa Yeung, MD, MSc, assistant professor of dermatology, Emory University, Atlanta. “Most of the time, they’re catching all the symptomatic cases before any need for dermatology in-person referrals.”

Dr. Howa Yeung

Still, the rapid rate of growth of the outbreak – up from 3,487 in the United States on July 25 to 12,689 as of Aug.16 – suggests that more dermatologists will see cases, and consultations may become more common too.
 

Know your lesions

Lesions are the telltale signs of symptomatic monkeypox. According to a recent New England Journal of Medicine study of 528 monkeypox cases from 16 nations, diagnosed between April 27 and June 24, 2022, 95% had skin lesions (58% were vesiculopustular), most commonly in the anogenital area (73%), and on the trunk/arms/or legs (55%) and face (25%), and the palms/soles (10%).

However, “the current monkeypox outbreak often presents differently from the multiple classic vesiculopustules on the skin we see in textbooks,” Dr. Yeung said. “Sometimes people can present with throat pain or rectal pain, with isolated pharyngitis or proctitis. Sometimes there are so few lesions on the skin that it can be easily confused with a bug bite, folliculitis, herpes, dyshidrotic eczema, or other skin problems. This is where dermatologists will get consulted to clarify the diagnosis while the monkeypox PCR test is pending.”

Dr. Rosenbach, who has provided consultation services to other physicians about cases, said the lesions often appear to be vesicles or pustules, “but if you go to ‘pop’ it – e.g., for testing – it’s firm and without fluid. This is likely due to pox virus inclusion, similar to other diseases such as molluscum,” caused by another pox virus, he said. Molluscum lesions are “characteristically umbilicated, with a dimple in the center, and monkeypox lesions seem to be showing a roughly similar morphology with many bowl- or caldera-shaped lesions that are donut-like in appearance,” he added.

Over time, Dr. Rosenbach said, “lesions tend to evolve slowly from smaller flesh-colored or vaguely white firm papules to broader more umbilicated/donut-shaped lesions which may erode, ulcerate, develop a crust or scab, and then heal. The amount of scarring is not yet clear, but we anticipate it to be significant, especially in patients with more widespread or severe disease.”

Jon Peebles, MD, a dermatologist at Kaiser Permanente in Largo, Md., who has treated a few in-person monkeypox cases, said the lesions can be “exquisitely painful,” although he’s also seen patients with asymptomatic lesions. “Lesions are showing a predilection for the anogenital skin, though they can occur anywhere and not uncommonly involve the oral mucosa,” said Dr. Peebles, also a member of the AAD monkeypox task force.

Dr. Jon Klint Peebles


Dr. Yeung said it’s important to ask patients about their sexual orientation, gender identity, and sexual behaviors. “That is the only way to know who your patients are and the only way to understand who else may be at risks and can benefit from contact tracing and additional prevention measures, such as vaccination for asymptomatic sex partners.” (The Jynneos smallpox vaccine is Food and Drug Administration–approved to prevent monkeypox, although its efficacy is not entirely clear, and there’s controversy over expanding its limited availability by administering the vaccine intradermally.)

It’s also important to keep in mind that sexually transmitted infections (STIs) are common in gay and bisexual men. “Just because the patient is diagnosed with gonorrhea or syphilis does not mean the patient cannot also have monkeypox,” Dr. Rosenbach said. Indeed, the NEJM study reported that of 377 patients screened, 29% had an STI other than HIV, mostly syphilis (9%) and gonorrhea (8%). Of all 528 patients in the study (all male or transgender/nonbinary), 41% were HIV-positive, and the median number of sex partners in the last 3 months was 5 (range, 3-15).


 
 

 

Testing is crucial to rule monkeypox in – or out

While monkeypox lesions can be confused for other diseases, Dr. Rosenbach said that a diagnosis can be confirmed through various tests. Varicella zoster virus (VZV) and herpes simplex virus (HSV) have distinct findings on Tzanck smears (nuclear molding, multinucleated cells), and have widely available fairly rapid tests (PCR, or in some places, DFA). “Staph and bacterial folliculitis can usually be cultured quickly,” he said. “If you have someone with no risk factors/exposure, and you test for VZV, HSV, folliculitis, and it’s negative – you should know within 24 hours in most places – then you can broaden your differential diagnosis and consider alternate explanations, including monkeypox.”

Quest Diagnostics and Labcorp, two of the largest commercial labs in the United States, are now offering monkeypox tests. Labcorp says its test has a 2- to 3-day turnaround time.

As for treatment, some physicians are prescribing off-label use of tecovirimat (also known as TPOXX or ST-246), a smallpox antiviral treatment. The CDC offers guidelines about its use. “It seems to work very fast, with patients improving in 24-72 hours,” Dr. Rosenbach said. However, “it is still very challenging to give and get. There’s a cumbersome system to prescribe it, and it needs to be shipped from the national stockpile. Dermatologists should be working with their state health department, infection control, and infectious disease doctors.”

It’s likely that dermatologists are not comfortable with the process to access the drug, he said, “but if we do not act quickly to control the current outbreak, we will all – unfortunately – need to learn to be comfortable prescribing it.”

In regard to pain control, an over-the-counter painkiller approach may be appropriate depending on comorbidities, Dr. Rosenbach said. “Some patients with very severe disease, such as perianal involvement and proctitis, have such severe pain they need to be hospitalized. This is less common.”

Recommendations pending on scarring prevention

There’s limited high-quality evidence about the prevention of scarring in diseases like monkeypox, Dr. Rosenbach noted. “Any recommendations are usually based on very small, limited, uncontrolled studies. In the case of monkeypox, truly we are off the edge of the map.”

He advises cleaning lesions with gentle soap and water – keeping in mind that contaminated towels may spread disease – and potentially using a topical ointment-based dressing such as a Vaseline/nonstick dressing or Vaseline-impregnated gauze. If there’s concern about superinfection, as can occur with staph infections, topical antibiotics such as mupirocin 2% ointment may be appropriate, he said.

“Some folks like to try silica gel sheets to prevent scarring,” Dr. Rosenbach said. “There’s not a lot of evidence to support that, but they’re unlikely to be harmful. I would personally consider them, but it really depends on the extent of disease, anatomic sites involved, and access to care.”

Emory University’s Dr. Yeung also suggested using silicone gel or sheets to optimize the scar appearance once the lesions have crusted over. “People have used lasers, microneedling, etc., to improve smallpox scar appearance,” he added, “and I’m sure dermatologists will be the ones to study what works best for treating monkeypox scars.”

As for the big picture, Dr. Yeung said that dermatologists are critical in the fight to control monkeypox: “We can help our colleagues and patients manage symptoms and wound care, advocate for vaccination and treatment, treat long-term scarring sequelae, and destigmatize LGBTQ health care.”

The dermatologists interviewed for this article report no disclosures.

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Phase 3 data: Zanubrutinib bests standard CLL treatment

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The second-generation selective Bruton tyrosine kinase inhibitor (BTKi) zanubrutinib outperformed the standard treatment bendamustine-rituximab in untreated chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), a new industry-funded phase-3 trial found.

At a median follow-up of 26.2 months, progression to worsening disease or death was much lower in patients with these conditions who took zanubrutinib (Brukinsa), compared with those who took bendamustine-rituximab (hazard ratio. 0.42; 95% confidence interval, 0.28-0.63; P < .00011). The study was published in The Lancet Oncology.

Researchers already knew that ibrutinib, another BTKi, improves progression-free survival, study coauthor Paolo Ghia, MD, PhD, professor of medical oncology at Vita-Salute San Raffaele University, Milan, said in an interview. “Now we confirmed that the same advantage can be seen” in zanubrutinib.

According to Dr. Ghia, bendamustine-rituximab has long been a standard treatment in blood cancers and is considered well tolerated and inexpensive. But BTKis such as first-in-line ibrutinib have shown better results, he said, “and progressively, we are going to abandon bendamustine-rituximab.”

However, ibrutinib causes significant adverse effects such as bleeding, worsening hypertension and arrhythmia, he noted. As a result, second-generation BTKi such as zanubrutinib have entered the picture. The Food and Drug Administration approved it in 2019 for mantle cell lymphoma, and it has since been approved for Waldenström’s macroglobulinemia and marginal zone lymphoma.

In 2021, an interim analysis in a trial of the drug in patients with previously treated CLL, compared with ibrutinib, found that “zanubrutinib was shown to have a superior response rate, an improved PFS, and a lower rate of atrial fibrillation/flutter.”

The drug’s manufacturer, BeiGene, launched the new open-label, multicenter study, in a bid for FDA approval of the drug as a frontline treatment for CLL and SLL. More than 150 hospitals in 14 countries participated in the trial from 2017 to 2019.

The subjects were all adults and at least 65 years old or with comorbidities; None had the genetic trait del(17)(p13.1); 241 were assigned to take zanubrutinib and 238 to bendamustine-rituximab. Another group consisted of 111 patients with CLL and del(17)(p13·1). According to the study authors, these patients are especially difficult to treat.

The vast majority of patients were White (92%-95% depending on group) and male (61%-71%); 90%-92% had CLL.

At follow-up, there was no difference in overall survival between the main zanubrutinib and bendamustine-rituximab groups; 29 (12%) of the 241 patients in the zanubrutinib group and 57 (24%) of 238 patients in the bendamustine-rituximab group had progressed or died (HR, 0.42; 95% CI, 0.27-0.66; P < .00011). Adverse events leading to discontinuation were more common in the bendamustine-rituximab group (14%) versus zanubrutinib (8%).

In the third group, which only received zanubrutinib, 14% of patients died at median follow-up of 30.5 months; 98% of patients had adverse effects, and 5% discontinued treatment.

The researchers wrote that “zanubrutinib showed superior progression­-free survival versus bendamustine-rituximab in older patients or those with comorbidities with untreated CLL, with a low incidence of cardiac arrhythmia. Similar efficacy was observed in patients with del(17p)­–positive disease.”

The study didn’t examine cost; zanubrutinib is quite expensive.

In an interview, hematologist-oncologist Anthony Mato, MD, of Memorial Sloan Kettering Cancer Center in New York said the new study is important although not surprising, since other medications in the same class have shown similar results. Zanubrutinib is an alternative to ibrutinib, although the latter remains “an excellent drug,” he said.

“The era of chemotherapy being a first choice is over,” he said. “We’ve had several randomized studies that show targeted therapies are better tolerated and have better outcomes. We now need to look through the choices to decide which one of these good options are the best for our patients.”

In an interview, hematologist-oncologist Joanna Rhodes, MD, of Northwell Health in Hempstead, N.Y., highlighted the side effect profile of zanubrutinib, noting that it is low and resembles that of other BTKis, making it “another excellent treatment option.”

“We are seeing that bruising, upper respiratory tract infections, diarrhea, and arthralgias are the most common side effects,” she said. “Bleeding also is a common side effect, which is consistent across the class of BTKis, with 5% of patients developing a major bleed. Also, 3% of patients treated with zanubrutinib developed atrial fibrillation, which is consistent with data from other trials. Treatment discontinuation rates were low (8%).”

The study was funded by BeiGene. The authors reported multiple disclosures. Dr. Mato reported research or consulting relationships with BeiGene, AstraZeneca, and AbbVie. Dr. Rhodes reported multiple research or consulting relationships with Abbvie, BeiGene, Genentech, and others.

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The second-generation selective Bruton tyrosine kinase inhibitor (BTKi) zanubrutinib outperformed the standard treatment bendamustine-rituximab in untreated chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), a new industry-funded phase-3 trial found.

At a median follow-up of 26.2 months, progression to worsening disease or death was much lower in patients with these conditions who took zanubrutinib (Brukinsa), compared with those who took bendamustine-rituximab (hazard ratio. 0.42; 95% confidence interval, 0.28-0.63; P < .00011). The study was published in The Lancet Oncology.

Researchers already knew that ibrutinib, another BTKi, improves progression-free survival, study coauthor Paolo Ghia, MD, PhD, professor of medical oncology at Vita-Salute San Raffaele University, Milan, said in an interview. “Now we confirmed that the same advantage can be seen” in zanubrutinib.

According to Dr. Ghia, bendamustine-rituximab has long been a standard treatment in blood cancers and is considered well tolerated and inexpensive. But BTKis such as first-in-line ibrutinib have shown better results, he said, “and progressively, we are going to abandon bendamustine-rituximab.”

However, ibrutinib causes significant adverse effects such as bleeding, worsening hypertension and arrhythmia, he noted. As a result, second-generation BTKi such as zanubrutinib have entered the picture. The Food and Drug Administration approved it in 2019 for mantle cell lymphoma, and it has since been approved for Waldenström’s macroglobulinemia and marginal zone lymphoma.

In 2021, an interim analysis in a trial of the drug in patients with previously treated CLL, compared with ibrutinib, found that “zanubrutinib was shown to have a superior response rate, an improved PFS, and a lower rate of atrial fibrillation/flutter.”

The drug’s manufacturer, BeiGene, launched the new open-label, multicenter study, in a bid for FDA approval of the drug as a frontline treatment for CLL and SLL. More than 150 hospitals in 14 countries participated in the trial from 2017 to 2019.

The subjects were all adults and at least 65 years old or with comorbidities; None had the genetic trait del(17)(p13.1); 241 were assigned to take zanubrutinib and 238 to bendamustine-rituximab. Another group consisted of 111 patients with CLL and del(17)(p13·1). According to the study authors, these patients are especially difficult to treat.

The vast majority of patients were White (92%-95% depending on group) and male (61%-71%); 90%-92% had CLL.

At follow-up, there was no difference in overall survival between the main zanubrutinib and bendamustine-rituximab groups; 29 (12%) of the 241 patients in the zanubrutinib group and 57 (24%) of 238 patients in the bendamustine-rituximab group had progressed or died (HR, 0.42; 95% CI, 0.27-0.66; P < .00011). Adverse events leading to discontinuation were more common in the bendamustine-rituximab group (14%) versus zanubrutinib (8%).

In the third group, which only received zanubrutinib, 14% of patients died at median follow-up of 30.5 months; 98% of patients had adverse effects, and 5% discontinued treatment.

The researchers wrote that “zanubrutinib showed superior progression­-free survival versus bendamustine-rituximab in older patients or those with comorbidities with untreated CLL, with a low incidence of cardiac arrhythmia. Similar efficacy was observed in patients with del(17p)­–positive disease.”

The study didn’t examine cost; zanubrutinib is quite expensive.

In an interview, hematologist-oncologist Anthony Mato, MD, of Memorial Sloan Kettering Cancer Center in New York said the new study is important although not surprising, since other medications in the same class have shown similar results. Zanubrutinib is an alternative to ibrutinib, although the latter remains “an excellent drug,” he said.

“The era of chemotherapy being a first choice is over,” he said. “We’ve had several randomized studies that show targeted therapies are better tolerated and have better outcomes. We now need to look through the choices to decide which one of these good options are the best for our patients.”

In an interview, hematologist-oncologist Joanna Rhodes, MD, of Northwell Health in Hempstead, N.Y., highlighted the side effect profile of zanubrutinib, noting that it is low and resembles that of other BTKis, making it “another excellent treatment option.”

“We are seeing that bruising, upper respiratory tract infections, diarrhea, and arthralgias are the most common side effects,” she said. “Bleeding also is a common side effect, which is consistent across the class of BTKis, with 5% of patients developing a major bleed. Also, 3% of patients treated with zanubrutinib developed atrial fibrillation, which is consistent with data from other trials. Treatment discontinuation rates were low (8%).”

The study was funded by BeiGene. The authors reported multiple disclosures. Dr. Mato reported research or consulting relationships with BeiGene, AstraZeneca, and AbbVie. Dr. Rhodes reported multiple research or consulting relationships with Abbvie, BeiGene, Genentech, and others.

The second-generation selective Bruton tyrosine kinase inhibitor (BTKi) zanubrutinib outperformed the standard treatment bendamustine-rituximab in untreated chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), a new industry-funded phase-3 trial found.

At a median follow-up of 26.2 months, progression to worsening disease or death was much lower in patients with these conditions who took zanubrutinib (Brukinsa), compared with those who took bendamustine-rituximab (hazard ratio. 0.42; 95% confidence interval, 0.28-0.63; P < .00011). The study was published in The Lancet Oncology.

Researchers already knew that ibrutinib, another BTKi, improves progression-free survival, study coauthor Paolo Ghia, MD, PhD, professor of medical oncology at Vita-Salute San Raffaele University, Milan, said in an interview. “Now we confirmed that the same advantage can be seen” in zanubrutinib.

According to Dr. Ghia, bendamustine-rituximab has long been a standard treatment in blood cancers and is considered well tolerated and inexpensive. But BTKis such as first-in-line ibrutinib have shown better results, he said, “and progressively, we are going to abandon bendamustine-rituximab.”

However, ibrutinib causes significant adverse effects such as bleeding, worsening hypertension and arrhythmia, he noted. As a result, second-generation BTKi such as zanubrutinib have entered the picture. The Food and Drug Administration approved it in 2019 for mantle cell lymphoma, and it has since been approved for Waldenström’s macroglobulinemia and marginal zone lymphoma.

In 2021, an interim analysis in a trial of the drug in patients with previously treated CLL, compared with ibrutinib, found that “zanubrutinib was shown to have a superior response rate, an improved PFS, and a lower rate of atrial fibrillation/flutter.”

The drug’s manufacturer, BeiGene, launched the new open-label, multicenter study, in a bid for FDA approval of the drug as a frontline treatment for CLL and SLL. More than 150 hospitals in 14 countries participated in the trial from 2017 to 2019.

The subjects were all adults and at least 65 years old or with comorbidities; None had the genetic trait del(17)(p13.1); 241 were assigned to take zanubrutinib and 238 to bendamustine-rituximab. Another group consisted of 111 patients with CLL and del(17)(p13·1). According to the study authors, these patients are especially difficult to treat.

The vast majority of patients were White (92%-95% depending on group) and male (61%-71%); 90%-92% had CLL.

At follow-up, there was no difference in overall survival between the main zanubrutinib and bendamustine-rituximab groups; 29 (12%) of the 241 patients in the zanubrutinib group and 57 (24%) of 238 patients in the bendamustine-rituximab group had progressed or died (HR, 0.42; 95% CI, 0.27-0.66; P < .00011). Adverse events leading to discontinuation were more common in the bendamustine-rituximab group (14%) versus zanubrutinib (8%).

In the third group, which only received zanubrutinib, 14% of patients died at median follow-up of 30.5 months; 98% of patients had adverse effects, and 5% discontinued treatment.

The researchers wrote that “zanubrutinib showed superior progression­-free survival versus bendamustine-rituximab in older patients or those with comorbidities with untreated CLL, with a low incidence of cardiac arrhythmia. Similar efficacy was observed in patients with del(17p)­–positive disease.”

The study didn’t examine cost; zanubrutinib is quite expensive.

In an interview, hematologist-oncologist Anthony Mato, MD, of Memorial Sloan Kettering Cancer Center in New York said the new study is important although not surprising, since other medications in the same class have shown similar results. Zanubrutinib is an alternative to ibrutinib, although the latter remains “an excellent drug,” he said.

“The era of chemotherapy being a first choice is over,” he said. “We’ve had several randomized studies that show targeted therapies are better tolerated and have better outcomes. We now need to look through the choices to decide which one of these good options are the best for our patients.”

In an interview, hematologist-oncologist Joanna Rhodes, MD, of Northwell Health in Hempstead, N.Y., highlighted the side effect profile of zanubrutinib, noting that it is low and resembles that of other BTKis, making it “another excellent treatment option.”

“We are seeing that bruising, upper respiratory tract infections, diarrhea, and arthralgias are the most common side effects,” she said. “Bleeding also is a common side effect, which is consistent across the class of BTKis, with 5% of patients developing a major bleed. Also, 3% of patients treated with zanubrutinib developed atrial fibrillation, which is consistent with data from other trials. Treatment discontinuation rates were low (8%).”

The study was funded by BeiGene. The authors reported multiple disclosures. Dr. Mato reported research or consulting relationships with BeiGene, AstraZeneca, and AbbVie. Dr. Rhodes reported multiple research or consulting relationships with Abbvie, BeiGene, Genentech, and others.

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